ASP Scan (Weekly) for Mar 30, 2018

Statewide hospital stewardship
New class of synthetic antibiotics
Candida auris in Europe
Experimental C diff drug
Urine culture and prescribing
MRSA, VRE contact precautions
Resistant Acinetobacter in SE Asia
Infection prevention and antibiotic stewardship
Cornerstones of stewardship
Resistant Acinetobacter in kids
C diff prediction tool
Perceived AMR risk in Germany

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

Statewide Colorado stewardship collaborative shows promise in UTI Rx

Today in Clinical Infectious Diseases Colorado researchers report declining fluoroquinolone use after initiating a statewide stewardship collaborative to improve the diagnosis and treatment of inpatient urinary tract infections (UTIs) and skin and other soft-tissue infections (SSTIs).

Twenty-six Colorado hospitals, including nine critical access hospitals, participated in the collaborative. Collaborative outcomes were: (1) proportion of UTI diagnoses meeting criteria for symptomatic UTI, (2) exposure to fluoroquinolones (UTI only), (3) duration of therapy (UTI and SSTI), and (4) exposure to antibiotics with broad gram-negative activity (SSTI only). The investigators compared outcomes between pre-intervention and intervention periods overall and by hospital.

The team found that the proportion of diagnosed UTIs meeting symptomatic UTI criteria and the median duration of UTI therapy were unchanged, but fluoroquinolone use dropped from 49% to 41%. For SSTIs, exposure to antibiotics with broad gram-negative activity declined from 61% to 53% and the median duration of therapy dropped from 11 to 10 days, but neither change was statistically significant. Only the decline in fluoroquinolone use was significant.

The authors concluded, "Performance improvement was observed for several outcomes overall but varied substantially by hospital."
Mar 30 Clin Infect Dis abstract


Experts report new class of synthetic antibiotics that kills MRSA in mice

US scientists have identified two synthetic retinoids that represent a new class of antibiotics and can kill both growing and persistent methicillin-resistant Staphylococcus aureus (MRSA) in mice, according to a new study in Nature.

The research team developed novel ways to screen 82,000 synthetic compounds to identify potential antibiotics that would not be toxic to humans. Of 185 compounds that decreased the ability of MRSA to kill laboratory roundworms, the scientists selected 2 synthetic retinoids, called CD437 and CD1530, as the best candidates. The retinoids impair bacterial membranes.

"The molecule weakens the cell membranes of bacteria, but human cells also have membranes," said study coauthor Bill Wuest, PhD, of Emory University, in a Lifespan news release. "We found a way to tweak the molecule so that it now selectively targets bacteria."

The researchers also combined CD437 with gentamicin, which was also effective against MRSA in the mice. The bacteria did not develop any noteworthy resistance to CD437 even after 100 days of serial passaging.

Further studies will have to ensure such compounds are not toxic to people. "Despite the potential advantages of membrane-active antimicrobials such as the retinoids described here—including fast killing, low probability of developing resistance, and anti-persister activity—the major obstacle for developing retinoids as therapeutics is their potential cytotoxicity," the authors wrote.

They concluded, "With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure."
Mar 28 Nature study
Mar 27 Lifespan news release


Candida auris cases in Europe on the rise, with 620 since 2013

Originally published by CIDRAP News Mar 29

From 2013 through 2017 European officials recorded 620 cases of Candida auris, mostly from four large outbreaks, and 110 of them (17.7%) involved bloodstream infections, according to a report today in Eurosurveillance.

Almost all the cases were in Spain (388) and the United Kingdom (221). More than 75% (466) cases were reported as colonizations, with no apparent illness. In addition to the 110 bloodstream infections, officials documented 40 other infections, while 4 cases were of unknown status. In addition, the incidence rose in recent years, with 23 cases reported in 2015, 290 in 2016, and 303 in 2017.

The authors of the report write, "The increasing number of sporadic cases, mostly invasive infections, compared with the ECDC rapid risk assessment in 2016 confirms that introduction of C. auris into hospitals in Europe is occurring repeatedly, each time with the potential risk for further transmission and healthcare-associated outbreaks. The reason why some cases of C. auris have caused large outbreaks while other cases were sporadic with no apparent further transmission remains unclear."

