ASP Scan (Weekly) for May 19, 2017

Allergy testing and stewardship
Antibiotic resistance in cattle
Veterinary antibiotic use
Candida auris cases rise
Antibiotic use in South Korea
Stewardship in a small hospital
Stewardship and virology testing
MDR Acinetobacter outbreak
Antibiotic-free grocery chicken
Access to older antibiotics

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Antibiotic allergy testing improves appropriate prescribing, study finds

Incorporating antibiotic allergy testing (AAT) into an antimicrobial stewardship (AMS) program can improve antibiotic usage and appropriateness, according to a study yesterday in Clinical Infectious Diseases.

In the multicenter prospective cohort study, researchers evaluated the effects of a multidisciplinary AAT-AMS implemented at two large Australian hospitals over a 14-month period beginning May 2015. Although they are often inaccurate, the prevalence of patient-reported antibiotic allergies (so-called antibiotic allergy labels [AALs]) has increased in recent years. Because AALs are associated with restricted and inappropriate antibiotic usage, the researcher hypothesized that an AAT-AMS could improve antibiotic use.

Study outcomes included the proportion of patients who were "de-labeled" of their AAL, the spectrum of antibiotic courses for the 12 months prior to testing and 3 months following testing, and antibiotic appropriateness.

From the 118 patients who were referred for AAT, 226 allergies were identified, with 56% harboring a penicillin AAL, 44% a cephalosporin AAL, and 30% aminopenicillin AAL. After formal AAT was performed, 94% of patients had AALs revised, with 83% having one or more AALs removed, including 83% of all patients with penicillin AALs. In the 3 months post-AAT, prescribing of more narrow-spectrum penicillins (adjusted odds ratio [aOR] 2.81), narrow-spectrum beta-lactams (aOR 3.54,), and appropriate antibiotics (aOR 12.27) was more likely than in the 12 months prior to testing, and less likely for restricted antibiotics (aOR 0.16).

"We demonstrated that AAT-AMS increased narrow-spectrum penicillin use, increased uptake of preferred therapies, and reduced restricted antibiotic use," the authors write. "To our knowledge, this is the first study to demonstrate the impact of AAT-AMS on improving the appropriateness of antibiotic prescribing."
May 18 Clin Infect Dis study


Researchers find no resistance in Enterococci from Australian cattle

Australian researchers found no resistance to antibiotics considered critically or highly important to human medicine in Enterococcus samples from cattle manure at slaughter, according to a study yesterday in PLoS One.

In this study, researchers collected fecal samples from 910 beef cattle, 210 dairy cattle, and 300 veal calves to determine the prevalence of antimicrobial resistance (AMR) among Enterococcus isolates. Enterococci are considered important targets for AMR surveillance in humans, animals, and food because they are ubiquitous, commonly isolated nosocomial pathogens that are known to rapidly acquire resistance when exposed to antimicrobials. Enterococcus faecium and Enterococcus faecalis, in particular, have become increasingly important pathogens because of their ability cause to life-threatening hospital infections.

A total of 1,296 Enterococcus isolates were collected from the cattle, and 800 isolates comprising 96 E faecalis, 120 E faecium, and 584 samples from other Enterococcus species were submitted for AMR analysis. The results showed that high levels of resistance to antibiotics that are not considered important to human medicine—flavomycin (80.2%) and lincomycin (85.4% to 94.2%)—was common. Resistance to erythromycin and tetracycline was low. None of the isolates were found to be resistant to vancomycin or ampicillin, an important finding given that ampicillin is the preferred therapy for uncomplicated enterococcal infections and that the absence of vancomycin resistance helps maintain optimal treatment options. 

While the initial tests found low levels of resistance to daptomycin and tigecycline, further testing found that minimum inhibitory concentrations (MICs) were all below clinical breakpoints, and therefore all isolates should be considered susceptible. 

"Importantly, it would appear that the production practices in Australian cattle populations are not generating pools of resistance that are likely to result in the inability to treat human infections caused by enterococci," the authors write.
May 18 PLoS One research article


Study finds antibiotic use in Australian dogs and cats generally appropriate

In another study out of Australia, researchers report in the Journal of Veterinary Internal Medicine that antimicrobial usage by Australian veterinarians in treatment of dogs and cats is generally appropriate.

The findings are based on a survey filled out by 892 Australian veterinary practitioners in which respondents were asked about their approach to antibiotic treatment of dogs and cats for 11 different medical conditions, 2 surgical conditions, and 8 dermatological conditions. Specifically, they were asked about how often they use empirical antimicrobial therapy versus therapy based on culture and susceptibility testing, choice of antimicrobials, and duration of therapy.

