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Antibiotic Therapy, Appendectomy for Uncomplicated Acute Appendicitis
Clinical question: Is antibiotic therapy noninferior to appendectomy for treatment of uncomplicated acute appendicitis?
Background: Previous randomized clinical trials have compared antibiotic therapy versus appendectomy for the treatment of uncomplicated, acute appendicitis. Each of these studies had significant limitations, and appendectomy has remained the standard of care.
Study design: Noninferiority, randomized clinical trial.
Setting: Six hospitals in Finland.
Synopsis: Investigators randomized 530 patients with uncomplicated appendicitis confirmed on CT to appendectomy or antibiotic therapy, with a noninferiority margin of 24%. Of the 256 patients randomized to antibiotics who were available for follow-up, 70 received surgical intervention within one year. This resulted in a difference between treatment groups of -27%. Further analysis revealed that five of those patients had normal appendices and did not actually require appendectomy. Secondary outcome analysis demonstrated a significantly lower complication rate among patients in the antibiotic group (2.8%) compared with the surgical group (20.5%); however, the open operative approach used on most patients may have resulted in increased wound complications.
Although noninferiority of antibiotic treatment was not demonstrated, the majority of patients in the antibiotic group (73%) were found to have successful treatment with antibiotics alone. None of these patients, including those eventually undergoing appendectomy, suffered major complications. Although the overall approach to uncomplicated appendicitis may not change, physicians and patients should utilize this data to make an informed decision between antibiotic treatment and appendectomy.
Bottom line: In patients with CT-proven, uncomplicated acute appendicitis, antibiotic treatment did not meet the pre-specified threshold for noninferiority compared with appendectomy, yet a significant majority of patients in the antibiotic arm had successful recovery.
Citation: Salminen P, Paajanen H, Rautio T, et al. Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis: The APPAC randomized clinical trial. JAMA. 2015;313(23):2340-2348
Clinical question: Is antibiotic therapy noninferior to appendectomy for treatment of uncomplicated acute appendicitis?
Background: Previous randomized clinical trials have compared antibiotic therapy versus appendectomy for the treatment of uncomplicated, acute appendicitis. Each of these studies had significant limitations, and appendectomy has remained the standard of care.
Study design: Noninferiority, randomized clinical trial.
Setting: Six hospitals in Finland.
Synopsis: Investigators randomized 530 patients with uncomplicated appendicitis confirmed on CT to appendectomy or antibiotic therapy, with a noninferiority margin of 24%. Of the 256 patients randomized to antibiotics who were available for follow-up, 70 received surgical intervention within one year. This resulted in a difference between treatment groups of -27%. Further analysis revealed that five of those patients had normal appendices and did not actually require appendectomy. Secondary outcome analysis demonstrated a significantly lower complication rate among patients in the antibiotic group (2.8%) compared with the surgical group (20.5%); however, the open operative approach used on most patients may have resulted in increased wound complications.
Although noninferiority of antibiotic treatment was not demonstrated, the majority of patients in the antibiotic group (73%) were found to have successful treatment with antibiotics alone. None of these patients, including those eventually undergoing appendectomy, suffered major complications. Although the overall approach to uncomplicated appendicitis may not change, physicians and patients should utilize this data to make an informed decision between antibiotic treatment and appendectomy.
Bottom line: In patients with CT-proven, uncomplicated acute appendicitis, antibiotic treatment did not meet the pre-specified threshold for noninferiority compared with appendectomy, yet a significant majority of patients in the antibiotic arm had successful recovery.
Citation: Salminen P, Paajanen H, Rautio T, et al. Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis: The APPAC randomized clinical trial. JAMA. 2015;313(23):2340-2348
Clinical question: Is antibiotic therapy noninferior to appendectomy for treatment of uncomplicated acute appendicitis?
Background: Previous randomized clinical trials have compared antibiotic therapy versus appendectomy for the treatment of uncomplicated, acute appendicitis. Each of these studies had significant limitations, and appendectomy has remained the standard of care.
Study design: Noninferiority, randomized clinical trial.
Setting: Six hospitals in Finland.
Synopsis: Investigators randomized 530 patients with uncomplicated appendicitis confirmed on CT to appendectomy or antibiotic therapy, with a noninferiority margin of 24%. Of the 256 patients randomized to antibiotics who were available for follow-up, 70 received surgical intervention within one year. This resulted in a difference between treatment groups of -27%. Further analysis revealed that five of those patients had normal appendices and did not actually require appendectomy. Secondary outcome analysis demonstrated a significantly lower complication rate among patients in the antibiotic group (2.8%) compared with the surgical group (20.5%); however, the open operative approach used on most patients may have resulted in increased wound complications.
Although noninferiority of antibiotic treatment was not demonstrated, the majority of patients in the antibiotic group (73%) were found to have successful treatment with antibiotics alone. None of these patients, including those eventually undergoing appendectomy, suffered major complications. Although the overall approach to uncomplicated appendicitis may not change, physicians and patients should utilize this data to make an informed decision between antibiotic treatment and appendectomy.
Bottom line: In patients with CT-proven, uncomplicated acute appendicitis, antibiotic treatment did not meet the pre-specified threshold for noninferiority compared with appendectomy, yet a significant majority of patients in the antibiotic arm had successful recovery.
Citation: Salminen P, Paajanen H, Rautio T, et al. Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis: The APPAC randomized clinical trial. JAMA. 2015;313(23):2340-2348
Study tracks long-term mortality risk in MRSA bacteremia patients
SAN DIEGO – Among patients with MRSA bacteremia, age, markers of severity of acute treatment, and duration of treatment are predictive of mortality risk at 90 days and 1 year, a long-term single-center study showed.
At the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, Renee-Claude Mercier, Pharm.D., presented results from an analysis which set out to describe the trajectory and long-term outcomes of patients with MRSA bacteremia, including the influence of bacterial, treatment, and host factors on outcomes.
Dr. Mercier and her associates identified 273 patients who were diagnosed with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia during admission to the University of New Mexico Hospital between 2003 and 2013. The main outcomes were mortality at 90 days and 1 year, while secondary outcomes were hospital readmission, nursing home placement, and continued need for hemodialysis. Dr. Mercier, professor of pharmacy and medicine at the University of New Mexico, Albuquerque, and her associates used multivariable logistic regression and survival analysis to evaluate predictors of outcomes.
The mean age of the 273 patients was 52 years, 71% were male, and USA300 accounted for more than half of the strains (57%). A total of 66 patients (24%) died. “Importantly, we do not know the [mortality] status of 30% of our [study] population,” said Dr. Mercier. “We’re working right now with the [Centers for Disease Control and Prevention] to determine the cause or whether or not some of our patients that were included died in the 365 days following their infection with MRSA.”
At 30 days, the mortality rate was 17.7%, most commonly because of MRSA infection (75% of cases), followed by cancer (6.8% of cases) and secondary infection (2.3% of cases). The researchers followed the patients for a median of 237 days. Nearly half (44.8%) were discharged to home, 40.6% were discharged to a skilled nursing facility, and 2.9% returned to prison. “If patients were to die, they died in the first 30 days after infection with MRSA,” Dr. Mercier said. Independent predictors of mortality at 30 days included older age, the presence of liver disease, an ICU stay, a higher Pitt bacteremia score, and unresolved fever.
When the researchers excluded mortality that occurred in the first 30 days, the mortality rate at 90 days was 5.8%, mainly because of MRSA infection (in 46% of the cases), followed by other infection and unspecified sepsis (9%). On multivariable analysis, independent predictors of mortality at 90 days were use of mechanical ventilation (hazard ratio, 4.8; P = .02) and duration of treatment in days (HR .97; P = .078). “Treatment duration was an important determinant of survival in our study,” Dr. Mercier said. “Whether used as a continuous variable or as a dichotomous variable, using 4 weeks as our cutoff showed that the longer the treatment, the [greater the] decrease in mortality.”
After excluding mortality that occurred in the first 30 days, the researchers found that the mortality rate at 1 year was 17.8%, mainly because of MRSA infection (in 28% of the cases), followed by cancer (in 16% of cases) and secondary infections and unspecified sepsis (in 4% of cases). On multivariable analysis, independent predictors of mortality at 90 days were use of mechanical ventilation (HR 1.04; P = .005) and duration of treatment in days (HR .98; P = .05).
The majority of patients (64%) were not readmitted to the hospital within 1 year, while 16% were readmitted for other types of infections not related to S. aureus. In addition, 4% were readmitted because of cardiovascular causes, and 3% were readmitted because of a S. aureus infection.
Finally, Dr. Mercier and her colleagues performed a competing risk regression analysis examining different factors and their impact on mortality. Having an ICU stay as well as the presence of liver disease and receiving antibiotics for less than 4 weeks were significant predictors of mortality.
The researchers reported having no financial disclosures.
SAN DIEGO – Among patients with MRSA bacteremia, age, markers of severity of acute treatment, and duration of treatment are predictive of mortality risk at 90 days and 1 year, a long-term single-center study showed.
At the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, Renee-Claude Mercier, Pharm.D., presented results from an analysis which set out to describe the trajectory and long-term outcomes of patients with MRSA bacteremia, including the influence of bacterial, treatment, and host factors on outcomes.
Dr. Mercier and her associates identified 273 patients who were diagnosed with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia during admission to the University of New Mexico Hospital between 2003 and 2013. The main outcomes were mortality at 90 days and 1 year, while secondary outcomes were hospital readmission, nursing home placement, and continued need for hemodialysis. Dr. Mercier, professor of pharmacy and medicine at the University of New Mexico, Albuquerque, and her associates used multivariable logistic regression and survival analysis to evaluate predictors of outcomes.
The mean age of the 273 patients was 52 years, 71% were male, and USA300 accounted for more than half of the strains (57%). A total of 66 patients (24%) died. “Importantly, we do not know the [mortality] status of 30% of our [study] population,” said Dr. Mercier. “We’re working right now with the [Centers for Disease Control and Prevention] to determine the cause or whether or not some of our patients that were included died in the 365 days following their infection with MRSA.”
At 30 days, the mortality rate was 17.7%, most commonly because of MRSA infection (75% of cases), followed by cancer (6.8% of cases) and secondary infection (2.3% of cases). The researchers followed the patients for a median of 237 days. Nearly half (44.8%) were discharged to home, 40.6% were discharged to a skilled nursing facility, and 2.9% returned to prison. “If patients were to die, they died in the first 30 days after infection with MRSA,” Dr. Mercier said. Independent predictors of mortality at 30 days included older age, the presence of liver disease, an ICU stay, a higher Pitt bacteremia score, and unresolved fever.