The study also noted gaps in European surveillance. The experts report that preparedness and response steps for C auris have been taken in only 20 of the 30 European Union nations. The most common measures were dissemination of laboratory alerts (18 countries), offers for reference identification and antifungal susceptibility testing to hospitals (13), and clinical alerts (10).
Mar 29 Eurosurveillance report


Experimental drug shown effective against recurrent C difficile

Originally published by CIDRAP News Mar 29

A phase 2 trial shows that one dose— but not two — of an experimental drug to prevent recurrent Clostridium difficile infection was more effective than a placebo, according to researchers who published their study today in Clinical Infectious Diseases.

The investigators included in the study 127 C difficile patients from 21 centers in the United States and Canada. Of those, 41 received two doses of the drug, called RBX2660; 44 received two doses of a placebo; and 42 received one dose or RBX2660 and one dose of the placebo.

Efficacy for the one-dose group was 67%, compared with 61% in the two-dose group and 45% in the placebo-only group, but the difference reached statistical significance only for the one-dose group.

Of the 54 patients whose treatment did not succeed in the first (blinded) phase, 5 elected to receive one additional dose of RBX2660 and 49 agreed to two additional doses. For this non-blinded (open-label) portion of the study, treatment success rates were 80% (4/5) and 78% (38/49), respectively. That brought the overall success rate for participants who received at least one dose of RBX2660 in the blinded or open-label phases to 89%.

The authors conclude, "These data provide important insights for a larger Phase 3 trial and continued clinical development of RBX2660."
Mar 29 Clin Infect Dis study


Urine culture on hospital admission tied to longer antibiotic therapy

Originally published by CIDRAP News Mar 28

Texas researchers who analyzed data from 230 US hospitals discovered that patients with a urine culture taken on the day of hospital admission receive more days of antibiotics and have a longer hospital stay than do patients who do not have a urine culture, according to their study yesterday in Infection Control and Hospital Epidemiology (ICHE).

The team looked at data on 88,481 adults hospitalized from 2009 through 2014. Of those, 41,070 had a culture taken on day 1 of hospitalization and 47,411 did not. Guidelines recommend generally avoiding antibiotic therapy for a positive urine culture if the patient has no symptoms.

Patients who had the early urine culture received an additional 36,607 aggregate days of inpatient antibiotic treatment, or 0.9 extra days per patient. They also had a 2.1% increase in their length of hospital stay, resulting in an additional 6,071 days of hospital care.

The authors conclude, "Targeted interventions may reduce the potential harms associated with low-yield urine cultures on day 1."
Mar 27 ICHE abstract on urine culture


Stopping MRSA, VRE contact precautions shown effective

Originally published by CIDRAP News Mar 28

Discontinuing contact precautions for patients infected by or colonized with MRSA or vancomycin-resistant Enterococcus (VRE), when combined with other infection prevention steps, was not associated with an increased incidence of device-associated MRSA and VRE infections, and the approach may represent a safe and cost-effective strategy, according to a separate ICHE study yesterday.

Virginia Commonwealth University scientists used an interrupted time series design to evaluate the effect of seven horizontal infection prevention interventions across intensive care units (ICUs) and hospital wards at their 865-bed medical center.

They noted that the rate of healthcare-associated infections (HAIs) declined (albeit not significantly) during the study period, from 2011 to 2016. Infection rates for MRSA and VRE decreased by 1.31 (P = .76) and 6.25 (P = .21) per 100,000 patient-days, respectively. In addition, the infection rate for either pathogen decreased by 2.44 per 10,000 patient-days (P = .23) for device-associated HAIs following discontinuation of contact precautions.

"This approach," the authors conclude, "may represent a safe and cost-effective strategy for managing these patients."
Mar 27 ICHE abstract on contact precautions


Review finds high prevalence of drug-resistant Acinetobacter in SE Asia

Originally published by CIDRAP News Mar 28

A new meta-analysis of studies that focused on multidrug-resistant (MDR) HAIs in ICUs in Southeast Asia found a high prevalence of MDR Acinetobacter baumannii, researchers report in a third ICHE study.

The investigators identified 41 studies that among them included data on 22,876 ICU patients in seven Southeast Asian countries. They report up to a 64.9% cumulative incidence of carbapenem-resistant A baumannii and up to a 58.5% incidence of MDR A baumannii among all A baumanniiinfections, rates that are much higher than reported in other regions. The experts also found a 23% higher death rate in MDR A baumannii, a 72% higher rate for extensively drug-resistant A baumannii, and an 82% higher rate among those with the pan-drug–resistant form of the pathogen.

