ASP Scan (Weekly) for Apr 13, 2018

MDR infections in cirrhosis
Antibiotics in treated manure
Carbapenem resistance in German hospital
Overreporting C difficile
MCR-1 in travelers
Drivers of irrational antibiotic use
MCR-5 in Chinese pigs
Drug combo shows promise
Infections, antimicrobial use in Scottish nursing homes
Superbugs in nursing homes

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

Multidrug-resistant bacteria found in many cirrhosis patients

An international team of researchers reported yesterday that more than a third of patients hospitalized with liver cirrhosis and bacterial infections were infected with multidrug-resistant (MDR) pathogens, according to a news release from the European Association for the Study of the Liver (EASL).

The research, presented yesterday at the International Liver Congress in Paris, evaluated 1,302 hospitalized patients with cirrhosis and bacterial or fungal infections from 46 sites in Asia, Europe, and North and South America. The most common infections identified were spontaneous bacterial peritonitis (27%), urinary tract infections (22%), and pneumonia (19%). A total of 740 patients (57%) had at least one positive culture.

The global prevalence of MDR bacteria was 34%, with the likelihood of having an MDR infection higher in Asia (odds ratio [OR], 2.79) and South America (OR, 2.23) and significantly higher in India (OR, 7.94). The use of antibiotics in the 3 months prior to hospitalization, the category of infection, and the site of infection were also associated with increased risk for MDR bacteria.

MedPage Today reports that extended-spectrum beta-lactamase producing Enterobacteriaceae were the most common MDR pathogens, found in 34% of the patients. Other MDR bacteria included Acinetobacter and vancomycin-resistant enterococci. In addition, 8% of the patients had extensively drug-resistant bacteria. Overall, nearly 20% of the patients in the study died.

"Not surprisingly, we found a significantly lower rate of response to empirical antibiotic treatment in patients with infections caused by MDR bacteria compared with those due to non-MDR bacteria," the authors of the study told the audience, according to the news release. "We also saw a significantly higher incidence of shock and new organ failures, and a higher rate of in-hospital mortality among those with MDR bacterial infections."
Apr 12 EASL news release
Apr 12 MedPage Today story


Studies highlight problem of antibiotics in treated animal manure

Two top methods of converting animal manure into fertilizer do not fully remove antibiotics during the process, creating a potential risk of environmental contamination, a news release from the University of Buffalo yesterday notes.

The two technologies—advanced anaerobic digestion and reverse osmosis filtration—leave behind both antibiotics and molecules that the drugs break down into. In addition, one study reported that solid excrement, which is often filtered out from raw, wet manure before the waste is treated, may contain higher concentrations of antibiotics than unprocessed manure. This finding is particularly disturbing because this material is often released into the environment when it's used as animal bedding or sold as fertilizer, according to the news release.

"We were hoping that these advanced treatment technologies could remove antibiotics. As it turns out, they were not as effective as we thought they could be," Aga says.

Researchers conducted the experiments at two dairy farms in upstate New York. The study on advanced anaerobic digestion, published in Chemosphere, examined tetracyclines and found that they and their breakdown products migrated from the fluid part of the sludge into the solid part during treatment. The study on reverse osmosis, published in Environmental Pollution, looked at how well this water purification technique removed synthetic antimicrobials called ionophores, which are used to promote growth in dairy cows and to treat coccidiosis but are not used in human medicine.

"This problem is not limited to agriculture," said Diana Aga, PhD, of the University of Buffalo, who led both studies. "Waste treatment systems today, including those designed to handle municipal wastewater, hospital wastes, and even waste from antibiotic manufacturing industries, do not have treatment of antibiotics in mind. This is an extremely important global issue."
Apr 12 University of Buffalo news release
April Chemosphere study
May Environ Pollut study


Study looks at incidence, treatment of MDR bacteria in German hospital

A study yesterday in PLoS One provides a look at the prevalence, characteristics, and treatment of multidrug-resistant gram-negative bacteria (MDR-GNB) in a German hospital.

The retrospective, observational cohort study, conducted at an academic tertiary medical center from September 2015 through August 2016, identified 119 patients who were colonized or infected with carbapenem-resistant MDR-GNB, corresponding to a prevalence of 0.22% of all hospital admissions. Carbapenem-resistant isolates of Pseudomonas aeruginosa were detected in 66 patients (55.5%), Enterobacteriaceae in 44 patients (37.0%), and Acinetobacter baumannii in 18 patients (15.1%).

