ASP Scan (Weekly) for Aug 30, 2019

Infection-linked pancreatic scopes
Oral antibiotic for skin infections
Resistant enterococci in Germany
End-of-life antibiotics
Klebsiella pneumoniae vaccine candidate
Antibiotic pollution initiative
Carbapenem-resistant Klebsiella spread
Contact precautions for ESBL patients
Candida auris uptick
Resistant Enterobacteriaceae in US

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

FDA urges hospitals to start using duodenoscopes with disposable parts

The US Food and Drug Administration (FDA) says it will now recommend that hospitals move away from using duodenoscopes with reusable parts because of concerns about patient infections that have been linked to cleaning issues.

In a safety communication issued yesterday, the FDA said it's recommending that hospitals and endoscopy facilities transition away from fixed endcap duodenoscopes, which are used to diagnose and treat conditions of the pancreas and bile ducts, to those with newer design features that "facilitate or eliminate the need for reprocessing." The agency says it's working with manufacturers to increase the supply of disposable cap duodenoscopes and encourage development of innovative device designs that reduce the risk of infection, and that it recognizes a full transition away from conventional duodenoscopes will take time.

Fixed endcap duodenoscopes have been linked to a number of outbreaks of multidrug-resistant bacteria at US and European hospitals in recent years, including a January 2015 carbapenem-resistant Enterobacteriaceae outbreak that resulted in two deaths at a Los Angeles hospital. Because of the complex design of the devices, they can be difficult to clean and have been found to harbor dangerous bacteria that can be transmitted to other patients, even after being properly cleaned. The FDA issued a safety warning in 2015 and device manufacturers updated their cleaning instructions, but problems have persisted.

Duodenoscopes are used in more than 500,000 endoscopic retrograde cholangiopancreatography procedures each year in the United States.

The FDA said that, during the transition period, hospitals and endoscopy facilities should ensure that staff members are meticulously following duodenoscope reprocessing instructions, institute quality control programs that include sampling and microbiologic culturing, and develop schedules for routine inspection. The agency also noted that patients should be aware that the risk of infection from inadequate cleaning is relatively low, and that they should discuss the risks and benefits with their providers before cancelling or delaying planned procedures.
Aug 29 FDA safety communication


Oral omadacycline found non-inferior to linezolid for skin infections

Drug maker Paratek Pharmaceuticals reported yesterday in The Lancet Infectious Diseases that and oral version of omadacycline—its FDA-approved antibiotic for community-acquired and pneumonia and skin infections—was found to be non-inferior to oral linezolid in adults with acute bacterial skin and skin-structure infection (ABSSSI).

In the phase 3 OASIS 2 trial, which was funded by Paratek, eligible adults with ABSSSI at 33 US hospitals were randomly assigned to receive one dose of oral omadacycline or two doses of linezolid for 7 to 14 days. The primary end points were early clinical response (48 to 72 hours after the first dose) in the modified intention-to-treat (mITT) population, and investigator-assessed clinical response at post-treatment evaluation in the mITT population and clinically evaluable population. The non-inferiority margin was 10%.

Overall, 735 participants were randomly assigned, with 368 receiving omadacycline and 367 receiving linezolid. The results showed that omadacycline (315 of 360, 88%) was non-inferior to linezolid (297 of 360, 83%) for early clinical response in the mITT population (percentage-point difference 5.0; 95% confidence interval [CI], −0.2 to 10.3). For investigator-assessed clinical response at post-treatment evaluation, omadacycline (303 of 360, 84%) was non-inferior to linezolid (291 of 360 81%) in the mITT population (percentage-point difference 3.3; 95% CI, −2.2 to 9.0) and in the clinically evaluable population (278 of 284 [98%] vs 279 of 292 [96%]; percentage-point difference, 2.3; 95% CI, −0.5 to 5.8).