They note, however, "a paucity of published data on additional length of stay and costs attributable to MDROs [MDR organisms]."

The authors conclude, "This review highlights the challenges in addressing MDROs in Southeast Asia, where HAIs caused by MDR gram-negative bacteria are abundant and have a strong impact on society."
Mar 27 ICHE Southeast Asia abstract


Position paper stresses infection control, antibiotic stewardship synergy

Originally published by CIDRAP News Mar 27

In an update to a 2012 document, a position paper from three professional medical groups emphasized that infection prevention and control (IPC) and antibiotic stewardship programs are inextricably linked. The Association for Professional in Infection Control (APIC), the Society for Healthcare Epidemiology of America (SHEA), and the Society of Infectious Disease Pharmacists (SIDP) published their update yesterday in two association journals, the American Journal of Infection Control and Infection Control and Hospital Epidemiology.

The new version of the position paper highlights the synergy of IPC and antibiotic stewardship programs, including the important of a well-functioning IPC program as a central component of a successful antibiotic stewardship strategy, according to a SHEA press release.

Mary Lou Manning, PhD, lead author of the position statement, said the vital work of both programs cannot be done independently. "They require interdependent and coordinated action across multiple and overlapping disciplines and clinical settings to achieve the larger purpose of keeping patients safe from infection and ensuring that effective antibiotic therapy is available for future generations," she said in the release. The groups note that multidrug-resistant organisms cause a significant share of healthcare-associated infections and are more difficult to great because of fewer and sometimes no antibiotics that can treat the illnesses.

Aligning the two programs makes them more effective than antibiotic stewardship measures alone, affirming that a well-functioning IPC program is key to antibiotic stewardship strategy success, the authors wrote.

The groups acknowledge that successful antibiotic stewardship programs require significant investments from healthcare facilities. Changing practices, prescribing patterns, and other medical team behaviors will take time but is critical for stemming the rise of antimicrobial-resistant and Clostridium difficile infections, the groups wrote. They also urged healthcare leaders to prioritize IPC and antibiotic stewardship as part of wider patient safety initiatives, adding that IPC and stewardship leaders should collaborate on their communications with hospital executive teams.
Mar 26 Infect Control Hosp Epidemiol position paper
Mar 26 SHEA
 press release


Survey finds audit and feedback key to antibiotic stewardship success

Originally published by CIDRAP News Mar 26

A survey of 244 members of three infectious diseases societies reveals that the most common approached to antimicrobial stewardship programs (ASPs) are antibiotic reviews with prospective audit and feedback (PAF), prior authorization for select antibiotics, and guideline development, according to a study today in Clinical Infectious Diseases.

The survey also revealed a staff-person-to-hospital-bed ratio to guide ASP resource allocation.

In 2016, IDSA, SHEA, and Pediatric Infectious Diseases Society (PIDS) convened an expert group of 13 physicians to identify resources for helping infectious disease specialists initiate and sustain ASPs. The group created a 73-question electronic survey, and 244 members of the three groups responded. Respondents had MD, MBBS, DO, or PharmD degrees, with 189 being physicians and 52 responding as pharmacists.

Respondents' ASPs were typically led by physicians (56%) or co-led by physicians and pharmacists (36%), but 19 (8%) lacked accountable physician leaders. Of the programs, 84% included antibiotic reviews with PAF, and 81% involved prior authorization. Of the 179 ASPs (73%) that included local antibiotic guidelines for common conditions, the most popular were for pneumonia (92%), surgical prophylaxis (86%), urinary tract infection (68%), and skin and other soft-tissue infection (66%).

All but one program included antibiograms, and 125 (51%) performed cascade reporting of antibiotic susceptibilities.

Through feedback on full-time equivalent (FTE) physician and pharmacist staffers devoted to ASPs, the expert group was able to calculate that each 0.50 FTE was tied to a 58% increase in the odds of a program being effective. They also charted potential mediators of ASP effectiveness, with PAF topping the list. The experts determined that, if a program had all the leading components plus technology add-ons, it had a 93% probability of demonstrable effectiveness with a combined 1.1 FTE of support, but the probability rose to 98% for 3.5 ASP FTE.

