Antimicrobial-resistant infections

The Centers for Disease Control and Prevention is highlighting a series of new and ongoing initiatives to combat antibiotic resistance this week, officially designated “Get Smart About Antibiotics Week” by President Barack Obama.

The CDC estimates that 2 million Americans are infected with an antibiotic-resistant bacteria annually and that 23,000 of those patients die. The agency has made combating antibiotic resistance a top priority.

“Antibiotic resistance is one of the deadliest health threats facing the world,” CDC Director Tom Frieden said in a statement. “These pledges will help protect the antibiotics we have so we can use these miracle drugs to save lives for years to come.”

The CDC is tracking antibiotic use and the spread of antibiotic-resistant infections in the United States and exploring new ways to stop the rise of antibiotic resistance. The agency is using data to identify hotspots in need of attention, and the CDC-run isolate bank assists industry in developing new antibiotics and rapid diagnostic tests, contributing to the global effort to combat antibiotic resistance.

The CDC is highlighting a number of projects this week to promote antibiotic stewardship:

Ascension Health launches stewardship initiative: Ascension, the largest nonprofit health system in the United States, is creating stewardship programs throughout its care sites. A new center of excellence will focus on antimicrobial stewardship efforts system-wide.

Hospital Corporation of America: HCA joined with the CDC to track antibiotic prescriptions in HCA facilities by automatically collecting and reporting monthly antibiotic-use data using CDC’s National Healthcare Safety Network. Data can be analyzed and fed back to caregivers to guide patient-care decisions.

Premier Safety Institute: First launch of a collaborative of more than 50 hospitals working to implement CDC Core Elements of an Antibiotic Stewardship Programs as well as reducing the overuse of specific antimicrobials that were identified in research conducted by Premier and in collaboration with the CDC.

Walmart public service announcement (PSA) on appropriate antibiotic use: Walmart created educational videos for checkout lines across the country so that customers get clear information on antibiotic resistance and what they can do to improve antibiotic use.

Major airlines run in-flight PSA: State health departments are partnering to improve educational awareness about antibiotic stewardship. An in-flight PSA about antibiotic stewardship, produced by the Michigan Antibiotic Resistance Reduction (MARR) Coalition, is now featured on Jet Blue and other airlines.

Pew Charitable Trust briefing on Capitol Hill: A Pew coalition of “Supermoms against superbugs” will join the Pew Charitable Trust and CDC director Dr. Frieden at a Capitol Hill briefing on Nov. 18, 2015. Pew also is partnering with the CDC to establish national targets to improve the use of antibiotics in support of the goals outlined in the National Action Plan on Combating Antibiotic-Resistant Bacteria.

Consumer Reports: The CDC is partnering with Consumer Reports and the American Board of Internal Medicine Foundation in support of the Choosing Wisely campaign.

U.S. State Department toolkit: The State Department is piloting a toolkit for use by 10 U.S. embassies with a focus on improving antibiotic use.

Society for Hospital Medicine’s educational campaign for hospitalists: The society’s antibiotic stewardship campaign targets hospitalists – an important group for improving antibiotic use.

Global Twitter chat: Hosted by the European Union’s Antibiotic Awareness Day (Nov. 18, 2015), the 24-hour chat will use the hashtag #antibioticresistance and unite CDC experts and partners in a global conversation about antibiotic resistance. CDC experts will lead the conversation from 2 p.m. to 4 p.m. ET.

The latest U.S. antibiotic prescribing rate map: Although overuse of antibiotics is happening in every state across the country, community antibiotic prescribing rates in some states are two times greater than in other states, suggesting opportunities for improvement.

U.S. hospital stewardship programs map: The percentage of hospitals reported by states as having antibiotic stewardship programs that follow all seven of CDC Core Elements of Antibiotic Stewardship Programs varies from state to state from a low of 7% to a high of 58%. The national goal is for 100% of all U.S. hospitals to have antibiotic stewardship programs by 2020.

[email protected]

On Twitter @richpizzi

The Centers for Disease Control and Prevention is highlighting a series of new and ongoing initiatives to combat antibiotic resistance this week, officially designated “Get Smart About Antibiotics Week” by President Barack Obama.

The CDC estimates that 2 million Americans are infected with an antibiotic-resistant bacteria annually and that 23,000 of those patients die. The agency has made combating antibiotic resistance a top priority.

“Antibiotic resistance is one of the deadliest health threats facing the world,” CDC Director Tom Frieden said in a statement. “These pledges will help protect the antibiotics we have so we can use these miracle drugs to save lives for years to come.”

The CDC is tracking antibiotic use and the spread of antibiotic-resistant infections in the United States and exploring new ways to stop the rise of antibiotic resistance. The agency is using data to identify hotspots in need of attention, and the CDC-run isolate bank assists industry in developing new antibiotics and rapid diagnostic tests, contributing to the global effort to combat antibiotic resistance.

The CDC is highlighting a number of projects this week to promote antibiotic stewardship:

Ascension Health launches stewardship initiative: Ascension, the largest nonprofit health system in the United States, is creating stewardship programs throughout its care sites. A new center of excellence will focus on antimicrobial stewardship efforts system-wide.

Hospital Corporation of America: HCA joined with the CDC to track antibiotic prescriptions in HCA facilities by automatically collecting and reporting monthly antibiotic-use data using CDC’s National Healthcare Safety Network. Data can be analyzed and fed back to caregivers to guide patient-care decisions.

Premier Safety Institute: First launch of a collaborative of more than 50 hospitals working to implement CDC Core Elements of an Antibiotic Stewardship Programs as well as reducing the overuse of specific antimicrobials that were identified in research conducted by Premier and in collaboration with the CDC.

Walmart public service announcement (PSA) on appropriate antibiotic use: Walmart created educational videos for checkout lines across the country so that customers get clear information on antibiotic resistance and what they can do to improve antibiotic use.

Major airlines run in-flight PSA: State health departments are partnering to improve educational awareness about antibiotic stewardship. An in-flight PSA about antibiotic stewardship, produced by the Michigan Antibiotic Resistance Reduction (MARR) Coalition, is now featured on Jet Blue and other airlines.

Pew Charitable Trust briefing on Capitol Hill: A Pew coalition of “Supermoms against superbugs” will join the Pew Charitable Trust and CDC director Dr. Frieden at a Capitol Hill briefing on Nov. 18, 2015. Pew also is partnering with the CDC to establish national targets to improve the use of antibiotics in support of the goals outlined in the National Action Plan on Combating Antibiotic-Resistant Bacteria.

Consumer Reports: The CDC is partnering with Consumer Reports and the American Board of Internal Medicine Foundation in support of the Choosing Wisely campaign.

U.S. State Department toolkit: The State Department is piloting a toolkit for use by 10 U.S. embassies with a focus on improving antibiotic use.

Society for Hospital Medicine’s educational campaign for hospitalists: The society’s antibiotic stewardship campaign targets hospitalists – an important group for improving antibiotic use.

Global Twitter chat: Hosted by the European Union’s Antibiotic Awareness Day (Nov. 18, 2015), the 24-hour chat will use the hashtag #antibioticresistance and unite CDC experts and partners in a global conversation about antibiotic resistance. CDC experts will lead the conversation from 2 p.m. to 4 p.m. ET.