The results of the survey showed that antimicrobial therapy was used in 51% of cases and guided by culture and susceptibility testing in 26% of cases, and empirical therapy was employed pending the results of culture and susceptibility testing in 24% of cases. Empirical antimicrobial therapy was more common in acute conditions (76%) than in chronic conditions (24%).

The most common antimicrobial classes used were potentiated aminopenicillins (36%), fluoroquinolones (15%), first- and second-generation cephalosporins (14%), and tetracyclines (11%). Use of antimicrobials with a high importance rating ranged from 12% to 47% in cats and 4% to 42% in dogs. Third-generation cephalosporin use was more frequent in cats than in dogs (16% vs 1.8%), while fluoroquinolone use was more frequent in dogs than in cats (18% vs 11%).

Agreement with Australasian Infectious Disease Advisory Panel guidelines was variable, ranging from 0 to 69% among conditions.

The authors conclude that while the survey results indicate that antimicrobial usage among Australian veterinarians is appropriate, the empirical use of antimicrobials of high importance for human medicine, particularly third-generation cephalosporins in cats and fluoroquinolones in cats, warrants further investigation.
May 17 J Vet Intern Med study


CDC reports count of US Candida auris infections up to 77 cases

Originally published by CIDRAP News May 18

In today's Morbidity and Mortality Weekly Report, investigators from the Centers for Disease Control and Prevention (CDC) and several state health departments say a total of 77 clinical cases of the emerging multidrug-resistant fungus Candida auris have now been reported from seven states. New York has the most reported cases with 53, followed by New Jersey (16), Illinois (4), Indiana (1), Maryland (1), Massachusetts (1), and Oklahoma (1).

C auris was originally discovered in 2009 in Japan and since then has emerged as a global health threat due to its growing resistance to all three major classes of antifungals used to treat Candida infections. The CDC estimates the mortality rate of C auris infections at approximately 60%. 

Among the 77 clinical cases, median patient age was 70 years and 55% were male, and nearly all patients had underlying health conditions and extensive exposure to healthcare facilities. The report says epidemiological connections have been found between most cases, with further investigation revealing that many of the New York and New Jersey patients had overlapping stays at interconnected long-term care facilities and acute care hospitals within a limited geographic area. The case in Massachusetts was linked to the Illinois cases, and the cases in Oklahoma and Maryland involved patients who had received healthcare outside the country. 

Antifungal susceptibility tests of the first 35 clinical isolates found that 30 (86%) were resistant to fluconazole, 15 (43%) were resistant to amphotericin B, and 1 (3%) was resistant to echinocandins. Whole-genome sequencing showed that isolates from within each state were highly related to one another and linked to isolates found in South Asia and South America, suggesting they had been introduced from outside the country and then transmitted locally.

Screening of 390 close contacts, primarily individuals who were on the same hospital ward as the infected patients, identified an additional 45 patients who were colonized with C auris (24 in New Jersey, 17 in New York, and 4 in Illinois). Environmental testing detected C auris on a variety of hospital surfaces.

To help curb the spread of the fungus, the CDC recommends using standard and contact precautions for infected and colonized patients, housing patients in private rooms, cleaning patient rooms daily with a disinfectant active against Clostridium difficile, and informing receiving healthcare facilities when an infected or colonized patient is being transferred.
May 18 MMWR Notes from the Field


Antibiotic use rises in South Korea

Originally published by CIDRAP News May 18

A review of a large health insurance claims database has found that antibiotic usage in South Korea rose by more than 17% from 2007 to 2014, researchers reported yesterday in PLoS One.

To investigate antibiotic usage in South Korea, a country known for high utilization of antibiotics and high rates of antibiotic resistance, researchers used data from the Health Insurance Review & Assessment Service, which represents nearly the entire South Korean population. Annual usage was calculated as defined daily doses per 1,000 inhabitants per day (DID). Antibiotic usage was analyzed for the entire population and for various subgroups.

Overall, the researchers found that total antibiotic usage in South Korea rose from 23.5 DID in 2007 to 27.7 DID in 2014, with inpatient use seeing a slight decrease but use among outpatients, male and female patients, and all age groups seeing an increase. Antibiotic use was highest among patients younger than age 6 in all years and rose from 47 DID in 2007 to 59.21 in 2014. DIDs of penicillins, cephalosporins, macrolides, and fluoroquinolones all increased over time.

The authors of the study say the findings could be a useful guide for designing public health intervention strategies to promote appropriate antibiotic use. 
May 17 PLoS One study


Study finds dramatic impact tied to stewardship at a small, rural hospital

Originally published by CIDRAP News May 17

Implementation of an antimicrobial stewardship program (ASP) at a rural community hospital in Georgia significantly reduced Clostridium difficile infections (CDIs), antimicrobial use, and overall drug costs, researchers reported yesterday in the American Journal of Infection Control.

