ASP Scan (Weekly) for Jul 20, 2018

Swiss VRE outbreak
CRE screening
Drug-resistant yeast
Best antibiotic practices for farms
Colistin resistance and MCR-1
Antibiotic persistence in goat's milk
C diff treatment comparison
Antifungal stewardship
Funds for resistant UTI drug

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

VRE outbreak identified in Swiss hospitals

Originally published by CIDRAP News Jul 19

Swiss researchers have identified a large outbreak of vancomycin-resistant enterococci (VRE) clone ST796 across multiple hospitals in Switzerland, according to a report today in Eurosurveillance.

The outbreak began on Dec 30, 2017, when two cases of vancomycin-resistant Enterococcus faecium bloodstream infection were reported in the hemato-oncology ward of Bern University Hospital. By April 30, 2018, screening of 3,096 samples from contact patients found that 89 patients in four hospitals were colonized or infected by VRE. Whole-genome sequencing (WGS) found that 77 of the 89 isolates (86.5%) were virtually indistinguishable, and core genome multilocus sequence typing (cgMLST) identified them as ST796, which was first recognized at an Australian hospital in 2011 and spread rapidly throughout Australia and New Zealand in the following years.

WGS analysis revealed a clear genomic relationship between isolates from the outbreak and those from Australia.

All 77 of the isolates carried the vanB resistance gene, and antimicrobial susceptibility profiles of 68 of the isolates showed resistance to ampicillin and levofloxacin and high-level resistance to gentamycin. Forty-six isolates were resistant to vancomycin, 21 were intermediate, and 1 was susceptible.

The authors conclude that the rapid spread of this VRE clone, and its history of rapid spread across hospitals, could seriously endanger healthcare facilities and warrants strengthening and synchronization of national infection control practices. The World Health Organization has listed VRE, which can be transmitted via the environment or healthcare workers, as a high priority for antibiotic development.
Jul 19 Eurosurveill rapid communication


Study shows benefits of targeted CRE screening on admission

Originally published by CIDRAP News Jul 19

A study today in Infection Control and Hospital Epidemiology suggests active screening to identify patients colonized with carbapenem-resistant Enterobacteriaceae (CRE) is feasible, especially if targeted toward high-risk admissions and units.

In the study, researchers from Rush University Medical Center in Chicago retrospectively analyzed the implementation and outcomes of CRE admission screening from 2013 to 2016 during two study periods. In period 1, the hospital implemented active CRE rectal culture screening for all adults admitted to an intensive care unit (ICU) and for those transferred from outside facilities to general wards. In period 2, the screening policy in the ICU was modified so that only patients transferred from outside facilities were screened.

Overall, 11,757 patients qualified for screening, and rectal cultures were performed for 8,569 (73%). Overall adherence to screening in the ICU was higher in period 1 than in period (83.4% vs. 67.3%). The CRE culture positivity rate (positive CRE screening cultures divided by the total number of screening cultures collected) was highest in the medical and surgical ICUs during period 2 (3.3% combined rate); this rate was higher than the aggregated rate in the medical and surgical ICUs in period 1 (0.7% combined rate) and higher than the rate in general wards for period 2 (0.6%).

Although moving from a universal to a targeted screening resulted in more efficient screening, the analysis of the two periods also showed that nearly half of the 21 CRE screen-positive patients identified during period 1 (47.6%) were not directly transferred from other institutions, and therefore would have been missed by targeted screening.

Analysis of a subset of CRE screen-positive patients identified during period 2 found that, of 13 patients previously identified by outside facilities as CRE-positive, only 4 had documentation of CRE in their medical records, a finding the authors suggest bolsters the case for admission screening.
Jul 19 Infect Control Hosp Epidemiol abstract


Study indicates common yeast, pathogenic yeast are same species

Originally published by CIDRAP News Jul 19

A type of yeast that's commonly used in the food production industry is the same species as a pathogenic, drug-resistant yeast that's one of the five most prevalent causes of yeast infections, according to a study today in PLoS Pathogens.

In the study, researchers at University College Dublin examined the genomes of 20 clinical isolates of Candida krusei, which causes 2% of all yeast infections and has innate resistance to the widely used antifungal drug fluconazol, with 12 environmental isolates of Pichia kudriavzevii, a yeast regarded as safe by the US Food and Drug Administration because it's been used for centuries to make fermented food products. P kudriavzevii also has biotechnology applications, having been used for producing ethanol and other chemicals.

The results showed that the genomes of the isolates were 99.6% identical in their DNA sequence, indicating they belong to the same species. In addition, the researchers found that the P kudriavzevii isolates had levels of drug resistance similar to those of the C krusei isolates.