The latest U.S. antibiotic prescribing rate map: Although overuse of antibiotics is happening in every state across the country, community antibiotic prescribing rates in some states are two times greater than in other states, suggesting opportunities for improvement.

U.S. hospital stewardship programs map: The percentage of hospitals reported by states as having antibiotic stewardship programs that follow all seven of CDC Core Elements of Antibiotic Stewardship Programs varies from state to state from a low of 7% to a high of 58%. The national goal is for 100% of all U.S. hospitals to have antibiotic stewardship programs by 2020.

[email protected]

On Twitter @richpizzi

The Centers for Disease Control and Prevention is highlighting a series of new and ongoing initiatives to combat antibiotic resistance this week, officially designated “Get Smart About Antibiotics Week” by President Barack Obama.

The CDC estimates that 2 million Americans are infected with an antibiotic-resistant bacteria annually and that 23,000 of those patients die. The agency has made combating antibiotic resistance a top priority.

“Antibiotic resistance is one of the deadliest health threats facing the world,” CDC Director Tom Frieden said in a statement. “These pledges will help protect the antibiotics we have so we can use these miracle drugs to save lives for years to come.”

The CDC is tracking antibiotic use and the spread of antibiotic-resistant infections in the United States and exploring new ways to stop the rise of antibiotic resistance. The agency is using data to identify hotspots in need of attention, and the CDC-run isolate bank assists industry in developing new antibiotics and rapid diagnostic tests, contributing to the global effort to combat antibiotic resistance.

The CDC is highlighting a number of projects this week to promote antibiotic stewardship:

Ascension Health launches stewardship initiative: Ascension, the largest nonprofit health system in the United States, is creating stewardship programs throughout its care sites. A new center of excellence will focus on antimicrobial stewardship efforts system-wide.

Hospital Corporation of America: HCA joined with the CDC to track antibiotic prescriptions in HCA facilities by automatically collecting and reporting monthly antibiotic-use data using CDC’s National Healthcare Safety Network. Data can be analyzed and fed back to caregivers to guide patient-care decisions.

Premier Safety Institute: First launch of a collaborative of more than 50 hospitals working to implement CDC Core Elements of an Antibiotic Stewardship Programs as well as reducing the overuse of specific antimicrobials that were identified in research conducted by Premier and in collaboration with the CDC.

Walmart public service announcement (PSA) on appropriate antibiotic use: Walmart created educational videos for checkout lines across the country so that customers get clear information on antibiotic resistance and what they can do to improve antibiotic use.

Major airlines run in-flight PSA: State health departments are partnering to improve educational awareness about antibiotic stewardship. An in-flight PSA about antibiotic stewardship, produced by the Michigan Antibiotic Resistance Reduction (MARR) Coalition, is now featured on Jet Blue and other airlines.

Pew Charitable Trust briefing on Capitol Hill: A Pew coalition of “Supermoms against superbugs” will join the Pew Charitable Trust and CDC director Dr. Frieden at a Capitol Hill briefing on Nov. 18, 2015. Pew also is partnering with the CDC to establish national targets to improve the use of antibiotics in support of the goals outlined in the National Action Plan on Combating Antibiotic-Resistant Bacteria.

Consumer Reports: The CDC is partnering with Consumer Reports and the American Board of Internal Medicine Foundation in support of the Choosing Wisely campaign.

U.S. State Department toolkit: The State Department is piloting a toolkit for use by 10 U.S. embassies with a focus on improving antibiotic use.

Society for Hospital Medicine’s educational campaign for hospitalists: The society’s antibiotic stewardship campaign targets hospitalists – an important group for improving antibiotic use.

Global Twitter chat: Hosted by the European Union’s Antibiotic Awareness Day (Nov. 18, 2015), the 24-hour chat will use the hashtag #antibioticresistance and unite CDC experts and partners in a global conversation about antibiotic resistance. CDC experts will lead the conversation from 2 p.m. to 4 p.m. ET.

The latest U.S. antibiotic prescribing rate map: Although overuse of antibiotics is happening in every state across the country, community antibiotic prescribing rates in some states are two times greater than in other states, suggesting opportunities for improvement.

U.S. hospital stewardship programs map: The percentage of hospitals reported by states as having antibiotic stewardship programs that follow all seven of CDC Core Elements of Antibiotic Stewardship Programs varies from state to state from a low of 7% to a high of 58%. The national goal is for 100% of all U.S. hospitals to have antibiotic stewardship programs by 2020.

[email protected]

On Twitter @richpizzi

SAN DIEGO – Experts in the field of Neisseria gonorrhoeae antimicrobial resistance are warily watching developments in China, where rates of nonsusceptibility to ceftriaxone are reportedly shooting through the roof.

In the United States at present, gonococcal resistance to ceftriaxone is exceedingly rare: well under 1% of isolates have elevated minimum inhibitory concentrations (MICs) to this cornerstone of empiric therapy. In Europe, the rate is about 3%. What’s really disturbing is that recent data from the World Health Organization Gonococcal Antimicrobial Surveillance Program indicate ceftriaxone nonsusceptibility rates in China are in the 20%-30%-plus range, Dr. Joseph Duncan said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

CDC

“This is very concerning for the potential spread of this type of resistance across the world at some point. It’s just ready to explode,” observed Dr. Duncan of the University of North Carolina, Chapel Hill.

Anytime gonococcal resistance rates to a drug reach about 5%, it spells trouble.

“Gonorrhea treatment is often syndromic. An isolated swab is taken, identified by Gram stain, you give them empiric therapy, and the patients walk out of the clinic and never come back. So you don’t want to have a 5% failure rate for your initial therapy,” he explained.

Neisseria gonorrhoeae has acquired resistance to virtually every antibiotic ever used to treat the infection. Treatment options are running out, which is why the Centers for Disease Control and Prevention has designated gonorrhea as an immediate public health threat requiring urgent and aggressive action.

The 2015 CDC Sexually Transmitted Disease Treatment Guidelines recommend only one front-line treatment for gonorrhea: dual therapy with ceftriaxone at 250 mg IM in a single dose plus azithromycin 1 g orally, also in a single dose. Given N. gonorrhoeae’s adaptability, experts believe that’s not a long-term solution.

After all, 5%-10% of gonococcal isolates in Europe and China are azithromycin-resistant, and while CDC surveillance data showed less than 1% of strains in the United States were azithromycin-resistant through 2013, preliminary data for 2014 show a concerning jump to 2.5%, according to Dr. Duncan’s fellow panelist Dr. Kimberly Workowski, professor of medicine at Emory University in Atlanta and lead author of the 2015 CDC STD guidelines.

Dr. Duncan described the state of the ongoing aggressive multipronged attempts to combat antimicrobial resistance in N. gonorrhoeae. This effort includes new antibiotics in the developmental pipeline, attempts to repurpose existing antibiotics, rapid point-of-care antibiotic susceptibility tests, and vaccine development.

He also highlighted the factors that have led to the bug’s capacity to acquire resistance to so many antibiotics having different mechanisms of action. One key factor is the organism’s sheer competence as expressed in genetic lability.

