ASP Scan (Weekly) for Jul 06, 2018

Global access to antibiotics without prescription
New MDR E coli clone
Carbapenem-resistant E coli in dogs, humans
UK AMR diagnostics group launches
Rising gram-negative resistance in Europe
MCR-1 in hospital-associated E coli
Audit and feedback in the ICU
Clinical decision support tool aids stewardship

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

Global review finds antibiotics frequently supplied without prescription

About three in four antibiotic requests and three in five consultations in community pharmacies around the world result in the sale of antibiotics without a prescription, according to a systematic review and meta-analysis published yesterday in the Journal of Infection.

In a review of 38 studies published from 2000 through 2017 on the frequency of non-prescription sale and supply of antibiotics in community pharmacies in 24 countries, an international team of researchers found that the overall pooled proportion of non-prescription supply of antibiotics following a patient request was 78%, and the non-prescription supply of antibiotics based on community pharmacy staff recommendation was 58%. Antibiotics were most commonly supplied to patients with symptoms of urinary tract infections (68%), upper respiratory tract infections (67%), and gastroenteritis (63%). Penicillins, fluoroquinolones, and macrolides, respectively, were the most commonly supplied antibiotics for these conditions.

Although all included countries, with the exception of one, classified antibiotics as prescription-only medicines, the overall pooled estimate of non-prescription supply of antibiotics was 62%, with non-prescription antibiotics being sold most frequently in community pharmacies in Indonesia (91%), Syria (87%), Saudi Arabia (85%), and Ethiopia (85%). Among regions, the supply of non-prescription antibiotics was highest in Latin America (78%).

"Despite the limitation of our review, the findings suggest that antibiotics are frequently supplied without prescription in many countries even where this supply remains illegal," the authors conclude. "This overuse of antibiotics could facilitate the development and spread of antibiotic resistance."

They add that while the findings underscore the need for countries to enforce laws that limit the supply of antibiotics without prescription in community pharmacies, they also highlight the role that community pharmacists, who are the first point of healthcare contact for patients in many countries, could play in promoting prudent antibiotic use.
Jul 5 J Infect study


Study shows US emergence of multidrug-resistant E coli clone

A new study in Clinical Infectious Diseases describes the emergence of a new multidrug-resistant Escherichia coli clone in the United States.

In a multicenter surveillance study conducted at nine sites in four US cities (Seattle, Los Angeles, Minneapolis, and New York) in 2016-2017, researchers collected 6,349 consecutive clinical E coliisolates from urine, blood, or wounds and tested them for susceptibility to antibiotics and production of extended-spectrum beta-lactamase (ESBL) production. They performed additional analysis on fluoroquinolone-resistant (FQ-R) E coli isolates to determine clonal identity and resistance mechanisms. They were looking to gain further insight into hospital reports of the occurrence of FQ-R E coli belonging to the clonal group ST1193.

Of the 6,349 E coli isolates, 1,314 (20.7%) were FQ-R and represented 45 clonal groups overall. At each site, the most prevalent clonal group among FQ-R isolates was ST131 H30 (per-site mean, 45.4%), which emerged in the late 1990s and has become the most prevalent worldwide pandemic clonal group of multidrug-resistant E coli. The second most prevalent was ST1193 (23.2%). But while the prevalence of H30 did not change between 2016 and 2017, either overall (45.8% in 2016 vs. 46.1% in 2017) or at any single site, the prevalence of ST1193 increased both overall (18.4% in 2016 vs. 25.9% in 2017) and at six sites. In addition, at four sites that provided data on 2011 FQ-R isolates, ST1193 exhibited a seven-fold overall prevalence increase (3.4% in 2011 to 23.4% in 2016-2017).

In addition to being FQ-R, the ST1193 isolates were often co-resistant to trimethoprim-sulfamethoxazole and tetracycline, but unlike ST131 H30 remain susceptible to most beta-lactam antibiotics. The researchers also found that ST1193 E coli appears to target younger patients and is less likely to be isolated from blood.

The authors say the findings, along with reports of ST1193 being isolated in hospitals in Europe and Asia, suggest that ST1193 is likely to be a pandemic clonal group similar to H30. They conclude, "Discovery of the basis for the global expansion of ST1193 could provide insights into how successful clonal groups of multidrug-resistant E. coli emerge and what interventions could limit their spread."
Jun 29 Clin Infect Dis abstract


Investigation suggests carbapenemase-producing E coli passed from humans to dogs

Originally published by CIDRAP News Jul 5

Finnish researchers are reporting the first transmission of carbapenemase-producing E coli between humans and dogs.

