Study finds antibiotic-rich wastewater affects bacterial diversity

Originally published by CIDRAP News on Nov 4.

A study of a plant that treats wastewater from bulk drug production facilities in India suggests that the high levels of antibiotics present in the water affect microbial diversity and may play a role in spreading antimicrobial resistance.

The study, published yesterday in PLOS One, analyzed wastewater treated at a plant in Hyderabad, India, that receives high levels of fluoroquinolones and uses active sludge technology to break down incoming chemicals. The analysis found a high level of drug-resistant bacteria in the water and low overall bacterial diversity, despite the regular addition of human sewage to uphold microbial activity. The overall bacterial diversity in samples taken from the plant's aeration tanks was considerably lower than corresponding samples from seven other wastewater treatment plants.

The authors of the study conclude that the high levels of antibiotics present in the waste modulates the microbial communities, which not only affects the efficiency of the waste treatment process but can also promote resistance.
Nov 3 PLOS One study

Study finds high prevalence of drug-resistant TB in West Africa

Originally published by CIDRAP News on Nov 3.

The prevalence of multidrug-resistant tuberculosis (MDR-TB) in West Africa is much higher than previously thought, according to a study published Tuesday in BMC Medicine.

In the study, investigators from the West African Network of Excellence for TB, AIDS, and Malaria (WANETAM) set out to determine the distribution of MDR-TB in eight West African countries. Although populations in the region are highly susceptible to infectious diseases, the lack of adequate laboratories means data on drug-resistant TB is scarce. To estimate the prevalence of MDR-TB, the investigators collected isolates from new and retreatment patients and tested them for susceptibility to first- and second-line drugs.

In total, the investigators found that 39% of the 974 isolates tested were resistant to one or more front-line drugs, while 22% were considered multi-drug resistant. The prevalence of MDR-TB was 6% in new patients and 35% in retreatment patients, much higher than the World Health Organization's (WHO's) previous estimates of 2% and 17%.

The highest prevalence for MDR-TB was found in retreatment patients in Mali (59%) and two Nigerian sites—Ibadan (39%) and Lagos (66%). Although no extensively drug resistant (XDR) TB isolates were identified, 21% of the isolates were identified as pre-XDR, which means they will develop extensive drug resistance if no effective interventions are instituted.

The authors of the study say their findings suggest MDR-TB could become a serious public health problem in West Africa if control measures aren’t taken.

"We recommend that efforts be put in place for containment of a potential West African TB epidemic at the earliest possible stage," lead investigator Martin Antonio, PhD, said in a news release from BioMed Central, the publisher of the journal. "This is especially important as West Africa with its 245 million inhabitants is one of the poorest regions globally, whose fragile health systems can easily be overwhelmed by infectious disease epidemics, as seen in the recent Ebola outbreak."

Antonio and his colleagues also say their findings should prompt the implementation of continuous surveillance of all retreatment patients in participating countries.
Nov 2 BMC Medicine study
Nov 2 BioMed Central news release

Increased risk of sepsis linked to antibiotic exposure

Originally published by CIDRAP News on Nov 3.

A study presented at IDWeek 2016 suggests that an increased risk of sepsis following infection-related hospitalization could be linked to antibiotics that disrupt the microbiome.

The study, conducted by researchers with the Centers for Disease Control and Prevention (CDC), used patient records from a hospital drug database to determine how many patients had been re-admitted for sepsis within 90 days of discharge, and how many of those patients had received antibiotics during their initial stay.

In particular, they were looking for antibiotics with a high risk for microbiome disruption, such as third- and fourth-generation cephalosporins, fluoroquinolones, carbapenems, lincosamides, beta-lactam/beta-lactamase inhibitor combinations, and oral vancomycin. Animal studies have shown that giving animals antibiotics that disrupt the balance of good and bad bacteria in the microbiome can have an increased risk of sepsis.

Overall, the data showed that among more than 9 million patients who visited 473 hospitals between 2006 and 2010, 0.6% had sepsis during readmission within 90 days of discharge. When the researchers compared patients who had received antibiotics during the index visit to those who had received no antibiotics, they found that the patients with antibiotic exposure were 50% more likely to be hospitalized with sepsis, and nearly 80% more likely if they had received high-risk antibiotics. Patients who received longer courses of treatment also had a higher risk of sepsis.

"The observed increased risk for subsequent sepsis following receipt of antibiotics that significantly disrupt the microbiome…supports the idea that microbiome disruption confers increased risk for subsequent severe infections, " the study authors concluded.