The authors of the study say the findings suggest P kudriavzevii could cause disease in humans, and that there should be limits on the levels of drug resistance in P kudriavzevii strains used in industry, particularly in food production.
Jul 19 PLos Pathog study


New UK program targets farmers', veterinarians' antibiotic use

Originally published by CIDRAP News Jul 18

The United Kingdom's National Office of Animal Health (NOAH) launched a new best practices program meant to guide the responsible use of antibiotics among farmers and veterinarians. The program, which includes online training modules, is aimed at all those working in the sheep, dairy, beef, and pig sectors.

"The UK is at the forefront of global efforts to tackle antibiotic resistance. Recent statistics show there has been a 27 per cent drop in use of antibiotics in food-producing animals in the UK since 2014—meeting a government commitment two years early," British Biosecurity Minister Lord Gardiner said in a NOAH press release. "Our farmers and vets must be commended for driving down antibiotic use in livestock to this all-time low—setting an excellent example for others around the world to follow. But it is vital we continue making progress."

The training modules are available on the NOAH website or through the online Lantra eLearning platform.  According to NOAH, veterinarians will also be to access resource materials, enabling them to help train their clients.

A number of stakeholders helped create the training program, including the Responsible Use of Medicines in Agriculture Alliance (RUMA), the Veterinary Medicines Directorate (VMD), the British Retail Consortium (BRC), and leading academics.
Jul 17 NOAH press release


Thai study finds high colistin resistance, MCR-1 rates

Originally published by CIDRAP News Jul 18

A single-center study of hospitalized Thai patients who received colistin for treating Escherichia coli or Klebsiella pneumoniae infections found that 47.5% had colistin-resistant pathogens and 13.0% of isolates harbored the MCR-1 colistin-resistance gene. The findings appeared yesterday in Antimicrobial Resistance & Infection Control.

Researchers analyzed data on 139 adult patients in Siriraj Hospital in Bangkok from December 2016 through November 2017. They collected culture samples from the stool and infection site of each patient who received colistin at study enrollment, 3 and 7 days after study enrollment, and once a week thereafter to determine colistin resistance.

Colistin has been used to treat carbapenem-resistant gram-negative infections in Thailand, especially carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, for more than 10 years, the authors report. The prevalence of colistin-resistant A baumannii and P aeruginosa, however, is still less than 5%.

The team found an overall prevalence of colistin-resistant E coli or K pneumoniae colonization of 47.5%, with the prevalence rising from 17.3% at study enrollment to 30.2% afterward. The researchers found the use of fluoroquinolones, aminoglycosides, and colistin to be significantly associated with colistin-resistant pathogen colonization. They detected the MCR-1 gene in 13.0% of isolates and in 27.3% of subjects with colistin-resistant colonization. Colonization with colistin-resistant E coli or K pneumoniae persisted in 65.2% of the patients at the end of the study.
Jul 17 Antimicrob Resist Infect Control study


Study hints that herbal drug may cut risk of antibiotic resistance in dairy animals

Originally published by CIDRAP News Jul 18

A polyherbal drug used in India to prevent mastitis in livestock appears to reduce the persistence of antibacterial drugs in milk, a team from West Bengal University of Animal and Fishery Sciences reported yesterday in Scientific Reports.

Ceftriaxone is used to treat mastitis in dairy settings, but persistence of antibacterial drugs for prolonged periods in milk is thought to increase the probability of antimicrobial resistance, the authors wrote. Fibrosin, a proprietary blend of herbal ingredients, is marketed by an Indian company to facilitate cleaning of the udder by clearing tissue debris and aiding the flow of milk during mastitis.

To assess the impact of the herbal drug on antibiotic clearance, researchers divided 18 healthy lactating goats into three groups: a control group that got a single dose of ceftriaxone, one group of healthy goats that got a single dose of Fibrosin 1 hour before ceftriaxone injection, and one group of goats with mastitis that got a dose of Fibrosin 1 hour before ceftriaxone injection. Then they collected milk samples at several points up to 720 hours after dosing.

They found that the polyherbal drug hastened the excretion of ceftizoxime from milk compared to the control group; ceftriaxone could not be detected in milk.

The team concluded that adjunct single or repeated therapy of the polyherbal drug may block the persistence of ceftriaxone and shorten the persistence of ceftizoxime.
Jul 18 Sci Rep abstract


Meta-analysis suggests fidaxomicin is most effective C diff treatment

Originally published by CIDRAP News Jul 17

A systematic review and meta-analysis of randomized controlled trials examining antibiotic therapy for non-recurrent Clostridium difficile infections has found that fidaxomicin provides a sustained symptomatic cure most frequently, researchers reported yesterday in The Lancet Infectious Diseases.