The safety analysis showed that at least one treatment-emergent adverse event occurred in 197 of 368 omadacycline patients (54%), compared with 137 of 367 linezolid patients (37%), and that mild-to-moderate nausea and vomiting were more frequent in omadacycline patients (111 of 368 [30%] and 62 of 368 [17%], respectively) than in linezolid patients (28 of 367 [8%] and 11 of 367 [3%], respectively).

The authors of the study write, "Considering the substantial burdens associated with initial inpatient management of skin infections, oral omadacycline is a new once-daily option to treat ABSSSI that might be considered as an alternative to linezolid."
Aug 29 Lancet Infect Dis study


Data show vancomycin-resistant Enterococcus faecium rising in Germany

Data from the German Antimicrobial Resistance Surveillance System show a 43% increase in vancomycin-resistant Enterococcus faecium (VREF) in German hospitals, according to a new study in Antimicrobial Resistance and Infection Control.

For the study, researchers from Germany's Robert Koch Institute analyzed data from routine vancomycin susceptibility testing of 35,906 clinical E faecium isolates collected from 148 hospitals from 2012 through 2017. The analysis found that the proportions of E faecium isolates exhibiting resistance to vancomycin increased from 11.2% in 2014 to 26.2% in 2017. The rise in VREF proportions was primarily seen in southern Germany, increasing from 10.8% in southwest Germany and 3.8% in southeastern Germany in 2014 to 36.7% and 36.8% in 2017, respectively.

Further analysis found that VREF proportions were considerably higher in isolates from patients aged 40 to 59 years compared with younger patients, and that E faecium samples collected in specialist care hospitals and prevention and rehabilitation care hospitals were more likely to be vancomycin resistant than those from secondary care hospitals (odds ratios: 2.4 [95% CI, 1.2 to 4.6] and 2.4 [95% CI, 1.9 to 3.0], respectively).

The authors of the study note that similar VREF increases have been found in countries neighboring Germany, including Denmark, Belgium, Poland, and the Czech Republic.

They conclude, "Continued surveillance and implementation of effective infection prevention and control measures accounting for local resistance differences are needed to reduce the spread of vancomycin-resistant E. faecium in German hospitals."
Aug 28 Antimicrob Resist Infect Control study


Israeli study finds antibiotics overused in some end-of-life patients

Originally published by CIDRAP News Aug 28

A survey of Israeli physicians and analysis of patient data has found that antibiotics are overused in patients with end-of-life advanced directives, Israeli researchers reported today in Infection Control and Hospital Epidemiology.

In the descriptive cross-sectional study, the researchers administered a questionnaire to 213 physicians at four acute care and two post-acute care hospitals and collected data on 932 of their patients, all of whom had died in the 4 months preceding the survey. The data included end-of-life patient diagnoses, medical treatment, antibiotic days of therapy (DOT), and consultations with infectious disease (ID) physicians. The survey contained questions on sociodemographic and organizational factors, physician knowledge, and burnout.

Of the 932 deaths, 435 of 664 were end-of-life patients with advanced directives. The rate of most treatments in end-of-life patients with advanced directives was significantly lower than in those with no advanced directives, except for antibiotics and blood products.

Of the end-of-life patients with advanced directives, 74% received antibiotics; 29.9% of those who received antibiotics had cultures with multidrug-resistant organisms, and antibiotics were discontinued in only 5%. Half of the physicians lacked knowledge concerning antibiotics use issues, and physicians caring for end-of-life patients with advanced directives had significantly fewer consultations with ID physicians (mean rate, 0.27) than those caring for patients without advanced directives (mean rate, 0.47).

ID physicians reported significantly higher emotional exhaustion levels (mean rate, 29) than other medical specialties (mean rate, 19.2). Antibiotic DOT was significantly higher when patients had ID consultations (mean rate, 21.6) than in patients who did not (mean rate, 16.2). Antibiotic DOT was significantly higher in post–acute-care hospitals or geriatric wards than in other types of hospitals or wards.

