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New Teen STD Data Reinforce Annual Screening
The pediatric and family medicine communities need to do a better job of assessing sexual activity in adolescent patients, screening sexually active teens for sexually transmitted diseases, and counseling them about how to avoid becoming infected in the future.
Recently, a report of data from the 2003–2004 National Health and Nutrition Examination Survey (NHANES) revealed that one in four American teenagers had at least one prior sexually transmitted disease (STD). This should provide strong support for clinicians to incorporate guidelines from the Centers for Disease Control and Prevention and the American Academy of Pediatrics into their practices.
The survey found that 26% of a nationally representative sample of 838 adolescent girls aged 14–19 years were infected with at least one STD, while 15% had more than one. For the entire U.S. population, this translates to more than 3.2 million adolescent girls with human papillomavirus, chlamydia, herpes simplex virus, and/or trichomonas infections. The analysis excluded the prevalence of gonorrhea, syphilis, and HIV infections, although of course our adolescent population can contract those as well.
The data confirm that although the rate of teen pregnancy has recently declined, adolescent sexual behavior remains prevalent. While I'm not aware of data regarding the reasons for the drop in pregnancies among teens, I suspect that it's due at least in part to increased use of birth control, as well as abortion, rather than a large shift away from sexual behavior.
Indeed, teenagers—and even some preteens—are having sex. Clinicians need to ask adolescent patients if they are engaging in sexual behavior, and if so, to test them annually for STDs, screen for HIV (“Screen Sexually Active Teens for HIV,” PEDIATRIC NEWS, February 2007, p. 20) and counsel those who choose sexual activity about how to approach it safely and responsibly. And we need to start early. The CDC found that these infections, especially HPV, occur quickly after sexual debut. In fact, the STD prevalence was already 20% among those who reported just 1 year of sexual activity.
While there were racial differences—48% of black teens had at least one STD, compared with 20% of white teens—we should never assume that any early sexual activity is limited to specific racial or socioeconomic groups. This is an issue for every clinician, whether you practice in an urban, suburban, small-town, or rural setting. Yes, some of your patients are at greater risk than others—but you can't be sure which ones without asking about sexual activity.
Screening should take place annually at routine visits as well as at acute care visits whenever possible. Particularly in the adolescent age group, I think we need to take advantage of every opportunity. Specifically, teens should be asked if they're sexually active, and if so, what kind of activity they engage in, whether it is with members of their own or the opposite gender, and whether they use barrier protection (condoms).
All sexually active teens should be counseled about the importance of condoms and their proper use. For a variety of reasons, condom use is currently quite low among adolescents. Teen boys often don't want to use them because they decrease sensitivity or simply aren't seen as “manly.” An excellent resource for how to talk to teens about condoms is available at www.hws.wsu.edu/healthycoug/Men/condoms.html
Sexually active females should be screened yearly for Neisseria gonorrhoeae and Chlamydia trachomatis using a cervical or urine GC/CT nucleic acid amplification test, with urine being the preferred method today.
For males who have had sex with other males in the past year, an annual RPR (rapid plasma reagin) test for syphilis is recommended, along with annual pharyngeal gonorrhea cultures for those who have engaged in oral sex and rectal GC/CT swabs for those engaging in receptive anal intercourse. Although there are no specific recommendations for heterosexual males, we have learned that STDs can be asymptomatic. Personally I think screening is appropriate because it can be done easily with a urine specimen.
Recent CDC guidelines recommend that all sexually active individuals be screened annually for HIV, beginning at age 13. I endorse that recommendation, although many states have maintained the requirement for written informed consent for HIV testing, which places a barrier to proceeding. At least now all 50 states allow adolescents to sign their own consent forms without the need for a parental signature.
Although screening for HPV is not recommended, we can now offer the HPV vaccine to all of our female patients prior to sexual debut. Potentially, we will soon be able to offer it to our male patients as well.
Finally, I think we also should make an effort to encourage abstinence among our adolescent patients who have not yet embarked on sexual activity. I recently read an article about a female Harvard student who said she felt isolated because she had chosen to abstain from casual sex and decided to form a support group for like-minded young people. Contrary to popular belief, not every adolescent or young adult who chooses to abstain from casual sex or sex in general is of a strict religious or right-wing persuasion. Some have simply weighed the risks and benefits for themselves, and decided it's not right for them at this early stage in their lives.
The pediatric and family medicine communities need to do a better job of assessing sexual activity in adolescent patients, screening sexually active teens for sexually transmitted diseases, and counseling them about how to avoid becoming infected in the future.
Recently, a report of data from the 2003–2004 National Health and Nutrition Examination Survey (NHANES) revealed that one in four American teenagers had at least one prior sexually transmitted disease (STD). This should provide strong support for clinicians to incorporate guidelines from the Centers for Disease Control and Prevention and the American Academy of Pediatrics into their practices.
The survey found that 26% of a nationally representative sample of 838 adolescent girls aged 14–19 years were infected with at least one STD, while 15% had more than one. For the entire U.S. population, this translates to more than 3.2 million adolescent girls with human papillomavirus, chlamydia, herpes simplex virus, and/or trichomonas infections. The analysis excluded the prevalence of gonorrhea, syphilis, and HIV infections, although of course our adolescent population can contract those as well.
The data confirm that although the rate of teen pregnancy has recently declined, adolescent sexual behavior remains prevalent. While I'm not aware of data regarding the reasons for the drop in pregnancies among teens, I suspect that it's due at least in part to increased use of birth control, as well as abortion, rather than a large shift away from sexual behavior.
Indeed, teenagers—and even some preteens—are having sex. Clinicians need to ask adolescent patients if they are engaging in sexual behavior, and if so, to test them annually for STDs, screen for HIV (“Screen Sexually Active Teens for HIV,” PEDIATRIC NEWS, February 2007, p. 20) and counsel those who choose sexual activity about how to approach it safely and responsibly. And we need to start early. The CDC found that these infections, especially HPV, occur quickly after sexual debut. In fact, the STD prevalence was already 20% among those who reported just 1 year of sexual activity.
While there were racial differences—48% of black teens had at least one STD, compared with 20% of white teens—we should never assume that any early sexual activity is limited to specific racial or socioeconomic groups. This is an issue for every clinician, whether you practice in an urban, suburban, small-town, or rural setting. Yes, some of your patients are at greater risk than others—but you can't be sure which ones without asking about sexual activity.
Screening should take place annually at routine visits as well as at acute care visits whenever possible. Particularly in the adolescent age group, I think we need to take advantage of every opportunity. Specifically, teens should be asked if they're sexually active, and if so, what kind of activity they engage in, whether it is with members of their own or the opposite gender, and whether they use barrier protection (condoms).
All sexually active teens should be counseled about the importance of condoms and their proper use. For a variety of reasons, condom use is currently quite low among adolescents. Teen boys often don't want to use them because they decrease sensitivity or simply aren't seen as “manly.” An excellent resource for how to talk to teens about condoms is available at www.hws.wsu.edu/healthycoug/Men/condoms.html
Sexually active females should be screened yearly for Neisseria gonorrhoeae and Chlamydia trachomatis using a cervical or urine GC/CT nucleic acid amplification test, with urine being the preferred method today.
For males who have had sex with other males in the past year, an annual RPR (rapid plasma reagin) test for syphilis is recommended, along with annual pharyngeal gonorrhea cultures for those who have engaged in oral sex and rectal GC/CT swabs for those engaging in receptive anal intercourse. Although there are no specific recommendations for heterosexual males, we have learned that STDs can be asymptomatic. Personally I think screening is appropriate because it can be done easily with a urine specimen.
Recent CDC guidelines recommend that all sexually active individuals be screened annually for HIV, beginning at age 13. I endorse that recommendation, although many states have maintained the requirement for written informed consent for HIV testing, which places a barrier to proceeding. At least now all 50 states allow adolescents to sign their own consent forms without the need for a parental signature.
Although screening for HPV is not recommended, we can now offer the HPV vaccine to all of our female patients prior to sexual debut. Potentially, we will soon be able to offer it to our male patients as well.
Finally, I think we also should make an effort to encourage abstinence among our adolescent patients who have not yet embarked on sexual activity. I recently read an article about a female Harvard student who said she felt isolated because she had chosen to abstain from casual sex and decided to form a support group for like-minded young people. Contrary to popular belief, not every adolescent or young adult who chooses to abstain from casual sex or sex in general is of a strict religious or right-wing persuasion. Some have simply weighed the risks and benefits for themselves, and decided it's not right for them at this early stage in their lives.
The pediatric and family medicine communities need to do a better job of assessing sexual activity in adolescent patients, screening sexually active teens for sexually transmitted diseases, and counseling them about how to avoid becoming infected in the future.
Recently, a report of data from the 2003–2004 National Health and Nutrition Examination Survey (NHANES) revealed that one in four American teenagers had at least one prior sexually transmitted disease (STD). This should provide strong support for clinicians to incorporate guidelines from the Centers for Disease Control and Prevention and the American Academy of Pediatrics into their practices.
The survey found that 26% of a nationally representative sample of 838 adolescent girls aged 14–19 years were infected with at least one STD, while 15% had more than one. For the entire U.S. population, this translates to more than 3.2 million adolescent girls with human papillomavirus, chlamydia, herpes simplex virus, and/or trichomonas infections. The analysis excluded the prevalence of gonorrhea, syphilis, and HIV infections, although of course our adolescent population can contract those as well.
The data confirm that although the rate of teen pregnancy has recently declined, adolescent sexual behavior remains prevalent. While I'm not aware of data regarding the reasons for the drop in pregnancies among teens, I suspect that it's due at least in part to increased use of birth control, as well as abortion, rather than a large shift away from sexual behavior.
Indeed, teenagers—and even some preteens—are having sex. Clinicians need to ask adolescent patients if they are engaging in sexual behavior, and if so, to test them annually for STDs, screen for HIV (“Screen Sexually Active Teens for HIV,” PEDIATRIC NEWS, February 2007, p. 20) and counsel those who choose sexual activity about how to approach it safely and responsibly. And we need to start early. The CDC found that these infections, especially HPV, occur quickly after sexual debut. In fact, the STD prevalence was already 20% among those who reported just 1 year of sexual activity.
While there were racial differences—48% of black teens had at least one STD, compared with 20% of white teens—we should never assume that any early sexual activity is limited to specific racial or socioeconomic groups. This is an issue for every clinician, whether you practice in an urban, suburban, small-town, or rural setting. Yes, some of your patients are at greater risk than others—but you can't be sure which ones without asking about sexual activity.
Screening should take place annually at routine visits as well as at acute care visits whenever possible. Particularly in the adolescent age group, I think we need to take advantage of every opportunity. Specifically, teens should be asked if they're sexually active, and if so, what kind of activity they engage in, whether it is with members of their own or the opposite gender, and whether they use barrier protection (condoms).
All sexually active teens should be counseled about the importance of condoms and their proper use. For a variety of reasons, condom use is currently quite low among adolescents. Teen boys often don't want to use them because they decrease sensitivity or simply aren't seen as “manly.” An excellent resource for how to talk to teens about condoms is available at www.hws.wsu.edu/healthycoug/Men/condoms.html
Sexually active females should be screened yearly for Neisseria gonorrhoeae and Chlamydia trachomatis using a cervical or urine GC/CT nucleic acid amplification test, with urine being the preferred method today.
For males who have had sex with other males in the past year, an annual RPR (rapid plasma reagin) test for syphilis is recommended, along with annual pharyngeal gonorrhea cultures for those who have engaged in oral sex and rectal GC/CT swabs for those engaging in receptive anal intercourse. Although there are no specific recommendations for heterosexual males, we have learned that STDs can be asymptomatic. Personally I think screening is appropriate because it can be done easily with a urine specimen.
Recent CDC guidelines recommend that all sexually active individuals be screened annually for HIV, beginning at age 13. I endorse that recommendation, although many states have maintained the requirement for written informed consent for HIV testing, which places a barrier to proceeding. At least now all 50 states allow adolescents to sign their own consent forms without the need for a parental signature.
Although screening for HPV is not recommended, we can now offer the HPV vaccine to all of our female patients prior to sexual debut. Potentially, we will soon be able to offer it to our male patients as well.
Finally, I think we also should make an effort to encourage abstinence among our adolescent patients who have not yet embarked on sexual activity. I recently read an article about a female Harvard student who said she felt isolated because she had chosen to abstain from casual sex and decided to form a support group for like-minded young people. Contrary to popular belief, not every adolescent or young adult who chooses to abstain from casual sex or sex in general is of a strict religious or right-wing persuasion. Some have simply weighed the risks and benefits for themselves, and decided it's not right for them at this early stage in their lives.
Serotype 19A Disease Doesn't Outweigh PCV7 Benefit
The emergence of pneumococcal “replacement” serotype 19A should not lead us to view the seven-valent pneumococcal conjugate vaccine in anything other than an overwhelmingly positive light.
Since the introduction of PCV7 (Prevnar) in the United States in 2000, there has been concern that Streptococcus pneumoniae serotypes other than the seven included in the vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F) could become more prevalent. Now, several recent reports—including one from our group at Boston University—have documented both the relative and absolute increase in the nonvaccine serotype 19A in particular, along with an associated increase in antimicrobial resistance among these isolates.
This emergence suggests that we may need to shift our treatment approach to both invasive pneumococcal disease and noninvasive respiratory tract disease. It also underscores the need for continued surveillance. However, it should not lessen our enthusiasm for immunizing children with PCV7, nor should it lead us to relinquish our embrace of a vaccine that continues to provide enormous benefit for both child and adult health.
Indeed, the most recent data from the Centers for Disease Control and Prevention show that the overall rate of invasive pneumococcal disease (IPD) in the United States dropped by 43%, from 24/100,000 in 1998–1999 to 13/100,000 in 2004 to 14/100,000 in 2005. Between 1998–1999 and 2005, PCV7 prevented approximately 34,900 cases of IPD caused by vaccine serotypes and 24,000 cases overall. The declines in IPD were significant in all age groups, ranging from 17% among 50- to 64-year-olds to 77% among children younger than 5 years of age, Tamara Pilishvili of the CDC reported in October of this year at the annual meeting of the Infectious Diseases Society of America (IDSA).
These data are impressive. Nonetheless, we do need to be attentive to “replacement disease” in general and serotype 19A specifically, particularly when it comes to pneumococcal disease in the most vulnerable patients: those with developing immune systems (infants), those with underlying immune system abnormalities, and those with chronic conditions that put them at increased risk for complicated pneumococcal infections.
Here in Massachusetts, surveillance identified 467 cases of IPD in residents younger than 18 years of age. Annual incidence rates were stable between 2002 and 2006, ranging from 15.9 to 18.6 per 100,000 children younger than 5 years of age. Compared with the pre-PCV7 era (1990–1991), when the annual IPD rate was about 56.9/100,000 in that age group, these numbers represent a major decline of about 70% (MMWR 2007;56:1077–80).
Of 353 isolates available for serotyping during 2001–2006, 27% (97) were serotype 19A. Both the number and proportion of cases caused by that serotype increased from 10% (6) during 2001–2002 to 41% (33) during 2005–2006, while there were no significant changes in the proportions of IPD caused by other PCV7 or PCV7-related serotypes or by non-PCV7 serotypes. Since 2005–2006, 19A has become the most common serotype isolated. The majority of these isolates were nonsusceptible to penicillin, and during 2001–2006 there were significant increases in the proportion that were nonsusceptible to amoxicillin, ceftriaxone, or three or more classes of antimicrobials (multidrug resistant). It was of concern that 14 of 94 (15%) 19A isolates were highly resistant to ceftriaxone. We could not identify any clinical or demographic factor that characterized individuals who developed highly ceftriaxone-resistant 19A IPD.