“This bacteria is continually sampling DNA from the environment. The organisms are constantly swapping genes and DNA segments with commensal Neisseria species. In fact, even human DNA sequences have been found inside the gonococcal genome,” Dr. Duncan said.

While high-level antibiotic resistance can be acquired in a single dramatic step, it can also come about through multiple smaller steps, each one yielding only low-level resistance. “This allows for the sort of creeping [minimum inhibitory concentration] that we’ve seen with the gonococcus, particularly with the extended-spectrum cephalosporin antibiotics,” Dr. Duncan continued.

Also, it’s apparent that even in the absence of antibiotics, other pressures can select for antibiotic-resistant strains. Dr. Duncan credited one of his mentors, William M. Shafer, Ph.D., of Emory University, with developing the hypothesis that fecal lipids might be an important driver of increased resistance rates. Supporting this hypothesis, he noted, is the finding in multiple studies that rectal gonococcal isolates consistently have a somewhat higher prevalence of resistance than those obtained from other sites.

Turning to the effort to curb antibiotic resistance, Dr. Duncan said the drug farthest along in the pipeline is solithromycin, a novel macrolide being developed by Cempra Pharmaceuticals in both oral and IV formulations. Solithromycin, a first-in-class fluoroketolide, is active against a broad range of Gram-positive organisms, among them Legionella, Chlamydia, Mycoplasma, and Ureaplasma, including macrolide-resistant strains. Its ability to bind to three ribosomal sites is thought to minimize development of resistance.

Two positive phase 3 clinical trials of solithromycin have been completed in patients with community-acquired bacterial pneumonia. A phase 3 trial in gonorrhea is ongoing after a positive phase 2 study.

Two bacterial topoisomerase inhibitors are in soon-to-be-completed phase 2 studies.

Delafloxacin, a new fluoroquinolone, was in a phase 3 clinical trial for gonorrhea that was terminated early due to ineffectiveness.

There is considerable interest in bringing back single-dose IM gentamicin (Garamycin) for the treatment of gonorrhea. A systematic review of five studies (Syst Rev. 2014 Sep 19;3:104. doi: 10.1186/2046-4053-3-104) reported cure rates that were mostly in the 90% range, but “not quite high enough to say you’d want to go to gentamicin as your front-line therapy,” in Dr. Duncan’s opinion.

Dr. Workowski noted that the National Institutes of Health is interested in trying to resurrect cefixime (Suprax) for gonorrhea after the CDC guidelines demoted it several years ago. An ongoing clinical trial is examining the impact of increasing the dose and duration of therapy.

Public health officials are also interested in spectinomycin, an antibiotic not currently available in the United States, which has achieved high cure rates as single-dose therapy in several foreign studies.

Dr. Duncan noted that a randomized trial of gentamicin plus azithromycin or gemifloxacin (Factive) plus azithromycin reported cure rates of 100% and 99.5%, respectively (Clin Infect Dis. 2014 Oct 15;59(8):1083-91). He found the study less than convincing, however: “These strains were almost all susceptibile to azithromycin, so you can’t actually say that gentamicin or gemifloxacin added a lot,” he said.

A number of researchers are working on rapid tests for susceptibility of a particular gonococcal strain so physicians could choose an effective antimicrobial for an individual patient right from the start.

“These are all in the developmental phase. It’s going to be difficult, because there are so many different mechanisms for resistance,” he said.

Similarly, vaccine development in the gonococcal field is a great challenge. The microorganism’s multiple mechanisms of immune evasion make it tough to identify correlates of protection, Dr. Duncan continued.

“Epidemiologic studies suggest there is not efficient development of natural immunity. Folks who get gonorrhea and then come back with reinfection often have the exact same strain,” he noted.

Dr. Duncan’s research is funded by the National Institutes of Health and the Burroughs Wellcome Fund. He reported having no financial conflicts of interest.

[email protected]

SAN DIEGO – Experts in the field of Neisseria gonorrhoeae antimicrobial resistance are warily watching developments in China, where rates of nonsusceptibility to ceftriaxone are reportedly shooting through the roof.

In the United States at present, gonococcal resistance to ceftriaxone is exceedingly rare: well under 1% of isolates have elevated minimum inhibitory concentrations (MICs) to this cornerstone of empiric therapy. In Europe, the rate is about 3%. What’s really disturbing is that recent data from the World Health Organization Gonococcal Antimicrobial Surveillance Program indicate ceftriaxone nonsusceptibility rates in China are in the 20%-30%-plus range, Dr. Joseph Duncan said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

CDC

“This is very concerning for the potential spread of this type of resistance across the world at some point. It’s just ready to explode,” observed Dr. Duncan of the University of North Carolina, Chapel Hill.

Anytime gonococcal resistance rates to a drug reach about 5%, it spells trouble.

“Gonorrhea treatment is often syndromic. An isolated swab is taken, identified by Gram stain, you give them empiric therapy, and the patients walk out of the clinic and never come back. So you don’t want to have a 5% failure rate for your initial therapy,” he explained.

Neisseria gonorrhoeae has acquired resistance to virtually every antibiotic ever used to treat the infection. Treatment options are running out, which is why the Centers for Disease Control and Prevention has designated gonorrhea as an immediate public health threat requiring urgent and aggressive action.

The 2015 CDC Sexually Transmitted Disease Treatment Guidelines recommend only one front-line treatment for gonorrhea: dual therapy with ceftriaxone at 250 mg IM in a single dose plus azithromycin 1 g orally, also in a single dose. Given N. gonorrhoeae’s adaptability, experts believe that’s not a long-term solution.

After all, 5%-10% of gonococcal isolates in Europe and China are azithromycin-resistant, and while CDC surveillance data showed less than 1% of strains in the United States were azithromycin-resistant through 2013, preliminary data for 2014 show a concerning jump to 2.5%, according to Dr. Duncan’s fellow panelist Dr. Kimberly Workowski, professor of medicine at Emory University in Atlanta and lead author of the 2015 CDC STD guidelines.

Dr. Duncan described the state of the ongoing aggressive multipronged attempts to combat antimicrobial resistance in N. gonorrhoeae. This effort includes new antibiotics in the developmental pipeline, attempts to repurpose existing antibiotics, rapid point-of-care antibiotic susceptibility tests, and vaccine development.

He also highlighted the factors that have led to the bug’s capacity to acquire resistance to so many antibiotics having different mechanisms of action. One key factor is the organism’s sheer competence as expressed in genetic lability.

“This bacteria is continually sampling DNA from the environment. The organisms are constantly swapping genes and DNA segments with commensal Neisseria species. In fact, even human DNA sequences have been found inside the gonococcal genome,” Dr. Duncan said.

While high-level antibiotic resistance can be acquired in a single dramatic step, it can also come about through multiple smaller steps, each one yielding only low-level resistance. “This allows for the sort of creeping [minimum inhibitory concentration] that we’ve seen with the gonococcus, particularly with the extended-spectrum cephalosporin antibiotics,” Dr. Duncan continued.

Also, it’s apparent that even in the absence of antibiotics, other pressures can select for antibiotic-resistant strains. Dr. Duncan credited one of his mentors, William M. Shafer, Ph.D., of Emory University, with developing the hypothesis that fecal lipids might be an important driver of increased resistance rates. Supporting this hypothesis, he noted, is the finding in multiple studies that rectal gonococcal isolates consistently have a somewhat higher prevalence of resistance than those obtained from other sites.