Researchers from the Mayo Clinic evaluated the performance of an ASP implemented at a small Georgia hospital with no previous ASP experience and an average occupied bed census of fewer than 100. The ASP was led by an infectious disease (ID) physician, used a prospective audit and feedback strategy with a targeted list of 12 antimicrobial agents, and included an educational grand rounds lecture series and algorithms to aid the selection of empirical antibiotics for specific infectious disease syndromes.

The targeted agents were amikacin, aztreonam, cefepime, ceftaroline, daptomycin, doripenem, ertapenem, fosfomycin, imipenem, linezolid, meropenem, and tigecycline. The researchers calculated rates of C difficile infection (CDI), total targeted antimicrobial costs, and drug usage rates prior to ASP implementation (January 2013 through September 2014) and after implementation (October 2014 through December 2015).

They found that nosocomial CDI rate declined from 3.35 cases per 1,000 occupied bed days (OBDs) at the end of the fourth quarter in 2013 to 1.35 cases per 1,000 OBDs at the end of the fourth quarter in 2015. Total targeted antimicrobial costs decreased by 50%, from $16.93 per patient day in 2013 to $8.44 per patient day in 2015, and annual savings in drug costs alone were estimated at $280,000, primarily because of the decreased use of 5 of the 12 targeted antimicrobials. Use of all antimicrobial agents decreased 10%.

"Our quality initiative shows that a new ASP can result in dramatic reduction in CDI rates, drug utilization rates, and antimicrobial cost savings within 1 year despite…perceived challenges in a small rural hospital," the authors write.
May 16 Am J Infect Control study


Researchers find rapid respiratory virus testing aids stewardship

Originally published by CIDRAP News May 17

In another study in the American Journal of Infection Control yesterday, Canadian researchers found that integrating point-of-care respiratory virus testing with an ASP audit and feedback intervention was associated with a 32% reduction in antibiotic days per patient in patients with viral respiratory tract infections.

From December 2015 through April 2016, the researchers conducted a prospective audit and feedback intervention for all adult inpatients who had a positive polymerase chain reaction (PCR) finding for a respiratory virus at two acute care hospitals in Vancouver. Inclusion of patients for an ASP consult was based on two criteria: microbiology (no positive bacterial cultures) and chest imaging (absence of pneumonia). For patients who met the inclusion criteria, the ASP team reviewed the case with the treating physician to determine if antibiotics for community-acquired pneumonia were required and to assess the need for the antiviral drug oseltamivir (Tamiflu).

To assess the impact of the intervention, the researchers conducted a quasi-experimental before-and-after intervention study. The primary outcome of interest was duration of antimicrobial therapy after viral diagnosis. Secondary outcomes included intensive care unit admission, mechanical ventilation, re-prescription of antibiotics within 14 days, and readmission, mortality, and C difficile infection within 30 days.

Overall, 92 patients were included in the prospective cohort and 118 in the retrospective cohort, with 76% (70/92) of the prospective cohort and 83% (98/118) of the retrospective cohort on antibiotics at the time of PCR testing. The prospective cohort had an average of 1.3 fewer days on antibiotics than the retrospective cohort after the PCR results were reported, and within the prospective cohort, patients whose ASP recommendation was accepted versus rejected had on average 3.6 fewer days on antibiotics. ASP recommendations were accepted 77% of the time.

In addition, patients found to have a positive influenza result were more likely to start oseltamivir in the prospective cohort than the retrospective cohort (95% vs. 72%). No significant differences were identified in secondary outcomes.

"Virology testing has advanced rapidly over the last decade, but the full value of such testing may not be realized if the results do not change [clinical] management," the authors write. "Using antimicrobial stewardship as a bridge to connect virology reporting with the treating physician facilitated a reduction in duration of antibiotic treatment and optimized oseltamivir therapy."
May 16 Am J Infect Control study


Resistant Acinetobacter outbreak in long-term care facility detailed

Originally published by CIDRAP News May 17

Austrian researchers report the detection of an outbreak of two multidrug-resistant (MDR) Acinetobacter baumannii strains among patients at an Austrian long-term care facility in a study yesterday in Antimicrobial Resistance and Infection Control.

The researchers conducted the point-prevalence study in August 2015, taking inguinal and perianal swabs from 38 patients at two wards caring for patients with disorders of consciousness and screening them for asymptomatic colonization by MDR gram-negative bacteria. Microbiological sampling was repeated 6 months later.

In the initial survey, 50% of the patients (19/38) were found to harbor MDR gram-negative isolates, with 13 found to be colonized with A baumannii isolates that were resistant to three antimicrobial classes but susceptible to carbapenems. Five other patients were found to be colonized with A baumannii that was not characterized as MDR. Of the 18 patients initially colonized with any A baumannii isolate, 10 were still colonized after 6 months.