Similar data from the U.S. Pediatric Multicenter Pneumococcal Surveillance Group were reported at IDSA by Dr. Sheldon L. Kaplan of Baylor College of Medicine, Houston. In eight U.S. children's hospitals, 19A has been the most common serotype causing invasive disease each year since 2003, accounting for 46% of all cases in 2006. Since 2000, penicillin nonsusceptibility and resistance increased—from 38% and 0%, respectively, in 2000, to 75% and 34% in 2006. No 19A isolates were ceftriaxone nonsusceptible or resistant in 2000; in 2006, those numbers had risen to 19% and 3%, respectively.
And the 19A story extends beyond invasive disease. In the widely publicized report last month by Dr. Michael E. Pichichero and Dr. Janet R. Casey, nine children with acute otitis media (AOM) were found to be infected with a 19A pneumococcal serotype that was resistant to all antibiotics approved by the Food and Drug Administration for use in children with the infection. Four of the children were ultimately treated with tympanostomy tube insertion, and the other five with levofloxacin (JAMA 2007;298:1772–8).
Although antimicrobial-resistant 19A has clearly taken hold in the PCV7 era, there is evidence that the vaccine is only one of several reasons for its emergence. In another IDSA abstract, Dr. Eunhwa Choi of Seoul (Republic of Korea) National University Medical College reported that increases in the proportion of 19A among clinical isolates of invasive disease occurred over a 15-year period prior to the introduction of PCV7 in Korea. In children under 5 years of age, 19A increased from 0% in 1991–1994 to 8% in 1995–1997, and to 20%–26% in 2001–2006. All of the 19A isolates were multidrug resistant.
Given these data, vancomycin remains first-line therapy for all suspected cases of pneumococcal meningitis, as well as for those who are severely ill. For the more common respiratory infections, we now need to consider serotype 19A as a potential etiology in a child who does not respond to traditional antibiotic therapy in 48–72 hours. In the case of AOM, tympanocentesis to identify the specific pathogen is the preferred approach. When that is not possible, a nasopharyngeal swab for identification of S. pneumoniae 19A is acceptable to identify children at risk for infection due to this multidrug resistant pathogen.
While waiting for the results in a child with respiratory tract infection who is well enough to be managed as an outpatient, ceftriaxone in doses of 75–100 mg/kg once per day, given either intramuscularly or intravenously for a minimum of 3 days is appropriate. Whether this will work depends on the level of resistance. If cultures reveal S. pneumoniae 19A and either the minimum inhibitory concentration is above 6–8 mg/mL or the child fails to respond to ceftriaxone, an alternative approach is necessary.
In that setting, I would use levofloxacin (the only fluoroquinolone available in a suspension). The American Academy of Pediatrics' recent guidelines on the use of fluoroquinolones in children (Pediatrics 2006;118:1287–92) did not specifically address this particular clinical scenario, but I agree with Dr. Pichichero and Dr. Casey that AOM caused by multidrug-resistant 19A S. pneumoniae is an appropriate off-label use once you have documentation that 19A is the likely pathogen. If the child can't tolerate levofloxacin or has a contraindication to a quinolone, surgical drainage of the ear with tube placement is the only remaining option.
Future vaccines may address the 19A problem. GlaxoSmithKline's 10-valent Synflorix will contain a 19F capsular polysaccharide that results in some functional activity against serotype 19A. Wyeth's 13-valent conjugate pneumococcal vaccine will actually contain serotype 19A capsular polysaccharide. Both vaccines are in phase III clinical trials and could be licensed in 2009–2010. While I don't expect IPD to ever completely disappear from the planet, these second-generation vaccines could further reduce the number of cases of IPD in children and potentially adults.
I am on the advisory board for both the GSK and Wyeth pneumococcal vaccine programs. I also have an investigator-initiated grant from Wyeth for statewide surveillance. I have no current relationship with the makers of levofloxacin.
The emergence of pneumococcal “replacement” serotype 19A should not lead us to view the seven-valent pneumococcal conjugate vaccine in anything other than an overwhelmingly positive light.
Since the introduction of PCV7 (Prevnar) in the United States in 2000, there has been concern that Streptococcus pneumoniae serotypes other than the seven included in the vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F) could become more prevalent. Now, several recent reports—including one from our group at Boston University—have documented both the relative and absolute increase in the nonvaccine serotype 19A in particular, along with an associated increase in antimicrobial resistance among these isolates.
This emergence suggests that we may need to shift our treatment approach to both invasive pneumococcal disease and noninvasive respiratory tract disease. It also underscores the need for continued surveillance. However, it should not lessen our enthusiasm for immunizing children with PCV7, nor should it lead us to relinquish our embrace of a vaccine that continues to provide enormous benefit for both child and adult health.
Indeed, the most recent data from the Centers for Disease Control and Prevention show that the overall rate of invasive pneumococcal disease (IPD) in the United States dropped by 43%, from 24/100,000 in 1998–1999 to 13/100,000 in 2004 to 14/100,000 in 2005. Between 1998–1999 and 2005, PCV7 prevented approximately 34,900 cases of IPD caused by vaccine serotypes and 24,000 cases overall. The declines in IPD were significant in all age groups, ranging from 17% among 50- to 64-year-olds to 77% among children younger than 5 years of age, Tamara Pilishvili of the CDC reported in October of this year at the annual meeting of the Infectious Diseases Society of America (IDSA).
These data are impressive. Nonetheless, we do need to be attentive to “replacement disease” in general and serotype 19A specifically, particularly when it comes to pneumococcal disease in the most vulnerable patients: those with developing immune systems (infants), those with underlying immune system abnormalities, and those with chronic conditions that put them at increased risk for complicated pneumococcal infections.
Here in Massachusetts, surveillance identified 467 cases of IPD in residents younger than 18 years of age. Annual incidence rates were stable between 2002 and 2006, ranging from 15.9 to 18.6 per 100,000 children younger than 5 years of age. Compared with the pre-PCV7 era (1990–1991), when the annual IPD rate was about 56.9/100,000 in that age group, these numbers represent a major decline of about 70% (MMWR 2007;56:1077–80).
Of 353 isolates available for serotyping during 2001–2006, 27% (97) were serotype 19A. Both the number and proportion of cases caused by that serotype increased from 10% (6) during 2001–2002 to 41% (33) during 2005–2006, while there were no significant changes in the proportions of IPD caused by other PCV7 or PCV7-related serotypes or by non-PCV7 serotypes. Since 2005–2006, 19A has become the most common serotype isolated. The majority of these isolates were nonsusceptible to penicillin, and during 2001–2006 there were significant increases in the proportion that were nonsusceptible to amoxicillin, ceftriaxone, or three or more classes of antimicrobials (multidrug resistant). It was of concern that 14 of 94 (15%) 19A isolates were highly resistant to ceftriaxone. We could not identify any clinical or demographic factor that characterized individuals who developed highly ceftriaxone-resistant 19A IPD.
Similar data from the U.S. Pediatric Multicenter Pneumococcal Surveillance Group were reported at IDSA by Dr. Sheldon L. Kaplan of Baylor College of Medicine, Houston. In eight U.S. children's hospitals, 19A has been the most common serotype causing invasive disease each year since 2003, accounting for 46% of all cases in 2006. Since 2000, penicillin nonsusceptibility and resistance increased—from 38% and 0%, respectively, in 2000, to 75% and 34% in 2006. No 19A isolates were ceftriaxone nonsusceptible or resistant in 2000; in 2006, those numbers had risen to 19% and 3%, respectively.
And the 19A story extends beyond invasive disease. In the widely publicized report last month by Dr. Michael E. Pichichero and Dr. Janet R. Casey, nine children with acute otitis media (AOM) were found to be infected with a 19A pneumococcal serotype that was resistant to all antibiotics approved by the Food and Drug Administration for use in children with the infection. Four of the children were ultimately treated with tympanostomy tube insertion, and the other five with levofloxacin (JAMA 2007;298:1772–8).
Although antimicrobial-resistant 19A has clearly taken hold in the PCV7 era, there is evidence that the vaccine is only one of several reasons for its emergence. In another IDSA abstract, Dr. Eunhwa Choi of Seoul (Republic of Korea) National University Medical College reported that increases in the proportion of 19A among clinical isolates of invasive disease occurred over a 15-year period prior to the introduction of PCV7 in Korea. In children under 5 years of age, 19A increased from 0% in 1991–1994 to 8% in 1995–1997, and to 20%–26% in 2001–2006. All of the 19A isolates were multidrug resistant.
Given these data, vancomycin remains first-line therapy for all suspected cases of pneumococcal meningitis, as well as for those who are severely ill. For the more common respiratory infections, we now need to consider serotype 19A as a potential etiology in a child who does not respond to traditional antibiotic therapy in 48–72 hours. In the case of AOM, tympanocentesis to identify the specific pathogen is the preferred approach. When that is not possible, a nasopharyngeal swab for identification of S. pneumoniae 19A is acceptable to identify children at risk for infection due to this multidrug resistant pathogen.
While waiting for the results in a child with respiratory tract infection who is well enough to be managed as an outpatient, ceftriaxone in doses of 75–100 mg/kg once per day, given either intramuscularly or intravenously for a minimum of 3 days is appropriate. Whether this will work depends on the level of resistance. If cultures reveal S. pneumoniae 19A and either the minimum inhibitory concentration is above 6–8 mg/mL or the child fails to respond to ceftriaxone, an alternative approach is necessary.
In that setting, I would use levofloxacin (the only fluoroquinolone available in a suspension). The American Academy of Pediatrics' recent guidelines on the use of fluoroquinolones in children (Pediatrics 2006;118:1287–92) did not specifically address this particular clinical scenario, but I agree with Dr. Pichichero and Dr. Casey that AOM caused by multidrug-resistant 19A S. pneumoniae is an appropriate off-label use once you have documentation that 19A is the likely pathogen. If the child can't tolerate levofloxacin or has a contraindication to a quinolone, surgical drainage of the ear with tube placement is the only remaining option.
Future vaccines may address the 19A problem. GlaxoSmithKline's 10-valent Synflorix will contain a 19F capsular polysaccharide that results in some functional activity against serotype 19A. Wyeth's 13-valent conjugate pneumococcal vaccine will actually contain serotype 19A capsular polysaccharide. Both vaccines are in phase III clinical trials and could be licensed in 2009–2010. While I don't expect IPD to ever completely disappear from the planet, these second-generation vaccines could further reduce the number of cases of IPD in children and potentially adults.
I am on the advisory board for both the GSK and Wyeth pneumococcal vaccine programs. I also have an investigator-initiated grant from Wyeth for statewide surveillance. I have no current relationship with the makers of levofloxacin.
The emergence of pneumococcal “replacement” serotype 19A should not lead us to view the seven-valent pneumococcal conjugate vaccine in anything other than an overwhelmingly positive light.
Since the introduction of PCV7 (Prevnar) in the United States in 2000, there has been concern that Streptococcus pneumoniae serotypes other than the seven included in the vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F) could become more prevalent. Now, several recent reports—including one from our group at Boston University—have documented both the relative and absolute increase in the nonvaccine serotype 19A in particular, along with an associated increase in antimicrobial resistance among these isolates.
This emergence suggests that we may need to shift our treatment approach to both invasive pneumococcal disease and noninvasive respiratory tract disease. It also underscores the need for continued surveillance. However, it should not lessen our enthusiasm for immunizing children with PCV7, nor should it lead us to relinquish our embrace of a vaccine that continues to provide enormous benefit for both child and adult health.
Indeed, the most recent data from the Centers for Disease Control and Prevention show that the overall rate of invasive pneumococcal disease (IPD) in the United States dropped by 43%, from 24/100,000 in 1998–1999 to 13/100,000 in 2004 to 14/100,000 in 2005. Between 1998–1999 and 2005, PCV7 prevented approximately 34,900 cases of IPD caused by vaccine serotypes and 24,000 cases overall. The declines in IPD were significant in all age groups, ranging from 17% among 50- to 64-year-olds to 77% among children younger than 5 years of age, Tamara Pilishvili of the CDC reported in October of this year at the annual meeting of the Infectious Diseases Society of America (IDSA).
These data are impressive. Nonetheless, we do need to be attentive to “replacement disease” in general and serotype 19A specifically, particularly when it comes to pneumococcal disease in the most vulnerable patients: those with developing immune systems (infants), those with underlying immune system abnormalities, and those with chronic conditions that put them at increased risk for complicated pneumococcal infections.
Here in Massachusetts, surveillance identified 467 cases of IPD in residents younger than 18 years of age. Annual incidence rates were stable between 2002 and 2006, ranging from 15.9 to 18.6 per 100,000 children younger than 5 years of age. Compared with the pre-PCV7 era (1990–1991), when the annual IPD rate was about 56.9/100,000 in that age group, these numbers represent a major decline of about 70% (MMWR 2007;56:1077–80).
Of 353 isolates available for serotyping during 2001–2006, 27% (97) were serotype 19A. Both the number and proportion of cases caused by that serotype increased from 10% (6) during 2001–2002 to 41% (33) during 2005–2006, while there were no significant changes in the proportions of IPD caused by other PCV7 or PCV7-related serotypes or by non-PCV7 serotypes. Since 2005–2006, 19A has become the most common serotype isolated. The majority of these isolates were nonsusceptible to penicillin, and during 2001–2006 there were significant increases in the proportion that were nonsusceptible to amoxicillin, ceftriaxone, or three or more classes of antimicrobials (multidrug resistant). It was of concern that 14 of 94 (15%) 19A isolates were highly resistant to ceftriaxone. We could not identify any clinical or demographic factor that characterized individuals who developed highly ceftriaxone-resistant 19A IPD.
Similar data from the U.S. Pediatric Multicenter Pneumococcal Surveillance Group were reported at IDSA by Dr. Sheldon L. Kaplan of Baylor College of Medicine, Houston. In eight U.S. children's hospitals, 19A has been the most common serotype causing invasive disease each year since 2003, accounting for 46% of all cases in 2006. Since 2000, penicillin nonsusceptibility and resistance increased—from 38% and 0%, respectively, in 2000, to 75% and 34% in 2006. No 19A isolates were ceftriaxone nonsusceptible or resistant in 2000; in 2006, those numbers had risen to 19% and 3%, respectively.
And the 19A story extends beyond invasive disease. In the widely publicized report last month by Dr. Michael E. Pichichero and Dr. Janet R. Casey, nine children with acute otitis media (AOM) were found to be infected with a 19A pneumococcal serotype that was resistant to all antibiotics approved by the Food and Drug Administration for use in children with the infection. Four of the children were ultimately treated with tympanostomy tube insertion, and the other five with levofloxacin (JAMA 2007;298:1772–8).
Although antimicrobial-resistant 19A has clearly taken hold in the PCV7 era, there is evidence that the vaccine is only one of several reasons for its emergence. In another IDSA abstract, Dr. Eunhwa Choi of Seoul (Republic of Korea) National University Medical College reported that increases in the proportion of 19A among clinical isolates of invasive disease occurred over a 15-year period prior to the introduction of PCV7 in Korea. In children under 5 years of age, 19A increased from 0% in 1991–1994 to 8% in 1995–1997, and to 20%–26% in 2001–2006. All of the 19A isolates were multidrug resistant.