When the researchers excluded mortality that occurred in the first 30 days, the mortality rate at 90 days was 5.8%, mainly because of MRSA infection (in 46% of the cases), followed by other infection and unspecified sepsis (9%). On multivariable analysis, independent predictors of mortality at 90 days were use of mechanical ventilation (hazard ratio, 4.8; P = .02) and duration of treatment in days (HR .97; P = .078). “Treatment duration was an important determinant of survival in our study,” Dr. Mercier said. “Whether used as a continuous variable or as a dichotomous variable, using 4 weeks as our cutoff showed that the longer the treatment, the [greater the] decrease in mortality.”
After excluding mortality that occurred in the first 30 days, the researchers found that the mortality rate at 1 year was 17.8%, mainly because of MRSA infection (in 28% of the cases), followed by cancer (in 16% of cases) and secondary infections and unspecified sepsis (in 4% of cases). On multivariable analysis, independent predictors of mortality at 90 days were use of mechanical ventilation (HR 1.04; P = .005) and duration of treatment in days (HR .98; P = .05).
The majority of patients (64%) were not readmitted to the hospital within 1 year, while 16% were readmitted for other types of infections not related to S. aureus. In addition, 4% were readmitted because of cardiovascular causes, and 3% were readmitted because of a S. aureus infection.
Finally, Dr. Mercier and her colleagues performed a competing risk regression analysis examining different factors and their impact on mortality. Having an ICU stay as well as the presence of liver disease and receiving antibiotics for less than 4 weeks were significant predictors of mortality.
The researchers reported having no financial disclosures.
SAN DIEGO – Among patients with MRSA bacteremia, age, markers of severity of acute treatment, and duration of treatment are predictive of mortality risk at 90 days and 1 year, a long-term single-center study showed.
At the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, Renee-Claude Mercier, Pharm.D., presented results from an analysis which set out to describe the trajectory and long-term outcomes of patients with MRSA bacteremia, including the influence of bacterial, treatment, and host factors on outcomes.
Dr. Mercier and her associates identified 273 patients who were diagnosed with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia during admission to the University of New Mexico Hospital between 2003 and 2013. The main outcomes were mortality at 90 days and 1 year, while secondary outcomes were hospital readmission, nursing home placement, and continued need for hemodialysis. Dr. Mercier, professor of pharmacy and medicine at the University of New Mexico, Albuquerque, and her associates used multivariable logistic regression and survival analysis to evaluate predictors of outcomes.
The mean age of the 273 patients was 52 years, 71% were male, and USA300 accounted for more than half of the strains (57%). A total of 66 patients (24%) died. “Importantly, we do not know the [mortality] status of 30% of our [study] population,” said Dr. Mercier. “We’re working right now with the [Centers for Disease Control and Prevention] to determine the cause or whether or not some of our patients that were included died in the 365 days following their infection with MRSA.”
At 30 days, the mortality rate was 17.7%, most commonly because of MRSA infection (75% of cases), followed by cancer (6.8% of cases) and secondary infection (2.3% of cases). The researchers followed the patients for a median of 237 days. Nearly half (44.8%) were discharged to home, 40.6% were discharged to a skilled nursing facility, and 2.9% returned to prison. “If patients were to die, they died in the first 30 days after infection with MRSA,” Dr. Mercier said. Independent predictors of mortality at 30 days included older age, the presence of liver disease, an ICU stay, a higher Pitt bacteremia score, and unresolved fever.
When the researchers excluded mortality that occurred in the first 30 days, the mortality rate at 90 days was 5.8%, mainly because of MRSA infection (in 46% of the cases), followed by other infection and unspecified sepsis (9%). On multivariable analysis, independent predictors of mortality at 90 days were use of mechanical ventilation (hazard ratio, 4.8; P = .02) and duration of treatment in days (HR .97; P = .078). “Treatment duration was an important determinant of survival in our study,” Dr. Mercier said. “Whether used as a continuous variable or as a dichotomous variable, using 4 weeks as our cutoff showed that the longer the treatment, the [greater the] decrease in mortality.”
After excluding mortality that occurred in the first 30 days, the researchers found that the mortality rate at 1 year was 17.8%, mainly because of MRSA infection (in 28% of the cases), followed by cancer (in 16% of cases) and secondary infections and unspecified sepsis (in 4% of cases). On multivariable analysis, independent predictors of mortality at 90 days were use of mechanical ventilation (HR 1.04; P = .005) and duration of treatment in days (HR .98; P = .05).
The majority of patients (64%) were not readmitted to the hospital within 1 year, while 16% were readmitted for other types of infections not related to S. aureus. In addition, 4% were readmitted because of cardiovascular causes, and 3% were readmitted because of a S. aureus infection.
Finally, Dr. Mercier and her colleagues performed a competing risk regression analysis examining different factors and their impact on mortality. Having an ICU stay as well as the presence of liver disease and receiving antibiotics for less than 4 weeks were significant predictors of mortality.
The researchers reported having no financial disclosures.
AT ICAAC 2015
Key clinical point: Longer treatment for MRSA infection was linked to lower mortality risk.
Major finding: The mortality rate at 1 year was 17.8%, mainly because of MRSA (in 28% of the cases) and cancer (16% of cases).
Data source: A study of 273 patients who were diagnosed with MRSA bacteremia during admission to the University of New Mexico Hospital between 2003 and 2013.
Disclosures: The researchers reported having no financial disclosures.
Long-term ceftaroline use associated with neutropenia
SAN DIEGO – The long-term use of ceftaroline is associated with neutropenia, results from a single-center retrospective study showed.
A fifth-generation cephalosporin antibiotic with activity against methicillin-resistant Staphylococcus aureus, ceftaroline is approved for the treatment of community-acquired pneumonia and skin and skin structure infections. It’s also an option for treating orthopedic and endovascular infections when primary therapy fails or is contraindicated, according to one of the study authors, Dr. Hollis R. O’Neal Jr. “There are small case reports of associations between ceftaroline use and neutropenia, and we were noticing that many patients in our clinical practice were developing neutropenia,” Dr. O’Neal, a pulmonologist at Louisiana State University Health Baton Rouge, said in an interview at the Interscience Conference on Antimicrobial Agents and Chemotherapy.
In an effort to determine the incidence, severity, and outcome of neutropenia in patients receiving long-term ceftaroline therapy, Dr. O’Neal and his associates retrospectively evaluated 38 patients who received at least 7 days of ceftaroline initiated at LSU Health Baton Rouge between June 2012 and December 2014. They defined clinically significant neutropenia as having an absolute neutrophil count (ANC) below 2500 cells/mm3 and gathered pertinent data from medical records including comorbidities, chronic medications, and diagnoses.
The median age of the 38 patients was 47 years and their median body mass index was 28 kg/m2. Of the 38 patients, 10 (26%) developed neutropenia. “That was surprising to me,” Dr. O’Neal said. “I thought we would find three or four cases.” Compared with those who were nonneutropenic, those who developed neutropenia tended to be younger (a median of 44 years vs. 51 years), have a lower body mass index (a median of 25 kg/m2 vs. 32 kg/m2), and be more likely to have a longer duration of ceftaroline therapy (a median of 36 days vs. 26 days).
Of the 10 neutropenic patients, 7 had an ANC below 1,500 cells/mm3, and 4 had an ANC below 500 cells/mm3. The median time to first neutropenic day was day 21, with a median nadir of 1,156 cells/mm3. One hospitalization occurred that was believed to be due to neutropenia, but all 30 patients were alive at least 30 days after completing ceftaroline therapy.
“Once the ANC falls below 2,500 cells/mm3, the risk of developing true neutropenia is high,” Dr. O’Neal said. “So what we’re doing is monitoring ANC levels weekly. When they fall below 2,500 we monitor [ANC levels] twice weekly. When they reach 1,500 we stop the drug. So it’s really changed how we monitor the drug’s use.”
The study’s lead author is Dr. Katherine W. Lavie, an infectious diseases fellow at LSU Health Baton Rouge. The researchers reported having no financial disclosures.
SAN DIEGO – The long-term use of ceftaroline is associated with neutropenia, results from a single-center retrospective study showed.
A fifth-generation cephalosporin antibiotic with activity against methicillin-resistant Staphylococcus aureus, ceftaroline is approved for the treatment of community-acquired pneumonia and skin and skin structure infections. It’s also an option for treating orthopedic and endovascular infections when primary therapy fails or is contraindicated, according to one of the study authors, Dr. Hollis R. O’Neal Jr. “There are small case reports of associations between ceftaroline use and neutropenia, and we were noticing that many patients in our clinical practice were developing neutropenia,” Dr. O’Neal, a pulmonologist at Louisiana State University Health Baton Rouge, said in an interview at the Interscience Conference on Antimicrobial Agents and Chemotherapy.
In an effort to determine the incidence, severity, and outcome of neutropenia in patients receiving long-term ceftaroline therapy, Dr. O’Neal and his associates retrospectively evaluated 38 patients who received at least 7 days of ceftaroline initiated at LSU Health Baton Rouge between June 2012 and December 2014. They defined clinically significant neutropenia as having an absolute neutrophil count (ANC) below 2500 cells/mm3 and gathered pertinent data from medical records including comorbidities, chronic medications, and diagnoses.
The median age of the 38 patients was 47 years and their median body mass index was 28 kg/m2. Of the 38 patients, 10 (26%) developed neutropenia. “That was surprising to me,” Dr. O’Neal said. “I thought we would find three or four cases.” Compared with those who were nonneutropenic, those who developed neutropenia tended to be younger (a median of 44 years vs. 51 years), have a lower body mass index (a median of 25 kg/m2 vs. 32 kg/m2), and be more likely to have a longer duration of ceftaroline therapy (a median of 36 days vs. 26 days).
Of the 10 neutropenic patients, 7 had an ANC below 1,500 cells/mm3, and 4 had an ANC below 500 cells/mm3. The median time to first neutropenic day was day 21, with a median nadir of 1,156 cells/mm3. One hospitalization occurred that was believed to be due to neutropenia, but all 30 patients were alive at least 30 days after completing ceftaroline therapy.