All but one of the MDR A baumannii isolates were found in patients from ward 2. In an attempt to isolate a source of the bacteria, swabs were taken from hospital items and surfaces in ward 2, and investigators found A baumannii isolates on a patient elevator into a bathtub and on a chair for visitors in a patient room. PCR testing indicated the A baumannii isolates belonged to two clusters (A and B), and that the isolate from the chair was identical to 15 patient isolates and was connected to cluster A, which was the larger of the two.

The authors of the study suggest that since the isolate on the chair was identical to 15 of the patient isolates, and the colonized patients had been at the ward longer before the study than the non-colonized patients, there is a good chance that cross-transmission between patients by staff had taken place.

In response to the outbreak, the facility has strengthened standard hygiene precautions and infection control practices and will screen all patients on both wards for MDR bacteria twice a year.
May 16 Antimicrob Resist Infect Control study


Grocery chains get poor marks for antibiotics policies

Originally published by CIDRAP News May 16

America's leading grocery chains are failing to address overuse of antibiotics in chicken, according to a report today from the Natural Resources Defense Council (NRDC).

The report evaluates and grades the five largest grocery retailers in North America—Costco, Publix, Walmart, Albertsons/Safeway, and Kroger—on their offerings of chicken brands from producers with responsible antibiotics practices and their public commitment to appropriate antibiotic use in food animals. In addition, it examines store signage and informational material directing consumers to chicken raised without antibiotics or from producers who've committed to phasing the drugs out.

The five chains each averaged a "D" grade. While all five offered at least one brand of chicken reflective of responsible antibiotic use practices, and some offered several brands, the report found that none of the chains had made a public commitment to eliminating routine use of antibiotics in their chicken supply chains, few had signage to direct consumers to antibiotic-free or responsible-use options, and most antibiotic-use claims lacked third-party verification. Walmart had the largest proportion of chicken brand choices sourced from producers who've committed to eliminating antibiotics in their chicken supply.

In the last few years, large chicken producers like Perdue and Tyson Farms have committed to phasing out the routine use of medically important antibiotics in their chickens, and several fast-food chains have pledged to purchase chicken raised without antibiotics. Now, the report adds, grocery retailers need to step up and meet consumer demand by promoting responsible use of antibiotics in their supply chains.

"In the absence of action at the federal level, consumers have been driving the move toward meat raised with responsible antibiotics use," NRDC staff scientist Carmen Cordova, PhD, said in a news release from the organization. "The fast food industry has been leading the way—but people want to be able to eat better meat [at] home, too. Our report shows that grocery stores have a lot of catching up to do."

The report recommends that grocery chains develop responsible antibiotic use policies and communicate them to consumers, improve signage, and advocate for third-party verification.
May 16 NRDC report
May 16 NRDC news release


Market forces limiting access to older antibiotics, experts say

Originally published by CIDRAP News May 15

Older antibiotics that are still effective are not widely marketed or universally available because they are not seen as profitable, according to a new commentary by European infectious disease experts in Clinical Microbiology and Infection, and the authors say limited access to these drugs is a threat to antibiotic stewardship.

According to the article, recent research has shown that 22 of 33 old but still useful antibiotics—including drugs like penicillin, nitrofurantoin, and fosfomycin—were marketed in fewer than 20 countries in 2011 mainly because of economics, with high registration costs and small market size leading to a perceived lack of return on investment for pharmaceutical companies. Meanwhile, another study showed that, in the United States, 148 antibiotics were in short supply from 2001 to 2013, with 22% of drugs experiencing multiple shortages.

The authors note that child-friendly formulations of old antibiotics also have limited availability. Some suspension liquids—considered superior in terms of absorption to crushed-up tablets—have been withdrawn from the market, while some parenterally administered antibiotics are not appropriately sized for administration of neonatal doses.

The result of this limited access to older antibiotics, the authors argue, is that physicians may be forced to use less optimal, broad-spectrum antibiotics that can produce negative patient outcomes because they are less effective or more toxic. In addition, use of broader-spectrum agents may encourage the emergence of resistance.

To rectify the situation, the authors call on international groups like the World Health Organization (WHO) and the European Commission to take the lead in developing a strategy to ensure the sustainable production, registration, and availability of older antibiotics. Suggested steps include defining a group of antibiotics for which there should be universal access and establishing a mechanism to monitor global availability and shortages.

"Significantly improved global access to key older antibiotics in their optimal formulation, quality and cost could result from a coordinated set of actions that several countries and WHO might be willing to support or engage in," the authors write. 
May 14 Clin Microbiol Infect article

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