Infection was diagnosed in 50 patients (42.0%), with nosocomial pneumonia diagnosed in 23 patients (19.3%) and bloodstream infections in 11 patients (9.2%). Major predisposing factors for acquisition of carbapenem-resistant MDR-GNB included treatment with broad-spectrum antibiotics in the previous 6 months, which was recorded in 105 patients (88.2%), and nosocomial transmission, which was documented in 29 patients (24.4%). The rate of detection was highest for the intensive care unit (55 patients, 46.2%) and the stem cell transplantation unit (19 patients, 16.0%), but infected or colonized patients were found in 10 other wards.

Analysis of treatment showed that 45 patients with clinically diagnosed infections (90%) were treated with colistin, and that 94.3% of isolates were susceptible to the drug. New beta-lactam/beta-lactamase inhibitor combinations ceftolozane/tazobactam and ceftazidime/avibactam were administered to three and five patients, respectively, but development of high-level resistance was observed during therapy.

The authors conclude that the high number of patients infected or colonized with these pathogens, in several hospital departments, highlights their clinical relevance in German tertiary care centers. They conclude, "There is an urgent need for infectious diseases specialists coordinating their multidisciplinary management in close collaboration with hospital hygiene experts."
Apr 12 PLoS One study


Study finds overreporting of healthcare-associated C diff in urban hospital

Originally published by CIDRAP News Apr 12

A study yesterday in the American Journal of Infection Control has found that only 62% of reported cases of healthcare facility–onset Clostridium difficile (HO-CDI) at a New York hospital met clinical criteria.

In the study, investigators at New York-Presbyterian Weill Cornell Medical Center performed a retrospective chart review on 212 cases of HO-CDI reported by the hospital to the Centers for Disease Control and Prevention in 2015. The cases had been identified using the polymerase chain reaction (PCR) test for the C difficile toxin B gene on unformed stool specimens collected more than 3 days after admission. They categorized the cases into six clinical surveillance groups: community-acquired infection, recurrence/relapse, asymptomatic colonization, colonization with self-limited symptoms, possible HO-CDI, and probable HO-CDI.

The investigators found that, of the 212 cases, 51 (24%) met the clinical surveillance definition of probable HO-CDI, and 81 (38.2%) could be considered possible HO-CDI cases. Thirty-nine cases (18.4%) were classified as colonization with self-limiting symptoms, 31 cases (14.6%) were classified as community-acquired, four cases (1.9%) were considered asymptomatic colonization, and six cases (2.8%) were classified as recurrence/relapse. All but two of the patients were treated with antibiotics.

The authors of the study suggest that the misclassification of HO-CDI may in part result from the use of stool softeners and laxatives, which were given to 73 patients (34.3%) within 24 hours of testing. But they also cite the inability of widely used PCR testing to distinguish active CDI infection from symptomatic colonization with diarrhea due to other causes.

They conclude, "Ongoing review of reported HO-CDI cases is critical for guiding efforts to improve the diagnosis, treatment, and control of C difficile to ensure the reliability of HO-CDI surveillance as a meaningful quality metric."
Apr 11 Am J Infect Control abstract


Small Japanese study finds MCR-1 gene in men who traveled to Vietnam

Originally published by CIDRAP News Apr 12

A small study by Japanese researchers in the journal Infection and Drug Resistance illustrates the role that international travel could play in the spread of dangerous antibiotic resistance genes.

The researchers from Osaka University followed 19 Japanese men who made 34 trips to Vietnam between June 2015 and August 2016. Recent reports have indicated the presence of Escherichia coli harboring the mobile colistin resistance gene MCR-1 in food animals, farmers, and urban residents in Vietnam. Because of the concerns about widespread dissemination of MCR-1, the researchers wanted to investigate whether travelers could bring MCR-1–harboring E coli back to Japan after a short-term stay in the country.

Fecal specimens were collected from travelers before and after their trips to Vietnam and analyzed for bacterial identification, antibiotic susceptibility, and production of genetic resistance elements. Overall, 175 isolates of extended-spectrum beta-lactamase (ESBL)-producing E coli were identified; in 30 of 34 travel events, the travelers brought the ESBL-producing E coli back to Japan. This is noteworthy because the dissemination of ESBL-producing E coli is low in Japan. The ESBL-producing isolates exhibited 100% resistance to ampicillin and cefotaxime.

In addition, the researchers found that three of the travelers brought back ESBL-producing E coli that also harbored the MCR-1 gene. None of the men were treated with antibiotics, and MCR-1 was not detected in samples collected 3 weeks later.