“Once the ANC falls below 2,500 cells/mm3, the risk of developing true neutropenia is high,” Dr. O’Neal said. “So what we’re doing is monitoring ANC levels weekly. When they fall below 2,500 we monitor [ANC levels] twice weekly. When they reach 1,500 we stop the drug. So it’s really changed how we monitor the drug’s use.”
The study’s lead author is Dr. Katherine W. Lavie, an infectious diseases fellow at LSU Health Baton Rouge. The researchers reported having no financial disclosures.
SAN DIEGO – The long-term use of ceftaroline is associated with neutropenia, results from a single-center retrospective study showed.
A fifth-generation cephalosporin antibiotic with activity against methicillin-resistant Staphylococcus aureus, ceftaroline is approved for the treatment of community-acquired pneumonia and skin and skin structure infections. It’s also an option for treating orthopedic and endovascular infections when primary therapy fails or is contraindicated, according to one of the study authors, Dr. Hollis R. O’Neal Jr. “There are small case reports of associations between ceftaroline use and neutropenia, and we were noticing that many patients in our clinical practice were developing neutropenia,” Dr. O’Neal, a pulmonologist at Louisiana State University Health Baton Rouge, said in an interview at the Interscience Conference on Antimicrobial Agents and Chemotherapy.
In an effort to determine the incidence, severity, and outcome of neutropenia in patients receiving long-term ceftaroline therapy, Dr. O’Neal and his associates retrospectively evaluated 38 patients who received at least 7 days of ceftaroline initiated at LSU Health Baton Rouge between June 2012 and December 2014. They defined clinically significant neutropenia as having an absolute neutrophil count (ANC) below 2500 cells/mm3 and gathered pertinent data from medical records including comorbidities, chronic medications, and diagnoses.
The median age of the 38 patients was 47 years and their median body mass index was 28 kg/m2. Of the 38 patients, 10 (26%) developed neutropenia. “That was surprising to me,” Dr. O’Neal said. “I thought we would find three or four cases.” Compared with those who were nonneutropenic, those who developed neutropenia tended to be younger (a median of 44 years vs. 51 years), have a lower body mass index (a median of 25 kg/m2 vs. 32 kg/m2), and be more likely to have a longer duration of ceftaroline therapy (a median of 36 days vs. 26 days).
Of the 10 neutropenic patients, 7 had an ANC below 1,500 cells/mm3, and 4 had an ANC below 500 cells/mm3. The median time to first neutropenic day was day 21, with a median nadir of 1,156 cells/mm3. One hospitalization occurred that was believed to be due to neutropenia, but all 30 patients were alive at least 30 days after completing ceftaroline therapy.
“Once the ANC falls below 2,500 cells/mm3, the risk of developing true neutropenia is high,” Dr. O’Neal said. “So what we’re doing is monitoring ANC levels weekly. When they fall below 2,500 we monitor [ANC levels] twice weekly. When they reach 1,500 we stop the drug. So it’s really changed how we monitor the drug’s use.”
The study’s lead author is Dr. Katherine W. Lavie, an infectious diseases fellow at LSU Health Baton Rouge. The researchers reported having no financial disclosures.
AT ICAAC 2015
Key clinical point: Long-term ceftaroline use is associated with neutropenia.
Major finding: Of 38 patients who received at least 7 days of ceftaroline, 10 (26%) developed neutropenia.
Data source: A retrospective cohort study of 38 patients who received long-term ceftaroline therapy between June 2012 and December 2014.
Disclosures: The researchers reported having no financial disclosures.
ICAAC: Prescribing guide successful in a children’s hospital
SAN DIEGO – The introduction and dissemination of an antibiotic prescribing guide in a children’s hospital resulted in a statistically significant increase in appropriate prescribing, a prospective study showed.
“Antimicrobial drugs are one of the largest groups of medications prescribed to hospitalized children worldwide,” Dr. Jacqueline Wong wrote in an abstract presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. “Inappropriate antibiotic use is a major factor driving increasing bacterial antibiotic resistance. There are few published data on the effectiveness of stewardship strategies in a pediatric setting.”
In a prospective observational study conducted during Dr. Wong’s pediatrics residency at British Columbia Children’s Hospital, Vancouver, she and her associates set out to compare the proportion of patients who received appropriate antimicrobials before and after the introduction of a new empiric antibiotic guide that was gradually rolled out at the hospital beginning in April of 2012 via lectures, paper copies, and pocket-sized and electronic versions. The time period studied was January 2012 to June 2013. All children admitted and treated with antibiotics were included in the analysis. Exclusion criteria included patients who were admitted to the neonatal unit or hematology/oncology ward, patients with cystic fibrosis, patients who were immunocompromised, and those receiving antibiotics solely for prophylaxis.
The researchers obtained prescribing information from hospital pharmacy data and electronic medical records, and two members of the study team used the updated empiric antibiotic guidelines to determine if the empiric prescribing was appropriate or not.
A total of 1,815 admissions were initially studied. Of these, 63% of the patients were younger than 3 months old, 16% were 4-6 months old, and 21% were 7-11 months old. These percentages did not vary significantly during the study time frame (P greater than .05). The five most common clinical syndromes were septicemia/meningitis (n = 556), respiratory tract infections (n = 532), intra-abdominal infections (n = 195), skin and soft tissue infections (n = 193), and urinary tract infections (n = 184).
Next, the researchers reviewed 752 admissions: 430 prior to introduction of the guidelines and 322 afterward. When they combined the five most common clinical syndromes, they observed a statistically significant increase in appropriate empiric antibiotic therapy between the preintervention period and postintervention period, from 65% to 74%, respectively (P = .035).
“What was interesting to learn from this study was the distribution of the various syndromes and distribution of the age groups of the children that were admitted,” Dr. Wong, now an infectious diseases fellow at The Hospital for Sick Children, Toronto, said in an interview. “The vast majority were 1 year and under.”
While the findings represent success in terms of patient care and cost savings, “the overall limited impact of such a passive antimicrobial stewardship program intervention suggests additional active strategies may be required to further enhance implementation, such as prospective audit with intervention, and feedback may be required to further enhance implementation of antimicrobial guidelines,” the researchers wrote in their abstract. For example, in response to the study findings, British Columbia Children’s Hospital implemented a formal multidisciplinary antimicrobial stewardship program including daily audit and feedback of all admitted patients on antimicrobials within 24 hours. “Data from this program are currently awaiting analysis,” they wrote.
The researchers reported having no financial disclosures.
SAN DIEGO – The introduction and dissemination of an antibiotic prescribing guide in a children’s hospital resulted in a statistically significant increase in appropriate prescribing, a prospective study showed.
“Antimicrobial drugs are one of the largest groups of medications prescribed to hospitalized children worldwide,” Dr. Jacqueline Wong wrote in an abstract presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. “Inappropriate antibiotic use is a major factor driving increasing bacterial antibiotic resistance. There are few published data on the effectiveness of stewardship strategies in a pediatric setting.”
In a prospective observational study conducted during Dr. Wong’s pediatrics residency at British Columbia Children’s Hospital, Vancouver, she and her associates set out to compare the proportion of patients who received appropriate antimicrobials before and after the introduction of a new empiric antibiotic guide that was gradually rolled out at the hospital beginning in April of 2012 via lectures, paper copies, and pocket-sized and electronic versions. The time period studied was January 2012 to June 2013. All children admitted and treated with antibiotics were included in the analysis. Exclusion criteria included patients who were admitted to the neonatal unit or hematology/oncology ward, patients with cystic fibrosis, patients who were immunocompromised, and those receiving antibiotics solely for prophylaxis.
The researchers obtained prescribing information from hospital pharmacy data and electronic medical records, and two members of the study team used the updated empiric antibiotic guidelines to determine if the empiric prescribing was appropriate or not.
A total of 1,815 admissions were initially studied. Of these, 63% of the patients were younger than 3 months old, 16% were 4-6 months old, and 21% were 7-11 months old. These percentages did not vary significantly during the study time frame (P greater than .05). The five most common clinical syndromes were septicemia/meningitis (n = 556), respiratory tract infections (n = 532), intra-abdominal infections (n = 195), skin and soft tissue infections (n = 193), and urinary tract infections (n = 184).
Next, the researchers reviewed 752 admissions: 430 prior to introduction of the guidelines and 322 afterward. When they combined the five most common clinical syndromes, they observed a statistically significant increase in appropriate empiric antibiotic therapy between the preintervention period and postintervention period, from 65% to 74%, respectively (P = .035).
“What was interesting to learn from this study was the distribution of the various syndromes and distribution of the age groups of the children that were admitted,” Dr. Wong, now an infectious diseases fellow at The Hospital for Sick Children, Toronto, said in an interview. “The vast majority were 1 year and under.”
While the findings represent success in terms of patient care and cost savings, “the overall limited impact of such a passive antimicrobial stewardship program intervention suggests additional active strategies may be required to further enhance implementation, such as prospective audit with intervention, and feedback may be required to further enhance implementation of antimicrobial guidelines,” the researchers wrote in their abstract. For example, in response to the study findings, British Columbia Children’s Hospital implemented a formal multidisciplinary antimicrobial stewardship program including daily audit and feedback of all admitted patients on antimicrobials within 24 hours. “Data from this program are currently awaiting analysis,” they wrote.
The researchers reported having no financial disclosures.
SAN DIEGO – The introduction and dissemination of an antibiotic prescribing guide in a children’s hospital resulted in a statistically significant increase in appropriate prescribing, a prospective study showed.
“Antimicrobial drugs are one of the largest groups of medications prescribed to hospitalized children worldwide,” Dr. Jacqueline Wong wrote in an abstract presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. “Inappropriate antibiotic use is a major factor driving increasing bacterial antibiotic resistance. There are few published data on the effectiveness of stewardship strategies in a pediatric setting.”
In a prospective observational study conducted during Dr. Wong’s pediatrics residency at British Columbia Children’s Hospital, Vancouver, she and her associates set out to compare the proportion of patients who received appropriate antimicrobials before and after the introduction of a new empiric antibiotic guide that was gradually rolled out at the hospital beginning in April of 2012 via lectures, paper copies, and pocket-sized and electronic versions. The time period studied was January 2012 to June 2013. All children admitted and treated with antibiotics were included in the analysis. Exclusion criteria included patients who were admitted to the neonatal unit or hematology/oncology ward, patients with cystic fibrosis, patients who were immunocompromised, and those receiving antibiotics solely for prophylaxis.
