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

BioMerieux tapped to provide diagnostics in LMICs to combat AMR

Originally published by CIDRAP News Dec 19

Yesterday, French diagnostics company bioMerieux announced that that the Fleming Fund has selected it as a supplier in a tender process to tackle antimicrobial resistance (AMR) in 18 low- and middle-income countries.

The Fleming Fund is investing £265 million ($345 million US) in the process, which will involve equipping one reference clinical lab and one veterinary lab in 18 countries across Africa and the Asia-Pacific with diagnostic, susceptibility, and data processing technology over the next 3 years, according to a bioMerieux news release.

"It is a pleasure to work in partnership with bioMerieux to help strengthen health systems and contribute to tackling the threat of antimicrobial resistance around the world," said Andy Leigh, a Fleming Fund program director.

BioMerieux will be active in 18 out of the 24 countries taking part in the program. The company will equip labs with its Vitek MS and Vitek 2 systems for pathogen identification and antimicrobial susceptibility testing, and with Myla software for data processing. 
Dec 18 bioMerieux news release

French stewardship study finds benefits from combined strategies

Originally published by CIDRAP News Dec 19

A study in France has found that the combination of simplified therapeutic guidelines (STGs) and accompanied self-antibiotic reassessment (ASAR) was associated with optimal antibiotic therapy and reduced antibiotic use at 15 hospitals, researchers reported yesterday in the Journal of Antimicrobial Chemotherapy.

The STGs resulted from at least two rounds of antibiotic audit and feedback at the 15 hospitals and were based on national and international guidelines, the medical and surgical activities of every institution, and on data regarding resistant bacteria. The STGs were explained to prescribers in ASAR sessions, which typically lasted 45 to 90 minutes and consisted of reviewing four to six patients' files. To measure the impact of these strategies, the researchers reviewed patients receiving antibiotic therapy and rated the quality of the antibiotic treatment before and after implementation. They also measured antibiotic consumption at the hospitals, focusing on amoxicillin/clavulanic acid, third-generation cephalosporins, and fluoroquinolones.

Comparison of prescriptions in five hospitals before and after implementation of STGs and ASAR showed that these tools were associated with optimal therapies (adjusted odds ratio [AOR], 3.28; 95% confidence interval [CI], 1.82 to 5.92), amoxicillin/clavulanic acid prescriptions (AOR, 2.18; 95% CI, 1.38 to 3.44) and fewer prescriptions for urine colonization (AOR, 0.20; 95% CI, 0.06 to 0.61). Comparison of prescriptions from 10 departments of three hospitals with STGs and ASAR for the first quarters of 2018 and 2019 revealed that the prescriptions by 23 ASAR participants more often complied with STGs than those by 28 other physicians (71% vs 60%; P = 0.003).

Comparing prescriptions in the 10 hospitals that adopted STGs alone with prescriptions at the 5 hospitals that adopted both tools, the researchers observed fewer unnecessary prescriptions in the latter (AOR, 0.52; 95% CI, 0.34 to 0.80). The variation in critical antibiotic consumption between 2017 and 2018 was -16% for the 5 hospitals that adopted both tools and +20% for the other 10.

"In conclusion, STGs + ASAR is a combination of tools that increase the efficiency of non-specialized prescribers, leading to an increase in optimal antibiotic therapy and a reduction in antibiotic consumption," the authors of the study write. "As these tools do not require financial support, our results would be helpful for low- and middle-income countries."
Dec 18 J Antimicrob Chemother abstract

Contact with puppies tied to MDR Campylobacter in 13 states

Originally published by CIDRAP News Dec 18

Puppies from Petland pet stores are again implicated in a multistate outbreak of multidrug-resistant (MDR) Campylobacter infections, this time affecting at least 30 people in 13 states, the Centers for Disease Control and Prevention (CDC) said yesterday in an update.

Four people have been hospitalized in this outbreak, caused by Campylobacter jejuni, but none have died. "Epidemiologic and laboratory evidence indicate that contact with puppies, especially those at pet stores, is the likely source of this outbreak," the CDC said. The agency added, "Laboratory evidence indicates that bacteria from ill people in this outbreak are closely related genetically to bacteria from ill people in the 2016–2018 outbreak of multidrug-resistant Campylobacter infections linked to pet store puppies."

In both the current and earlier outbreaks, the CDC named Petland stores as a likely source of the contaminated puppies. Of 15 people in the current outbreak who reported contact with a puppy from a pet store, 12 (80%) were linked to Petland, including 5 employees.