In light of the findings, the authors of the study recommend supplementing antibiotic stewardship guidelines in Israeli hospitals with guidance on end-of-life prescribing, adding simulation-based education to deal with end-of-life issues, and encouraging providers to consult with ID physicians. 
Aug 28 Infect Control Hosp Epidemiol abstract


Vaccine for hypervirulent Klebsiella pneumoniae shows promise in mice

Originally published by CIDRAP News Aug 28

A vaccine targeting hypervirulent strains of Klebsiella pneumoniae has shown early promise in mouse experiments, researchers from the Washington University School of Medicine in St. Louis and biotechnology start-up VaxNewMo reported yesterday in the Proceedings of the National Academy of Sciences.

The bioconjugate vaccine was designed to target the two most common hypervirulent serotypes of K pneumoniae, K1 and K2, which account for 70% of hypervirulent K pneumoniae cases. While most K pneumonia infections occur in hospital patients with compromised immune systems, hypervirulent strains that cause invasive infections in otherwise healthy people are on the rise, and there have been increasing reports of hypervirulent, multidrug-resistant strains that are extremely difficult to treat. The researchers believe a vaccine against these strains could help avert a serious public health threat.

In preclinical studies, the researchers tested the vaccine, which was produced using genetically modified Escherichia coli cells, in four groups of five mice each, with one group receiving a placebo. After three doses, they then infected the mice with K1 and K2 strains of K pneumoniae, using an amount of bacteria that had previously been shown to be lethal in mice.

The results showed that 80% of the placebo-treated mice challenged with the K1 strain died, while only 20% of the vaccine-treated mice died. Of the mice infected with the K2 strain, 30% of those who received the placebo died, compared with none of the mice who received the vaccine. The vaccine was less successful when the mice were exposed to higher doses of the K1 strain, but the vaccinated mice still had a statistically significant increase in survival compared with the placebo group.

"We are very happy with how effective this vaccine was," study co-author Mario Feldman, PhD, a professor of molecular microbiology at Washington University School of Medicine and co-founder of VaxNewMo, said in a university press release. "We're working on scaling up production and optimizing the protocol so we can be ready to take the vaccine into clinical trials soon."
Aug 27 Proc Natl Acad Sci study
Aug 27 Washington University press release


New initiative aims to clean up antibiotics manufacturing

Originally published by CIDRAP News Aug 27

The United Nations Development Programme (UNDP) yesterday announced a joint initiative with environmental and industry groups to reduce the amount of antibiotic discharge from pharmaceutical manufacturing facilities.

The REAP (Reducing Emissions from Antibiotics Production) project will bring together organizations on the supply and demand side of antibiotics manufacturing to advocate for technologies, incentives, and policies that help the pharmaceutical industry shift to more sustainable production practices. Partners in the initiative include the Stockholm International Water Institute, Centrient Pharmaceuticals, and contract manufacturer Recipharm.

The release of antibiotic residues into waterways by pharmaceutical manufacturing plants is considered one of the factors that contribute to antimicrobial resistance (AMR). Once in the water, the antibiotic residues interact with natural bacterial communities and with human and animal bacteria, and can exert selective pressure that promotes the development of AMR. Studies in parts of India where pharmaceutical manufacturing is concentrated have found high concentrations of antibiotic residues and an abundance of AMR genes in local waterways.

"The UN purchases large volumes of antibiotics. Developing a Sustainable Procurement Index for Health is a way for us to promote more sustainable manufacturing and procurement," Rosemary Kumwenda, MD, UNDP's regional team leader for HIV, Health, and Development, said in a press release from the UN's Sustainable Procurement in the Health Sector (SPHS) task force. "Through REAP, we can engage with manufacturers and suppliers and in the long run, incentivise a more sustainable production and procurement system."

The initiative was announced at World Water Week 2019.
Aug 26 SPHS press release


Study highlights regional spread of carbapenem-resistant Klebsiella

Originally published by CIDRAP News Aug 27

A genomic study of clinical isolates from long-term acute care hospitals (LTACHs) in the United States indicates patient transfer is driving regional proliferation of carbapenem-resistant K pneumoniae (CRKP), researchers reported yesterday in Antimicrobial Agents and Chemotherapy.