The researchers obtained prescribing information from hospital pharmacy data and electronic medical records, and two members of the study team used the updated empiric antibiotic guidelines to determine if the empiric prescribing was appropriate or not.
A total of 1,815 admissions were initially studied. Of these, 63% of the patients were younger than 3 months old, 16% were 4-6 months old, and 21% were 7-11 months old. These percentages did not vary significantly during the study time frame (P greater than .05). The five most common clinical syndromes were septicemia/meningitis (n = 556), respiratory tract infections (n = 532), intra-abdominal infections (n = 195), skin and soft tissue infections (n = 193), and urinary tract infections (n = 184).
Next, the researchers reviewed 752 admissions: 430 prior to introduction of the guidelines and 322 afterward. When they combined the five most common clinical syndromes, they observed a statistically significant increase in appropriate empiric antibiotic therapy between the preintervention period and postintervention period, from 65% to 74%, respectively (P = .035).
“What was interesting to learn from this study was the distribution of the various syndromes and distribution of the age groups of the children that were admitted,” Dr. Wong, now an infectious diseases fellow at The Hospital for Sick Children, Toronto, said in an interview. “The vast majority were 1 year and under.”
While the findings represent success in terms of patient care and cost savings, “the overall limited impact of such a passive antimicrobial stewardship program intervention suggests additional active strategies may be required to further enhance implementation, such as prospective audit with intervention, and feedback may be required to further enhance implementation of antimicrobial guidelines,” the researchers wrote in their abstract. For example, in response to the study findings, British Columbia Children’s Hospital implemented a formal multidisciplinary antimicrobial stewardship program including daily audit and feedback of all admitted patients on antimicrobials within 24 hours. “Data from this program are currently awaiting analysis,” they wrote.
The researchers reported having no financial disclosures.
AT ICAAC 2015
Key clinical point: A new antibiotic prescribing guide introduced at a children’s hospital resulted in a statistically significant increase in appropriate prescribing.
Major finding: Following introduction of a new antibiotic prescribing guide, the rate of appropriate empiric antibiotic therapy between rose significantly from 65% to 74% (P = .035).
Data source: A prospective observational study of 752 pediatric hospital admissions.
Disclosures: The researchers reported having no financial disclosures.
Antibiotic Stewardship and Hospitalists: How to Educate Patients on Antibiotics
Editor’s note: This article originally appeared on SHM’s official blog, “The Hospital Leader,” in June 2015.
“Tell me what you know about antibiotics.”
That’s the discussion I start with hospitalized patients all the time, right after they ask me to prescribe antibiotics for their simple cough or other viral-like illness.
And, from their perspective, asking for antibiotics makes sense. After all, antibiotics have been the physician’s knee-jerk reaction to a number of patient symptoms for decades, especially for a cough or upper respiratory infection. We have inadvertently trained our patients that there is an easy solution to almost any common medical problem.
But patients often answer my question with something like “not much,” coupled with a little surprise that I haven’t already started ordering the prescription.
That’s when I talk about the potential harms of antibiotics. And that’s also when their eyebrows go up. I start with the easy harms, like the fact that many antibiotics can cause diarrhea, a symptom nobody wants to deal with along with their runny nose. Then I move on to the big ones: Use of antibiotics today could make the patient resistant to antibiotics later in life, when they might really need them, and using antibiotics can lead to other painful and even fatal conditions, like Clostridium difficile.
After that, every patient agrees with my recommendations that we hold off on antibiotics for certain, particularly viral-like, ailments.
Change the Conversation. Change the Approach.
It’s a longer conversation, but it’s worth it. Overuse of antibiotics affects not only the patient in front of me, but also entire communities. By creating antibiotic-resistant bacteria, we make everyone more vulnerable to the very diseases the antibiotics were originally intended to treat, like tuberculosis, staph infections, and numerous others.
That’s why the hospitalists in my hospital at Johns Hopkins Bayview teamed up with the infectious diseases division to improve our approach to cellulitis and antibiotic use.
In short, cellulitis is a bacterial skin infection. The most feared bacterial skin infection is MRSA (methicillin-resistant Staphylococcus aureus), a “super bug” that requires highly selective antibiotics like vancomycin; however, other more common and less virulent bacteria also cause cellulitis, and they don’t need super bug fighter medications. Some types of skin ailments, like those caused by poor circulation in the legs, are not infectious at all but can look like cellulitis, even to experienced doctors.
Thanks to the collaboration between infectious disease doctors and hospitalists, the hospitalists are much less likely to prescribe inappropriate antibiotics. That’s a triple-win: It reduces the length of stay for the patient, the incidence of C. diff, and costs.
The Front Line
This concern isn’t limited to a single hospital. There are now more than 44,000 hospitalists nationwide, and every one of us plays an important role in antibiotic stewardship. The bedside is the front line of the fight against antibiotic resistance.
tuberculosis, staph infections, and numerous others.
—Eric Howell, MD, SFHM
There are more than 5,000 hospitals across the country, and hospitalists in every one of them must take responsibility for the appropriate use of antibiotics for their patients.
Announcing SHM’s National Commitment to Antibiotic Stewardship
SHM was proud to join more than 150 major organizations at the White House Forum on Antibiotic Stewardship to announce commitments to implement changes over the next five years that will slow the emergence of antibiotic-resistant bacteria, detect resistant strains, preserve the efficacy of our existing antibiotics, and prevent the spread of resistant infections.
Specifically, SHM has committed to three national initiatives that are aligned with our organizational goal of providing the best possible care for the hospitalized patient and the federal government’s dedication to this important issue:
- Enhance hospitalists’ awareness of key antimicrobial stewardship best practices and ask them to formally commit to at least two behavior changes to reduce inappropriate antimicrobial use and antimicrobial resistance;
- Support national initiatives that advocate for the appropriate use of antimicrobials and promote strategies to reduce antimicrobial resistance; and
- Identify partnerships and other opportunities to support the development of a comprehensive program to implement antimicrobial stewardship best practices in America’s hospitals.
These commitments, which I shared with White House Forum participants, play to the strengths of hospitalists in healthcare: advocacy on behalf of patients and quality improvement and collaboration with others.
What Hospitalists Can Do Now
I also know, however, that you aren’t the kind of people to wait for official pronouncements and campaigns to start a program that will improve the care of hospitalized patients. That’s why SHM and I are recommending that all hospitalists begin to take steps immediately to address this national healthcare crisis:
- Start the conversation with your patients. It’s easy to prescribe antibiotics, but it can also be harmful. Talk with your patients about when antibiotics are medically appropriate and the potential harms they may cause.
- Prescribe antibiotics for specific diagnoses. Prescribing “just in case” is a prescription for antibiotic resistance. Make sure you understand the signs and symptoms of the conditions for which you’re prescribing antibiotics. As we learned at our hospital, cellulitis and venous insufficiency can look similar, but only one responds to antibiotic treatment.
- Work with your infectious disease colleagues. They can help you create systems and diagnose patients to help improve your hospital’s antibiotic stewardship.
After all, we are on the front lines, protecting our current and future patients. And we can’t afford to wait.
Dr. Howell is a veteran hospitalist at Johns Hopkins Bayview Hospital in Baltimore and a past president of SHM.
Editor’s note: This article originally appeared on SHM’s official blog, “The Hospital Leader,” in June 2015.
“Tell me what you know about antibiotics.”
That’s the discussion I start with hospitalized patients all the time, right after they ask me to prescribe antibiotics for their simple cough or other viral-like illness.
And, from their perspective, asking for antibiotics makes sense. After all, antibiotics have been the physician’s knee-jerk reaction to a number of patient symptoms for decades, especially for a cough or upper respiratory infection. We have inadvertently trained our patients that there is an easy solution to almost any common medical problem.
But patients often answer my question with something like “not much,” coupled with a little surprise that I haven’t already started ordering the prescription.
That’s when I talk about the potential harms of antibiotics. And that’s also when their eyebrows go up. I start with the easy harms, like the fact that many antibiotics can cause diarrhea, a symptom nobody wants to deal with along with their runny nose. Then I move on to the big ones: Use of antibiotics today could make the patient resistant to antibiotics later in life, when they might really need them, and using antibiotics can lead to other painful and even fatal conditions, like Clostridium difficile.
After that, every patient agrees with my recommendations that we hold off on antibiotics for certain, particularly viral-like, ailments.
Change the Conversation. Change the Approach.
It’s a longer conversation, but it’s worth it. Overuse of antibiotics affects not only the patient in front of me, but also entire communities. By creating antibiotic-resistant bacteria, we make everyone more vulnerable to the very diseases the antibiotics were originally intended to treat, like tuberculosis, staph infections, and numerous others.
That’s why the hospitalists in my hospital at Johns Hopkins Bayview teamed up with the infectious diseases division to improve our approach to cellulitis and antibiotic use.
In short, cellulitis is a bacterial skin infection. The most feared bacterial skin infection is MRSA (methicillin-resistant Staphylococcus aureus), a “super bug” that requires highly selective antibiotics like vancomycin; however, other more common and less virulent bacteria also cause cellulitis, and they don’t need super bug fighter medications. Some types of skin ailments, like those caused by poor circulation in the legs, are not infectious at all but can look like cellulitis, even to experienced doctors.
Thanks to the collaboration between infectious disease doctors and hospitalists, the hospitalists are much less likely to prescribe inappropriate antibiotics. That’s a triple-win: It reduces the length of stay for the patient, the incidence of C. diff, and costs.
The Front Line
This concern isn’t limited to a single hospital. There are now more than 44,000 hospitalists nationwide, and every one of us plays an important role in antibiotic stewardship. The bedside is the front line of the fight against antibiotic resistance.
tuberculosis, staph infections, and numerous others.
—Eric Howell, MD, SFHM
There are more than 5,000 hospitals across the country, and hospitalists in every one of them must take responsibility for the appropriate use of antibiotics for their patients.
Announcing SHM’s National Commitment to Antibiotic Stewardship
SHM was proud to join more than 150 major organizations at the White House Forum on Antibiotic Stewardship to announce commitments to implement changes over the next five years that will slow the emergence of antibiotic-resistant bacteria, detect resistant strains, preserve the efficacy of our existing antibiotics, and prevent the spread of resistant infections.