The 2016-18 MDR Campylobacter outbreak involved 113 cases and 23 hospitalizations in 17 states. The CDC posted its final outbreak notice on that event on Jan 30, 2018.

Illnesses in this year's outbreak began from Jan 6 to Nov 10, with patients ranging from 8 months to 70 years. Whole-genome sequencing of 26 isolates from patients predicted antibiotic resistance to tetracycline (26 isolates), ciprofloxacin (25), nalidixic acid (25), azithromycin (23), erythromycin (23), clindamycin (23), telithromycin (23), and gentamicin (18).
Dec 17 CDC statement
Jan 30, 2018, CDC final notice on previous outbreak

ECDC details CRE outbreak in Lithuanian hospitals

Originally published by CIDRAP News Dec 18

The European Centre for Disease Prevention and Control (ECDC) today issued a report on an outbreak of Klebsiella pneumoniae carbapenemase-producing carbapenem-resistant Enterobacteriaceae (KPC-CRE) in Lithuania.

According to the ECDC's rapid risk assessment, 199 KPC-CRE cases were detected from Feb 1 through Nov 26, with 186 cases (93%) occurring in a single hospital (hospital 1). The cases include infections as well as carriage, and most of the isolates were Klebsiella pneumoniae (186 cases, 93%), followed by Escherichia coli (16 cases, 8%), Citrobacter freundii (2 cases), and Enterobacter aerogenese (1 case). In all isolates, carbapenem resistance was mediated by the KPC enzyme. Additional resistance to colistin was detected in 26 of 52 isolates tested.

The outbreak was first identified in April 2019, with the first case detected in a patient with a surgical-site infection admitted to the intensive care unit of hospital 1, and was still ongoing as of Dec 11.

"The risk of further spread of CRE in the most-affected hospital is high, as a large number of cases have been identified from multiple wards and new cases continue to be detected at the time of this risk assessment," the report says. "While enhanced infection control measures have been implemented, the outbreak appears not yet to have been controlled."

Six additional hospitals have also reported KPC-CRE cases, and the ECDC says the risk of further spread in the Lithuanian health system is high, since screening for CRE carriage was not in place in Lithuanian hospitals before December 2019. Lithuania reported only 5 and 12 cases of CRE in 2017 and 2018, respectively.

The ECDC says screening of patients at high risk for digestive tract carriage of CRE due to healthcare contact in the preceding 12 month, along with pre-emptive contact precautions and isolation, should be considered. Further epidemiologic investigations are ongoing.
Dec 18 ECDC rapid risk assessment

Resistant E coli intestinal carriage found in VA patients, housemates

Originally published by CIDRAP News Dec 18

Veterans Affairs (VA) patients and members of their household commonly carry and share a strain of multidrug-resistant E coli that's emerged as a common source of extra-intestinal infections in hospitals, researchers from the University of Minnesota and the Minneapolis VA Medical Center reported today in the Journal of Infectious Diseases.

For the study, the researchers screened fecal samples from 741 volunteers (383 VA patients and 358 household members, including pets) for fluoroquinolone-resistant E coli (FQREC) and E coli sequence type (ST) 131. They were specifically interested in the H30 subclone within ST131, and its fluoroquinolone-resistant H30R subset, both of which have expanded rapidly in recent years. Because these extra-intestinal pathogenic E coli strains usually originate in patients' gut microbiota before causing extra-intestinal infections, it's been theorized that widespread gut colonization could underlie epidemic clonal emergence.

The results showed that colonization prevalence was 5.1% for H30R, 8% for ST131 (67% FQREC), and 10% for FQREC (52% ST131). Among the 425 strains that underwent virulence genotyping, ST131 isolates exhibited more virulence genes than non-ST131 isolates. Strain sharing appeared in 27% of the 100 assessed multi-subject households and 18% of corresponding subjects, and was associated with the elderly, FQREC, H30R, H30Rx, E coli ST73, and specific virulence genes. Comparison of fecal ST131 and FQREC isolates with a collection of clinical E coli isolates from Minneapolis VA patients found similarities in virulence gene content, resistance profiles, and other traits, a finding that supports the idea that the clinical strains emerge from the gut reservoir.

"In conclusion, as an intestinal colonizer of uninfected veterans and their human household members, H30R was much more prevalent than any other FQREC strain, largely independent of the studied host characteristics," the authors of the study write.