Given these data, vancomycin remains first-line therapy for all suspected cases of pneumococcal meningitis, as well as for those who are severely ill. For the more common respiratory infections, we now need to consider serotype 19A as a potential etiology in a child who does not respond to traditional antibiotic therapy in 48–72 hours. In the case of AOM, tympanocentesis to identify the specific pathogen is the preferred approach. When that is not possible, a nasopharyngeal swab for identification of S. pneumoniae 19A is acceptable to identify children at risk for infection due to this multidrug resistant pathogen.
While waiting for the results in a child with respiratory tract infection who is well enough to be managed as an outpatient, ceftriaxone in doses of 75–100 mg/kg once per day, given either intramuscularly or intravenously for a minimum of 3 days is appropriate. Whether this will work depends on the level of resistance. If cultures reveal S. pneumoniae 19A and either the minimum inhibitory concentration is above 6–8 mg/mL or the child fails to respond to ceftriaxone, an alternative approach is necessary.
In that setting, I would use levofloxacin (the only fluoroquinolone available in a suspension). The American Academy of Pediatrics' recent guidelines on the use of fluoroquinolones in children (Pediatrics 2006;118:1287–92) did not specifically address this particular clinical scenario, but I agree with Dr. Pichichero and Dr. Casey that AOM caused by multidrug-resistant 19A S. pneumoniae is an appropriate off-label use once you have documentation that 19A is the likely pathogen. If the child can't tolerate levofloxacin or has a contraindication to a quinolone, surgical drainage of the ear with tube placement is the only remaining option.
Future vaccines may address the 19A problem. GlaxoSmithKline's 10-valent Synflorix will contain a 19F capsular polysaccharide that results in some functional activity against serotype 19A. Wyeth's 13-valent conjugate pneumococcal vaccine will actually contain serotype 19A capsular polysaccharide. Both vaccines are in phase III clinical trials and could be licensed in 2009–2010. While I don't expect IPD to ever completely disappear from the planet, these second-generation vaccines could further reduce the number of cases of IPD in children and potentially adults.
I am on the advisory board for both the GSK and Wyeth pneumococcal vaccine programs. I also have an investigator-initiated grant from Wyeth for statewide surveillance. I have no current relationship with the makers of levofloxacin.
Screen Sexually Active Teens for HIV
Screening for HIV should be routine for all sexually active adolescents.
In September 2006, the Centers for Disease Control and Prevention issued new recommendations calling for annual routine HIV screening in health care settings for all patients aged 13–64 years, regardless of perceived risk status. The guidelines are notable in that they call for a policy of “opt-out” screening rather than requiring written informed consent, and they allow for screening to occur without pre-test counseling in situations where such a requirement would present a barrier (MMWR 2006;55:RR-14).
The CDC believes—and I agree—that these changes are necessary. Our current practice of screening only those individuals perceived to be at high risk isn't working. There are about 1 million HIV-infected people in the United States, as many as 25% of whom are undiagnosed. Not only are they missing out on the potential benefits of antiretroviral therapy, but their sexual activity represents a threat for transmission to others. Current HIV testing programs identify approximately 40,000 new cases every year, a number that has not changed in nearly a decade.
Teenagers are among those at risk. The CDC guidelines note that in the 2005 national Youth Risk Behavior Survey, 47% of high school students reported having had sexual intercourse at least once, and 37% of those who were sexually active had not used a condom during their most recent act of sexual intercourse. In 2005, according to the CDC, heterosexual intercourse overall accounted for 15% of HIV transmission in males and 80% in females. (Male-to-male sexual contact made up 67% of transmission among males.)
I strongly support routine screening for our adolescent patients but with certain modifications to the CDC's stated policy. While the idea of eliminating all risk profiling makes sense for the adult community, in adolescents I think it boils down to one question: Are you sexually active? If the answer is yes, no matter what the circumstances, screening is indicated. Clearly, this is an issue for every physician who treats adolescents.
I also think that, contrary to the guideline for adults, adolescents do need counseling about HIV before and after testing. Simply telling a teenager that you plan to test them for HIV unless they opt out is not adequate. At a minimum, we need to tell teens that sexual activity is a risk factor for the transmission of HIV, and for that reason we believe they should be tested. Just because a teen is monogamous doesn't mean her or his partner is. We must impress upon them that even if they're sure their partner is “safe,” they can't be confident that the same applied to their partner's previous partners.
We also should explain that the testing is a two-step process. The initial step (ELISA) identifies HIV-specific antibodies but sometimes is falsely positive. If the ELISA is positive, a Western blot test is done for confirmation. No matter what the result, a second visit is highly recommended. If the adolescent is HIV positive, this visit should be used to assess how the teen is handling the diagnosis emotionally, to determine the best course of action for treatment and to refer the teen for other support services.
If the test comes back negative, the primary care physician should still use the opportunity to remind teens that if they're sexually active and not using condoms, they're always at risk. The test was only a snapshot in time.
It's also important to explain beforehand what a positive test means: It indicates that there is an HIV infection, but it gives no information about what stage of the disease they're in. They could be very early in the course of disease, or very late in the course of disease and already have AIDS.
Just as the CDC recommends for adults, I believe that physicians should use every medical encounter with an adolescent, be it a sports physical or an acute illness visit, to do HIV counseling and screening.
The issue of parental consent is still problematic and a potential barrier. Ideally, of course, the teenager is willing to have his or her parent or guardian consent to testing. But if not, the laws concerning consent and confidentiality vary by state. In general, public health statute and legal precedent allow for evaluation and treatment of minors for sexually transmitted diseases without parental knowledge or consent. The Guttmacher Institute's Web site is an excellent resource for specific state-by-state information on laws governing minors' consent to medical care, access to STD services, and sex and STD/HIV education (www.guttmacher.org
Most state laws, however, don't yet address the issue of consent for screening for HIV in asymptomatic adolescents. The American Academy of Pediatrics advises that physicians obtain advice regarding the disposition of laws in their state addressing consent or other legal obligations from their attorney or another trusted local source, such as their hospital's office of legal compliance. The AAP Committee on Pediatric AIDS is expected to issue a statement in response to the CDC guidelines sometime in 2007.
Screening for HIV should be routine for all sexually active adolescents.
In September 2006, the Centers for Disease Control and Prevention issued new recommendations calling for annual routine HIV screening in health care settings for all patients aged 13–64 years, regardless of perceived risk status. The guidelines are notable in that they call for a policy of “opt-out” screening rather than requiring written informed consent, and they allow for screening to occur without pre-test counseling in situations where such a requirement would present a barrier (MMWR 2006;55:RR-14).
The CDC believes—and I agree—that these changes are necessary. Our current practice of screening only those individuals perceived to be at high risk isn't working. There are about 1 million HIV-infected people in the United States, as many as 25% of whom are undiagnosed. Not only are they missing out on the potential benefits of antiretroviral therapy, but their sexual activity represents a threat for transmission to others. Current HIV testing programs identify approximately 40,000 new cases every year, a number that has not changed in nearly a decade.
Teenagers are among those at risk. The CDC guidelines note that in the 2005 national Youth Risk Behavior Survey, 47% of high school students reported having had sexual intercourse at least once, and 37% of those who were sexually active had not used a condom during their most recent act of sexual intercourse. In 2005, according to the CDC, heterosexual intercourse overall accounted for 15% of HIV transmission in males and 80% in females. (Male-to-male sexual contact made up 67% of transmission among males.)
I strongly support routine screening for our adolescent patients but with certain modifications to the CDC's stated policy. While the idea of eliminating all risk profiling makes sense for the adult community, in adolescents I think it boils down to one question: Are you sexually active? If the answer is yes, no matter what the circumstances, screening is indicated. Clearly, this is an issue for every physician who treats adolescents.
I also think that, contrary to the guideline for adults, adolescents do need counseling about HIV before and after testing. Simply telling a teenager that you plan to test them for HIV unless they opt out is not adequate. At a minimum, we need to tell teens that sexual activity is a risk factor for the transmission of HIV, and for that reason we believe they should be tested. Just because a teen is monogamous doesn't mean her or his partner is. We must impress upon them that even if they're sure their partner is “safe,” they can't be confident that the same applied to their partner's previous partners.
We also should explain that the testing is a two-step process. The initial step (ELISA) identifies HIV-specific antibodies but sometimes is falsely positive. If the ELISA is positive, a Western blot test is done for confirmation. No matter what the result, a second visit is highly recommended. If the adolescent is HIV positive, this visit should be used to assess how the teen is handling the diagnosis emotionally, to determine the best course of action for treatment and to refer the teen for other support services.
If the test comes back negative, the primary care physician should still use the opportunity to remind teens that if they're sexually active and not using condoms, they're always at risk. The test was only a snapshot in time.
It's also important to explain beforehand what a positive test means: It indicates that there is an HIV infection, but it gives no information about what stage of the disease they're in. They could be very early in the course of disease, or very late in the course of disease and already have AIDS.
Just as the CDC recommends for adults, I believe that physicians should use every medical encounter with an adolescent, be it a sports physical or an acute illness visit, to do HIV counseling and screening.
The issue of parental consent is still problematic and a potential barrier. Ideally, of course, the teenager is willing to have his or her parent or guardian consent to testing. But if not, the laws concerning consent and confidentiality vary by state. In general, public health statute and legal precedent allow for evaluation and treatment of minors for sexually transmitted diseases without parental knowledge or consent. The Guttmacher Institute's Web site is an excellent resource for specific state-by-state information on laws governing minors' consent to medical care, access to STD services, and sex and STD/HIV education (www.guttmacher.org
Most state laws, however, don't yet address the issue of consent for screening for HIV in asymptomatic adolescents. The American Academy of Pediatrics advises that physicians obtain advice regarding the disposition of laws in their state addressing consent or other legal obligations from their attorney or another trusted local source, such as their hospital's office of legal compliance. The AAP Committee on Pediatric AIDS is expected to issue a statement in response to the CDC guidelines sometime in 2007.
Screening for HIV should be routine for all sexually active adolescents.
In September 2006, the Centers for Disease Control and Prevention issued new recommendations calling for annual routine HIV screening in health care settings for all patients aged 13–64 years, regardless of perceived risk status. The guidelines are notable in that they call for a policy of “opt-out” screening rather than requiring written informed consent, and they allow for screening to occur without pre-test counseling in situations where such a requirement would present a barrier (MMWR 2006;55:RR-14).
The CDC believes—and I agree—that these changes are necessary. Our current practice of screening only those individuals perceived to be at high risk isn't working. There are about 1 million HIV-infected people in the United States, as many as 25% of whom are undiagnosed. Not only are they missing out on the potential benefits of antiretroviral therapy, but their sexual activity represents a threat for transmission to others. Current HIV testing programs identify approximately 40,000 new cases every year, a number that has not changed in nearly a decade.
Teenagers are among those at risk. The CDC guidelines note that in the 2005 national Youth Risk Behavior Survey, 47% of high school students reported having had sexual intercourse at least once, and 37% of those who were sexually active had not used a condom during their most recent act of sexual intercourse. In 2005, according to the CDC, heterosexual intercourse overall accounted for 15% of HIV transmission in males and 80% in females. (Male-to-male sexual contact made up 67% of transmission among males.)
I strongly support routine screening for our adolescent patients but with certain modifications to the CDC's stated policy. While the idea of eliminating all risk profiling makes sense for the adult community, in adolescents I think it boils down to one question: Are you sexually active? If the answer is yes, no matter what the circumstances, screening is indicated. Clearly, this is an issue for every physician who treats adolescents.
I also think that, contrary to the guideline for adults, adolescents do need counseling about HIV before and after testing. Simply telling a teenager that you plan to test them for HIV unless they opt out is not adequate. At a minimum, we need to tell teens that sexual activity is a risk factor for the transmission of HIV, and for that reason we believe they should be tested. Just because a teen is monogamous doesn't mean her or his partner is. We must impress upon them that even if they're sure their partner is “safe,” they can't be confident that the same applied to their partner's previous partners.
We also should explain that the testing is a two-step process. The initial step (ELISA) identifies HIV-specific antibodies but sometimes is falsely positive. If the ELISA is positive, a Western blot test is done for confirmation. No matter what the result, a second visit is highly recommended. If the adolescent is HIV positive, this visit should be used to assess how the teen is handling the diagnosis emotionally, to determine the best course of action for treatment and to refer the teen for other support services.
If the test comes back negative, the primary care physician should still use the opportunity to remind teens that if they're sexually active and not using condoms, they're always at risk. The test was only a snapshot in time.
It's also important to explain beforehand what a positive test means: It indicates that there is an HIV infection, but it gives no information about what stage of the disease they're in. They could be very early in the course of disease, or very late in the course of disease and already have AIDS.
Just as the CDC recommends for adults, I believe that physicians should use every medical encounter with an adolescent, be it a sports physical or an acute illness visit, to do HIV counseling and screening.
The issue of parental consent is still problematic and a potential barrier. Ideally, of course, the teenager is willing to have his or her parent or guardian consent to testing. But if not, the laws concerning consent and confidentiality vary by state. In general, public health statute and legal precedent allow for evaluation and treatment of minors for sexually transmitted diseases without parental knowledge or consent. The Guttmacher Institute's Web site is an excellent resource for specific state-by-state information on laws governing minors' consent to medical care, access to STD services, and sex and STD/HIV education (www.guttmacher.org
Most state laws, however, don't yet address the issue of consent for screening for HIV in asymptomatic adolescents. The American Academy of Pediatrics advises that physicians obtain advice regarding the disposition of laws in their state addressing consent or other legal obligations from their attorney or another trusted local source, such as their hospital's office of legal compliance. The AAP Committee on Pediatric AIDS is expected to issue a statement in response to the CDC guidelines sometime in 2007.
E. coli: Prevention Is Best Cure
The recent outbreaks of Escherichia coli O157:H7 linked to spinach and lettuce remind us yet again how limited our tools are when it comes to treating this infection and its sequelae. Focusing our efforts on prevention is by far the best medicine.
As of Oct. 6, a total of 199 people infected with the outbreak strain of E. coli serotype 0157:H7 had been reported to the Centers for Disease Control and Prevention from 26 states, including 22 cases in children younger than 5 years of age. Of the total group, 51% were hospitalized and 16% developed hemolytic uremic syndrome (HUS). Twenty-nine percent of children younger than 18 years developed HUS, compared with 8% of adults aged 18–59 years and 14% of those aged 60 years and older, confirming the increased risk for HUS in children and the elderly.
There were three deaths, including a 2-year-old child with HUS whose stool sample contained evidence of the outbreak strain confirmed by “DNA fingerprinting.”
About 73,000 infections with E. coli 0157:H7 occur annually in the United States. Such infections are reportable nationally as well as in most states. In most states, HUS is reportable to departments of public health as well. The CDC investigates all reported cases to ascertain whether they are outbreak-associated or isolated. Most are the latter. Half of all cases occur between June and September.
Produce was the source in the recent outbreak, but in the past we've seen disease in children associated with undercooked meat, nonpasteurized milk products, and even water. Petting zoos are a major hazard.