In an article today in Eurosurveillance, the researchers report that a strain of carbapenemase-producing E coli—ST167 NDM-5—was found in two dogs and one human from the family that owned the dogs. The E coli was originally identified in the ears of the two dogs, both of which had histories of ear infections, and later in rectal swabs from the family member. Molecular analysis and whole-genome sequencing of 10 of the isolates (7 from the dogs, 3 from the human) revealed that the isolates were nearly identical. The dogs and additional family members also carried an identical strain of extended-spectrum beta-lactamase (ESBL)-producing E coli, ST69 CTX-M-9.

These findings suggest interspecies transmission, with the pathogen likely being passed from the humans to the dogs. While carbapenemase-producing E coli is rare in humans in Finland, the authors of the article note that carbapenem-resistant bacteria had not been observed in dogs in Finland before this report. In addition, carbapenems are not authorized for veterinary use in Finland, and the investigation did not reveal any use of carbapenems in the two dogs in the study. But they suggest that the dogs' frequent exposure to other antibiotics to treat their ear infections probably sustained and facilitated the propagation of the NDM-producing E coli after it had been acquired.

"The widespread use of antimicrobials in companion animals could thus enable them to act as reservoirs for CPE [carbapenemase-producing Enterobacteriaceae] isolates and other resistant bacteria," they write.

The authors conclude that veterinary laboratories should remain alert and should screen Enterobacteriaceae for carbapenem resistance, and that the veterinary community should continue to emphasize the importance of prudent antimicrobial use.
Jul 5 Eurosurveill research article


UK groups launch AMR diagnostics collaborative

Originally published by CIDRAP News Jul 5

To help support antimicrobial stewardship efforts in the United Kingdom, health officials today announced the formal launch of the UK Antimicrobial Resistance (AMR) Diagnostic Collaborative.

The group brings together partners from the National Health Service, academic institutions, industry, and other national groups to coordinate the development of guidance and evaluation of interventions to integrate high-quality diagnostics.

Fiona Carragher, MSc, chair of the new UK AMR Diagnostic Collaborative, who is also deputy chief science officer with NHS England, said in a post on Global Cause, a global health news site, that diagnostics are a crucial weapon in the battle against antimicrobial resistance, "but they can only deliver their true potential if we get right the what, when, where and how of diagnostic use."

Rapid point-of-care testing has the potential to help guide appropriate treatment decisions, and as new technology, but the new devices need to meet high expectations, she said, adding that effective evaluation will need a coordinated approach at all steps, from innovation to implementation. Carragher also said a structured approach is needed for education and training for staff that will be involved in using the new tests.
Global Cause report


ECDC report shows rising resistance in gram-negative bacteria

Originally published by CIDRAP News Jul 3

A new European surveillance report shows rising resistance to key antibiotics, and increasing trends in multidrug resistance, in invasive gram-negative bacteria.

The report from the European Centre for Disease Prevention and Control (ECDC), based on data for 2014 from the European Antimicrobial Resistance Surveillance Network (EARS-Net), shows that the European Union/European Economic Area (EU/EEA) population-weighted mean percentages of invasive Klebsiella pneumoniae isolates resistant to fluoroquinolones, third-generation cephalosporins, and aminoglycosides increased significantly from 2011 through 2014, and combined resistance to all three drugs rose from 16.7% in 2011 to 19.6% in 2014. In addition, the population-weighted mean percentage of K pneumoniae isolates resistant to carbapenems rose from 6.0% in 2011 to 7.3% in 2014. Resistance to carbapenems was more frequently reported in bloodstream infections in southern and southeastern Europe.

During the same period, the percentage of invasive E coli isolates resistant to third-generation cephalosporins increased from 9.6% to 12.0%, and combined resistance to third-generation cephalosporins, fluoroquinolones, and aminoglycosides rose from 3.8% to 4.8%. Antimicrobial resistance in Acinetobacter species showed large variations across Europe, with generally high resistance percentages reported from Baltic countries, southern, and southeastern Europe. Combined resistance to fluoroquinolones, aminoglycosides, and carbapenems was the most frequently reported resistance phenotype in 2014.

Large inter-country variations in the percentage of methicillin-resistant Staphylococcus aureus(MRSA) isolates were also observed, but the EU/EEA population-weighted mean percentage decreased from 18.6% in 2011 to 17.4% in 2014, continuing the downward trend reported in the 2009-2012 period.

The authors of the report warn that the combination of rising multidrug resistance in gram-negative bacteria, plus additional resistance to carbapenems, means that very few options are left for patients infected with these pathogens. "The ongoing increase in resistance to a number of key antimicrobial groups in invasive bacterial isolates reported to EARS-Net is therefore of great concern and constitutes a serious threat to patient safety in Europe," they conclude.
Jul 3 ECDC surveillance report


Genomic analysis shows diversity of MCR-1-carrying E coli 

Originally published by CIDRAP News Jul 3

A study today in the journal mBio provides new insights into the transmission and epidemiology of the MCR-1 colistin-resistance gene.