Turning to the effort to curb antibiotic resistance, Dr. Duncan said the drug farthest along in the pipeline is solithromycin, a novel macrolide being developed by Cempra Pharmaceuticals in both oral and IV formulations. Solithromycin, a first-in-class fluoroketolide, is active against a broad range of Gram-positive organisms, among them Legionella, Chlamydia, Mycoplasma, and Ureaplasma, including macrolide-resistant strains. Its ability to bind to three ribosomal sites is thought to minimize development of resistance.

Two positive phase 3 clinical trials of solithromycin have been completed in patients with community-acquired bacterial pneumonia. A phase 3 trial in gonorrhea is ongoing after a positive phase 2 study.

Two bacterial topoisomerase inhibitors are in soon-to-be-completed phase 2 studies.

Delafloxacin, a new fluoroquinolone, was in a phase 3 clinical trial for gonorrhea that was terminated early due to ineffectiveness.

There is considerable interest in bringing back single-dose IM gentamicin (Garamycin) for the treatment of gonorrhea. A systematic review of five studies (Syst Rev. 2014 Sep 19;3:104. doi: 10.1186/2046-4053-3-104) reported cure rates that were mostly in the 90% range, but “not quite high enough to say you’d want to go to gentamicin as your front-line therapy,” in Dr. Duncan’s opinion.

Dr. Workowski noted that the National Institutes of Health is interested in trying to resurrect cefixime (Suprax) for gonorrhea after the CDC guidelines demoted it several years ago. An ongoing clinical trial is examining the impact of increasing the dose and duration of therapy.

Public health officials are also interested in spectinomycin, an antibiotic not currently available in the United States, which has achieved high cure rates as single-dose therapy in several foreign studies.

Dr. Duncan noted that a randomized trial of gentamicin plus azithromycin or gemifloxacin (Factive) plus azithromycin reported cure rates of 100% and 99.5%, respectively (Clin Infect Dis. 2014 Oct 15;59(8):1083-91). He found the study less than convincing, however: “These strains were almost all susceptibile to azithromycin, so you can’t actually say that gentamicin or gemifloxacin added a lot,” he said.

A number of researchers are working on rapid tests for susceptibility of a particular gonococcal strain so physicians could choose an effective antimicrobial for an individual patient right from the start.

“These are all in the developmental phase. It’s going to be difficult, because there are so many different mechanisms for resistance,” he said.

Similarly, vaccine development in the gonococcal field is a great challenge. The microorganism’s multiple mechanisms of immune evasion make it tough to identify correlates of protection, Dr. Duncan continued.

“Epidemiologic studies suggest there is not efficient development of natural immunity. Folks who get gonorrhea and then come back with reinfection often have the exact same strain,” he noted.

Dr. Duncan’s research is funded by the National Institutes of Health and the Burroughs Wellcome Fund. He reported having no financial conflicts of interest.

[email protected]

SAN DIEGO – Experts in the field of Neisseria gonorrhoeae antimicrobial resistance are warily watching developments in China, where rates of nonsusceptibility to ceftriaxone are reportedly shooting through the roof.

In the United States at present, gonococcal resistance to ceftriaxone is exceedingly rare: well under 1% of isolates have elevated minimum inhibitory concentrations (MICs) to this cornerstone of empiric therapy. In Europe, the rate is about 3%. What’s really disturbing is that recent data from the World Health Organization Gonococcal Antimicrobial Surveillance Program indicate ceftriaxone nonsusceptibility rates in China are in the 20%-30%-plus range, Dr. Joseph Duncan said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

CDC

“This is very concerning for the potential spread of this type of resistance across the world at some point. It’s just ready to explode,” observed Dr. Duncan of the University of North Carolina, Chapel Hill.

Anytime gonococcal resistance rates to a drug reach about 5%, it spells trouble.

“Gonorrhea treatment is often syndromic. An isolated swab is taken, identified by Gram stain, you give them empiric therapy, and the patients walk out of the clinic and never come back. So you don’t want to have a 5% failure rate for your initial therapy,” he explained.

Neisseria gonorrhoeae has acquired resistance to virtually every antibiotic ever used to treat the infection. Treatment options are running out, which is why the Centers for Disease Control and Prevention has designated gonorrhea as an immediate public health threat requiring urgent and aggressive action.

The 2015 CDC Sexually Transmitted Disease Treatment Guidelines recommend only one front-line treatment for gonorrhea: dual therapy with ceftriaxone at 250 mg IM in a single dose plus azithromycin 1 g orally, also in a single dose. Given N. gonorrhoeae’s adaptability, experts believe that’s not a long-term solution.

After all, 5%-10% of gonococcal isolates in Europe and China are azithromycin-resistant, and while CDC surveillance data showed less than 1% of strains in the United States were azithromycin-resistant through 2013, preliminary data for 2014 show a concerning jump to 2.5%, according to Dr. Duncan’s fellow panelist Dr. Kimberly Workowski, professor of medicine at Emory University in Atlanta and lead author of the 2015 CDC STD guidelines.

Dr. Duncan described the state of the ongoing aggressive multipronged attempts to combat antimicrobial resistance in N. gonorrhoeae. This effort includes new antibiotics in the developmental pipeline, attempts to repurpose existing antibiotics, rapid point-of-care antibiotic susceptibility tests, and vaccine development.

He also highlighted the factors that have led to the bug’s capacity to acquire resistance to so many antibiotics having different mechanisms of action. One key factor is the organism’s sheer competence as expressed in genetic lability.

“This bacteria is continually sampling DNA from the environment. The organisms are constantly swapping genes and DNA segments with commensal Neisseria species. In fact, even human DNA sequences have been found inside the gonococcal genome,” Dr. Duncan said.

While high-level antibiotic resistance can be acquired in a single dramatic step, it can also come about through multiple smaller steps, each one yielding only low-level resistance. “This allows for the sort of creeping [minimum inhibitory concentration] that we’ve seen with the gonococcus, particularly with the extended-spectrum cephalosporin antibiotics,” Dr. Duncan continued.

Also, it’s apparent that even in the absence of antibiotics, other pressures can select for antibiotic-resistant strains. Dr. Duncan credited one of his mentors, William M. Shafer, Ph.D., of Emory University, with developing the hypothesis that fecal lipids might be an important driver of increased resistance rates. Supporting this hypothesis, he noted, is the finding in multiple studies that rectal gonococcal isolates consistently have a somewhat higher prevalence of resistance than those obtained from other sites.

Turning to the effort to curb antibiotic resistance, Dr. Duncan said the drug farthest along in the pipeline is solithromycin, a novel macrolide being developed by Cempra Pharmaceuticals in both oral and IV formulations. Solithromycin, a first-in-class fluoroketolide, is active against a broad range of Gram-positive organisms, among them Legionella, Chlamydia, Mycoplasma, and Ureaplasma, including macrolide-resistant strains. Its ability to bind to three ribosomal sites is thought to minimize development of resistance.