Specifically, SHM has committed to three national initiatives that are aligned with our organizational goal of providing the best possible care for the hospitalized patient and the federal government’s dedication to this important issue:
- Enhance hospitalists’ awareness of key antimicrobial stewardship best practices and ask them to formally commit to at least two behavior changes to reduce inappropriate antimicrobial use and antimicrobial resistance;
- Support national initiatives that advocate for the appropriate use of antimicrobials and promote strategies to reduce antimicrobial resistance; and
- Identify partnerships and other opportunities to support the development of a comprehensive program to implement antimicrobial stewardship best practices in America’s hospitals.
These commitments, which I shared with White House Forum participants, play to the strengths of hospitalists in healthcare: advocacy on behalf of patients and quality improvement and collaboration with others.
What Hospitalists Can Do Now
I also know, however, that you aren’t the kind of people to wait for official pronouncements and campaigns to start a program that will improve the care of hospitalized patients. That’s why SHM and I are recommending that all hospitalists begin to take steps immediately to address this national healthcare crisis:
- Start the conversation with your patients. It’s easy to prescribe antibiotics, but it can also be harmful. Talk with your patients about when antibiotics are medically appropriate and the potential harms they may cause.
- Prescribe antibiotics for specific diagnoses. Prescribing “just in case” is a prescription for antibiotic resistance. Make sure you understand the signs and symptoms of the conditions for which you’re prescribing antibiotics. As we learned at our hospital, cellulitis and venous insufficiency can look similar, but only one responds to antibiotic treatment.
- Work with your infectious disease colleagues. They can help you create systems and diagnose patients to help improve your hospital’s antibiotic stewardship.
After all, we are on the front lines, protecting our current and future patients. And we can’t afford to wait.
Dr. Howell is a veteran hospitalist at Johns Hopkins Bayview Hospital in Baltimore and a past president of SHM.
Editor’s note: This article originally appeared on SHM’s official blog, “The Hospital Leader,” in June 2015.
“Tell me what you know about antibiotics.”
That’s the discussion I start with hospitalized patients all the time, right after they ask me to prescribe antibiotics for their simple cough or other viral-like illness.
And, from their perspective, asking for antibiotics makes sense. After all, antibiotics have been the physician’s knee-jerk reaction to a number of patient symptoms for decades, especially for a cough or upper respiratory infection. We have inadvertently trained our patients that there is an easy solution to almost any common medical problem.
But patients often answer my question with something like “not much,” coupled with a little surprise that I haven’t already started ordering the prescription.
That’s when I talk about the potential harms of antibiotics. And that’s also when their eyebrows go up. I start with the easy harms, like the fact that many antibiotics can cause diarrhea, a symptom nobody wants to deal with along with their runny nose. Then I move on to the big ones: Use of antibiotics today could make the patient resistant to antibiotics later in life, when they might really need them, and using antibiotics can lead to other painful and even fatal conditions, like Clostridium difficile.
After that, every patient agrees with my recommendations that we hold off on antibiotics for certain, particularly viral-like, ailments.
Change the Conversation. Change the Approach.
It’s a longer conversation, but it’s worth it. Overuse of antibiotics affects not only the patient in front of me, but also entire communities. By creating antibiotic-resistant bacteria, we make everyone more vulnerable to the very diseases the antibiotics were originally intended to treat, like tuberculosis, staph infections, and numerous others.
That’s why the hospitalists in my hospital at Johns Hopkins Bayview teamed up with the infectious diseases division to improve our approach to cellulitis and antibiotic use.
In short, cellulitis is a bacterial skin infection. The most feared bacterial skin infection is MRSA (methicillin-resistant Staphylococcus aureus), a “super bug” that requires highly selective antibiotics like vancomycin; however, other more common and less virulent bacteria also cause cellulitis, and they don’t need super bug fighter medications. Some types of skin ailments, like those caused by poor circulation in the legs, are not infectious at all but can look like cellulitis, even to experienced doctors.
Thanks to the collaboration between infectious disease doctors and hospitalists, the hospitalists are much less likely to prescribe inappropriate antibiotics. That’s a triple-win: It reduces the length of stay for the patient, the incidence of C. diff, and costs.
The Front Line
This concern isn’t limited to a single hospital. There are now more than 44,000 hospitalists nationwide, and every one of us plays an important role in antibiotic stewardship. The bedside is the front line of the fight against antibiotic resistance.
tuberculosis, staph infections, and numerous others.
—Eric Howell, MD, SFHM
There are more than 5,000 hospitals across the country, and hospitalists in every one of them must take responsibility for the appropriate use of antibiotics for their patients.
Announcing SHM’s National Commitment to Antibiotic Stewardship
SHM was proud to join more than 150 major organizations at the White House Forum on Antibiotic Stewardship to announce commitments to implement changes over the next five years that will slow the emergence of antibiotic-resistant bacteria, detect resistant strains, preserve the efficacy of our existing antibiotics, and prevent the spread of resistant infections.
Specifically, SHM has committed to three national initiatives that are aligned with our organizational goal of providing the best possible care for the hospitalized patient and the federal government’s dedication to this important issue:
- Enhance hospitalists’ awareness of key antimicrobial stewardship best practices and ask them to formally commit to at least two behavior changes to reduce inappropriate antimicrobial use and antimicrobial resistance;
- Support national initiatives that advocate for the appropriate use of antimicrobials and promote strategies to reduce antimicrobial resistance; and
- Identify partnerships and other opportunities to support the development of a comprehensive program to implement antimicrobial stewardship best practices in America’s hospitals.
These commitments, which I shared with White House Forum participants, play to the strengths of hospitalists in healthcare: advocacy on behalf of patients and quality improvement and collaboration with others.
What Hospitalists Can Do Now
I also know, however, that you aren’t the kind of people to wait for official pronouncements and campaigns to start a program that will improve the care of hospitalized patients. That’s why SHM and I are recommending that all hospitalists begin to take steps immediately to address this national healthcare crisis:
- Start the conversation with your patients. It’s easy to prescribe antibiotics, but it can also be harmful. Talk with your patients about when antibiotics are medically appropriate and the potential harms they may cause.
- Prescribe antibiotics for specific diagnoses. Prescribing “just in case” is a prescription for antibiotic resistance. Make sure you understand the signs and symptoms of the conditions for which you’re prescribing antibiotics. As we learned at our hospital, cellulitis and venous insufficiency can look similar, but only one responds to antibiotic treatment.
- Work with your infectious disease colleagues. They can help you create systems and diagnose patients to help improve your hospital’s antibiotic stewardship.
After all, we are on the front lines, protecting our current and future patients. And we can’t afford to wait.
Dr. Howell is a veteran hospitalist at Johns Hopkins Bayview Hospital in Baltimore and a past president of SHM.
Avoid Trimethoprim-Sulfamethoxazole for Severe MRSA Infections
Clinical question: Is trimethoprim-sulfamethoxazole equivalent to vancomycin for the treatment of severe infections caused by methicillin-resistant Staphyloccus aureus?
Bottom line: Trimethoprim-sulfamethoxazole (TMP-SMX) did not achieve noninferiority as compared with vancomycin for the treatment of severe methicillin-resistant Staphyloccus aureus (MRSA) infections in hospitalized patients, and it may lead to increased mortality in the subset of patients with bacteremia. (LOE = 1b)
Reference: Paul M, Bishara J, Yahav D, et al. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin-resistant Staphylococcus aureus. BMJ 2015;350:h2219.
Study design: Randomized controlled trial (nonblinded)
Funding source: Foundation
Allocation: Concealed
Setting: Inpatient (any location)
Synopsis
Although TMP-SMX can be used to treat uncomplicated skin and soft-tissue infections caused by MRSA, it is not currently recommended for more serious MRSA infections such as bacteremia or pneumonia. In this study, investigators tested whether TMP-SMX is noninferior to vancomycin for the treatment of hospitalized patients with severe MRSA infections. Patients included in the study (N = 252) had microbiologically documented MRSA infections, including complicated skin and soft-tissue infections, bone or joint infections, pneumonia, or primary bacteremia. Patients with MRSA isolates resistant to TMP-SMX or vancomycin were excluded.
Using concealed allocation, the investigators randomized the patients to receive either high-dose TMP-SMX (320 mg trimethoprim/1600 mg sulfamethoxazole intravenously twice daily) or vancomycin (1 mg intravenously twice daily) for at least 7 days. In the TMP-SMX group, treatment could be transitioned to an oral regimen of an equivalent dose at the clinician's discretion. The 2 groups had similar baseline characteristics with a mean age of 66 years and similar comorbidities, though the vancomycin group had a higher percentage of patients with bacteremia than the TMP-SMX group (30% vs 43%; P = .042). The primary outcome was treatment failure at 7 days, defined as a composite of death, persistent fever or hypotension, stable or worsening Sequential Organ Failure Assessment score, or persistent bacteremia. There was no statistically significant difference detected between the 2 groups for this outcome (38% treatment failure with TMP-SMX vs 27% with vancomycin; absolute difference 10.4%, 95% CI -1.2% to 21.5%).
However, since the 95% confidence interval for the absolute difference fell outside the predefined lower limit of noninferiority of 15%, the authors concluded that TMP-SMX failed to achieve noninferiority as compared with vancomycin. Additionally, in the subgroup of patients with bacteremia, patients were more likely to die in the TMP-SMX group as compared with the vancomycin group, although this difference again was not statistically significant (34% with TMP-SMX vs 18% with vancomycin; relative risk 1.90, 0.92-3.93).
Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.
Clinical question: Is trimethoprim-sulfamethoxazole equivalent to vancomycin for the treatment of severe infections caused by methicillin-resistant Staphyloccus aureus?
Bottom line: Trimethoprim-sulfamethoxazole (TMP-SMX) did not achieve noninferiority as compared with vancomycin for the treatment of severe methicillin-resistant Staphyloccus aureus (MRSA) infections in hospitalized patients, and it may lead to increased mortality in the subset of patients with bacteremia. (LOE = 1b)
Reference: Paul M, Bishara J, Yahav D, et al. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin-resistant Staphylococcus aureus. BMJ 2015;350:h2219.
Study design: Randomized controlled trial (nonblinded)
Funding source: Foundation
Allocation: Concealed
Setting: Inpatient (any location)
Synopsis
Although TMP-SMX can be used to treat uncomplicated skin and soft-tissue infections caused by MRSA, it is not currently recommended for more serious MRSA infections such as bacteremia or pneumonia. In this study, investigators tested whether TMP-SMX is noninferior to vancomycin for the treatment of hospitalized patients with severe MRSA infections. Patients included in the study (N = 252) had microbiologically documented MRSA infections, including complicated skin and soft-tissue infections, bone or joint infections, pneumonia, or primary bacteremia. Patients with MRSA isolates resistant to TMP-SMX or vancomycin were excluded.