"Comparative prevalence values suggested that, relative to other FQREC, H30R is likely both a better gut colonizer and more capable of causing infections in colonized hosts, phenotypes possibly promoted by H30R's extensive repertoire of virulence factors, which may also represent colonization factors. Thus, colonization fitness, virulence, and within-household strain sharing may all underlie H30R's epidemic success, and could be targets for preventive interventions."
Dec 18 J Infect Dis abstract

BARDA to fund development of antibiotics for resistant gram-negatives

Originally published by CIDRAP News Dec 16

San Diego-based biopharmaceutical company Qpex Biopharma today announced it will receive a second round of funding from the Biomedical Advanced Research and Development Authority (BARDA) to develop a portfolio of antibiotics targeting antibiotic-resistant gram-negative bacteria.

Under the Other Transaction Authority (OTA) agreement with BARDA, Qpex will receive $20 million to advance three products into clinical studies: ORAvanceTM, an orally administered beta-lactamase inhibitor (BLI)-based product for treating infections caused by extended-spectrum beta-lactamase (ESBL)- and carbapenemase-producing Enterobacteriaceae; OMNIvanceTM, an intravenous (IV) BLI-based product; and QPX9003, a next-generation IV-administered polymyxin designed to address highly-resistant Pseudomonas and Acinetobacter infections.

The $20 million option is the second award under the OTA agreement, which provides for up to $132 million in funding.

"We are grateful for our successful and longstanding partnership with BARDA, whose commitment to address the global and growing threat of antimicrobial resistance has been unparalleled," Qpex Biopharma President and CEO Michael Dudley, PharmD, said in a company press release. "Our team has made rapid progress since forming the company just over a year ago, and the continued support from BARDA puts us in a strong position as we transition to a clinical-stage company."
Dec 16 Qpex Biopharma press release

WHO announces updates to drug-resistant TB treatment

Originally published by CIDRAP News Dec 16

The World Health Organization (WHO) last week issued a rapid communication outlining updated treatment recommendations for patients with drug-resistant tuberculosis (TB), based on evidence reviewed in a November meeting of its Guideline Development Group (GDG).

The main change suggested by the GDG is the introduction of a shorter, all-oral, bedaquiline-containing drug regimen for patients with multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB) that would replace shorter regimens with injectables. The recommendation is based on analysis of data from a South African TB program that showed that replacing the injectable with bedaquiline resulted in significantly better treatment success and a considerable reduction in loss-to-follow up in MDR/RR-TB patients who had no previous exposure to second-line drugs, confirmed fluoroquinolone-susceptibility, and no extensive disease or severe extrapulmonary TB.

The group also recommended that in certain patients with extensively drug-resistant TB (XDR-TB), the novel 6- to 9-month bedaquiline, pretomanid, and linezolid (BPaL) regimen may be used under operational research conditions as an alternative to the standard, 18-to-24 month regimen. That recommendation is based on results from the phase 3 Nix-TB trial, in which the BPaL regimen showed high treatment success in 108 South African XDR-TB patients. But the WHO says that the regimen may not considered for programmatic use worldwide until additional safety and efficacy evidence has been generated.

The communication was released to inform national TB programs in advance of the WHO's updated guidelines on drug-resistant TB treatment, which are expected to be published in 2020.
Dec 11 WHO rapid communication

FDA clears disposable duodenoscope

Originally published by CIDRAP News Dec 16

The US Food and Drug Administration (FDA) recently announced that it has cleared the first fully disposable duodenoscope, which is designed to reduce the risk of infection due to difficulties sterilizing the devices.

Duodenoscopes are threaded through a patient's mouth into the top of the small intestine and are used to visualize the upper gastrointestinal tract, and they provide a less invasive way to treat some problems, such as removing pancreatic and biliary duct blockages. However, the devices have many small parts, making them difficult to clean. Some models have been linked to a number of outbreaks involving multidrug-resistant bacteria in US and European hospitals.

The disposable model, called the EXALT Model D single-use duodenoscope, is made by Boston Scientific Corp. In a Dec 13 statement, the company said the device is made for use in endoscopic retrograde cholangiopancreatography procedures (ERCP), and the FDA had granted it breakthrough device designation. Each year, more than 1.5 million ERCPs are performed in the world, according to the company, which added that it plans to start selling the device on a limited basis during the first quarter of 2020.

Jeff Shuren, MD, JD, who directs the FDA Center for Devices and Radiological Health, said in the FDA statement, "The availability of a fully disposable duodenoscope represents another major step forward for improving the safety of these devices, which are used in more than 500,000 procedures in the U.S. each year."

The new approval comes about a month after the FDA approved a new type of duodenoscope with fewer parts needing disinfection.
Dec 13 FDA statement
Dec 13 Boston Scientific press release
Nov 18 CIDRAP News scan "FDA clears duodenoscope with fewer parts needing disinfection"