Two positive phase 3 clinical trials of solithromycin have been completed in patients with community-acquired bacterial pneumonia. A phase 3 trial in gonorrhea is ongoing after a positive phase 2 study.

Two bacterial topoisomerase inhibitors are in soon-to-be-completed phase 2 studies.

Delafloxacin, a new fluoroquinolone, was in a phase 3 clinical trial for gonorrhea that was terminated early due to ineffectiveness.

There is considerable interest in bringing back single-dose IM gentamicin (Garamycin) for the treatment of gonorrhea. A systematic review of five studies (Syst Rev. 2014 Sep 19;3:104. doi: 10.1186/2046-4053-3-104) reported cure rates that were mostly in the 90% range, but “not quite high enough to say you’d want to go to gentamicin as your front-line therapy,” in Dr. Duncan’s opinion.

Dr. Workowski noted that the National Institutes of Health is interested in trying to resurrect cefixime (Suprax) for gonorrhea after the CDC guidelines demoted it several years ago. An ongoing clinical trial is examining the impact of increasing the dose and duration of therapy.

Public health officials are also interested in spectinomycin, an antibiotic not currently available in the United States, which has achieved high cure rates as single-dose therapy in several foreign studies.

Dr. Duncan noted that a randomized trial of gentamicin plus azithromycin or gemifloxacin (Factive) plus azithromycin reported cure rates of 100% and 99.5%, respectively (Clin Infect Dis. 2014 Oct 15;59(8):1083-91). He found the study less than convincing, however: “These strains were almost all susceptibile to azithromycin, so you can’t actually say that gentamicin or gemifloxacin added a lot,” he said.

A number of researchers are working on rapid tests for susceptibility of a particular gonococcal strain so physicians could choose an effective antimicrobial for an individual patient right from the start.

“These are all in the developmental phase. It’s going to be difficult, because there are so many different mechanisms for resistance,” he said.

Similarly, vaccine development in the gonococcal field is a great challenge. The microorganism’s multiple mechanisms of immune evasion make it tough to identify correlates of protection, Dr. Duncan continued.

“Epidemiologic studies suggest there is not efficient development of natural immunity. Folks who get gonorrhea and then come back with reinfection often have the exact same strain,” he noted.

Dr. Duncan’s research is funded by the National Institutes of Health and the Burroughs Wellcome Fund. He reported having no financial conflicts of interest.

[email protected]

Shared decision making between doctors and patients for the treatment of acute respiratory infections can achieve significant short-term reductions in antibiotic use, according to a Cochrane review published Nov. 11.

“Shared decision making is … a set of communication and evidence-based practice skills that elicits patients’ expectations, clarifies any misperceptions, and discusses the best available evidence for benefits and harms of treatment,” wrote Peter Coxeter of the Centre for Research in Evidence-Based Practice at Bond University, Australia.

©rasslava/thinkstockphotos.com

Dr. Coxeter and his coauthors analyzed 10 published reports from nine randomized controlled trials involving more than 1,100 physicians and 492,000 patients, and found that shared decision making interventions were associated with a 39% overall reduction in antibiotic use (95% confidence interval, 0.55-0.68) within 6 weeks of the consultation, with a trend suggesting those reductions were maintained in the longer term.

The analysis also showed that this reduction did not lead to an increase in patient-initiated reconsultations or a decrease in patient satisfaction, although there were not enough data to determine the impact of these interventions on longer-term outcomes such as hospital admissions, pneumonia, or mortality (Cochrane Database Syst Rev. 2015 Nov 11. doi: 10.1002/14651858.CD010907.pub2).

“Further research should also aim to determine which aspects of these interventions provide the greatest benefit to adapt program implementation and uptake in diverse clinical settings,” the authors wrote.

The review was supported by the National Health and Medical Research Council (Australia). No conflicts of interest were declared.

Shared decision making between doctors and patients for the treatment of acute respiratory infections can achieve significant short-term reductions in antibiotic use, according to a Cochrane review published Nov. 11.

“Shared decision making is … a set of communication and evidence-based practice skills that elicits patients’ expectations, clarifies any misperceptions, and discusses the best available evidence for benefits and harms of treatment,” wrote Peter Coxeter of the Centre for Research in Evidence-Based Practice at Bond University, Australia.

©rasslava/thinkstockphotos.com

Dr. Coxeter and his coauthors analyzed 10 published reports from nine randomized controlled trials involving more than 1,100 physicians and 492,000 patients, and found that shared decision making interventions were associated with a 39% overall reduction in antibiotic use (95% confidence interval, 0.55-0.68) within 6 weeks of the consultation, with a trend suggesting those reductions were maintained in the longer term.

The analysis also showed that this reduction did not lead to an increase in patient-initiated reconsultations or a decrease in patient satisfaction, although there were not enough data to determine the impact of these interventions on longer-term outcomes such as hospital admissions, pneumonia, or mortality (Cochrane Database Syst Rev. 2015 Nov 11. doi: 10.1002/14651858.CD010907.pub2).

“Further research should also aim to determine which aspects of these interventions provide the greatest benefit to adapt program implementation and uptake in diverse clinical settings,” the authors wrote.

The review was supported by the National Health and Medical Research Council (Australia). No conflicts of interest were declared.

Shared decision making between doctors and patients for the treatment of acute respiratory infections can achieve significant short-term reductions in antibiotic use, according to a Cochrane review published Nov. 11.

“Shared decision making is … a set of communication and evidence-based practice skills that elicits patients’ expectations, clarifies any misperceptions, and discusses the best available evidence for benefits and harms of treatment,” wrote Peter Coxeter of the Centre for Research in Evidence-Based Practice at Bond University, Australia.

©rasslava/thinkstockphotos.com

Dr. Coxeter and his coauthors analyzed 10 published reports from nine randomized controlled trials involving more than 1,100 physicians and 492,000 patients, and found that shared decision making interventions were associated with a 39% overall reduction in antibiotic use (95% confidence interval, 0.55-0.68) within 6 weeks of the consultation, with a trend suggesting those reductions were maintained in the longer term.

The analysis also showed that this reduction did not lead to an increase in patient-initiated reconsultations or a decrease in patient satisfaction, although there were not enough data to determine the impact of these interventions on longer-term outcomes such as hospital admissions, pneumonia, or mortality (Cochrane Database Syst Rev. 2015 Nov 11. doi: 10.1002/14651858.CD010907.pub2).

“Further research should also aim to determine which aspects of these interventions provide the greatest benefit to adapt program implementation and uptake in diverse clinical settings,” the authors wrote.

The review was supported by the National Health and Medical Research Council (Australia). No conflicts of interest were declared.

HONOLULU – Could gut microbiota be a better predictor than clinical factors of a patient’s response to treatment for Clostridium difficile infection?

In a study of 88 patients with C. difficile, the overall treatment failure rate was 12.5% – but clinical factors such as age, sex, ongoing antibiotic exposure, and hospitalization status failed to predict which patients wouldn’t respond to treatment.

So, “we aimed to identify if there are any gut microbiota signatures to predict treatment response and treatment failure,” explained the study’s lead author, Dr. Sahil Khanna of the Mayo Clinic, Rochester, Minn.