Using concealed allocation, the investigators randomized the patients to receive either high-dose TMP-SMX (320 mg trimethoprim/1600 mg sulfamethoxazole intravenously twice daily) or vancomycin (1 mg intravenously twice daily) for at least 7 days. In the TMP-SMX group, treatment could be transitioned to an oral regimen of an equivalent dose at the clinician's discretion. The 2 groups had similar baseline characteristics with a mean age of 66 years and similar comorbidities, though the vancomycin group had a higher percentage of patients with bacteremia than the TMP-SMX group (30% vs 43%; P = .042). The primary outcome was treatment failure at 7 days, defined as a composite of death, persistent fever or hypotension, stable or worsening Sequential Organ Failure Assessment score, or persistent bacteremia. There was no statistically significant difference detected between the 2 groups for this outcome (38% treatment failure with TMP-SMX vs 27% with vancomycin; absolute difference 10.4%, 95% CI -1.2% to 21.5%).
However, since the 95% confidence interval for the absolute difference fell outside the predefined lower limit of noninferiority of 15%, the authors concluded that TMP-SMX failed to achieve noninferiority as compared with vancomycin. Additionally, in the subgroup of patients with bacteremia, patients were more likely to die in the TMP-SMX group as compared with the vancomycin group, although this difference again was not statistically significant (34% with TMP-SMX vs 18% with vancomycin; relative risk 1.90, 0.92-3.93).
Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.
Clinical question: Is trimethoprim-sulfamethoxazole equivalent to vancomycin for the treatment of severe infections caused by methicillin-resistant Staphyloccus aureus?
Bottom line: Trimethoprim-sulfamethoxazole (TMP-SMX) did not achieve noninferiority as compared with vancomycin for the treatment of severe methicillin-resistant Staphyloccus aureus (MRSA) infections in hospitalized patients, and it may lead to increased mortality in the subset of patients with bacteremia. (LOE = 1b)
Reference: Paul M, Bishara J, Yahav D, et al. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin-resistant Staphylococcus aureus. BMJ 2015;350:h2219.
Study design: Randomized controlled trial (nonblinded)
Funding source: Foundation
Allocation: Concealed
Setting: Inpatient (any location)
Synopsis
Although TMP-SMX can be used to treat uncomplicated skin and soft-tissue infections caused by MRSA, it is not currently recommended for more serious MRSA infections such as bacteremia or pneumonia. In this study, investigators tested whether TMP-SMX is noninferior to vancomycin for the treatment of hospitalized patients with severe MRSA infections. Patients included in the study (N = 252) had microbiologically documented MRSA infections, including complicated skin and soft-tissue infections, bone or joint infections, pneumonia, or primary bacteremia. Patients with MRSA isolates resistant to TMP-SMX or vancomycin were excluded.
Using concealed allocation, the investigators randomized the patients to receive either high-dose TMP-SMX (320 mg trimethoprim/1600 mg sulfamethoxazole intravenously twice daily) or vancomycin (1 mg intravenously twice daily) for at least 7 days. In the TMP-SMX group, treatment could be transitioned to an oral regimen of an equivalent dose at the clinician's discretion. The 2 groups had similar baseline characteristics with a mean age of 66 years and similar comorbidities, though the vancomycin group had a higher percentage of patients with bacteremia than the TMP-SMX group (30% vs 43%; P = .042). The primary outcome was treatment failure at 7 days, defined as a composite of death, persistent fever or hypotension, stable or worsening Sequential Organ Failure Assessment score, or persistent bacteremia. There was no statistically significant difference detected between the 2 groups for this outcome (38% treatment failure with TMP-SMX vs 27% with vancomycin; absolute difference 10.4%, 95% CI -1.2% to 21.5%).
However, since the 95% confidence interval for the absolute difference fell outside the predefined lower limit of noninferiority of 15%, the authors concluded that TMP-SMX failed to achieve noninferiority as compared with vancomycin. Additionally, in the subgroup of patients with bacteremia, patients were more likely to die in the TMP-SMX group as compared with the vancomycin group, although this difference again was not statistically significant (34% with TMP-SMX vs 18% with vancomycin; relative risk 1.90, 0.92-3.93).
Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.
Childhood Bacteremia and Antibiotics Usage in the Emergency Department
Clinical question: Have the causative organisms in pediatric bacteremia changed over time concurrent with introduction of the pneumococcal conjugate vaccine?
Background: Previous research has shown introduction of polyvalent pneumococcal conjugate vaccine led to changes in the organisms causing meningitis and otitis media, and patterns of nasopharyngeal colonization. Pneumococcus, historically, was a common cause of bacteremia. The availability of pneumococcal conjugate vaccine may have changed the organisms causing bacteremia in children.
Study design: Retrospective chart review and time series.
Setting: Children presenting to the ED of Alder Hey Children’s Hospital in Liverpool, England, from 2001 to 2011.
Synopsis: Five hundred seventy-five episodes of bacteremia were found in 525 children. Infants most commonly had E. coli and Group B streptococcal infections; children over age five most commonly had S. aureus. The introduction of the pneumococcal conjugate vaccine decreased pneumococcal bacteremia by 49% over the study period. This decrease was accompanied by an increase in Gram-negative bacteremia. Susceptibility to empiric antibiotics (third-generation cephalosporins) dropped from 96% to 83%. Over the study period, more children presented with central venous lines, which was felt to be due to increasing outpatient use of total parenteral nutrition (TPN).
Bottom line: Vaccination against pneumococcus is changing the microbiology of pediatric bacteremia, with fewer vaccine-preventable Gram-positive infections and more Gram-negative infections. This increases the likelihood of resistance to third-generation cephalosporins as empiric antibiotic.
Citation: Irwin AD, Drew RJ, Marshall P, et al. Etiology of childhood bacteremia and timely antibiotics administration in the emergency department. Pediatrics. 2015;135(4): 635-642.
Clinical question: Have the causative organisms in pediatric bacteremia changed over time concurrent with introduction of the pneumococcal conjugate vaccine?
Background: Previous research has shown introduction of polyvalent pneumococcal conjugate vaccine led to changes in the organisms causing meningitis and otitis media, and patterns of nasopharyngeal colonization. Pneumococcus, historically, was a common cause of bacteremia. The availability of pneumococcal conjugate vaccine may have changed the organisms causing bacteremia in children.
Study design: Retrospective chart review and time series.
Setting: Children presenting to the ED of Alder Hey Children’s Hospital in Liverpool, England, from 2001 to 2011.
Synopsis: Five hundred seventy-five episodes of bacteremia were found in 525 children. Infants most commonly had E. coli and Group B streptococcal infections; children over age five most commonly had S. aureus. The introduction of the pneumococcal conjugate vaccine decreased pneumococcal bacteremia by 49% over the study period. This decrease was accompanied by an increase in Gram-negative bacteremia. Susceptibility to empiric antibiotics (third-generation cephalosporins) dropped from 96% to 83%. Over the study period, more children presented with central venous lines, which was felt to be due to increasing outpatient use of total parenteral nutrition (TPN).
Bottom line: Vaccination against pneumococcus is changing the microbiology of pediatric bacteremia, with fewer vaccine-preventable Gram-positive infections and more Gram-negative infections. This increases the likelihood of resistance to third-generation cephalosporins as empiric antibiotic.
Citation: Irwin AD, Drew RJ, Marshall P, et al. Etiology of childhood bacteremia and timely antibiotics administration in the emergency department. Pediatrics. 2015;135(4): 635-642.
Clinical question: Have the causative organisms in pediatric bacteremia changed over time concurrent with introduction of the pneumococcal conjugate vaccine?
Background: Previous research has shown introduction of polyvalent pneumococcal conjugate vaccine led to changes in the organisms causing meningitis and otitis media, and patterns of nasopharyngeal colonization. Pneumococcus, historically, was a common cause of bacteremia. The availability of pneumococcal conjugate vaccine may have changed the organisms causing bacteremia in children.
Study design: Retrospective chart review and time series.
Setting: Children presenting to the ED of Alder Hey Children’s Hospital in Liverpool, England, from 2001 to 2011.
Synopsis: Five hundred seventy-five episodes of bacteremia were found in 525 children. Infants most commonly had E. coli and Group B streptococcal infections; children over age five most commonly had S. aureus. The introduction of the pneumococcal conjugate vaccine decreased pneumococcal bacteremia by 49% over the study period. This decrease was accompanied by an increase in Gram-negative bacteremia. Susceptibility to empiric antibiotics (third-generation cephalosporins) dropped from 96% to 83%. Over the study period, more children presented with central venous lines, which was felt to be due to increasing outpatient use of total parenteral nutrition (TPN).
Bottom line: Vaccination against pneumococcus is changing the microbiology of pediatric bacteremia, with fewer vaccine-preventable Gram-positive infections and more Gram-negative infections. This increases the likelihood of resistance to third-generation cephalosporins as empiric antibiotic.
Citation: Irwin AD, Drew RJ, Marshall P, et al. Etiology of childhood bacteremia and timely antibiotics administration in the emergency department. Pediatrics. 2015;135(4): 635-642.
Patient Complexities Associated With Antibiotic Ordering
Clinical question: What is the influence of patient complexities on providers’ decisions to prescribe antibiotics in three common hospital-based clinical vignettes?
Background: Antibiotic treatment decisions for medically complex patients are complicated, because the risk of undertreatment may be severe, while overtreatment may be associated with adverse effects and the emergence of resistant pathogens. It is believed that physicians are more likely than not to prescribe antibiotics for complex patients.
Study design: Hospital-based, physician survey.
Setting: Three urban academic medical centers in Los Angeles County, Calif.
Synopsis: Physicians were presented with three clinical vignettes, with variations by age, comorbidity, functional status, and follow-up, and asked to choose the best antibiotic regimen. Of the 874 invited physicians, 255 (29%) responded to the survey; 245 physicians were eligible for the study.
Study results showed 28% to 49% of physicians recommended antibiotics that were inconsistent with national guidelines. This percentage increased to 48% to 63% for medically complex patients, defined as those with older age, high medical comorbidity burden, poor functional status, or limited follow-up after hospital discharge (P<0.01). Resident physicians (n=183) were more likely than attending physicians (n=57) to have recommended antibiotics in the baseline vignettes (43% vs. 34%, P<0.05) and in all four vignettes with patient complexities.