To better understand the epidemiology of CRKP in LTACHs, which are increasingly recognized as reservoirs of multidrug-resistant organisms (MDROs) because of their critically ill patient population, the researchers performed whole-genome sequencing (WGS) on a collection of 451 CRKP isolates from LTACH patients in four geographic regions. The vast majority of the isolates (395, 87.6%) were from 11 facilities in the Los Angeles area. Patients with CRKP had a high rate of multiple comorbidities, and indwelling device and broad-spectrum antibiotic use was common.

Analysis of the sequence types revealed that more than 90% of the isolates belonged to ST258, an epidemic K pneumoniae lineage that has accounted for most of the carbapenem-resistant Enterobacteriaceae infections in US hospitals, and phylogenetic reconstruction showed that dissemination of the lineage started in Los Angeles–area LTACHs with a small number of introductions in 2012, then spread among the facilities via patient transfers.

A transmission map constructed from 363 isolates indicated that CRKP transmission was associated with rates of patient flow between LTACHs, with higher transmission frequencies found between geographically proximate facilities. But the CRKP prevalence at each LTACH was associated with intra-facility transmission rates, which varied according to the clinical characteristics of patients.

The researchers say the study illustrates how WGS and patient-level clinical meta-data can help identify pathways and drivers of MDRO transmission in regional healthcare networks, which could aid development of targeted interventions. "The ability to tease apart the relative contributions of inter- and intra-facility transmission across regional healthcare facilities, and to identify drivers of these processes, is a critical first step in the development of effective regional interventions to control the spread of MDROs," they write.
Aug 26 Antimicrob Agents Chemother abstract


Study supports multiple-bed room strategy for isolating ESBL patients

Originally published by CIDRAP News Aug 26

A study conducted in Dutch hospitals has found that an isolation strategy of contact precautions in a multiple-bed hospital room was non-inferior to a strategy of contact precautions in a single-bed room for preventing the spread of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, Dutch researchers reported in The Lancet Infectious Diseases.

In the cluster-randomized, crossover study, medical and surgical wards at 16 Dutch hospitals applied, over two study periods, contact precautions in either a single-bed or multiple-bed hospital room as the preferred strategy for isolating patients with ESBL-producing Enterobacteriaceae cultured from a routine clinical sample. Under current European Society for Clinical Microbiology and Infectious Diseases guidelines, contact precautions (i.e., use of gloves and gowns for all direct contact with a patient) are recommended for such patients, preferably in a single room, but studies on the added benefit of a single room have been inconsistent. Compared with other multidrug-resistant pathogens, ESBL-producing Enterobacteriaceae have the highest prevalence in European hospitals and have become an increasing burden.

The hospitals were assigned in a 1:1 ratio to either strategy during the first study period, then switched strategies in the second study period. The primary outcome was transmission of ESBL-producing Enterobacteriaceae to wardmates, which was defined as rectal carriage of an ESBL-producing Enterobacteriaceae isolate that was clonally related to the index patient's isolates. The non-inferiority margin was 10%.

Thirteen hospitals completed both study periods and assessed 1,652 index patients and 12,875 wardmates for eligibility from April 2011 through February 2014. Of those, 693 index patients and 9,527 wardmates were enrolled, with 463 index patients and 7,093 wardmates included in the per-protocol population. For the per-protocol population, transmission of ESBL-producing Enterobacteriaceae to at least one wardmate was identified for 11 of 275 index patients (4%) during the single-bed room strategy period and for 14 of 188 index patients (7%) during the multiple-bed room strategy period (crude risk difference 3.4%; 90% CI, −0.3 to 7.1). For both isolation strategies, the median length of hospital stay was 11 days, and the 30-day mortality was 4%.