In an interview at the annual meeting of the American College of Gastroenterology, Dr. Khanna discussed the study results and why gut microbiota may be an effective predictor of treatment responders and nonresponders.

HONOLULU – Could gut microbiota be a better predictor than clinical factors of a patient’s response to treatment for Clostridium difficile infection?

In a study of 88 patients with C. difficile, the overall treatment failure rate was 12.5% – but clinical factors such as age, sex, ongoing antibiotic exposure, and hospitalization status failed to predict which patients wouldn’t respond to treatment.

So, “we aimed to identify if there are any gut microbiota signatures to predict treatment response and treatment failure,” explained the study’s lead author, Dr. Sahil Khanna of the Mayo Clinic, Rochester, Minn.

In an interview at the annual meeting of the American College of Gastroenterology, Dr. Khanna discussed the study results and why gut microbiota may be an effective predictor of treatment responders and nonresponders.

HONOLULU – Could gut microbiota be a better predictor than clinical factors of a patient’s response to treatment for Clostridium difficile infection?

In a study of 88 patients with C. difficile, the overall treatment failure rate was 12.5% – but clinical factors such as age, sex, ongoing antibiotic exposure, and hospitalization status failed to predict which patients wouldn’t respond to treatment.

So, “we aimed to identify if there are any gut microbiota signatures to predict treatment response and treatment failure,” explained the study’s lead author, Dr. Sahil Khanna of the Mayo Clinic, Rochester, Minn.

In an interview at the annual meeting of the American College of Gastroenterology, Dr. Khanna discussed the study results and why gut microbiota may be an effective predictor of treatment responders and nonresponders.

SAN DIEGO – Fecal microbiota transplantation (FMT) is now first-line therapy for Clostridium difficile infection (CDI) in much of Scandinavia. At an annual conference on infectious diseases, two specialists debated whether that should be the case in the United States, too.

The epidemiology of CDI has changed greatly in the past decade, as other researchers have noted (Infect Drug Resist. 2014;7:63-72). Incidence, severity, and case-fatality rates have risen substantially, and individuals who lack the usual risk factors for CDI are now acquiring it in community settings. Moreover, CDI adds about 5-6 days to a patient’s average hospital stay, and almost one in three affected patients is rehospitalized (Am J Infect Control. 2015 Apr 1;43[4]:314-7.) – most often within a week of discharge, said Dr. Thomas Moore, who is at the University of Kansas, Wichita.

“Should FMT be used as first-line therapy? Not just yes, but hell, yes! It has superior efficacy,” Dr. Moore said.

Courtesy CDC/Dr. Gilda Jones

He pointed to the recent landmark study (N Engl J Med. 2013;368:407-15) of CDI in which duodenal infusions of donor feces more than tripled the rates of relapse-free cure, compared with vancomycin monotherapy or vancomycin with bowel lavage (P less than .001 for both comparisons). Moreover, diarrhea resolved for 81% of patients after the first fecal infusion, and the observed superiority over the vancomycin regimens was so marked that investigators stopped the study after the interim analysis.

Evidence suggests FMT is safe as well as effective, said Dr. Moore. Centers in Norway, Sweden, Denmark, Finland, and Holland have treated at least 900 patients with no reported adverse effects and with cure rates of about 90%, he noted. Of more than 1,000 published FMT studies worldwide, there has been one only report of peritonitis after colonoscopy, one case of irritable bowel syndrome, three reports of mild enteritis, one case of upper gastrointestinal bleeding, one death from sepsis from a dislodged gastrostomy tube, and one case of new-onset obesity, which occurred after a patient received fecal microbiota donated by an obese relative, he added (Open Forum Infect Dis. 2015 Feb 1. doi: 10.1093/ofid/ofv004). Patients now receive fecal microbiota donations from normal-weight individuals, he noted (http://www.openbiome.org/stool-donation/).

“Fecal microbiota transplantation could save lives,” Dr. Moore concluded. Donor material is “cheap and unlimited, the procedure is cost-effective, easy to perform, can even be done at home, and patient satisfaction is very high.”

But Dr. Johan S. Bakken, an infectious disease specialist at St. Luke’s Hospital in Duluth, Minn., argued that FMT is not ready for first-line use for CDI in the United States. “There are no published FMT practice guidelines for initial therapy, even in Scandinavia, and no randomized controlled trials of FMT conducted anywhere,” said Dr. Bakken. He noted that because the Food and Drug Administration has not approved FMT for first-line use in CDI, utilization could require an approved Investigational New Drug application, leading to “unavoidable” treatment delays.

Clinicians also should not gloss over concerns about adverse effects with FMT, Dr. Bakken said. In addition to the case of new-onset obesity, there are risks of aspirating fecal material or perforating hollow viscera. Furthermore, the potential long-term adverse consequences of FMT are unknown, he said.

In contrast, the rate of resolution of initial CDI with per oral vancomycin or fidaxomicin is more than 80%, Dr. Bakken said. Moreover, liquid vancomycin at an appropriate dose and frequency for CDI costs about $4.25 per day in Duluth, he added. “No comparative outcomes data are available for FMT, but it is more costly than vancomycin, may not be locally available, and requires several days or weeks of planning,” he emphasized.

Cost-reimbursement issues with third-party payers are also likely with FMT, according to Dr. Bakken. “There also are potential or perceived medicolegal issues with FMT,” he said. “Keep in mind that about 80% of the world’s lawyers work and practice in the U.S.A.”

Dr. Moore had no disclosures. Dr. Bakken reported being an advisory board member of Rebiotix, which is developing a biologic drug to treat recurrent CDI.

SAN DIEGO – Fecal microbiota transplantation (FMT) is now first-line therapy for Clostridium difficile infection (CDI) in much of Scandinavia. At an annual conference on infectious diseases, two specialists debated whether that should be the case in the United States, too.

The epidemiology of CDI has changed greatly in the past decade, as other researchers have noted (Infect Drug Resist. 2014;7:63-72). Incidence, severity, and case-fatality rates have risen substantially, and individuals who lack the usual risk factors for CDI are now acquiring it in community settings. Moreover, CDI adds about 5-6 days to a patient’s average hospital stay, and almost one in three affected patients is rehospitalized (Am J Infect Control. 2015 Apr 1;43[4]:314-7.) – most often within a week of discharge, said Dr. Thomas Moore, who is at the University of Kansas, Wichita.

“Should FMT be used as first-line therapy? Not just yes, but hell, yes! It has superior efficacy,” Dr. Moore said.

Courtesy CDC/Dr. Gilda Jones

He pointed to the recent landmark study (N Engl J Med. 2013;368:407-15) of CDI in which duodenal infusions of donor feces more than tripled the rates of relapse-free cure, compared with vancomycin monotherapy or vancomycin with bowel lavage (P less than .001 for both comparisons). Moreover, diarrhea resolved for 81% of patients after the first fecal infusion, and the observed superiority over the vancomycin regimens was so marked that investigators stopped the study after the interim analysis.