During 2004–2005, a total of 173 cases of E. coli 0157:H7 were reported from outbreaks in Arizona, Florida, and North Carolina. Illnesses primarily affected children who had visited petting zoos at agricultural fairs or festivals. There were 22 cases of HUS, but fortunately no fatalities (MMWR 2005;54:1277–80).
In a study the CDC conducted at a petting zoo, illness was associated with touching or stepping in manure, falling or sitting on the ground, using a pacifier or “sippy” cup, and thumb-sucking. Use of alcohol-based sanitizer was not protective, but reported awareness by the accompanying adults of the risk for disease from contact with livestock was. We should counsel parents about the potential risk and the preventive strategies such as avoidance of manure and of the use of a pacifier or eating while at the petting zoo.
Direct human-to-human contact is a rarer source of E. coli infection, but it's important to keep in mind when we see a child with bloody diarrhea, particularly if that child is in day care.
Unfortunately, we don't have a way to interrupt the progression from colitis to HUS. The role of antibiotics in children with E. coli gastrointestinal infection remains controversial. Epidemiologic data have suggested that antibiotics may increase the risk for HUS, perhaps by increased toxin exposure to the kidneys following bacteriolysis in the gut. A meta-analysis of 26 studies conducted between January 1983 and February 2001 did not show a higher risk of HUS due to antibiotic use. However, the authors concluded that a randomized trial of adequate power is needed to conclusively answer the question (JAMA 2002;288:996–1001).
Until then, the potential benefit of antimicrobial therapy in a specific patient presenting with gastroenteritis must be weighed against the potential risk. Stool cultures should be obtained from any child who presents with bloody diarrhea and abdominal pain. If the child is afebrile and otherwise does not appear ill, supportive care is advised. But of course, a child with gastroenteritis who is hypotensive and appears septic requires urgent intervention that may include antimicrobial therapy.
Although we don't know which children with E. coli-associated diarrhea will progress to HUS, we do know that certain risk factors, such as young age, long duration of diarrhea, elevated leukocyte count, and proteinuria, are predictive (Emerg. Infect. Dis. 2005;11:1955–7). Fortunately, there is usually a lag time of several days to a week between the onset of bloody diarrhea and renal failure. If we see the child soon enough, we can intervene with fluid replacement and close monitoring.
At the time of progression to HUS, stool cultures often are negative. The diagnosis is made clinically, on the basis of renal failure and hemolytic anemia, with or without thrombocytopenia. Treatment is supportive: Dialysis has dramatically reduced HUS mortality from about 21% before 1974 to about 4% today.
Intriguing early work is now being done looking at treating HUS with infusion of the human plasma protein serum amyloid P component (J. Infect. Dis. 2006;193:1120–4) and use of specific neutralizing antibodies directed against the A subunit of the toxin (Clin. Microbiol. Rev. 2004;17:926–41). Clinical use is probably years away, however.
For now, we need to continue to educate our patients about thoroughly cooking meat, washing produce, and exercising caution around farm animals and in petting zoos.
The recent outbreaks of Escherichia coli O157:H7 linked to spinach and lettuce remind us yet again how limited our tools are when it comes to treating this infection and its sequelae. Focusing our efforts on prevention is by far the best medicine.
As of Oct. 6, a total of 199 people infected with the outbreak strain of E. coli serotype 0157:H7 had been reported to the Centers for Disease Control and Prevention from 26 states, including 22 cases in children younger than 5 years of age. Of the total group, 51% were hospitalized and 16% developed hemolytic uremic syndrome (HUS). Twenty-nine percent of children younger than 18 years developed HUS, compared with 8% of adults aged 18–59 years and 14% of those aged 60 years and older, confirming the increased risk for HUS in children and the elderly.
There were three deaths, including a 2-year-old child with HUS whose stool sample contained evidence of the outbreak strain confirmed by “DNA fingerprinting.”
About 73,000 infections with E. coli 0157:H7 occur annually in the United States. Such infections are reportable nationally as well as in most states. In most states, HUS is reportable to departments of public health as well. The CDC investigates all reported cases to ascertain whether they are outbreak-associated or isolated. Most are the latter. Half of all cases occur between June and September.
Produce was the source in the recent outbreak, but in the past we've seen disease in children associated with undercooked meat, nonpasteurized milk products, and even water. Petting zoos are a major hazard.
During 2004–2005, a total of 173 cases of E. coli 0157:H7 were reported from outbreaks in Arizona, Florida, and North Carolina. Illnesses primarily affected children who had visited petting zoos at agricultural fairs or festivals. There were 22 cases of HUS, but fortunately no fatalities (MMWR 2005;54:1277–80).
In a study the CDC conducted at a petting zoo, illness was associated with touching or stepping in manure, falling or sitting on the ground, using a pacifier or “sippy” cup, and thumb-sucking. Use of alcohol-based sanitizer was not protective, but reported awareness by the accompanying adults of the risk for disease from contact with livestock was. We should counsel parents about the potential risk and the preventive strategies such as avoidance of manure and of the use of a pacifier or eating while at the petting zoo.
Direct human-to-human contact is a rarer source of E. coli infection, but it's important to keep in mind when we see a child with bloody diarrhea, particularly if that child is in day care.
Unfortunately, we don't have a way to interrupt the progression from colitis to HUS. The role of antibiotics in children with E. coli gastrointestinal infection remains controversial. Epidemiologic data have suggested that antibiotics may increase the risk for HUS, perhaps by increased toxin exposure to the kidneys following bacteriolysis in the gut. A meta-analysis of 26 studies conducted between January 1983 and February 2001 did not show a higher risk of HUS due to antibiotic use. However, the authors concluded that a randomized trial of adequate power is needed to conclusively answer the question (JAMA 2002;288:996–1001).
Until then, the potential benefit of antimicrobial therapy in a specific patient presenting with gastroenteritis must be weighed against the potential risk. Stool cultures should be obtained from any child who presents with bloody diarrhea and abdominal pain. If the child is afebrile and otherwise does not appear ill, supportive care is advised. But of course, a child with gastroenteritis who is hypotensive and appears septic requires urgent intervention that may include antimicrobial therapy.
Although we don't know which children with E. coli-associated diarrhea will progress to HUS, we do know that certain risk factors, such as young age, long duration of diarrhea, elevated leukocyte count, and proteinuria, are predictive (Emerg. Infect. Dis. 2005;11:1955–7). Fortunately, there is usually a lag time of several days to a week between the onset of bloody diarrhea and renal failure. If we see the child soon enough, we can intervene with fluid replacement and close monitoring.
At the time of progression to HUS, stool cultures often are negative. The diagnosis is made clinically, on the basis of renal failure and hemolytic anemia, with or without thrombocytopenia. Treatment is supportive: Dialysis has dramatically reduced HUS mortality from about 21% before 1974 to about 4% today.
Intriguing early work is now being done looking at treating HUS with infusion of the human plasma protein serum amyloid P component (J. Infect. Dis. 2006;193:1120–4) and use of specific neutralizing antibodies directed against the A subunit of the toxin (Clin. Microbiol. Rev. 2004;17:926–41). Clinical use is probably years away, however.
For now, we need to continue to educate our patients about thoroughly cooking meat, washing produce, and exercising caution around farm animals and in petting zoos.
The recent outbreaks of Escherichia coli O157:H7 linked to spinach and lettuce remind us yet again how limited our tools are when it comes to treating this infection and its sequelae. Focusing our efforts on prevention is by far the best medicine.
As of Oct. 6, a total of 199 people infected with the outbreak strain of E. coli serotype 0157:H7 had been reported to the Centers for Disease Control and Prevention from 26 states, including 22 cases in children younger than 5 years of age. Of the total group, 51% were hospitalized and 16% developed hemolytic uremic syndrome (HUS). Twenty-nine percent of children younger than 18 years developed HUS, compared with 8% of adults aged 18–59 years and 14% of those aged 60 years and older, confirming the increased risk for HUS in children and the elderly.
There were three deaths, including a 2-year-old child with HUS whose stool sample contained evidence of the outbreak strain confirmed by “DNA fingerprinting.”
About 73,000 infections with E. coli 0157:H7 occur annually in the United States. Such infections are reportable nationally as well as in most states. In most states, HUS is reportable to departments of public health as well. The CDC investigates all reported cases to ascertain whether they are outbreak-associated or isolated. Most are the latter. Half of all cases occur between June and September.
Produce was the source in the recent outbreak, but in the past we've seen disease in children associated with undercooked meat, nonpasteurized milk products, and even water. Petting zoos are a major hazard.
During 2004–2005, a total of 173 cases of E. coli 0157:H7 were reported from outbreaks in Arizona, Florida, and North Carolina. Illnesses primarily affected children who had visited petting zoos at agricultural fairs or festivals. There were 22 cases of HUS, but fortunately no fatalities (MMWR 2005;54:1277–80).
In a study the CDC conducted at a petting zoo, illness was associated with touching or stepping in manure, falling or sitting on the ground, using a pacifier or “sippy” cup, and thumb-sucking. Use of alcohol-based sanitizer was not protective, but reported awareness by the accompanying adults of the risk for disease from contact with livestock was. We should counsel parents about the potential risk and the preventive strategies such as avoidance of manure and of the use of a pacifier or eating while at the petting zoo.
Direct human-to-human contact is a rarer source of E. coli infection, but it's important to keep in mind when we see a child with bloody diarrhea, particularly if that child is in day care.
Unfortunately, we don't have a way to interrupt the progression from colitis to HUS. The role of antibiotics in children with E. coli gastrointestinal infection remains controversial. Epidemiologic data have suggested that antibiotics may increase the risk for HUS, perhaps by increased toxin exposure to the kidneys following bacteriolysis in the gut. A meta-analysis of 26 studies conducted between January 1983 and February 2001 did not show a higher risk of HUS due to antibiotic use. However, the authors concluded that a randomized trial of adequate power is needed to conclusively answer the question (JAMA 2002;288:996–1001).
Until then, the potential benefit of antimicrobial therapy in a specific patient presenting with gastroenteritis must be weighed against the potential risk. Stool cultures should be obtained from any child who presents with bloody diarrhea and abdominal pain. If the child is afebrile and otherwise does not appear ill, supportive care is advised. But of course, a child with gastroenteritis who is hypotensive and appears septic requires urgent intervention that may include antimicrobial therapy.
Although we don't know which children with E. coli-associated diarrhea will progress to HUS, we do know that certain risk factors, such as young age, long duration of diarrhea, elevated leukocyte count, and proteinuria, are predictive (Emerg. Infect. Dis. 2005;11:1955–7). Fortunately, there is usually a lag time of several days to a week between the onset of bloody diarrhea and renal failure. If we see the child soon enough, we can intervene with fluid replacement and close monitoring.
At the time of progression to HUS, stool cultures often are negative. The diagnosis is made clinically, on the basis of renal failure and hemolytic anemia, with or without thrombocytopenia. Treatment is supportive: Dialysis has dramatically reduced HUS mortality from about 21% before 1974 to about 4% today.
Intriguing early work is now being done looking at treating HUS with infusion of the human plasma protein serum amyloid P component (J. Infect. Dis. 2006;193:1120–4) and use of specific neutralizing antibodies directed against the A subunit of the toxin (Clin. Microbiol. Rev. 2004;17:926–41). Clinical use is probably years away, however.
For now, we need to continue to educate our patients about thoroughly cooking meat, washing produce, and exercising caution around farm animals and in petting zoos.
Physician, Immunize Thyself!
Do the right thing: Immunize yourself and your office staff!
With the recent licensure of a new acellular pertussis vaccine for adults, now is a good time to review the immunization status of heath care workers in your setting. We should protect ourselves against vaccine-preventable diseases such as pertussis, influenza, varicella, and hepatitis A so that our patients will be protected as well.
Indeed, the federal government has prioritized immunization of health care workers in its pandemic influenza preparedness plan. Without the personnel to care for affected individuals in the event of a human H5N1 outbreak, we would be risking a greater disaster.
Health care workers who treat children have a particular responsibility to protect themselves. As we know, children less than 6 months of age are vulnerable to a wide variety of infections for which they have not yet been fully immunized. Infants born prematurely—more of whom are surviving today—also remain at high risk for infection during the first year of life.
We also are seeing increasing numbers of older children with chronic diseases such as asthma, as well as more of those left immunosuppressed from formerly fatal diseases such as cancer and HIV. We simply cannot allow ourselves to become the agents for transmission to these vulnerable patients.
I want to touch on four adult vaccines in particular:
Pertussis
Earlier this year, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) recommended that health care workers in hospitals or ambulatory care settings and those who have direct patient contact should receive the recently licensed adult formulation of the tetanus-diphtheria-acellular pertussis vaccine (Adacel, Sanofi Pasteur). Priority should be given to providers who have direct contact with infants who are less than 12 months of age.
Because the efficacy of routine childhood pertussis immunization decays after about 10 years, most adults are currently susceptible to pertussis. Although the disease is rarely fatal in adults (as it can be in infants), it does cause prolonged cough lasting for 3 or more weeks in 80%–100% of adults, and posttussive vomiting in 50%. Missed work for illness or medical care occurs in 78% of adults for a mean of 9.8 days, according to data from the CDC.
Transmission of pertussis is most likely to occur during the early phase of disease (catarrhal stage), when cough and coryza are unlikely to be recognized as anything other than a cold. Now that there's a licensed vaccine that will prevent pertussis transmission—not to mention updating our tetanus and diphtheria immunity—it's in everybody's best interest for health care workers to just get vaccinated.
Influenza
Protection against annual influenza also is essential for health care workers who see children. Both the ACIP and the American Academy of Pediatrics now recommend that all children aged 6–59 months receive an annual influenza vaccination. However, children under 6 months of age remain susceptible. Moreover, any child who has not previously received an influenza vaccine needs two doses over a 6-week period, and remains susceptible for several weeks after receiving the second dose.
Health care workers who are younger than 50 years of age and don't have high-risk chronic conditions have the option of choosing the live attenuated virus influenza vaccine (FluMist, MedImmune Inc.) as an alternative to the inactivated injectable vaccine.
For the vast majority of health care workers, there is no need to refrain from working after receipt of the live virus vaccine.
The only exception is those who have direct contact with severely immunosuppressed patients, such as bone marrow recipients.
Varicella
Although the routine childhood vaccine has dramatically reduced its incidence and severity, varicella still persists in the community. When it does occur in adults, it tends to be far more serious than it is in children.
The importance of immunity to varicella is even more critical now that varicella zoster immune globulin—previously given following a known exposure to varicella—is no longer being manufactured in the United States. It's available as an experimental product from Canada, but even if you were able to obtain a supply, it would not likely be in enough time to avert the full-blown clinical picture. You can still take acyclovir prophylactically, but only if you know you've been exposed.
Most pediatricians practicing today have already had chickenpox and are, therefore, immune.
However, that may not be true much longer. Every year my hospital tests incoming medical students for antibodies to varicella, and this past year we found that 10% of these young adults lacked immunity.
Hepatitis A
Last fall, ACIP recommended that all children at least 1 year of age receive the hepatitis A vaccine. Typically, children with hepatitis A infection are either asymptomatic or have nonspecific symptoms such as fever and gastroenteritis. Jaundice is uncommon. If you are treating a child with hepatitis A, you are at high risk for clinically significant illness, including jaundice.