"Non-inferiority of the multiple-bed room strategy could change the current single-bed room preference for isolation of patients with ESBL-producing Enterobacteriaceae and, thus, broaden infection-control options for ESBL-producing Enterobacteriaceae in daily clinical practice," the authors of the study conclude. 
Aug 23 Lancet Infect Dis study


CDC update shows US Candida auris cases continue to rise

Originally published by CIDRAP News Aug 26

The number of confirmed and probable Candida auris cases in the United States rose to 755 as of June 30, reflecting an increase of 39 cases, according to the most recent case-count update from the Centers for Disease Control and Prevention (CDC).

Of the cases reported to the CDC, 30 are probable and 725 have been lab-confirmed. In its previous update, involving cases through May 31, the CDC reported 716 cases. An additional 1,474 patients have been found to be colonized with the multidrug-resistant yeast, as determined by targeted screening in 10 states with clinical cases.

The number of states affected remains at 12, with New York (359), Illinois (199), and New Jersey (148) reporting the vast majority of C auris cases. Other states reporting cases include Florida (22), Massachusetts (8), California (5), Maryland (5), Texas (4), Oklahoma (2), Connecticut (1), Indiana (1), and Virginia (1).

Since it was identified in 2009 in Japan, C auris has triggered outbreaks in healthcare facilities in 23 countries, and 13 countries have reported single cases. C auris can cause serious invasive infections in immunocompromised patients, and has shown resistance to three major antifungal drug classes. The CDC has estimated that 30% to 60% of patients with infections have died.
Aug 16 CDC update


Resistant Enterobacteriaceae on the rise US hospitals, study finds

Originally published by CIDRAP News Aug 26

An analysis of more than a million Enterobacteriaceae isolates collected from US hospitals has found a rise in ESBL-producing and carbapenem-nonsusceptible Enterobacteriaceae, US researchers reported in BMC Infectious Diseases.

In the study, researchers from Becton, Dickinson and Company and Tetraphase Pharmaceuticals analyzed the antimicrobial susceptibility of non-duplicated isolates from multiple culture sources collected from hospitalized patients at 411 US hospitals from 2013 through 2017. The resistance profiles of interest were ESBL-producing, multidrug-resistant (MDR), and carbapenem-nonsusceptible phenotypes of Enterobacteriaceae, and MDR and carbapenem-nonsusceptible Acinetobacter spp. The outcomes assessed were the rate of bacterial resistance or non-susceptibility per 100 hospital admissions and the proportion of resistant isolates for each year-quarter from Q1 2013 through Q4 2017. 

The analysis found that 12.05% of Enterobacteriaceae isolates were identified as ESBL phenotype, 1.21% were carbapenem-nonsusceptible, and 7.08% were MDR, with urine cultures accounting for the majority of resistant isolates. Of the more 19,000 Acinetobacter isolates tested, 37.48% were identified as carbapenem-nonsusceptible and 47.66% as MDR, and the most common source was skin/wound cultures. Trend analyses showed that the rates of ESBL-producing and carbapenem non-susceptible Enterobacteriaceae per 100 hospital admissions increased significantly between 2013 and 2017, with average slopes of 0.0089 and 0.0004 per quarter, respectively. Rates of MDR Enterobacteriaceae and carbapenem-nonsusceptible and MDR Acinetobacter spp., however, decreased during this time period.

The analysis also found that trends in proportions of resistant isolates generally mirrored trends in rates per 100 hospital admissions, and that MDR Enterobacteriaceae and carbapenem-nonsusceptible and MDR Acinetobacter spp. were more common in winter than summer.

The authors of the study say the observed increase in ESBL-producing and carbapenem-nonsusceptible Enterobacteriaceae supports continuing efforts by the CDC and the World Health Organization to combat these pathogens. They conclude, "Continued infection control efforts, together with diagnostic and antimicrobial stewardship and new antibiotics to expand treatment options, will be required to manage these antibiotic-resistant Gram-negative pathogens."
Aug 23 BMC Infect Dis study

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