Evidence suggests FMT is safe as well as effective, said Dr. Moore. Centers in Norway, Sweden, Denmark, Finland, and Holland have treated at least 900 patients with no reported adverse effects and with cure rates of about 90%, he noted. Of more than 1,000 published FMT studies worldwide, there has been one only report of peritonitis after colonoscopy, one case of irritable bowel syndrome, three reports of mild enteritis, one case of upper gastrointestinal bleeding, one death from sepsis from a dislodged gastrostomy tube, and one case of new-onset obesity, which occurred after a patient received fecal microbiota donated by an obese relative, he added (Open Forum Infect Dis. 2015 Feb 1. doi: 10.1093/ofid/ofv004). Patients now receive fecal microbiota donations from normal-weight individuals, he noted (http://www.openbiome.org/stool-donation/).

“Fecal microbiota transplantation could save lives,” Dr. Moore concluded. Donor material is “cheap and unlimited, the procedure is cost-effective, easy to perform, can even be done at home, and patient satisfaction is very high.”

But Dr. Johan S. Bakken, an infectious disease specialist at St. Luke’s Hospital in Duluth, Minn., argued that FMT is not ready for first-line use for CDI in the United States. “There are no published FMT practice guidelines for initial therapy, even in Scandinavia, and no randomized controlled trials of FMT conducted anywhere,” said Dr. Bakken. He noted that because the Food and Drug Administration has not approved FMT for first-line use in CDI, utilization could require an approved Investigational New Drug application, leading to “unavoidable” treatment delays.

Clinicians also should not gloss over concerns about adverse effects with FMT, Dr. Bakken said. In addition to the case of new-onset obesity, there are risks of aspirating fecal material or perforating hollow viscera. Furthermore, the potential long-term adverse consequences of FMT are unknown, he said.

In contrast, the rate of resolution of initial CDI with per oral vancomycin or fidaxomicin is more than 80%, Dr. Bakken said. Moreover, liquid vancomycin at an appropriate dose and frequency for CDI costs about $4.25 per day in Duluth, he added. “No comparative outcomes data are available for FMT, but it is more costly than vancomycin, may not be locally available, and requires several days or weeks of planning,” he emphasized.

Cost-reimbursement issues with third-party payers are also likely with FMT, according to Dr. Bakken. “There also are potential or perceived medicolegal issues with FMT,” he said. “Keep in mind that about 80% of the world’s lawyers work and practice in the U.S.A.”

Dr. Moore had no disclosures. Dr. Bakken reported being an advisory board member of Rebiotix, which is developing a biologic drug to treat recurrent CDI.

SAN DIEGO – Fecal microbiota transplantation (FMT) is now first-line therapy for Clostridium difficile infection (CDI) in much of Scandinavia. At an annual conference on infectious diseases, two specialists debated whether that should be the case in the United States, too.

The epidemiology of CDI has changed greatly in the past decade, as other researchers have noted (Infect Drug Resist. 2014;7:63-72). Incidence, severity, and case-fatality rates have risen substantially, and individuals who lack the usual risk factors for CDI are now acquiring it in community settings. Moreover, CDI adds about 5-6 days to a patient’s average hospital stay, and almost one in three affected patients is rehospitalized (Am J Infect Control. 2015 Apr 1;43[4]:314-7.) – most often within a week of discharge, said Dr. Thomas Moore, who is at the University of Kansas, Wichita.

“Should FMT be used as first-line therapy? Not just yes, but hell, yes! It has superior efficacy,” Dr. Moore said.

Courtesy CDC/Dr. Gilda Jones

He pointed to the recent landmark study (N Engl J Med. 2013;368:407-15) of CDI in which duodenal infusions of donor feces more than tripled the rates of relapse-free cure, compared with vancomycin monotherapy or vancomycin with bowel lavage (P less than .001 for both comparisons). Moreover, diarrhea resolved for 81% of patients after the first fecal infusion, and the observed superiority over the vancomycin regimens was so marked that investigators stopped the study after the interim analysis.

Evidence suggests FMT is safe as well as effective, said Dr. Moore. Centers in Norway, Sweden, Denmark, Finland, and Holland have treated at least 900 patients with no reported adverse effects and with cure rates of about 90%, he noted. Of more than 1,000 published FMT studies worldwide, there has been one only report of peritonitis after colonoscopy, one case of irritable bowel syndrome, three reports of mild enteritis, one case of upper gastrointestinal bleeding, one death from sepsis from a dislodged gastrostomy tube, and one case of new-onset obesity, which occurred after a patient received fecal microbiota donated by an obese relative, he added (Open Forum Infect Dis. 2015 Feb 1. doi: 10.1093/ofid/ofv004). Patients now receive fecal microbiota donations from normal-weight individuals, he noted (http://www.openbiome.org/stool-donation/).

“Fecal microbiota transplantation could save lives,” Dr. Moore concluded. Donor material is “cheap and unlimited, the procedure is cost-effective, easy to perform, can even be done at home, and patient satisfaction is very high.”

But Dr. Johan S. Bakken, an infectious disease specialist at St. Luke’s Hospital in Duluth, Minn., argued that FMT is not ready for first-line use for CDI in the United States. “There are no published FMT practice guidelines for initial therapy, even in Scandinavia, and no randomized controlled trials of FMT conducted anywhere,” said Dr. Bakken. He noted that because the Food and Drug Administration has not approved FMT for first-line use in CDI, utilization could require an approved Investigational New Drug application, leading to “unavoidable” treatment delays.

Clinicians also should not gloss over concerns about adverse effects with FMT, Dr. Bakken said. In addition to the case of new-onset obesity, there are risks of aspirating fecal material or perforating hollow viscera. Furthermore, the potential long-term adverse consequences of FMT are unknown, he said.

In contrast, the rate of resolution of initial CDI with per oral vancomycin or fidaxomicin is more than 80%, Dr. Bakken said. Moreover, liquid vancomycin at an appropriate dose and frequency for CDI costs about $4.25 per day in Duluth, he added. “No comparative outcomes data are available for FMT, but it is more costly than vancomycin, may not be locally available, and requires several days or weeks of planning,” he emphasized.

Cost-reimbursement issues with third-party payers are also likely with FMT, according to Dr. Bakken. “There also are potential or perceived medicolegal issues with FMT,” he said. “Keep in mind that about 80% of the world’s lawyers work and practice in the U.S.A.”

Dr. Moore had no disclosures. Dr. Bakken reported being an advisory board member of Rebiotix, which is developing a biologic drug to treat recurrent CDI.

SAN DIEGO – A “time-out” to review antibiotic therapy 72-96 hours into treatment increased appropriate discontinuations of vancomycin by 31%, researchers said at an annual scientific meeting on infectious diseases.

The practice fit into hospital work flow, streamlined other antibiotic stewardship practices, and respected provider autonomy, said Dr. Christopher Graber of VA Greater Los Angeles Healthcare System and the University of California, Los Angeles. It also was durable, persisting into the second 6 months of the program even though active research support had ended, he and his associates said.

©TongRo Images/thinkstock.com

The Centers for Disease Control and Prevention endorses the antibiotic time-out as a way to encourage providers to switch from empirical treatment with broad-spectrum antibiotics to a more tailored plan after culture and other laboratory results become available. The Veterans Affairs teaching hospital in greater Los Angeles created a self-directed time-out program to encourage reconsideration of broad-spectrum therapy with vancomycin and piperacillin-tazobactam after the first 3 days of empirical treatment. The program included an antimicrobial “dashboard” report, an electronic template to document time-outs, and a marketing program consisting of educational documents, lectures, “clinical champions,” and reminder notes and fliers posted near computers.