"Our study supports the notion that even short-term travel can bring colistin-resistant strains back to the country of origin," senior author Yoshimasa Yamamoto, PhD, said in a university press release. "In a globalized community in which travel to developing countries is common, the spread of colistin-resistant bacteria is a significant concern to worldwide health. We need to ensure that proper surveillance and public hygiene measures are in place, so that we can minimize the dissemination of highly resistant strains to the greatest extent possible."
Mar 12 Infect Drug Resist study
Mar 30 Osaka University press release


New report lists drivers of irrational antibiotic use in Europe

Originally published by CIDRAP News Apr 12

The European nonprofit organization Health Action International has released a new report outlining the major drivers of irrational antibiotic use in Europe, along with potential remedies.

The report, written by researchers from Sweden's Karolinska Institutet, suggests that among the general public, the lack of knowledge and awareness about antibiotics and antibiotic resistance, access to antibiotics without a prescription, and leftover antibiotics from earlier prescriptions are the most significant drivers of inappropriate antibiotic use. For healthcare providers, they cite attitudes toward antibiotic use and resistance, lack of adequate education on antibiotic prescribing, pharmaceutical promotion, lack of rapid diagnostic tests, and patient pressure.

To counter irrational antibiotic use, the authors recommend more education for healthcare providers and the public, strategies to optimize antibiotic use (including infection prevention and control measures and take-back programs for unused antibiotics), stronger data on antibiotic use and resistance, tougher regulations on pharmaceutical promotion, and the development, implementation, and coordination of national action plans on antibiotic resistance. They also call for more support for research into new antibiotics and diagnostics.

Research by the European Surveillance of Antimicrobial Consumption Network has shown that large variations in antibiotic use exist across Europe, with higher use in southern Europe and lower use in northern Europe. 
Apr 5 Health Action International report


Plasmid-mediated MCR-5 gene detected in isolates from Chinese pigs

Originally published by CIDRAP News Apr 11

Chinese and Swedish researchers have detected the colistin resistance gene MCR-5 in an Aeromonas hydrophila isolate from pigs in rural China, according to a study today in the Journal of Antimicrobial Chemotherapy.

The MCR-5-harboring isolate was found among fecal samples collected from backyard pigs from 194 households in rural areas of Shandong Province in August 2017. The identified isolate, I064-2, was resistant to colistin and displayed intermediate susceptibility to tetracycline, but was susceptible to several other antibiotics, including amikacin, gentamicin, ciprofloxacin, and meropenem.

Whole-genome sequencing of the isolate confirmed that the MCR-5 gene was located on a plasmid with genetic features similar to those found in other Aeromonas species, Enterobacteriaceae, and Pseudomonas species, a finding that suggests the possibility of horizontal transfer of the MCR-5-carrying segment among these bacterial species and genera.

Bacteria belonging to the Aeromonas genus cause diarrheal diseases and wound infections in humans and animals. Prior to this study, the MCR-5 gene had only been found in Salmonella spp. from poultry- and animal-derived food products in Germany.

"Further studies should focus on the surveillance of mcr-5 in colistin-resistant Gram-negative pathogens derived from animals, humans and the environment," the authors write.
Apr 11 J Antimicrob Chemother study 


Study finds beta-lactamase inhibitor restores susceptibility to carbapenem

Originally published by CIDRAP News Apr 11

In another study today in the Journal of Antimicrobial Chemotherapy, an international team of researchers report that the novel beta-lactamase inhibitor relebactam restored susceptibility to imipenem in gram-negative pathogens.

For the study, which was funded by Merck & Co., the researchers tested the in vitro activity of imipenem and imipenem/relebactam against isolates of Gram-negative ESKAPE pathogens (Klebsiella pneumoniaeA baumanniiP aeruginosa and Enterobacter spp.) submitted by hospital laboratories in 17 European countries. The isolates were from intra-abdominal infections, urinary tract infections, and lower respiratory tract infections. Relebactam was tested at a fixed concentration of 4 mg/L in combination with doubling dilutions of imipenem.

Rates of susceptibility to imipenem and imipenem/relebactam among isolates of P aeruginosa, K pneumoniae, and Enterobacter spp. were 72/94.7%, 88.7/94.8%, and 95.6/96.8%, respectively. In addition, relebactam restored in vitro imipenem susceptibility in 81.1%, 54.2%, and 26.5% of imipenem-non-susceptible isolates of P aeruginosa, K pneumoniae, and Enterobacter spp. Against A baumannii, however, relebactam did not increase the number of isolates susceptible to imipenem. Most imipenem/relebactam-non-susceptible isolates harbored metallo-beta-lactamase, OXA-48, or GES carbapenemase genes.