While there is no specific recommendation for hepatitis A vaccination of health care workers, the CDC does state that the vaccine can be given to “any person wishing to obtain immunity.” For those of us whose job is to protect our patients and ourselves, I think it's a good idea.
For more on adult immunization, go to www.cdc.gov/nip/recs/adult-schedule.htm
Do the right thing: Immunize yourself and your office staff!
With the recent licensure of a new acellular pertussis vaccine for adults, now is a good time to review the immunization status of heath care workers in your setting. We should protect ourselves against vaccine-preventable diseases such as pertussis, influenza, varicella, and hepatitis A so that our patients will be protected as well.
Indeed, the federal government has prioritized immunization of health care workers in its pandemic influenza preparedness plan. Without the personnel to care for affected individuals in the event of a human H5N1 outbreak, we would be risking a greater disaster.
Health care workers who treat children have a particular responsibility to protect themselves. As we know, children less than 6 months of age are vulnerable to a wide variety of infections for which they have not yet been fully immunized. Infants born prematurely—more of whom are surviving today—also remain at high risk for infection during the first year of life.
We also are seeing increasing numbers of older children with chronic diseases such as asthma, as well as more of those left immunosuppressed from formerly fatal diseases such as cancer and HIV. We simply cannot allow ourselves to become the agents for transmission to these vulnerable patients.
I want to touch on four adult vaccines in particular:
Pertussis
Earlier this year, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) recommended that health care workers in hospitals or ambulatory care settings and those who have direct patient contact should receive the recently licensed adult formulation of the tetanus-diphtheria-acellular pertussis vaccine (Adacel, Sanofi Pasteur). Priority should be given to providers who have direct contact with infants who are less than 12 months of age.
Because the efficacy of routine childhood pertussis immunization decays after about 10 years, most adults are currently susceptible to pertussis. Although the disease is rarely fatal in adults (as it can be in infants), it does cause prolonged cough lasting for 3 or more weeks in 80%–100% of adults, and posttussive vomiting in 50%. Missed work for illness or medical care occurs in 78% of adults for a mean of 9.8 days, according to data from the CDC.
Transmission of pertussis is most likely to occur during the early phase of disease (catarrhal stage), when cough and coryza are unlikely to be recognized as anything other than a cold. Now that there's a licensed vaccine that will prevent pertussis transmission—not to mention updating our tetanus and diphtheria immunity—it's in everybody's best interest for health care workers to just get vaccinated.
Influenza
Protection against annual influenza also is essential for health care workers who see children. Both the ACIP and the American Academy of Pediatrics now recommend that all children aged 6–59 months receive an annual influenza vaccination. However, children under 6 months of age remain susceptible. Moreover, any child who has not previously received an influenza vaccine needs two doses over a 6-week period, and remains susceptible for several weeks after receiving the second dose.
Health care workers who are younger than 50 years of age and don't have high-risk chronic conditions have the option of choosing the live attenuated virus influenza vaccine (FluMist, MedImmune Inc.) as an alternative to the inactivated injectable vaccine.
For the vast majority of health care workers, there is no need to refrain from working after receipt of the live virus vaccine.
The only exception is those who have direct contact with severely immunosuppressed patients, such as bone marrow recipients.
Varicella
Although the routine childhood vaccine has dramatically reduced its incidence and severity, varicella still persists in the community. When it does occur in adults, it tends to be far more serious than it is in children.
The importance of immunity to varicella is even more critical now that varicella zoster immune globulin—previously given following a known exposure to varicella—is no longer being manufactured in the United States. It's available as an experimental product from Canada, but even if you were able to obtain a supply, it would not likely be in enough time to avert the full-blown clinical picture. You can still take acyclovir prophylactically, but only if you know you've been exposed.
Most pediatricians practicing today have already had chickenpox and are, therefore, immune.
However, that may not be true much longer. Every year my hospital tests incoming medical students for antibodies to varicella, and this past year we found that 10% of these young adults lacked immunity.
Hepatitis A
Last fall, ACIP recommended that all children at least 1 year of age receive the hepatitis A vaccine. Typically, children with hepatitis A infection are either asymptomatic or have nonspecific symptoms such as fever and gastroenteritis. Jaundice is uncommon. If you are treating a child with hepatitis A, you are at high risk for clinically significant illness, including jaundice.
While there is no specific recommendation for hepatitis A vaccination of health care workers, the CDC does state that the vaccine can be given to “any person wishing to obtain immunity.” For those of us whose job is to protect our patients and ourselves, I think it's a good idea.
For more on adult immunization, go to www.cdc.gov/nip/recs/adult-schedule.htm
Do the right thing: Immunize yourself and your office staff!
With the recent licensure of a new acellular pertussis vaccine for adults, now is a good time to review the immunization status of heath care workers in your setting. We should protect ourselves against vaccine-preventable diseases such as pertussis, influenza, varicella, and hepatitis A so that our patients will be protected as well.
Indeed, the federal government has prioritized immunization of health care workers in its pandemic influenza preparedness plan. Without the personnel to care for affected individuals in the event of a human H5N1 outbreak, we would be risking a greater disaster.
Health care workers who treat children have a particular responsibility to protect themselves. As we know, children less than 6 months of age are vulnerable to a wide variety of infections for which they have not yet been fully immunized. Infants born prematurely—more of whom are surviving today—also remain at high risk for infection during the first year of life.
We also are seeing increasing numbers of older children with chronic diseases such as asthma, as well as more of those left immunosuppressed from formerly fatal diseases such as cancer and HIV. We simply cannot allow ourselves to become the agents for transmission to these vulnerable patients.
I want to touch on four adult vaccines in particular:
Pertussis
Earlier this year, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) recommended that health care workers in hospitals or ambulatory care settings and those who have direct patient contact should receive the recently licensed adult formulation of the tetanus-diphtheria-acellular pertussis vaccine (Adacel, Sanofi Pasteur). Priority should be given to providers who have direct contact with infants who are less than 12 months of age.
Because the efficacy of routine childhood pertussis immunization decays after about 10 years, most adults are currently susceptible to pertussis. Although the disease is rarely fatal in adults (as it can be in infants), it does cause prolonged cough lasting for 3 or more weeks in 80%–100% of adults, and posttussive vomiting in 50%. Missed work for illness or medical care occurs in 78% of adults for a mean of 9.8 days, according to data from the CDC.
Transmission of pertussis is most likely to occur during the early phase of disease (catarrhal stage), when cough and coryza are unlikely to be recognized as anything other than a cold. Now that there's a licensed vaccine that will prevent pertussis transmission—not to mention updating our tetanus and diphtheria immunity—it's in everybody's best interest for health care workers to just get vaccinated.
Influenza
Protection against annual influenza also is essential for health care workers who see children. Both the ACIP and the American Academy of Pediatrics now recommend that all children aged 6–59 months receive an annual influenza vaccination. However, children under 6 months of age remain susceptible. Moreover, any child who has not previously received an influenza vaccine needs two doses over a 6-week period, and remains susceptible for several weeks after receiving the second dose.
Health care workers who are younger than 50 years of age and don't have high-risk chronic conditions have the option of choosing the live attenuated virus influenza vaccine (FluMist, MedImmune Inc.) as an alternative to the inactivated injectable vaccine.
For the vast majority of health care workers, there is no need to refrain from working after receipt of the live virus vaccine.
The only exception is those who have direct contact with severely immunosuppressed patients, such as bone marrow recipients.
Varicella
Although the routine childhood vaccine has dramatically reduced its incidence and severity, varicella still persists in the community. When it does occur in adults, it tends to be far more serious than it is in children.
The importance of immunity to varicella is even more critical now that varicella zoster immune globulin—previously given following a known exposure to varicella—is no longer being manufactured in the United States. It's available as an experimental product from Canada, but even if you were able to obtain a supply, it would not likely be in enough time to avert the full-blown clinical picture. You can still take acyclovir prophylactically, but only if you know you've been exposed.
Most pediatricians practicing today have already had chickenpox and are, therefore, immune.
However, that may not be true much longer. Every year my hospital tests incoming medical students for antibodies to varicella, and this past year we found that 10% of these young adults lacked immunity.
Hepatitis A
Last fall, ACIP recommended that all children at least 1 year of age receive the hepatitis A vaccine. Typically, children with hepatitis A infection are either asymptomatic or have nonspecific symptoms such as fever and gastroenteritis. Jaundice is uncommon. If you are treating a child with hepatitis A, you are at high risk for clinically significant illness, including jaundice.
While there is no specific recommendation for hepatitis A vaccination of health care workers, the CDC does state that the vaccine can be given to “any person wishing to obtain immunity.” For those of us whose job is to protect our patients and ourselves, I think it's a good idea.
For more on adult immunization, go to www.cdc.gov/nip/recs/adult-schedule.htm
Recalcitrant Otorrhea 'After the Tubes'
Novel approaches are necessary to address the emerging problem of the child who fails conventional therapy for acute otorrhea following tympanostomy tube insertion.
We've seen an increase in the number of children with otorrhea through a tympanostomy tube lasting more than 10 days in the past few years, primarily due to the emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Another contributing factor is the increased use of quinolone ear drops, which are thought to promote the occurrence of fungal infections.
Approximately 30% of children who undergo tube placement develop acute otorrhea. Haemophilus influenzae and Streptococcus pneumoniae are responsible for 40%–45% of these cases, particularly in children under 2 years of age and in those who develop symptoms during the winter months. It's hypothesized that these children have ongoing eustachian tube dysfunction that permits nasopharyngeal pathogens to ascend to the middle ear, resulting in acute otorrhea through the tympanostomy tube.
The other 55%–60% of cases are caused by pathogens from the external canal, most commonly Staphylococcus aureus and Pseudomonas aeruginosa. These patients tend to be older, to develop symptoms during the warmer months, and to have a malodorous discharge (in contrast to the nasopharyngeal pathogens, which are odorless).
There appears to be a contribution from water in the ear, which triggers an inflammatory response.
In the past, standard treatment for ear drainage in children was oral antibiotics aimed at H. influenzae and pneumococcus, such as amoxicillin, amoxicillin-clavulanate, or a cephalosporin.
More recently, there has been a shift to greater use of topical fluoroquinolones—particularly ofloxacin and ciprofloxacin—with the increased recognition that the staphylococcus and pseudomonas pathogens also contribute to the microbiology of this disease.
Even in young children, otic preparations are often considered superior to oral antibiotics because they are active against all four of the main pathogens, safely achieve high concentrations in the middle ear, and are less likely to contribute to the emergence of resistance because they are not given systemically.
And of course, they eliminate the bad taste problem.
Now, however, we're starting to see clinical failures with both oral and topical antibiotics, primarily due to CA-MRSA. Among otherwise healthy children, the risk for the development of otorrhea due to MRSA appears to increase with the number of acute otitis media episodes prior to tube placement, as well as with the number of courses and duration of treatment prior to tube placement (Arch. Otolaryngol. Head Neck Surg. 2005;131:868–73).
For MRSA-associated skin and soft tissue infections, drugs such as trimethoprim-sulfamethoxazole, linezolid, or even intravenous vancomycin are usually effective. However, these agents are often ineffective or associated with relapse as soon as therapy is discontinued when a foreign body such as a tympanostomy tube is involved, because of the lack of blood supply and the formation of biofilm.
What does appear to work, at least in small case reports, is the use of either topical vancomycin or combination topical plus oral treatment.
In one report, a group in Thailand combined a 500-mg vial of vancomycin powder with 20 mL of sterile distilled water to create a 25-mg/mL vancomycin solution. Two 0.8-mg drops were placed into the ear three times daily for 10 days in 35 patients with MRSA otorrhea. A control group of 20 patients was treated with the same regimen of gentamycin 0.3% drops (J. Laryngol. Otol. 2004;118:645–7).
Clinical cure was achieved in 30 (86%) of the vancomycin recipients, compared with 2 (10%) of those treated with gentamycin. Failures occurred in just 2 (6%) patients given vancomycin versus 16 (80%) given gentamycin.
Of course, this is a small study, but it is based on sound biologic principles and there appear to be no adverse effects. We certainly need more long-term data, but I think topical vancomycin may represent a good alternative to removal of the tubes in some patients. If your pharmacy is able to make this formulation, I think it offers an option to tube removal if CA-MRSA is cultured and the child fails initial oral or topical therapy.
In another small study, successful eradication of MRSA was achieved using a combination of oral trimethoprim-sulfamethoxazole plus topical gentamycin sulfate or polymyxin B sulfate-neomycin sulfate-hydrocortisone (Cortisporin) in six children (five with prior tympanostomy tube placement and one with perforation of the tympanic membrane) who had failed either oral antibiotics or fluoroquinolone ear drops alone (Arch. Otolaryngol. Head Neck Surg. 2005;131:782–4). However, I'd be less apt to use this approach because of concerns about potential ototoxicity of the gentamycin/neomycin on the vestibular system.
In addition to CA-MRSA, otorrhea due to fungal organisms is now being seen increasingly in children who have been treated previously for bacterial infections following tube placement.
In a retrospective review conducted at a pediatric otolaryngology clinic, out of a total 1,242 patients who underwent ear culture between 1996 and 2003, 166 patients (119 with otitis media, 41 with otitis externa, and 6 with both) aged 16 days to 18 years (mean 4 years) were found to have fungal organisms. The proportion of fungus-positive cultures increased dramatically in the years following the availability of the fluoroquinolone drops, from just 4.2% of 356 cultures obtained during 1996–1998 to 18.2% of the 457 cultures done during 1999–2001 (Int. J. Pediatr. Otorhinolaryngol. 2005;69:1503–8).
The most common of the fungi were Candida albicans (43% of the 166), Candida parapsilosis (23.5%), and Aspergillus fumigatus (21%). Although reporting of medications was inconsistent, the authors estimated that the patients had previously received an average of 1.7 oral antibiotics and 1.1 ototopical agents before the culture was taken. Infection resolved in all the patients with treatment, which included clotrimazole topical and tolnaftate topical in 27 patients each, fluconazole in 25, acetic acid alone in 14, and topical plus fluconazole in 10. The thinking is that the use of broad-spectrum quinolone drops may be promoting the emergence of fungus by eliminating the colonizers in the external ear canal, thereby allowing the fungus to grow. This doesn't imply we should stop using quinolone-containing otic solutions, but I do think we need to be aware of the possibility and culture the middle ear in a child who still has otorrhea after 5–7 days of treatment.
Of course, we all know that prevention is the best medicine.
A group from Turkey recently published a comparison of 1 mL intraoperative isotonic saline irrigation, postoperative antibiotic treatment (sulbactam/ampicillin 25 mg/kg for 5 days), postoperative ofloxacin drops (twice a day for 5 days), or placebo in 280 children (mean age 5.9 years) undergoing bilateral ventilation tube insertion because of serous otitis media during 2000–2004 (Am. J. Otolaryngol. 2005;26:123–7).
At 2 weeks post surgery, purulent otorrhea was observed in 15.7% of the saline group, 14.2% of those who received prophylactic oral antibiotics, and 8.6% of the topical antibiotic group, all significantly lower than the 30% rate among the controls. It appears that saline irrigation of the middle ear prior to tube placement offers a low-cost intervention for reducing early post-tympanostomy tube otorrhea.
Novel approaches are necessary to address the emerging problem of the child who fails conventional therapy for acute otorrhea following tympanostomy tube insertion.