To evaluate early and late responses to the program, Dr. Graber and his associates tracked discontinuations of vancomycin and piperacillin-tazobactam, as well as decisions to continue these antibiotics through day 5 when doing so contradicted guidelines. Among 276 vancomycin episodes during the program, clinicians discontinued 175 (63%) – significantly more than before the program started (96 of 199; 48%; P = .001). They documented vancomycin time-outs 46% of the time, continued patients on vancomycin through day 5 without a time-out in 7.6% of cases, and allowed vancomycin to expire without a time-out 46% of the time.

The rate of inappropriate discontinuations of vancomycin during the program exceeded baseline (4.7% vs. none; P = .001), but this trend was balanced out by the overall rise in vancomycin discontinuations, the researchers said. Furthermore, providers documented vancomycin time-outs more often during the second 6 months, compared with the first (54% vs. 37%; P = .005). The increase in vancomycin discontinuations also was durable (about 63% throughout the two 6-month periods), and inappropriate continuations remained stable at about 4.5%.

“Piperacillin-tazobactam did not see any change in discontinuations between the two study periods,” said the researchers. The discontinuation rate was about 62% before and during the program. Clinicians performed time-outs about half the time, and inappropriately continued the antibiotics beyond day 5 in 10% of cases, compared with 2% before the program started (P = .02). Clinicians continued performing piperacillin-tazobactam time-outs at the same rate in the second 6 months of the program as during the beginning, and rates of discontinuation and inappropriate continuations also remained similar.

The investigators reported these results at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

CDC funded the research with a grant to the University of Utah. The researchers reported no conflicts of interest.

SAN DIEGO – A “time-out” to review antibiotic therapy 72-96 hours into treatment increased appropriate discontinuations of vancomycin by 31%, researchers said at an annual scientific meeting on infectious diseases.

The practice fit into hospital work flow, streamlined other antibiotic stewardship practices, and respected provider autonomy, said Dr. Christopher Graber of VA Greater Los Angeles Healthcare System and the University of California, Los Angeles. It also was durable, persisting into the second 6 months of the program even though active research support had ended, he and his associates said.

©TongRo Images/thinkstock.com

The Centers for Disease Control and Prevention endorses the antibiotic time-out as a way to encourage providers to switch from empirical treatment with broad-spectrum antibiotics to a more tailored plan after culture and other laboratory results become available. The Veterans Affairs teaching hospital in greater Los Angeles created a self-directed time-out program to encourage reconsideration of broad-spectrum therapy with vancomycin and piperacillin-tazobactam after the first 3 days of empirical treatment. The program included an antimicrobial “dashboard” report, an electronic template to document time-outs, and a marketing program consisting of educational documents, lectures, “clinical champions,” and reminder notes and fliers posted near computers.

To evaluate early and late responses to the program, Dr. Graber and his associates tracked discontinuations of vancomycin and piperacillin-tazobactam, as well as decisions to continue these antibiotics through day 5 when doing so contradicted guidelines. Among 276 vancomycin episodes during the program, clinicians discontinued 175 (63%) – significantly more than before the program started (96 of 199; 48%; P = .001). They documented vancomycin time-outs 46% of the time, continued patients on vancomycin through day 5 without a time-out in 7.6% of cases, and allowed vancomycin to expire without a time-out 46% of the time.

The rate of inappropriate discontinuations of vancomycin during the program exceeded baseline (4.7% vs. none; P = .001), but this trend was balanced out by the overall rise in vancomycin discontinuations, the researchers said. Furthermore, providers documented vancomycin time-outs more often during the second 6 months, compared with the first (54% vs. 37%; P = .005). The increase in vancomycin discontinuations also was durable (about 63% throughout the two 6-month periods), and inappropriate continuations remained stable at about 4.5%.

“Piperacillin-tazobactam did not see any change in discontinuations between the two study periods,” said the researchers. The discontinuation rate was about 62% before and during the program. Clinicians performed time-outs about half the time, and inappropriately continued the antibiotics beyond day 5 in 10% of cases, compared with 2% before the program started (P = .02). Clinicians continued performing piperacillin-tazobactam time-outs at the same rate in the second 6 months of the program as during the beginning, and rates of discontinuation and inappropriate continuations also remained similar.

The investigators reported these results at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

CDC funded the research with a grant to the University of Utah. The researchers reported no conflicts of interest.

SAN DIEGO – A “time-out” to review antibiotic therapy 72-96 hours into treatment increased appropriate discontinuations of vancomycin by 31%, researchers said at an annual scientific meeting on infectious diseases.

The practice fit into hospital work flow, streamlined other antibiotic stewardship practices, and respected provider autonomy, said Dr. Christopher Graber of VA Greater Los Angeles Healthcare System and the University of California, Los Angeles. It also was durable, persisting into the second 6 months of the program even though active research support had ended, he and his associates said.

©TongRo Images/thinkstock.com

The Centers for Disease Control and Prevention endorses the antibiotic time-out as a way to encourage providers to switch from empirical treatment with broad-spectrum antibiotics to a more tailored plan after culture and other laboratory results become available. The Veterans Affairs teaching hospital in greater Los Angeles created a self-directed time-out program to encourage reconsideration of broad-spectrum therapy with vancomycin and piperacillin-tazobactam after the first 3 days of empirical treatment. The program included an antimicrobial “dashboard” report, an electronic template to document time-outs, and a marketing program consisting of educational documents, lectures, “clinical champions,” and reminder notes and fliers posted near computers.

To evaluate early and late responses to the program, Dr. Graber and his associates tracked discontinuations of vancomycin and piperacillin-tazobactam, as well as decisions to continue these antibiotics through day 5 when doing so contradicted guidelines. Among 276 vancomycin episodes during the program, clinicians discontinued 175 (63%) – significantly more than before the program started (96 of 199; 48%; P = .001). They documented vancomycin time-outs 46% of the time, continued patients on vancomycin through day 5 without a time-out in 7.6% of cases, and allowed vancomycin to expire without a time-out 46% of the time.

The rate of inappropriate discontinuations of vancomycin during the program exceeded baseline (4.7% vs. none; P = .001), but this trend was balanced out by the overall rise in vancomycin discontinuations, the researchers said. Furthermore, providers documented vancomycin time-outs more often during the second 6 months, compared with the first (54% vs. 37%; P = .005). The increase in vancomycin discontinuations also was durable (about 63% throughout the two 6-month periods), and inappropriate continuations remained stable at about 4.5%.

“Piperacillin-tazobactam did not see any change in discontinuations between the two study periods,” said the researchers. The discontinuation rate was about 62% before and during the program. Clinicians performed time-outs about half the time, and inappropriately continued the antibiotics beyond day 5 in 10% of cases, compared with 2% before the program started (P = .02). Clinicians continued performing piperacillin-tazobactam time-outs at the same rate in the second 6 months of the program as during the beginning, and rates of discontinuation and inappropriate continuations also remained similar.

The investigators reported these results at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

CDC funded the research with a grant to the University of Utah. The researchers reported no conflicts of interest.