"It's one more call to really focus our efforts on using antibiotics only when we need them, because the adverse effects are really big," Arjun Srinivasan, MD, told reporters. Srinivasan, who directs CDC programs aimed at preventing healthcare-associated infections, was not involved in the study.
Oct 27 IDWeek abstract

AAP updates guidelines on fluoroquinolone use in children

Originally published by CIDRAP News on Nov 1.

The American Academy of Pediatrics (AAP) yesterday released updated guidelines on the use of fluoroquinolones in children. The clinical report, published in Pediatrics by the AAP Committee on Infectious Diseases, highlights the indications, adverse event profile, and practical prescribing information for pediatricians and includes new data available since the report was last published in 2011.

The core message of the updated AAP guidelines remains unchanged from 2011. It advises that fluoroquinolones are broad-spectrum agents that should not be used as first-line systemic therapy in children and should be considered selectively for children or adolescents only for specific clinical situations. Those situations include when an infection is caused by a multidrug-resistant pathogen for which there is no safe and effective alternative, or when oral therapy is preferable to parenteral therapy.

Currently, fluoroquinolones have limited Food and Drug Administration (FDA) approval for systemic use in children. Ciprofloxacin is FDA-approved for inhalation anthrax, plague, complicated urinary tract infections, and pyelonephritis in children. Levofloxacin is approved for inhalation anthrax and plague.

But the new guidelines also indicate that levofloxacin can be considered in lower respiratory tract infections when a child has a severe allergy to penicillin and in upper respiratory tract infections when the pathogens shows high resistance to penicillin. Ciprofloxacin is suggested as a viable alternative for gastrointestinal infections due to Salmonella or Shigella, but only when alternative antibiotics are unavailable. In addition, the report notes that several topical fluoroquinolones are approved for treatment of bacterial conjunctivitis and otitis externa.

"In the case of fluoroquinolones, as is appropriate with all antimicrobial agents, prescribing clinicians should verbally review common, anticipated, potential adverse events, such as rash, diarrhea, and potential musculoskeletal or neurologic events, and indicate why a fluoroquinolone is the most appropriate antibiotic agent for a child's infection," the authors conclude.
Oct 31 AAP clinical report

Study finds colistin resistance in bacteria exposed to common disinfectant

Originally published by CIDRAP News on Nov 1.

A study published yesterday in Antimicrobial Agents and Chemotherapy has found that Klebsiella pneumoniae bacteria exposed to an antiseptic commonly used in homes and healthcare settings can become resistant to the last-resort antibiotic colistin.

The study, conducted in England, builds on previous research showing that K pneumoniae strains are able to adapt to increasing concentrations of chlorhexidine, an antiseptic that is found in mouthwash, wound dressings, and solutions for skin antisepsis. The purpose was to determine whether adaptation to chlorhexidine can cause cross resistance to other antibiotics, and to determine the underlying mechanisms of resistance. To figure that out, investigators selected specific strains of K pneumoniae typically found in clinical settings and exposed them to increasing concentrations of chlorhexidine.

The investigators found that in five of six K pneumoniae strains, adaptation to chlorhexidine also led to resistance to colistin without significant loss of fitness or virulence. In addition, they found that adaptation to chlorhexidine and resistance to colistin appeared to be linked to specific gene mutations.

The findings are significant for several reasons. One is that chlorhexidine is a critical part of current infection control practices, especially the treatment of wounds. "The development of increased resistance to this compound has potential implications for our ability to prevent infections during routine and emergency surgery, and during admission to hospitals," study co-author J. Mark Sutton, PhD, of Public Health England, said in an American Society for Microbiology (ASM) news release.

Furthermore, the findings indicate another source of selection pressure for colistin, a powerful antibiotic that is becoming more necessary with the growth of multidrug-resistant organisms. The emergence of colistin resistance in Klebsiella—which is already increasingly resistant to several antibiotic classes, including carbapenems—could present healthcare providers with life-threatening infections that are extremely hard to treat.

In addition, there is concern that specific selective pressures from antiseptics could create similar mutations that confer increased resistance to antibiotics in different species of bacteria.
Oct 31 Antimicrob Agents Chemother study
Oct 31 ASM news release

New AHRQ guide to help nursing homes implement stewardship programs

Originally published by CIDRAP News on Oct 31.

The Agency for Healthcare Research and Quality has released a new online guide to help nursing homes address the challenge of creating and implementing an antimicrobial stewardship program (ASP).