Imipenem/relebactam has successfully completed two phase 2 clinical trials for treating complicated intra-abdominal infections and complicated urinary tract infections, and is currently in phase 3 development.

"Further development of imipenem/relebactam appears worthwhile as it may provide a valuable therapeutic option for treating patients with infections caused by carbapenem-non-susceptible isolates of Gram-negative bacilli, including ESKAPE pathogens," the authors write.
Apr 11 J Antimicrob Chemother study


Troubling rate of infections, antimicrobial use found in Scottish nursing homes

Originally published by CIDRAP News Apr 11

A national point prevalence survey (PPS) indicates that healthcare associated infections (HCAIs) affect three residents in every long-term care facility (LTCF) in Scotland, Health Protection Scotland reported yesterday.

The PPS, which was conducted in October 2017 and included data from 2,147 residents in 52 LTCFs in Scotland, found that the prevalence of HCAIs was 5.9%. Respiratory tract infections (38.1%), urinary tract infections (31%), and skin and soft-tissue infections (23%) were the most commonly reported HCAIs. The HCAI prevalence was more than twice the rate found in a PPS conducted by the European Centre for Disease Prevention and Control in 2010, though the results aren't directly comparable due to differences in survey protocol.

The PPS also found that the overall prevalence of systemic antimicrobial prescribing in Scottish LTCF was 6.5%, down slightly from the 2010 PPS (7.3%). The prevalence of antimicrobial prescribing for treatment of infections was 4.5%, and the prevalence of prescribing for prevention of infections was 1.3%. The most commonly prescribed antimicrobials for treatment of infection were amoxicillin, trimethoprim, flucloxacillin, and nitrofurantoin.

Scottish health officials said in a news release that the prevalence of HCAIs and the rate of antimicrobial prescribing at LTCFs, along with the challenges of infection prevention and control in these settings, represent a public health threat with implications for resident safety and antimicrobial resistance.

"Healthcare associated infections remain a public health threat across all care settings," said Health Protection Scotland's Jacqui Reilly, PhD. "Health Protection Scotland will develop national programmes to tackle these new threats and work with colleagues across health and social care settings to preserve antibiotics for future use."

The report concludes that a broader and coordinated public health approach to infection prevention and control and antimicrobial stewardship in LTCFs is needed.
Apr 10 Health Protection Scotland PPS
Apr 10 Health Protection Scotland news release


Study finds high rate of MDRO colonization in new nursing home patients

Originally published by CIDRAP News Apr 10

Nearly 57% of short-stay nursing home residents harbor multidrug-resistant organisms (MDROs) near the time of admission and at discharge, according to University of Michigan researchers.

In a longitudinal cohort study published yesterday in Clinical Infectious Diseases, the researchers evaluated MDRO colonization prevalence in 651 recently admitted nursing facility (NF) patients from November 2013 through May 2016. Patients at six NFs in southeast Michigan were enrolled within 14 days of admission and followed for up to 6 months. The researchers evaluated for MDRO prevalence upon enrollment, MDRO acquisition and loss during their stay, prevalence upon discharge, and identified risk factors for colonization.

The results showed that 56.8% of the patients were colonized with an MDRO at enrollment: 16.1% with methicillin-resistant Staphylococcus aureus (MRSA), 33.2% with vancomycin-resistant enterococci (VRE), and 32% with resistant gram-negative bacilli (R-GNB). Risk factors for colonization at enrollment included prolonged hospitalization, functional disability, antibiotic use, or device use.

Among the 456 patients with one or more follow-up sampling visits, the incidence rate per 1,000 patient-days for new MDRO acquisition was 3.4 from MRSA, 8.2 for VRE, and 13.6 for R-GNB. MDRO colonization at discharge was 56.4%: 18.4% for MRSA, 30.3% for VRE, and 33.6% for R-GNB. More than half of the patients discharged to the community (52.4%) and 70.9% of those readmitted to a hospital were colonized with one or more MDROs at discharge.

The authors of the study say the findings illustrate the potential for NFs to be a reservoir for MDROs that can then spread between institutions and within community healthcare settings. They suggest that patients with long prior hospitalizations and other risk factors for MDRO colonization should be targets for aggressive prevention efforts. 
Apr 9 Clin Infect Dis study

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