Bottom line: Inappropriate antibiotic use was prevalent and occurred more often for patients with medical complexities.
Citation: Wooten D, Kahn K, Grein JD, Eells SJ, Miller LG. The association of patient complexities with antibiotic ordering. J Hosp Med. 2015;10:1-7.
Clinical question: What is the influence of patient complexities on providers’ decisions to prescribe antibiotics in three common hospital-based clinical vignettes?
Background: Antibiotic treatment decisions for medically complex patients are complicated, because the risk of undertreatment may be severe, while overtreatment may be associated with adverse effects and the emergence of resistant pathogens. It is believed that physicians are more likely than not to prescribe antibiotics for complex patients.
Study design: Hospital-based, physician survey.
Setting: Three urban academic medical centers in Los Angeles County, Calif.
Synopsis: Physicians were presented with three clinical vignettes, with variations by age, comorbidity, functional status, and follow-up, and asked to choose the best antibiotic regimen. Of the 874 invited physicians, 255 (29%) responded to the survey; 245 physicians were eligible for the study.
Study results showed 28% to 49% of physicians recommended antibiotics that were inconsistent with national guidelines. This percentage increased to 48% to 63% for medically complex patients, defined as those with older age, high medical comorbidity burden, poor functional status, or limited follow-up after hospital discharge (P<0.01). Resident physicians (n=183) were more likely than attending physicians (n=57) to have recommended antibiotics in the baseline vignettes (43% vs. 34%, P<0.05) and in all four vignettes with patient complexities.
Bottom line: Inappropriate antibiotic use was prevalent and occurred more often for patients with medical complexities.
Citation: Wooten D, Kahn K, Grein JD, Eells SJ, Miller LG. The association of patient complexities with antibiotic ordering. J Hosp Med. 2015;10:1-7.
Clinical question: What is the influence of patient complexities on providers’ decisions to prescribe antibiotics in three common hospital-based clinical vignettes?
Background: Antibiotic treatment decisions for medically complex patients are complicated, because the risk of undertreatment may be severe, while overtreatment may be associated with adverse effects and the emergence of resistant pathogens. It is believed that physicians are more likely than not to prescribe antibiotics for complex patients.
Study design: Hospital-based, physician survey.
Setting: Three urban academic medical centers in Los Angeles County, Calif.
Synopsis: Physicians were presented with three clinical vignettes, with variations by age, comorbidity, functional status, and follow-up, and asked to choose the best antibiotic regimen. Of the 874 invited physicians, 255 (29%) responded to the survey; 245 physicians were eligible for the study.
Study results showed 28% to 49% of physicians recommended antibiotics that were inconsistent with national guidelines. This percentage increased to 48% to 63% for medically complex patients, defined as those with older age, high medical comorbidity burden, poor functional status, or limited follow-up after hospital discharge (P<0.01). Resident physicians (n=183) were more likely than attending physicians (n=57) to have recommended antibiotics in the baseline vignettes (43% vs. 34%, P<0.05) and in all four vignettes with patient complexities.
Bottom line: Inappropriate antibiotic use was prevalent and occurred more often for patients with medical complexities.
Citation: Wooten D, Kahn K, Grein JD, Eells SJ, Miller LG. The association of patient complexities with antibiotic ordering. J Hosp Med. 2015;10:1-7.
MRSA coverage in cellulitis treatment
A 57-year-old man presents with pain and swelling in his leg. He has had low-grade fevers. He has a history of type 2 diabetes. On exam, his right lower extremity is warm, erythematous, and swollen to the midcalf. There is no purulence, fluctuance, or weeping skin. Labs are: WBC, 12,000; Na, 134; K, 5.2; BUN, 20; creatinine, 1.4.
What therapy would you recommend?
A) Ciprofloxacin.
B) Cefazolin.
C) Vancomycin.
D) Trimethoprim-sulfamethoxazole.
Myth: Cellulitis treatment should include MRSA coverage.
Cellulitis is almost always caused by group A streptococcus. There are exceptional circumstances where other organisms must be considered; but for the most part, those situations are rare. With the growing concern for community-associated methicillin-resistant Staphylococcus aureus infection (MRSA), more and more patients are receiving empiric coverage for MRSA for all skin infections. Is this coverage for MRSA in patients with cellulitis a new myth in evolution?
In a study by Dr. Arthur Jeng and colleagues, all patients admitted to one hospital over a 3-year period with diffuse cellulitis were studied (Medicine 2010;89:217-26). A total of 179 patients were enrolled in the study; all patients had serologic studies for exposure to streptococci and what antibiotics they received, and outcomes were recorded.
Almost all patients with positive antibodies to streptococci responded to beta-lactam antibiotics (97%). But 91% of the patients who did not develop streptococcal antibodies also responded to beta-lactam antibiotics, for an overall response rate of 95% for treatment with beta-lactam antibiotics.
The most recent clinical practice guidelines published by the Infectious Diseases Society of America recommend treatment for infection with beta-hemolytic streptococci for outpatients with nonpurulent cellulitis (Clin. Infect. Dis. 2011;52:285-92). The addition of vancomycin is reserved for patients with purulence/evidence of abscess or exudate.
How common is it to prescribe antibiotics that cover MRSA in patients with cellulitis?
In a 2013 study, 61% of patients treated for cellulitis received antibiotics that included community-acquired MRSA coverage (Am. J. Med. 2013;126:1099-106).
A recent study looked at whether additional community-associated MRSA coverage with trimethoprim-sulfamethoxazole in addition to beta-lactam therapy for cellulitis showed any benefit over therapy with only a beta-lactam (Clin. Infect. Dis. 2013;56:1754-62). The study was a randomized, double-blind, placebo-controlled trial. The experimental group received trimethoprim-sulfamethoxazole and cephalexin, while the control group received cephalexin plus placebo.
There was no difference in outcome between the two groups, with the conclusion that addition of trimethoprim-sulfamethoxazole to cephalexin did not lead to a better outcome than cephalexin alone in patients with nonpurulent cellulitis.
A study by Dr. Thana Khawcharoenporn and Dr. Alan Tice looked at whether cephalexin, trimethoprim-sulfamethoxazole, or clindamycin was superior for the treatment of outpatient cellulitis (Am. J. Med. 2010;123:942-50). They concluded that trimethoprim-sulfamethoxazole and clindamycin were better than cephalexin. However, more than 50% of patients in this study had abscesses or ulcers – clinical criteria that increase the possibility of MRSA.
The most commonly used oral antibiotic for the coverage of community-associated MRSA is trimethoprim-sulfamethoxazole. This increasing use of TMP-sulfa has its risks, especially in elderly populations (Ann. Emerg. Med. 2014; 63:783-4). Trimethoprim-sulfamethoxazole can cause serious skin reactions and hyperkalemia (especially in the elderly and those with renal impairment), and the drug has a marked drug interaction with warfarin, leading to high risk of excessive anticoagulation.
These risks of TMP-sulfa use make it extremely important to have clear and worthwhile indications for its use.
The best evidence right now is that for simple cellulitis (no purulence, abscess, or exudate), treatment with a beta-lactam antibiotic is the best option. There is no need to add MRSA coverage to beta-lactam therapy.
If there is no response to treatment, then broadening coverage to include MRSA would be appropriate.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
A 57-year-old man presents with pain and swelling in his leg. He has had low-grade fevers. He has a history of type 2 diabetes. On exam, his right lower extremity is warm, erythematous, and swollen to the midcalf. There is no purulence, fluctuance, or weeping skin. Labs are: WBC, 12,000; Na, 134; K, 5.2; BUN, 20; creatinine, 1.4.
What therapy would you recommend?
A) Ciprofloxacin.
B) Cefazolin.
C) Vancomycin.
D) Trimethoprim-sulfamethoxazole.
Myth: Cellulitis treatment should include MRSA coverage.
Cellulitis is almost always caused by group A streptococcus. There are exceptional circumstances where other organisms must be considered; but for the most part, those situations are rare. With the growing concern for community-associated methicillin-resistant Staphylococcus aureus infection (MRSA), more and more patients are receiving empiric coverage for MRSA for all skin infections. Is this coverage for MRSA in patients with cellulitis a new myth in evolution?
In a study by Dr. Arthur Jeng and colleagues, all patients admitted to one hospital over a 3-year period with diffuse cellulitis were studied (Medicine 2010;89:217-26). A total of 179 patients were enrolled in the study; all patients had serologic studies for exposure to streptococci and what antibiotics they received, and outcomes were recorded.
Almost all patients with positive antibodies to streptococci responded to beta-lactam antibiotics (97%). But 91% of the patients who did not develop streptococcal antibodies also responded to beta-lactam antibiotics, for an overall response rate of 95% for treatment with beta-lactam antibiotics.
The most recent clinical practice guidelines published by the Infectious Diseases Society of America recommend treatment for infection with beta-hemolytic streptococci for outpatients with nonpurulent cellulitis (Clin. Infect. Dis. 2011;52:285-92). The addition of vancomycin is reserved for patients with purulence/evidence of abscess or exudate.
How common is it to prescribe antibiotics that cover MRSA in patients with cellulitis?
In a 2013 study, 61% of patients treated for cellulitis received antibiotics that included community-acquired MRSA coverage (Am. J. Med. 2013;126:1099-106).
A recent study looked at whether additional community-associated MRSA coverage with trimethoprim-sulfamethoxazole in addition to beta-lactam therapy for cellulitis showed any benefit over therapy with only a beta-lactam (Clin. Infect. Dis. 2013;56:1754-62). The study was a randomized, double-blind, placebo-controlled trial. The experimental group received trimethoprim-sulfamethoxazole and cephalexin, while the control group received cephalexin plus placebo.
There was no difference in outcome between the two groups, with the conclusion that addition of trimethoprim-sulfamethoxazole to cephalexin did not lead to a better outcome than cephalexin alone in patients with nonpurulent cellulitis.
A study by Dr. Thana Khawcharoenporn and Dr. Alan Tice looked at whether cephalexin, trimethoprim-sulfamethoxazole, or clindamycin was superior for the treatment of outpatient cellulitis (Am. J. Med. 2010;123:942-50). They concluded that trimethoprim-sulfamethoxazole and clindamycin were better than cephalexin. However, more than 50% of patients in this study had abscesses or ulcers – clinical criteria that increase the possibility of MRSA.