We've seen an increase in the number of children with otorrhea through a tympanostomy tube lasting more than 10 days in the past few years, primarily due to the emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Another contributing factor is the increased use of quinolone ear drops, which are thought to promote the occurrence of fungal infections.
Approximately 30% of children who undergo tube placement develop acute otorrhea. Haemophilus influenzae and Streptococcus pneumoniae are responsible for 40%–45% of these cases, particularly in children under 2 years of age and in those who develop symptoms during the winter months. It's hypothesized that these children have ongoing eustachian tube dysfunction that permits nasopharyngeal pathogens to ascend to the middle ear, resulting in acute otorrhea through the tympanostomy tube.
The other 55%–60% of cases are caused by pathogens from the external canal, most commonly Staphylococcus aureus and Pseudomonas aeruginosa. These patients tend to be older, to develop symptoms during the warmer months, and to have a malodorous discharge (in contrast to the nasopharyngeal pathogens, which are odorless).
There appears to be a contribution from water in the ear, which triggers an inflammatory response.
In the past, standard treatment for ear drainage in children was oral antibiotics aimed at H. influenzae and pneumococcus, such as amoxicillin, amoxicillin-clavulanate, or a cephalosporin.
More recently, there has been a shift to greater use of topical fluoroquinolones—particularly ofloxacin and ciprofloxacin—with the increased recognition that the staphylococcus and pseudomonas pathogens also contribute to the microbiology of this disease.
Even in young children, otic preparations are often considered superior to oral antibiotics because they are active against all four of the main pathogens, safely achieve high concentrations in the middle ear, and are less likely to contribute to the emergence of resistance because they are not given systemically.
And of course, they eliminate the bad taste problem.
Now, however, we're starting to see clinical failures with both oral and topical antibiotics, primarily due to CA-MRSA. Among otherwise healthy children, the risk for the development of otorrhea due to MRSA appears to increase with the number of acute otitis media episodes prior to tube placement, as well as with the number of courses and duration of treatment prior to tube placement (Arch. Otolaryngol. Head Neck Surg. 2005;131:868–73).
For MRSA-associated skin and soft tissue infections, drugs such as trimethoprim-sulfamethoxazole, linezolid, or even intravenous vancomycin are usually effective. However, these agents are often ineffective or associated with relapse as soon as therapy is discontinued when a foreign body such as a tympanostomy tube is involved, because of the lack of blood supply and the formation of biofilm.
What does appear to work, at least in small case reports, is the use of either topical vancomycin or combination topical plus oral treatment.
In one report, a group in Thailand combined a 500-mg vial of vancomycin powder with 20 mL of sterile distilled water to create a 25-mg/mL vancomycin solution. Two 0.8-mg drops were placed into the ear three times daily for 10 days in 35 patients with MRSA otorrhea. A control group of 20 patients was treated with the same regimen of gentamycin 0.3% drops (J. Laryngol. Otol. 2004;118:645–7).
Clinical cure was achieved in 30 (86%) of the vancomycin recipients, compared with 2 (10%) of those treated with gentamycin. Failures occurred in just 2 (6%) patients given vancomycin versus 16 (80%) given gentamycin.
Of course, this is a small study, but it is based on sound biologic principles and there appear to be no adverse effects. We certainly need more long-term data, but I think topical vancomycin may represent a good alternative to removal of the tubes in some patients. If your pharmacy is able to make this formulation, I think it offers an option to tube removal if CA-MRSA is cultured and the child fails initial oral or topical therapy.
In another small study, successful eradication of MRSA was achieved using a combination of oral trimethoprim-sulfamethoxazole plus topical gentamycin sulfate or polymyxin B sulfate-neomycin sulfate-hydrocortisone (Cortisporin) in six children (five with prior tympanostomy tube placement and one with perforation of the tympanic membrane) who had failed either oral antibiotics or fluoroquinolone ear drops alone (Arch. Otolaryngol. Head Neck Surg. 2005;131:782–4). However, I'd be less apt to use this approach because of concerns about potential ototoxicity of the gentamycin/neomycin on the vestibular system.
In addition to CA-MRSA, otorrhea due to fungal organisms is now being seen increasingly in children who have been treated previously for bacterial infections following tube placement.
In a retrospective review conducted at a pediatric otolaryngology clinic, out of a total 1,242 patients who underwent ear culture between 1996 and 2003, 166 patients (119 with otitis media, 41 with otitis externa, and 6 with both) aged 16 days to 18 years (mean 4 years) were found to have fungal organisms. The proportion of fungus-positive cultures increased dramatically in the years following the availability of the fluoroquinolone drops, from just 4.2% of 356 cultures obtained during 1996–1998 to 18.2% of the 457 cultures done during 1999–2001 (Int. J. Pediatr. Otorhinolaryngol. 2005;69:1503–8).
The most common of the fungi were Candida albicans (43% of the 166), Candida parapsilosis (23.5%), and Aspergillus fumigatus (21%). Although reporting of medications was inconsistent, the authors estimated that the patients had previously received an average of 1.7 oral antibiotics and 1.1 ototopical agents before the culture was taken. Infection resolved in all the patients with treatment, which included clotrimazole topical and tolnaftate topical in 27 patients each, fluconazole in 25, acetic acid alone in 14, and topical plus fluconazole in 10. The thinking is that the use of broad-spectrum quinolone drops may be promoting the emergence of fungus by eliminating the colonizers in the external ear canal, thereby allowing the fungus to grow. This doesn't imply we should stop using quinolone-containing otic solutions, but I do think we need to be aware of the possibility and culture the middle ear in a child who still has otorrhea after 5–7 days of treatment.
Of course, we all know that prevention is the best medicine.
A group from Turkey recently published a comparison of 1 mL intraoperative isotonic saline irrigation, postoperative antibiotic treatment (sulbactam/ampicillin 25 mg/kg for 5 days), postoperative ofloxacin drops (twice a day for 5 days), or placebo in 280 children (mean age 5.9 years) undergoing bilateral ventilation tube insertion because of serous otitis media during 2000–2004 (Am. J. Otolaryngol. 2005;26:123–7).
At 2 weeks post surgery, purulent otorrhea was observed in 15.7% of the saline group, 14.2% of those who received prophylactic oral antibiotics, and 8.6% of the topical antibiotic group, all significantly lower than the 30% rate among the controls. It appears that saline irrigation of the middle ear prior to tube placement offers a low-cost intervention for reducing early post-tympanostomy tube otorrhea.
Novel approaches are necessary to address the emerging problem of the child who fails conventional therapy for acute otorrhea following tympanostomy tube insertion.
We've seen an increase in the number of children with otorrhea through a tympanostomy tube lasting more than 10 days in the past few years, primarily due to the emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Another contributing factor is the increased use of quinolone ear drops, which are thought to promote the occurrence of fungal infections.
Approximately 30% of children who undergo tube placement develop acute otorrhea. Haemophilus influenzae and Streptococcus pneumoniae are responsible for 40%–45% of these cases, particularly in children under 2 years of age and in those who develop symptoms during the winter months. It's hypothesized that these children have ongoing eustachian tube dysfunction that permits nasopharyngeal pathogens to ascend to the middle ear, resulting in acute otorrhea through the tympanostomy tube.
The other 55%–60% of cases are caused by pathogens from the external canal, most commonly Staphylococcus aureus and Pseudomonas aeruginosa. These patients tend to be older, to develop symptoms during the warmer months, and to have a malodorous discharge (in contrast to the nasopharyngeal pathogens, which are odorless).
There appears to be a contribution from water in the ear, which triggers an inflammatory response.
In the past, standard treatment for ear drainage in children was oral antibiotics aimed at H. influenzae and pneumococcus, such as amoxicillin, amoxicillin-clavulanate, or a cephalosporin.
More recently, there has been a shift to greater use of topical fluoroquinolones—particularly ofloxacin and ciprofloxacin—with the increased recognition that the staphylococcus and pseudomonas pathogens also contribute to the microbiology of this disease.
Even in young children, otic preparations are often considered superior to oral antibiotics because they are active against all four of the main pathogens, safely achieve high concentrations in the middle ear, and are less likely to contribute to the emergence of resistance because they are not given systemically.
And of course, they eliminate the bad taste problem.
Now, however, we're starting to see clinical failures with both oral and topical antibiotics, primarily due to CA-MRSA. Among otherwise healthy children, the risk for the development of otorrhea due to MRSA appears to increase with the number of acute otitis media episodes prior to tube placement, as well as with the number of courses and duration of treatment prior to tube placement (Arch. Otolaryngol. Head Neck Surg. 2005;131:868–73).
For MRSA-associated skin and soft tissue infections, drugs such as trimethoprim-sulfamethoxazole, linezolid, or even intravenous vancomycin are usually effective. However, these agents are often ineffective or associated with relapse as soon as therapy is discontinued when a foreign body such as a tympanostomy tube is involved, because of the lack of blood supply and the formation of biofilm.
What does appear to work, at least in small case reports, is the use of either topical vancomycin or combination topical plus oral treatment.
In one report, a group in Thailand combined a 500-mg vial of vancomycin powder with 20 mL of sterile distilled water to create a 25-mg/mL vancomycin solution. Two 0.8-mg drops were placed into the ear three times daily for 10 days in 35 patients with MRSA otorrhea. A control group of 20 patients was treated with the same regimen of gentamycin 0.3% drops (J. Laryngol. Otol. 2004;118:645–7).
Clinical cure was achieved in 30 (86%) of the vancomycin recipients, compared with 2 (10%) of those treated with gentamycin. Failures occurred in just 2 (6%) patients given vancomycin versus 16 (80%) given gentamycin.
Of course, this is a small study, but it is based on sound biologic principles and there appear to be no adverse effects. We certainly need more long-term data, but I think topical vancomycin may represent a good alternative to removal of the tubes in some patients. If your pharmacy is able to make this formulation, I think it offers an option to tube removal if CA-MRSA is cultured and the child fails initial oral or topical therapy.
In another small study, successful eradication of MRSA was achieved using a combination of oral trimethoprim-sulfamethoxazole plus topical gentamycin sulfate or polymyxin B sulfate-neomycin sulfate-hydrocortisone (Cortisporin) in six children (five with prior tympanostomy tube placement and one with perforation of the tympanic membrane) who had failed either oral antibiotics or fluoroquinolone ear drops alone (Arch. Otolaryngol. Head Neck Surg. 2005;131:782–4). However, I'd be less apt to use this approach because of concerns about potential ototoxicity of the gentamycin/neomycin on the vestibular system.
In addition to CA-MRSA, otorrhea due to fungal organisms is now being seen increasingly in children who have been treated previously for bacterial infections following tube placement.
In a retrospective review conducted at a pediatric otolaryngology clinic, out of a total 1,242 patients who underwent ear culture between 1996 and 2003, 166 patients (119 with otitis media, 41 with otitis externa, and 6 with both) aged 16 days to 18 years (mean 4 years) were found to have fungal organisms. The proportion of fungus-positive cultures increased dramatically in the years following the availability of the fluoroquinolone drops, from just 4.2% of 356 cultures obtained during 1996–1998 to 18.2% of the 457 cultures done during 1999–2001 (Int. J. Pediatr. Otorhinolaryngol. 2005;69:1503–8).
The most common of the fungi were Candida albicans (43% of the 166), Candida parapsilosis (23.5%), and Aspergillus fumigatus (21%). Although reporting of medications was inconsistent, the authors estimated that the patients had previously received an average of 1.7 oral antibiotics and 1.1 ototopical agents before the culture was taken. Infection resolved in all the patients with treatment, which included clotrimazole topical and tolnaftate topical in 27 patients each, fluconazole in 25, acetic acid alone in 14, and topical plus fluconazole in 10. The thinking is that the use of broad-spectrum quinolone drops may be promoting the emergence of fungus by eliminating the colonizers in the external ear canal, thereby allowing the fungus to grow. This doesn't imply we should stop using quinolone-containing otic solutions, but I do think we need to be aware of the possibility and culture the middle ear in a child who still has otorrhea after 5–7 days of treatment.
Of course, we all know that prevention is the best medicine.
A group from Turkey recently published a comparison of 1 mL intraoperative isotonic saline irrigation, postoperative antibiotic treatment (sulbactam/ampicillin 25 mg/kg for 5 days), postoperative ofloxacin drops (twice a day for 5 days), or placebo in 280 children (mean age 5.9 years) undergoing bilateral ventilation tube insertion because of serous otitis media during 2000–2004 (Am. J. Otolaryngol. 2005;26:123–7).
At 2 weeks post surgery, purulent otorrhea was observed in 15.7% of the saline group, 14.2% of those who received prophylactic oral antibiotics, and 8.6% of the topical antibiotic group, all significantly lower than the 30% rate among the controls. It appears that saline irrigation of the middle ear prior to tube placement offers a low-cost intervention for reducing early post-tympanostomy tube otorrhea.
Tale of Two Winter Respiratory Illnesses
November marks the season of two viral respiratory illnesses for which steroids are part of the treatment. But although the role of steroids is now established for croup, their use in bronchiolitis remains controversial.
Croup, otherwise known as laryngotracheal bronchitis, typically begins with an upper respiratory infection and proceeds to a barking cough, hoarseness, and then stridor. Caused mostly by the parainfluenza viruses (1,2, or 3) or respiratory syncytial virus (RSV), it is usually mild and self-limited, although in rare cases, obstruction can occur.
It's important to differentiate croup from bacterial tracheitis, which is characterized by thick, purulent exudate in a child who is highly febrile and toxic with an elevated WBC count, and from the rare case of epiglottitis, in which the child is typically drooling, looks very toxic, has significant airway obstruction, and is air hungry.
Humidified air is the primary treatment for the child with mild croup, despite the lack of clinical trials supporting its use. Anecdotally, using a humidifier or placing the child in hot shower mist results in resolution of croupy symptoms relatively rapidly, whereas respiratory symptoms might progress without treatment. Although there are no controlled trials to support this treatment, such an approach is frequently successful.
Though steroids have been well-established in the treatment of severe croup, in recent years, oral dexamethasone, along with oxygen, has become standard for the child with moderate croup, as well. Recent data have pointed to its benefit, and physicians have become more comfortable using steroids in such children in the context of asthma.
In a recent Cochrane metaanalysis of 31 controlled trials involving a total of 3,736 children with croup, glucocorticoid treatment was associated with significant improvements in the Westley croup score at 6 and 12 hours. The steroid-treated children had half the number of return visits/readmissions and spent a mean of 12 fewer hours in the emergency department and/or hospital (Cochrane Database Syst. Rev. 2004;CD001955).
Epinephrine use was also 10% lower among the steroid-treated children in the Cochrane analysis. When nebulized epinephrine is needed—typically if stridor is moderate, worse, or persistent after initiation of steroids—it's important to observe the child for 3–4 hours after initiation of epinephrine, to make sure stridor does not return, given that the effects of epinephrine do not usually last beyond 2 hours.
For the child with severe croup, the initial treatment is oxygen along with nebulized epinephrine to break the spasm. Steroids are clearly indicated after that; it's just a matter of determining whether the child can tolerate them orally or needs to receive them intravenously.
In contrast to croup, the treatment of bronchiolitis—and indeed its clinical identification—are less well defined. A near-universal illness within the first 2 years of life during the months of November-April, bronchiolitis is usually caused by RSV, although now it appears that human metapneumovirus may account for up to 15% of cases.