The AHRQ Antimicrobial Stewardship Guide comes on the heels of a new rule finalized by the Centers for Medicare and Medicaid Services (CMS) in early October that requires nursing homes and other long-term care facilities to have an antibiotic stewardship program that includes antibiotic use protocols and a system to monitor antibiotic use. According to the CDC, an estimated 70% of nursing home residents receive one or more courses of antibiotics during a year, and studies have indicated that anywhere from 40% to 70% of those antibiotics prescriptions are inappropriate.

Among the challenges facing nursing homes in creating and implementing an ASP are a lack of financial resources, antibiotic stewardship expertise, and diagnostic and support services. In addition, medical care at nursing homes is often poorly coordinated.

The guide, which was pilot-tested in nine nursing homes, provides several toolkits to help nursing homes optimize their use of antibiotics. The toolkits offer guidance on how to implement and sustain an ASP, how to determine when antibiotics are necessary, how to choose the right antibiotic for treating an infection, and how to educate residents and family members about antibiotics.

"We're committed to ASPs because they're essential to our broad national effort to maintain the effectiveness and safety of the nation's antibiotics," writes James Cleeman, MD, director of AHRQ's division of healthcare-associated infections, in a blog post.
AHRQ Nursing Home Antimicrobial Stewardship Guide
Oct 27 AHRQ Views blog post


Study examines types of stewardship at small community hospitals

Originally published by CIDRAP News on Oct 31.

A study presented at IDWeek 2016 found that higher-level antibiotic stewardship programs (ASPs) resulted in greater reduction in antibiotic use in small community hospitals.

The purpose of the study, which was the featured oral abstract of the Society for Healthcare Epidemiology of America, was to compare the impact of three different types of ASP in a network of small community hospitals operated by Utah-based Intermountain Healthcare. Small community hospitals account for nearly 75% of all US hospitals, but only about 22% have an ASP.

In the cluster-randomized control trial, investigators randomly assigned the 15 small community hospitals to one of the three ASP models: Five hospitals were assigned to program 1, a reference group that had a minimal ASP program; five hospitals were assigned to program 2, which featured stewardship education, a limited prospective audit and feedback program, and antibiotic restrictions that were controlled by local pharmacy staff; and five hospitals were in program 3, which featured an expanded prospective audit and feedback program, antibiotic restrictions overseen by both a pharmacist and an infectious disease (ID) physician, and ID physician review of all culture results.

The primary outcomes were total antibiotic use and broad-spectrum antibiotic use. Secondary outcomes included mortality rates, readmission rates, and incidence of Clostridium difficile.

In the final analysis, the investigators found that the small community hospitals in program 3 reduced total antibiotic use by 17% compared to program 1, but the hospitals in program 2 showed no statistically significant reduction compared to those in program 1. Both program 2 and 3 hospitals reduced broad spectrum use by 31% and 27%, respectively, compared to hospitals in program 1. An analysis of secondary outcomes showed no difference in mortality or patient readmission rates among the different programs, but programs 2 and 3 saw 45% fewer cases of C difficile compared to program 1.

"Stewardship programs are now known to be feasible in small community hospitals, and they can reduce antibiotic use if the appropriate resources are out there," lead author Edward Stenehjem, MD, MSc, told the audience.
Oct 28 Stewardship in community hospitals abstract

ID consultations can save lives, single-center study finds

Originally published by CIDRAP News on Oct 31.

Consulting an infectious diseases (ID) specialist can reduce mortality in patients with multi-drug resistant Gram-negative infections, according to a study presented at IDWeek 2016.

The single-center, retrospective, case-cohort study included 205 patients at SUNY Downstate Medical Center in Brooklyn, N.Y., who were being treated for bacteremias and urinary tract infections. Of the 205 patients, 40 patients received early ID consultation (within 48 hours), 25 received late ID consultation (after 48 hours), and 140 received no consultation. The two most common organisms isolated were extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae.

Overall, 60 patients died during the study. Forty-five of the deaths occurred in patients who received no ID consult, and 15 occurred among those patients who received late ID consultation. None of the patients who received early ID consultation died. In addition, mean time to defervescence (fever reduction) was estimated at 1.8 days for early consult, 5.3 days for late consult, and 4.9 days for no consult.

The study adds to research showing that when an ID specialist is involved in a patient's care, patients are correctly diagnosed more often, have fewer complications, and have better outcomes.
Oct 29 ID consultations abstract