The authors concluded, "Prospective audit and feedback should be the cornerstone of stewardship programs, and both physician leadership and pharmacists with expertise in stewardship are crucial for success."
Mar 26 Clin Infect Dis study


Study tracks increase in antibiotic-resistant Acinetobacter in US kids

Originally published by CIDRAP News Mar 26

The prevalence of antibiotic-resistant Acinetobacter baumannii in US kids rose markedly from 1999 to 2012, but steadily decreased after its peak in 2008,US researchers reported in the Journal of the Pediatric Infectious Diseases Society.

Investigators from Rush University Medical Center in Chicago and the Center for Disease Dynamics, Economics & Policy (CDDEP) in Washington, D.C., analyzed antimicrobial susceptibility data from The Surveillance Network to phenotypically identify antibiotic resistance in A baumannii isolates in children from January 1999 to July 2012.

They found that the crude proportion of cephalosporin-resistant (CephR) A baumannii increased from 13.2% in 1999 to 23.4% in 2012, with a peak of 32.5% in 2008. The proportion of carbapenem-resistant (CR) A baumannii, meanwhile, increased from 0.6% in 1999 to 6.1% in 2012, with a peak of 12.7% in 2008. From 1999 to 2012, the proportion of CephR and CR A baumannii increased each year by 3% and 8%, respectively. After 2008, though, the researchers observed a significant decrease in the trend, but resistance remained higher than in 1999.

The group concluded, "There is a need for ongoing surveillance of A baumannii infections and continued assessment of effective prevention strategies in vulnerable populations."
Mar 22 J Pediatr Infect Dis Soc study


New tool predicts risk of C diff infections early

Originally published by CIDRAP News Mar 26

A new modeling tool could help institutions predict which patients are most likely at risk for C difficile infections, one of the most common and dangerous healthcare-associated infections.

Researchers at the University of Michigan, Massachusetts General Hospital, Massachusetts institute of Technology published their preliminary study on the tool in Infection Control and Hospital Epidemiology today. Unlike previous modeling tools, this approach takes a hospital-specific approach to train the prediction model to individual healthcare institutions. The model generates daily risk scores for each patient at a hospital based on electronic health records, admission records, and medical history.

"When data are simply pooled into a one-size-fits-all model, institutional differences in patient populations, hospital layouts, testing and treatment protocols, or even in the way staff interact with the HER [electronic health record] can lead to differences in the underlying data distributions and ultimately to poor performance of such a model," said Jenna Wiens, PhD, at the University of Michigan, in a Massachusetts General Hospital news release. "To mitigate these issues, we take a hospital-specific approach, training a model tailored to each institution."

To test the model, the researchers retroactively applied it to electronic records collected from almost 257,000 admissions to theUniversity of Michigan Hospitals and Massachusetts General. On average, for half of patients who had C difficile infections, the model predicted the infections 5 days earlier than traditional diagnostics.The investigators have made their model freely available.

C difficile, which is resistant to a growing number of antibiotics, sickens nearly 500,000 Americans and is associated with 15,000 to 30,000 deaths annually. Early treatment and intervention can help reduce healthcare-associated costs, the researchers said. 
Mar 26 Infect Control Hosp Epidemiol study
Mar 26 Massachusetts General news release


Different groups estimate risk of antimicrobial resistance in Germany

Originally published by CIDRAP News Mar 26

A new study took survey of the antibiotic resistance (ABR) landscape in Germany, by questioning general practitioners (GPs), hospitalists, veterinarians, pig farmers, and members of the general public on their perceptions of the topic. The study was published in the Journal of Antimicrobial Chemotherapy.

A total of 1789 participants (340 GPs, 170 hospital physicians, 215 pig farmers, 60 veterinarians and 1004 members of the public) participated in a telephone surveys. The vast majority of hospital physicians (85%) believed their prescribing practices impacted ABR development, as did 70% of GPs and 53% of veterinarians.

Pig farmers were much more likely to correctly answer basic questions about ABR science than the general public (75% compared to 24%). All medical subscribers questioned said they relied on ABR guidelines and meetings with experts for the latest knowledge on ABR.

"About two-thirds of both GPs and veterinarians stated that they discussed ABR with their patients or farmers, respectively, when prescribing an AB. Interestingly, considerably lower numbers of patients than farmers stated that they received information on ABR when they received an AB prescription," the study authors wrote. 
Mar 26 J Antimicrob Chemother study

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