Children at greatest risk for serious disease are those younger than 6 months, those born prior to 35 weeks' gestation, and those with chronic lung disease (particularly bronchopulmonary dysplasia), heart disease, or severe immunocompromise, such as bone marrow transplant recipients.
Although the classical presentation of bronchiolitis is coryza, stridor, and mild to moderate respiratory distress, a small proportion of children will present with apnea alone.
Most experts would agree that oxygen and fluids (usually given intravenously) are part of the treatment, though there is some debate about how much fluid is appropriate to prevent dehydration but avoid excess fluid in the lungs. More controversial, however, are the roles of bronchodilators and of steroids.
Results of various studies looking at the response to β-agonist therapy among children with bronchiolitis have been mixed. The problem with these studies appears to be that the results have depended upon the population selected: Studies that have included only children with nasal washings positive for RSV or “pure” bronchiolitis tend to show less benefit, whereas bronchodilators have tended to work better in studies that use a clinical definition for bronchiolitis that includes repeated wheezing, which overlaps with asthma.
Indeed, it's nearly impossible to distinguish RSV bronchiolitis from a first asthma episode in a 6-month-old.
Some of these infants may have more of an atopic illness than a true respiratory viral illness, and we do know that bronchodilators work best in children with atopic disease.
But, it has been hypothesized that RSV may act as a trigger for wheezing in an atopic child, so the presence of RSV certainly doesn't eliminate the potential of allergic bronchospasm.
My approach, then, is to give a trial of inhaled albuterol when the child's symptoms are severe enough to be in the hospital or emergency department and to assess oxygenation, respiratory effort, and respiration rate/retraction after 1–2 hours. If the child has had recurrent episodes or has underlying lung disease, a consideration of steroids is appropriate. Studies to date have found inconsistent results as to the benefit of steroids in first episodes with potential benefit in those with underlying lung pathology or recurrent episodes—the hypothesis being that decreasing bronchiolar inflammation and swelling relieves the airway obstruction. More data support the use of oral than nebulized steroids in children who can take them by mouth. Otherwise, intravenous steroids are required.
Interestingly, recent data have come out suggesting racial differences in response to both glucocorticoids and to inhaled albuterol.
One study, for example, found that black asthmatics required greater concentrations of glucocorticoid in vitro to suppress T-lympocyte activation (Chest 2005;127:571–8), while another found significant differences in bronchodilator response between Puerto Rican and Mexican asthmatic subjects, based on pharmacogenetic differences (Am. J. Respir. Crit. Care. Med. 2005;171:535–6).
More studies are necessary so we can begin to incorporate these avenues of research into clinical practice.
November marks the season of two viral respiratory illnesses for which steroids are part of the treatment. But although the role of steroids is now established for croup, their use in bronchiolitis remains controversial.
Croup, otherwise known as laryngotracheal bronchitis, typically begins with an upper respiratory infection and proceeds to a barking cough, hoarseness, and then stridor. Caused mostly by the parainfluenza viruses (1,2, or 3) or respiratory syncytial virus (RSV), it is usually mild and self-limited, although in rare cases, obstruction can occur.
It's important to differentiate croup from bacterial tracheitis, which is characterized by thick, purulent exudate in a child who is highly febrile and toxic with an elevated WBC count, and from the rare case of epiglottitis, in which the child is typically drooling, looks very toxic, has significant airway obstruction, and is air hungry.
Humidified air is the primary treatment for the child with mild croup, despite the lack of clinical trials supporting its use. Anecdotally, using a humidifier or placing the child in hot shower mist results in resolution of croupy symptoms relatively rapidly, whereas respiratory symptoms might progress without treatment. Although there are no controlled trials to support this treatment, such an approach is frequently successful.
Though steroids have been well-established in the treatment of severe croup, in recent years, oral dexamethasone, along with oxygen, has become standard for the child with moderate croup, as well. Recent data have pointed to its benefit, and physicians have become more comfortable using steroids in such children in the context of asthma.
In a recent Cochrane metaanalysis of 31 controlled trials involving a total of 3,736 children with croup, glucocorticoid treatment was associated with significant improvements in the Westley croup score at 6 and 12 hours. The steroid-treated children had half the number of return visits/readmissions and spent a mean of 12 fewer hours in the emergency department and/or hospital (Cochrane Database Syst. Rev. 2004;CD001955).
Epinephrine use was also 10% lower among the steroid-treated children in the Cochrane analysis. When nebulized epinephrine is needed—typically if stridor is moderate, worse, or persistent after initiation of steroids—it's important to observe the child for 3–4 hours after initiation of epinephrine, to make sure stridor does not return, given that the effects of epinephrine do not usually last beyond 2 hours.
For the child with severe croup, the initial treatment is oxygen along with nebulized epinephrine to break the spasm. Steroids are clearly indicated after that; it's just a matter of determining whether the child can tolerate them orally or needs to receive them intravenously.
In contrast to croup, the treatment of bronchiolitis—and indeed its clinical identification—are less well defined. A near-universal illness within the first 2 years of life during the months of November-April, bronchiolitis is usually caused by RSV, although now it appears that human metapneumovirus may account for up to 15% of cases.
Children at greatest risk for serious disease are those younger than 6 months, those born prior to 35 weeks' gestation, and those with chronic lung disease (particularly bronchopulmonary dysplasia), heart disease, or severe immunocompromise, such as bone marrow transplant recipients.
Although the classical presentation of bronchiolitis is coryza, stridor, and mild to moderate respiratory distress, a small proportion of children will present with apnea alone.
Most experts would agree that oxygen and fluids (usually given intravenously) are part of the treatment, though there is some debate about how much fluid is appropriate to prevent dehydration but avoid excess fluid in the lungs. More controversial, however, are the roles of bronchodilators and of steroids.
Results of various studies looking at the response to β-agonist therapy among children with bronchiolitis have been mixed. The problem with these studies appears to be that the results have depended upon the population selected: Studies that have included only children with nasal washings positive for RSV or “pure” bronchiolitis tend to show less benefit, whereas bronchodilators have tended to work better in studies that use a clinical definition for bronchiolitis that includes repeated wheezing, which overlaps with asthma.
Indeed, it's nearly impossible to distinguish RSV bronchiolitis from a first asthma episode in a 6-month-old.
Some of these infants may have more of an atopic illness than a true respiratory viral illness, and we do know that bronchodilators work best in children with atopic disease.
But, it has been hypothesized that RSV may act as a trigger for wheezing in an atopic child, so the presence of RSV certainly doesn't eliminate the potential of allergic bronchospasm.
My approach, then, is to give a trial of inhaled albuterol when the child's symptoms are severe enough to be in the hospital or emergency department and to assess oxygenation, respiratory effort, and respiration rate/retraction after 1–2 hours. If the child has had recurrent episodes or has underlying lung disease, a consideration of steroids is appropriate. Studies to date have found inconsistent results as to the benefit of steroids in first episodes with potential benefit in those with underlying lung pathology or recurrent episodes—the hypothesis being that decreasing bronchiolar inflammation and swelling relieves the airway obstruction. More data support the use of oral than nebulized steroids in children who can take them by mouth. Otherwise, intravenous steroids are required.
Interestingly, recent data have come out suggesting racial differences in response to both glucocorticoids and to inhaled albuterol.
One study, for example, found that black asthmatics required greater concentrations of glucocorticoid in vitro to suppress T-lympocyte activation (Chest 2005;127:571–8), while another found significant differences in bronchodilator response between Puerto Rican and Mexican asthmatic subjects, based on pharmacogenetic differences (Am. J. Respir. Crit. Care. Med. 2005;171:535–6).
More studies are necessary so we can begin to incorporate these avenues of research into clinical practice.
November marks the season of two viral respiratory illnesses for which steroids are part of the treatment. But although the role of steroids is now established for croup, their use in bronchiolitis remains controversial.
Croup, otherwise known as laryngotracheal bronchitis, typically begins with an upper respiratory infection and proceeds to a barking cough, hoarseness, and then stridor. Caused mostly by the parainfluenza viruses (1,2, or 3) or respiratory syncytial virus (RSV), it is usually mild and self-limited, although in rare cases, obstruction can occur.
It's important to differentiate croup from bacterial tracheitis, which is characterized by thick, purulent exudate in a child who is highly febrile and toxic with an elevated WBC count, and from the rare case of epiglottitis, in which the child is typically drooling, looks very toxic, has significant airway obstruction, and is air hungry.
Humidified air is the primary treatment for the child with mild croup, despite the lack of clinical trials supporting its use. Anecdotally, using a humidifier or placing the child in hot shower mist results in resolution of croupy symptoms relatively rapidly, whereas respiratory symptoms might progress without treatment. Although there are no controlled trials to support this treatment, such an approach is frequently successful.
Though steroids have been well-established in the treatment of severe croup, in recent years, oral dexamethasone, along with oxygen, has become standard for the child with moderate croup, as well. Recent data have pointed to its benefit, and physicians have become more comfortable using steroids in such children in the context of asthma.
In a recent Cochrane metaanalysis of 31 controlled trials involving a total of 3,736 children with croup, glucocorticoid treatment was associated with significant improvements in the Westley croup score at 6 and 12 hours. The steroid-treated children had half the number of return visits/readmissions and spent a mean of 12 fewer hours in the emergency department and/or hospital (Cochrane Database Syst. Rev. 2004;CD001955).
Epinephrine use was also 10% lower among the steroid-treated children in the Cochrane analysis. When nebulized epinephrine is needed—typically if stridor is moderate, worse, or persistent after initiation of steroids—it's important to observe the child for 3–4 hours after initiation of epinephrine, to make sure stridor does not return, given that the effects of epinephrine do not usually last beyond 2 hours.
For the child with severe croup, the initial treatment is oxygen along with nebulized epinephrine to break the spasm. Steroids are clearly indicated after that; it's just a matter of determining whether the child can tolerate them orally or needs to receive them intravenously.
In contrast to croup, the treatment of bronchiolitis—and indeed its clinical identification—are less well defined. A near-universal illness within the first 2 years of life during the months of November-April, bronchiolitis is usually caused by RSV, although now it appears that human metapneumovirus may account for up to 15% of cases.
Children at greatest risk for serious disease are those younger than 6 months, those born prior to 35 weeks' gestation, and those with chronic lung disease (particularly bronchopulmonary dysplasia), heart disease, or severe immunocompromise, such as bone marrow transplant recipients.
Although the classical presentation of bronchiolitis is coryza, stridor, and mild to moderate respiratory distress, a small proportion of children will present with apnea alone.
Most experts would agree that oxygen and fluids (usually given intravenously) are part of the treatment, though there is some debate about how much fluid is appropriate to prevent dehydration but avoid excess fluid in the lungs. More controversial, however, are the roles of bronchodilators and of steroids.
Results of various studies looking at the response to β-agonist therapy among children with bronchiolitis have been mixed. The problem with these studies appears to be that the results have depended upon the population selected: Studies that have included only children with nasal washings positive for RSV or “pure” bronchiolitis tend to show less benefit, whereas bronchodilators have tended to work better in studies that use a clinical definition for bronchiolitis that includes repeated wheezing, which overlaps with asthma.
Indeed, it's nearly impossible to distinguish RSV bronchiolitis from a first asthma episode in a 6-month-old.
Some of these infants may have more of an atopic illness than a true respiratory viral illness, and we do know that bronchodilators work best in children with atopic disease.
But, it has been hypothesized that RSV may act as a trigger for wheezing in an atopic child, so the presence of RSV certainly doesn't eliminate the potential of allergic bronchospasm.
My approach, then, is to give a trial of inhaled albuterol when the child's symptoms are severe enough to be in the hospital or emergency department and to assess oxygenation, respiratory effort, and respiration rate/retraction after 1–2 hours. If the child has had recurrent episodes or has underlying lung disease, a consideration of steroids is appropriate. Studies to date have found inconsistent results as to the benefit of steroids in first episodes with potential benefit in those with underlying lung pathology or recurrent episodes—the hypothesis being that decreasing bronchiolar inflammation and swelling relieves the airway obstruction. More data support the use of oral than nebulized steroids in children who can take them by mouth. Otherwise, intravenous steroids are required.
Interestingly, recent data have come out suggesting racial differences in response to both glucocorticoids and to inhaled albuterol.
One study, for example, found that black asthmatics required greater concentrations of glucocorticoid in vitro to suppress T-lympocyte activation (Chest 2005;127:571–8), while another found significant differences in bronchodilator response between Puerto Rican and Mexican asthmatic subjects, based on pharmacogenetic differences (Am. J. Respir. Crit. Care. Med. 2005;171:535–6).
More studies are necessary so we can begin to incorporate these avenues of research into clinical practice.
Pediatric HIV Still a Problem
We've made great strides in combating pediatric HIV/AIDS in the last few years, but children living with HIV still face enormous difficulties.
Indeed, the number of new cases of vertical transmission has dropped to an all-time low, from about 1,000 in the early 1990's to less than 50 in 2003. The obstetric community is now doing a far better job of identifying women with HIV; delivering medical care to them; and, thereby, reducing the rate of vertical transmission to just 1%-2%, from 25%-30% in the 1990's.
Unfortunately, this great success in reducing vertical transmission and the effectiveness of highly active antiretroviral treatment (HAART) in maintaining immune function in HIV-infected children has created a public perception that pediatric HIV/AIDS is no longer an issue.
In fact, there are approximately 5,000 children currently living with HIV/AIDS in the United States, with 250 of them here in Massachusetts. These children have substantial, ongoing problems that place them at increasing risk as they get older. Ongoing services will be required to meet their needs, as will innovative research to ensure that our current approach is safe and effective over a prolonged time period.
Yet, as a result of a shift in public focus to HIV in Africa, there has been a dramatic decrease in both federal and private funds for HIV here in the United States. In Massachusetts, for example, money for HIV programs has declined about 40% in the last 5 years, from about $50 million to about $30 million, without any decline in the number of patients needing services.
Although the numbers of vertically infected newborns have dropped dramatically in the United States, a small number of cases still occur when a woman is tested early in pregnancy and is found to be uninfected, but then acquires the infection later during pregnancy, prior to delivery. We've had a couple of cases in the last year or 2, in which the infant has presented with advanced HIV in the first 6 months of life.
Moreover, increasing numbers of HIV-infected pregnant women and children are coming to the United States from other countries. We currently have two new patients—one is an HIV-infected child from Haiti who was adopted by a New Hampshire couple, the other the child of a mother who had recently come from Cape Verde.
But by far, the greatest number of new cases of pediatric HIV in the United States is now among adolescents who acquire the infection through risky behavior. We see a newly infected adolescent every few months.
Once adolescents become infected with HIV, it can be a challenge to engage them, to convince them that they must take their medications regularly even though they're feeling fine, and to be responsible with regard to their sexual behavior. We've had several of our teenage HIV-infected girls become pregnant, and some of our boys have fathered babies.
Regardless of how children acquire HIV, they face significant health challenges despite the dramatic increase in lifespan that has come with the success of HAART.
Resistance is a major problem. About 50% of all HIV-infected children have some degree of resistance to at least one of the currently licensed antiretroviral agents, while about 10%-15% are completely out of treatment options. The latter scenario, which arises after long-term treatment with multiple agents from multiple classes, will likely only get worse with time.