The most commonly used oral antibiotic for the coverage of community-associated MRSA is trimethoprim-sulfamethoxazole. This increasing use of TMP-sulfa has its risks, especially in elderly populations (Ann. Emerg. Med. 2014; 63:783-4). Trimethoprim-sulfamethoxazole can cause serious skin reactions and hyperkalemia (especially in the elderly and those with renal impairment), and the drug has a marked drug interaction with warfarin, leading to high risk of excessive anticoagulation.
These risks of TMP-sulfa use make it extremely important to have clear and worthwhile indications for its use.
The best evidence right now is that for simple cellulitis (no purulence, abscess, or exudate), treatment with a beta-lactam antibiotic is the best option. There is no need to add MRSA coverage to beta-lactam therapy.
If there is no response to treatment, then broadening coverage to include MRSA would be appropriate.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
A 57-year-old man presents with pain and swelling in his leg. He has had low-grade fevers. He has a history of type 2 diabetes. On exam, his right lower extremity is warm, erythematous, and swollen to the midcalf. There is no purulence, fluctuance, or weeping skin. Labs are: WBC, 12,000; Na, 134; K, 5.2; BUN, 20; creatinine, 1.4.
What therapy would you recommend?
A) Ciprofloxacin.
B) Cefazolin.
C) Vancomycin.
D) Trimethoprim-sulfamethoxazole.
Myth: Cellulitis treatment should include MRSA coverage.
Cellulitis is almost always caused by group A streptococcus. There are exceptional circumstances where other organisms must be considered; but for the most part, those situations are rare. With the growing concern for community-associated methicillin-resistant Staphylococcus aureus infection (MRSA), more and more patients are receiving empiric coverage for MRSA for all skin infections. Is this coverage for MRSA in patients with cellulitis a new myth in evolution?
In a study by Dr. Arthur Jeng and colleagues, all patients admitted to one hospital over a 3-year period with diffuse cellulitis were studied (Medicine 2010;89:217-26). A total of 179 patients were enrolled in the study; all patients had serologic studies for exposure to streptococci and what antibiotics they received, and outcomes were recorded.
Almost all patients with positive antibodies to streptococci responded to beta-lactam antibiotics (97%). But 91% of the patients who did not develop streptococcal antibodies also responded to beta-lactam antibiotics, for an overall response rate of 95% for treatment with beta-lactam antibiotics.
The most recent clinical practice guidelines published by the Infectious Diseases Society of America recommend treatment for infection with beta-hemolytic streptococci for outpatients with nonpurulent cellulitis (Clin. Infect. Dis. 2011;52:285-92). The addition of vancomycin is reserved for patients with purulence/evidence of abscess or exudate.
How common is it to prescribe antibiotics that cover MRSA in patients with cellulitis?
In a 2013 study, 61% of patients treated for cellulitis received antibiotics that included community-acquired MRSA coverage (Am. J. Med. 2013;126:1099-106).
A recent study looked at whether additional community-associated MRSA coverage with trimethoprim-sulfamethoxazole in addition to beta-lactam therapy for cellulitis showed any benefit over therapy with only a beta-lactam (Clin. Infect. Dis. 2013;56:1754-62). The study was a randomized, double-blind, placebo-controlled trial. The experimental group received trimethoprim-sulfamethoxazole and cephalexin, while the control group received cephalexin plus placebo.
There was no difference in outcome between the two groups, with the conclusion that addition of trimethoprim-sulfamethoxazole to cephalexin did not lead to a better outcome than cephalexin alone in patients with nonpurulent cellulitis.
A study by Dr. Thana Khawcharoenporn and Dr. Alan Tice looked at whether cephalexin, trimethoprim-sulfamethoxazole, or clindamycin was superior for the treatment of outpatient cellulitis (Am. J. Med. 2010;123:942-50). They concluded that trimethoprim-sulfamethoxazole and clindamycin were better than cephalexin. However, more than 50% of patients in this study had abscesses or ulcers – clinical criteria that increase the possibility of MRSA.
The most commonly used oral antibiotic for the coverage of community-associated MRSA is trimethoprim-sulfamethoxazole. This increasing use of TMP-sulfa has its risks, especially in elderly populations (Ann. Emerg. Med. 2014; 63:783-4). Trimethoprim-sulfamethoxazole can cause serious skin reactions and hyperkalemia (especially in the elderly and those with renal impairment), and the drug has a marked drug interaction with warfarin, leading to high risk of excessive anticoagulation.
These risks of TMP-sulfa use make it extremely important to have clear and worthwhile indications for its use.
The best evidence right now is that for simple cellulitis (no purulence, abscess, or exudate), treatment with a beta-lactam antibiotic is the best option. There is no need to add MRSA coverage to beta-lactam therapy.
If there is no response to treatment, then broadening coverage to include MRSA would be appropriate.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
Antibiotic Regimens Compared for Treating Uncomplicated Skin Infections
Clinical question: What are the efficacy and safety of clindamycin and trimethoprim-sulfamethoxazole (TMP-SMX) for treatment of uncomplicated soft tissue infections in adults and children?
Background: Clindamycin and TMP-SMX are commonly used treatments for uncomplicated skin infections in adults and children, but no head-to-head comparison of efficacy or side effect profile for these medications exists.
Study design: Multi-center, prospective, double-blind, randomized clinical trial of superiority.
Setting: Four academic medical centers.
Synopsis: A group of 524 adults (n=369) and children with uncomplicated cellulitis, abscess, or both was enrolled. For patients with abscess, only those with larger lesions (based on age) were included. All abscesses were incised and drained, and patients were randomly treated with either clindamycin or TMP-SMX for 10 days. A total of 41% of cultures from suppurative wounds grew Staphylococcus aureus; 77% of these were methicillin-resistant.
The primary outcome was clinical cure assessed at 7 to 10 days and one month after completing treatment. No significant difference in cure or reported side effects was seen between drug treatment groups, age groups, lesion types, or isolates cultured. Some 80.3% of patients in the clindamycin group and 77.3% of patients in the TMP-SMX group were cured. Side effect profiles assessed by patient questionnaires showed similar rates of self-limited gastrointestinal (~19%) and dermatologic (~1%) complaints. No cases of Clostridium difficile–associated diarrhea were found.
Limitations include exclusion of patients with significant comorbidities and hospitalized patients. Also, other antibiotic regimens were not compared. Patients were followed for only one month to assess recurrence. Finally, no attempt was made to optimize antibiotic dose.
Bottom line: Clindamycin and TMP-SMX had similar cure rates and side effect profiles in otherwise healthy patients with uncomplicated skin infections.
Citation: Miller LG, Daum RS, Creech CB, et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med. 2015;372:1093–1103.
Visit our website for more hospitalist-focused literature reviews.
Clinical question: What are the efficacy and safety of clindamycin and trimethoprim-sulfamethoxazole (TMP-SMX) for treatment of uncomplicated soft tissue infections in adults and children?
Background: Clindamycin and TMP-SMX are commonly used treatments for uncomplicated skin infections in adults and children, but no head-to-head comparison of efficacy or side effect profile for these medications exists.
Study design: Multi-center, prospective, double-blind, randomized clinical trial of superiority.
Setting: Four academic medical centers.
Synopsis: A group of 524 adults (n=369) and children with uncomplicated cellulitis, abscess, or both was enrolled. For patients with abscess, only those with larger lesions (based on age) were included. All abscesses were incised and drained, and patients were randomly treated with either clindamycin or TMP-SMX for 10 days. A total of 41% of cultures from suppurative wounds grew Staphylococcus aureus; 77% of these were methicillin-resistant.
The primary outcome was clinical cure assessed at 7 to 10 days and one month after completing treatment. No significant difference in cure or reported side effects was seen between drug treatment groups, age groups, lesion types, or isolates cultured. Some 80.3% of patients in the clindamycin group and 77.3% of patients in the TMP-SMX group were cured. Side effect profiles assessed by patient questionnaires showed similar rates of self-limited gastrointestinal (~19%) and dermatologic (~1%) complaints. No cases of Clostridium difficile–associated diarrhea were found.
Limitations include exclusion of patients with significant comorbidities and hospitalized patients. Also, other antibiotic regimens were not compared. Patients were followed for only one month to assess recurrence. Finally, no attempt was made to optimize antibiotic dose.
Bottom line: Clindamycin and TMP-SMX had similar cure rates and side effect profiles in otherwise healthy patients with uncomplicated skin infections.
Citation: Miller LG, Daum RS, Creech CB, et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med. 2015;372:1093–1103.
Visit our website for more hospitalist-focused literature reviews.
Clinical question: What are the efficacy and safety of clindamycin and trimethoprim-sulfamethoxazole (TMP-SMX) for treatment of uncomplicated soft tissue infections in adults and children?
Background: Clindamycin and TMP-SMX are commonly used treatments for uncomplicated skin infections in adults and children, but no head-to-head comparison of efficacy or side effect profile for these medications exists.
Study design: Multi-center, prospective, double-blind, randomized clinical trial of superiority.
Setting: Four academic medical centers.
Synopsis: A group of 524 adults (n=369) and children with uncomplicated cellulitis, abscess, or both was enrolled. For patients with abscess, only those with larger lesions (based on age) were included. All abscesses were incised and drained, and patients were randomly treated with either clindamycin or TMP-SMX for 10 days. A total of 41% of cultures from suppurative wounds grew Staphylococcus aureus; 77% of these were methicillin-resistant.
The primary outcome was clinical cure assessed at 7 to 10 days and one month after completing treatment. No significant difference in cure or reported side effects was seen between drug treatment groups, age groups, lesion types, or isolates cultured. Some 80.3% of patients in the clindamycin group and 77.3% of patients in the TMP-SMX group were cured. Side effect profiles assessed by patient questionnaires showed similar rates of self-limited gastrointestinal (~19%) and dermatologic (~1%) complaints. No cases of Clostridium difficile–associated diarrhea were found.
Limitations include exclusion of patients with significant comorbidities and hospitalized patients. Also, other antibiotic regimens were not compared. Patients were followed for only one month to assess recurrence. Finally, no attempt was made to optimize antibiotic dose.
Bottom line: Clindamycin and TMP-SMX had similar cure rates and side effect profiles in otherwise healthy patients with uncomplicated skin infections.
Citation: Miller LG, Daum RS, Creech CB, et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med. 2015;372:1093–1103.
Visit our website for more hospitalist-focused literature reviews.