For the network meta-analysis, researchers from the University of Leeds screened more than 23,000 studies published through June 2017 to compare and rank the efficacy of 13 different treatments for non-recurrent C difficile infections. The primary outcome was sustained symptomatic cure, defined as the number of patients with resolution of diarrhea minus the number with recurrence or death.

The final analysis included 24 randomized controlled trials, which comprised 5,361 patients. The overall quality of evidence was rated as moderate to low. For sustained symptomatic cure, fidaxomicin (odds ratio [OR], 0.67) and teicoplanin (OR, 0.37) were significantly better than vancomycin, while teicoplanin (OR, 0.27), ridinilazole (OR, 0.41), fidaxomicin (OR, 0.49), surotomycin (OR, 0.66), and vancomycin (OR, 0.73) were better than metronidazole. Bacitracin was inferior to teicoplanin (OR, 0.22) and fidaxomicin (OR, 0.40), and tolevamer was inferior to all drugs except for LFF571 (OR, 0.50) and bacitracin (OR, 0.67). Global heterogeneity of the entire network was low.

"The findings of this network meta-analysis suggest that, of the currently approved treatments, fidaxomicin has the strongest evidence for being the most effective treatment in providing a long-term cure against C difficile," the authors write. "Apart from affordability, there is little evidence to support use of metronidazole as a first-line treatment against infections with C difficile."

They add that teicoplanin and ridinilazole could also be effective treatments, but that routine implementation of these drugs should await results from large trials.
Jul 16 Lancet Infect Dis study


Antifungal stewardship reduces antifungal costs, study finds

Originally published by CIDRAP News Jul 17

Introduction of an antifungal stewardship team to a tertiary cardiopulmonary hospital significantly reduced monthly antifungal expenditures, UK researchers reported yesterday in Antimicrobial Agents and Chemotherapy.

The stewardship team, consisting of a medical mycologist and a specialist pharmacist, provided weekly stewardship ward rounds, twice monthly multidisciplinary team meetings, and a dedicated weekly outpatient clinic. Data for the first 18 months of fungal stewardship implementation was recorded.

A total of 178 patients were reviewed by the stewardship team over the 18-month period, with 285 recommendations made to inpatients and 287 recommendations made to outpatients. The most common diagnoses treated were allergic bronchopulmonary asperilligosis and chronic pulmonary asperilligosis. Cystic fibrosis patients were the largest patient group. Among the recommendations of the stewardship team were stepping down treatment to oral antifungals, ensuring appropriate dosing to attain therapeutic levels and avoid toxicity, and stopping treatment in patients without confirmed fungal disease or those likely to only be colonized.

The intervention was associated with an overall reduction in antifungal expenditure of 44.8%, from £290,000 ($380,000) per month to £160,000 ($209,000) per month, largely driven by reduced use of intravenous voriconazole and caspofungin. In addition, there was a reduction in defined daily dose per 100 bed-days of all antifungal medications (P = 0.017). There was no increase in morbidity or mortality.

The authors of the study conclude that with the use of antifungals in patients with chronic respiratory disease likely to continue rising due to better recognition of fungal disease, this stewardship model could be introduced in other facilities where antifungal expenditures are climbing.
Jul 16 Antimicrob Agents Chemother abstract


Spero awarded $16 million to develop treatment for drug-resistant UTI

Originally published by CIDRAP News Jul 17

The Biomedical Advanced Research and Development Authority (BARDA) awarded Spero Therapeutics, Inc, a biopharmaceutical company in Cambridge, Mass., up to $54 million to develop SPR994, Spero's oral carbapenem product candidate.

SP994 would be used to treat complicated urinary tract infections (cUTIs) caused by antibiotic resistant gram-negative bacteria. The award includes an initial $15.7 million, with the potential for an additional $28.5 million to be given over 5 years.

"As part of the inter-agency collaboration with Spero, a series of studies to assess the efficacy of SPR994 in the treatment of infections caused by biodefense threats such as anthrax, plague and melioidosis will be conducted by the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). In addition, the Defense Threat Reduction Agency (DTRA) will provide support up to $10 million to fund the nonclinical biodefense aspects of the inter-agency collaboration," Spero said in a press release.

Spero said it plans to initiate a phase 3 clinical trial of SPR994 for the treatment of cUTI at the end of this year.  In preclinical studies, SPR994 showed potent antibiotic activity against gram-negative bacteria, including extended-spectrum beta-lactamases (ESBLs) and ESBL-producing K pneumoniae
Jul 16 Spero press release

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