Unfortunately, there have been no major breakthroughs in terms of new drug classes introduced for the treatment of pediatric HIV in the last 3-4 years. The problem is particularly bad for younger children who can't take large capsules and are relegated to taking liquids or suspensions. The best of these are poor tasting, and the worst ones are foul tasting. Many children simply refuse to take them and end up with inadequate dosing, which increases their risk for developing resistance.
Among the 10%-15% of children whose viruses have mutated to the point that they are 100-fold less susceptible than are wild-type viruses, the only options are to try using five or six different medications, often in combination with a relatively new agent called T20. But T20 can only be given by injection, which is a problem in children. We have one patient on the drug, a very slender boy who now has exquisitely sensitive nodules all over his arms.
The metabolic and cardiovascular changes we're seeing in adults on long-term HAART therapy are also a major cause for concern among children. Although we haven't seen coronary artery disease yet in children, some do have quite high cholesterol and triglyceride levels. I have one child right now with a cholesterol level of more than 700 mg/dL, with visible deposits in his elbows and knees.
My expectation is that our adult medicine colleagues are the ones who will see serious heart disease in these patients, probably in their 20s or 30s, just as the adults are now getting coronary artery disease in their 30s, 40s, and 50s. Currently there is disagreement about how aggressively to treat cardiovascular risk factors in these children. Some argue that these kids have HIV and we should simply leave them alone. My attitude is that because these children have HIV and may live into their 50s, 60s, or 70s, we can't afford to leave them alone.
Body changes—typically increased weight and fat deposition in the trunk—are also a major problem, especially for the teenagers. Girls often have enlarged breasts, big abdomens, a “buffalo hump,” and very large shoulders. Boys tend to develop barrel chests and gynecomastia. As you can imagine, these changes are quite disturbing to teenagers, and may lead them to stop taking their medications. While this syndrome, lipodystrophy, is being extensively studied in adults, little progress has been made in understanding its pathogenesis in children and adolescents.
Disclosure may be yet another problem for many HIV-infected teenagers. We've had several young adolescent patients who don't know their diagnosis. The parents often think they're protecting their kids by not telling them, but we believe that the more the children know, the more likely they are to take an active part in their own care as they mature. We begin discussing disclosure with families when their child reaches 8-10 years of age, depending on individual maturity and intellectual capacity.
A fourth cause for concern—and possibly the greatest—comes from a recent study published by the Pediatric AIDS Clinical Trials Group, in which I participate. We found that neuropsychological function was significantly poorer among HIV-infected children, and was worse with higher viral loads. Moreover, only one measure of neuropsychological functioning improved after effective viral suppression with combination protease inhibitor therapy, and that improvement was relatively minor (Pediatrics 2005;115:380-7).
While it had been previously recognized that HIV-infected children have cognitive and behavioral difficulties, this is the first time it has been looked at with regard to response to HAART therapy. Although the correlation with viral load suggests the problem is disease related, we have not yet determined the relative contributions of disease, treatment, and the often adverse socioeconomic environments these children live in.
We must continue to search for better and safer approaches to preventing vertical transmission. Currently, we give antiretrovirals as early as the second trimester, continue them through labor and delivery, and in the newborn for up to 6 weeks. With all the new drugs that are being introduced, we must be certain that the therapies we're delivering are safe. Now that 98%-99% of these children won't have HIV, we have to make sure they don't have toxicity from the medications, either.
We need to find safer regimens without losing what we've accomplished in preventing vertical transmission, which is in my mind the biggest accomplishment in the prevention of HIV to date.
We've made great strides in combating pediatric HIV/AIDS in the last few years, but children living with HIV still face enormous difficulties.
Indeed, the number of new cases of vertical transmission has dropped to an all-time low, from about 1,000 in the early 1990's to less than 50 in 2003. The obstetric community is now doing a far better job of identifying women with HIV; delivering medical care to them; and, thereby, reducing the rate of vertical transmission to just 1%-2%, from 25%-30% in the 1990's.
Unfortunately, this great success in reducing vertical transmission and the effectiveness of highly active antiretroviral treatment (HAART) in maintaining immune function in HIV-infected children has created a public perception that pediatric HIV/AIDS is no longer an issue.
In fact, there are approximately 5,000 children currently living with HIV/AIDS in the United States, with 250 of them here in Massachusetts. These children have substantial, ongoing problems that place them at increasing risk as they get older. Ongoing services will be required to meet their needs, as will innovative research to ensure that our current approach is safe and effective over a prolonged time period.
Yet, as a result of a shift in public focus to HIV in Africa, there has been a dramatic decrease in both federal and private funds for HIV here in the United States. In Massachusetts, for example, money for HIV programs has declined about 40% in the last 5 years, from about $50 million to about $30 million, without any decline in the number of patients needing services.
Although the numbers of vertically infected newborns have dropped dramatically in the United States, a small number of cases still occur when a woman is tested early in pregnancy and is found to be uninfected, but then acquires the infection later during pregnancy, prior to delivery. We've had a couple of cases in the last year or 2, in which the infant has presented with advanced HIV in the first 6 months of life.
Moreover, increasing numbers of HIV-infected pregnant women and children are coming to the United States from other countries. We currently have two new patients—one is an HIV-infected child from Haiti who was adopted by a New Hampshire couple, the other the child of a mother who had recently come from Cape Verde.
But by far, the greatest number of new cases of pediatric HIV in the United States is now among adolescents who acquire the infection through risky behavior. We see a newly infected adolescent every few months.
Once adolescents become infected with HIV, it can be a challenge to engage them, to convince them that they must take their medications regularly even though they're feeling fine, and to be responsible with regard to their sexual behavior. We've had several of our teenage HIV-infected girls become pregnant, and some of our boys have fathered babies.
Regardless of how children acquire HIV, they face significant health challenges despite the dramatic increase in lifespan that has come with the success of HAART.
Resistance is a major problem. About 50% of all HIV-infected children have some degree of resistance to at least one of the currently licensed antiretroviral agents, while about 10%-15% are completely out of treatment options. The latter scenario, which arises after long-term treatment with multiple agents from multiple classes, will likely only get worse with time.
Unfortunately, there have been no major breakthroughs in terms of new drug classes introduced for the treatment of pediatric HIV in the last 3-4 years. The problem is particularly bad for younger children who can't take large capsules and are relegated to taking liquids or suspensions. The best of these are poor tasting, and the worst ones are foul tasting. Many children simply refuse to take them and end up with inadequate dosing, which increases their risk for developing resistance.
Among the 10%-15% of children whose viruses have mutated to the point that they are 100-fold less susceptible than are wild-type viruses, the only options are to try using five or six different medications, often in combination with a relatively new agent called T20. But T20 can only be given by injection, which is a problem in children. We have one patient on the drug, a very slender boy who now has exquisitely sensitive nodules all over his arms.
The metabolic and cardiovascular changes we're seeing in adults on long-term HAART therapy are also a major cause for concern among children. Although we haven't seen coronary artery disease yet in children, some do have quite high cholesterol and triglyceride levels. I have one child right now with a cholesterol level of more than 700 mg/dL, with visible deposits in his elbows and knees.
My expectation is that our adult medicine colleagues are the ones who will see serious heart disease in these patients, probably in their 20s or 30s, just as the adults are now getting coronary artery disease in their 30s, 40s, and 50s. Currently there is disagreement about how aggressively to treat cardiovascular risk factors in these children. Some argue that these kids have HIV and we should simply leave them alone. My attitude is that because these children have HIV and may live into their 50s, 60s, or 70s, we can't afford to leave them alone.
Body changes—typically increased weight and fat deposition in the trunk—are also a major problem, especially for the teenagers. Girls often have enlarged breasts, big abdomens, a “buffalo hump,” and very large shoulders. Boys tend to develop barrel chests and gynecomastia. As you can imagine, these changes are quite disturbing to teenagers, and may lead them to stop taking their medications. While this syndrome, lipodystrophy, is being extensively studied in adults, little progress has been made in understanding its pathogenesis in children and adolescents.
Disclosure may be yet another problem for many HIV-infected teenagers. We've had several young adolescent patients who don't know their diagnosis. The parents often think they're protecting their kids by not telling them, but we believe that the more the children know, the more likely they are to take an active part in their own care as they mature. We begin discussing disclosure with families when their child reaches 8-10 years of age, depending on individual maturity and intellectual capacity.
A fourth cause for concern—and possibly the greatest—comes from a recent study published by the Pediatric AIDS Clinical Trials Group, in which I participate. We found that neuropsychological function was significantly poorer among HIV-infected children, and was worse with higher viral loads. Moreover, only one measure of neuropsychological functioning improved after effective viral suppression with combination protease inhibitor therapy, and that improvement was relatively minor (Pediatrics 2005;115:380-7).
While it had been previously recognized that HIV-infected children have cognitive and behavioral difficulties, this is the first time it has been looked at with regard to response to HAART therapy. Although the correlation with viral load suggests the problem is disease related, we have not yet determined the relative contributions of disease, treatment, and the often adverse socioeconomic environments these children live in.
We must continue to search for better and safer approaches to preventing vertical transmission. Currently, we give antiretrovirals as early as the second trimester, continue them through labor and delivery, and in the newborn for up to 6 weeks. With all the new drugs that are being introduced, we must be certain that the therapies we're delivering are safe. Now that 98%-99% of these children won't have HIV, we have to make sure they don't have toxicity from the medications, either.
We need to find safer regimens without losing what we've accomplished in preventing vertical transmission, which is in my mind the biggest accomplishment in the prevention of HIV to date.
We've made great strides in combating pediatric HIV/AIDS in the last few years, but children living with HIV still face enormous difficulties.
Indeed, the number of new cases of vertical transmission has dropped to an all-time low, from about 1,000 in the early 1990's to less than 50 in 2003. The obstetric community is now doing a far better job of identifying women with HIV; delivering medical care to them; and, thereby, reducing the rate of vertical transmission to just 1%-2%, from 25%-30% in the 1990's.
Unfortunately, this great success in reducing vertical transmission and the effectiveness of highly active antiretroviral treatment (HAART) in maintaining immune function in HIV-infected children has created a public perception that pediatric HIV/AIDS is no longer an issue.
In fact, there are approximately 5,000 children currently living with HIV/AIDS in the United States, with 250 of them here in Massachusetts. These children have substantial, ongoing problems that place them at increasing risk as they get older. Ongoing services will be required to meet their needs, as will innovative research to ensure that our current approach is safe and effective over a prolonged time period.
Yet, as a result of a shift in public focus to HIV in Africa, there has been a dramatic decrease in both federal and private funds for HIV here in the United States. In Massachusetts, for example, money for HIV programs has declined about 40% in the last 5 years, from about $50 million to about $30 million, without any decline in the number of patients needing services.
Although the numbers of vertically infected newborns have dropped dramatically in the United States, a small number of cases still occur when a woman is tested early in pregnancy and is found to be uninfected, but then acquires the infection later during pregnancy, prior to delivery. We've had a couple of cases in the last year or 2, in which the infant has presented with advanced HIV in the first 6 months of life.
Moreover, increasing numbers of HIV-infected pregnant women and children are coming to the United States from other countries. We currently have two new patients—one is an HIV-infected child from Haiti who was adopted by a New Hampshire couple, the other the child of a mother who had recently come from Cape Verde.
But by far, the greatest number of new cases of pediatric HIV in the United States is now among adolescents who acquire the infection through risky behavior. We see a newly infected adolescent every few months.
Once adolescents become infected with HIV, it can be a challenge to engage them, to convince them that they must take their medications regularly even though they're feeling fine, and to be responsible with regard to their sexual behavior. We've had several of our teenage HIV-infected girls become pregnant, and some of our boys have fathered babies.
Regardless of how children acquire HIV, they face significant health challenges despite the dramatic increase in lifespan that has come with the success of HAART.
Resistance is a major problem. About 50% of all HIV-infected children have some degree of resistance to at least one of the currently licensed antiretroviral agents, while about 10%-15% are completely out of treatment options. The latter scenario, which arises after long-term treatment with multiple agents from multiple classes, will likely only get worse with time.
Unfortunately, there have been no major breakthroughs in terms of new drug classes introduced for the treatment of pediatric HIV in the last 3-4 years. The problem is particularly bad for younger children who can't take large capsules and are relegated to taking liquids or suspensions. The best of these are poor tasting, and the worst ones are foul tasting. Many children simply refuse to take them and end up with inadequate dosing, which increases their risk for developing resistance.
Among the 10%-15% of children whose viruses have mutated to the point that they are 100-fold less susceptible than are wild-type viruses, the only options are to try using five or six different medications, often in combination with a relatively new agent called T20. But T20 can only be given by injection, which is a problem in children. We have one patient on the drug, a very slender boy who now has exquisitely sensitive nodules all over his arms.
The metabolic and cardiovascular changes we're seeing in adults on long-term HAART therapy are also a major cause for concern among children. Although we haven't seen coronary artery disease yet in children, some do have quite high cholesterol and triglyceride levels. I have one child right now with a cholesterol level of more than 700 mg/dL, with visible deposits in his elbows and knees.
My expectation is that our adult medicine colleagues are the ones who will see serious heart disease in these patients, probably in their 20s or 30s, just as the adults are now getting coronary artery disease in their 30s, 40s, and 50s. Currently there is disagreement about how aggressively to treat cardiovascular risk factors in these children. Some argue that these kids have HIV and we should simply leave them alone. My attitude is that because these children have HIV and may live into their 50s, 60s, or 70s, we can't afford to leave them alone.
Body changes—typically increased weight and fat deposition in the trunk—are also a major problem, especially for the teenagers. Girls often have enlarged breasts, big abdomens, a “buffalo hump,” and very large shoulders. Boys tend to develop barrel chests and gynecomastia. As you can imagine, these changes are quite disturbing to teenagers, and may lead them to stop taking their medications. While this syndrome, lipodystrophy, is being extensively studied in adults, little progress has been made in understanding its pathogenesis in children and adolescents.
Disclosure may be yet another problem for many HIV-infected teenagers. We've had several young adolescent patients who don't know their diagnosis. The parents often think they're protecting their kids by not telling them, but we believe that the more the children know, the more likely they are to take an active part in their own care as they mature. We begin discussing disclosure with families when their child reaches 8-10 years of age, depending on individual maturity and intellectual capacity.
A fourth cause for concern—and possibly the greatest—comes from a recent study published by the Pediatric AIDS Clinical Trials Group, in which I participate. We found that neuropsychological function was significantly poorer among HIV-infected children, and was worse with higher viral loads. Moreover, only one measure of neuropsychological functioning improved after effective viral suppression with combination protease inhibitor therapy, and that improvement was relatively minor (Pediatrics 2005;115:380-7).
While it had been previously recognized that HIV-infected children have cognitive and behavioral difficulties, this is the first time it has been looked at with regard to response to HAART therapy. Although the correlation with viral load suggests the problem is disease related, we have not yet determined the relative contributions of disease, treatment, and the often adverse socioeconomic environments these children live in.
We must continue to search for better and safer approaches to preventing vertical transmission. Currently, we give antiretrovirals as early as the second trimester, continue them through labor and delivery, and in the newborn for up to 6 weeks. With all the new drugs that are being introduced, we must be certain that the therapies we're delivering are safe. Now that 98%-99% of these children won't have HIV, we have to make sure they don't have toxicity from the medications, either.
We need to find safer regimens without losing what we've accomplished in preventing vertical transmission, which is in my mind the biggest accomplishment in the prevention of HIV to date.