In the study, scientists from China and the United Kingdom conducted a comprehensive genomic analysis of 80 MCR-1-positive E coli (MCRPEC) strains isolated from clinical samples and fecal samples of inpatients and healthy volunteers at a hospital in Hangzhou. They wanted to better understand the genetic diversity of the isolates and how the MCR-1 gene circulates in a hospital setting, which could help inform infection control policies.

The results of the analysis showed that the 80 MCRPEC were significantly diverse, distributed throughout four phylogroups and represented by 50 ST clades, a finding that indicates a lack of clonal spread and implies there was no outbreak of MRCPEC in the hospital. But similarities in isolates from two patients who were kept in the same surgical ward at the same time suggests the possibility of nosocomial transmission of MCRPEC exists.

Further analysis revealed that in 73 of the 80 MCRPEC isolates, the MCR-1 gene was carried on plasmids, and that the genetic context of the plasmids showed great diversity, as evidenced by the different functional insertion sequence elements, toxin-antitoxin systems, and heavy metal resistance determinants. Additionally, MCR-1 was found to be frequently associated with genes encoding beta-lactam and fluoroquinolone resistance. Antibiotic resistance profiling showed that all strains were resistant to multiple categories of drugs.

"These findings provide important information on the transmission and epidemiology of mcr-1 and are of significant public health importance as the information is expected to facilitate the control of this significant antibiotic resistance threat," the authors write.
Jul 3 mBio study


Meta-analysis finds no ICU mortality increase with audit and feedback

Originally published by CIDRAP News Jul 3

A systematic review and analysis of studies on antimicrobial stewardship in the intensive care unit (ICU) has found that the use of audit and feedback did not increase mortality, Canadian researchers report in Clinical Infectious Diseases.

Following a review of 2,448 unique citations, the researchers found 11 studies that evaluated prospective audit and feedback in an ICU setting and reported any measure of mortality. Prospective audit and feedback was defined as an intervention in which healthcare workers with antimicrobial stewardship expertise, independent of the clinical team, provided written or oral instructions on antimicrobial use for specific patients to the ICU clinical team on a regular basis.

The selected studies included three interrupted time series analyses and eight uncontrolled before-after studies. Six studies involved audit and feedback for all ICU patients, while the other five studies focused only on patients on broad spectrum antibiotics, patients with positive cultures, or patients with hematological malignancies. Frequency of feedback varied from 3 days per week to daily.

In the meta-analysis of the five studies where the intervention was similar, and the outcome was measured in the same population (all ICU patients) and defined in the same way (ICU mortality), the pooled relative risk for mortality was 1.03. A second meta-analysis of three smaller studies that evaluated mortality only in patients directly assessed by the ASP found a pooled relative risk of ICU mortality of 1.06. Three studies were not appropriate for meta-analysis, but their results were consistent with the overall findings.

The authors say that while the findings have several limitations—including the variability between studies with respect to patient populations and the nature of intervention, the lack of adjustment for confounding variables, and the possibility of publication bias—the results provide the strongest evidence to date that implementing audit and feedback in the ICU setting does not increase patient mortality.
Jun 30 Clin Infect Dis abstract


Study: Stewardship module increases antimicrobial reviews, interventions

Originally published by CIDRAP News Jul 2

A new study by researchers with the University of Chicago Medical Center has found that use of a clinical decision support system at the hospital significantly increased the number of antimicrobial reviews and interventions while maintaining a sustained impact on antimicrobial utilization.

The single-center retrospective cohort study, published in Infection Control and Hospital Epidemiology, assessed the impact of the Epic Antimicrobial Stewardship Module (EAM) on antibiotic stewardship program (ASP) interventions by comparing the total number of interventions during the preimplementation period (February 2014 through January 2015) versus the postimplementation period (May 2016 through April 2017). EAM uses specific criteria to generate a list of alerts for the ASP team to review, including new start restricted antimicrobials, intravenous to oral administration, azole therapeutic drug monitoring, anti-retrovirals, pathogen-drug mismatch, and Staphylococcus aureus or yeast in blood culture. The EAM also provides a list of patients with specific pathogens, such as multidrug-resistant organisms or organisms with elevated minimum inhibitory concentrations to certain antibiotics.

Results of the analysis showed that prior to EAM implementation, the ASP team documented 5,433 antimicrobial reviews and made 1,436 interventions (119.7 interventions per month). After EAM implementation, the ASP team documented 8,288 reviews and made 7,444 interventions (620.3 interventions per month). A marked increase in the rate of all types of interventions was observed, with optimization and monitoring of antimicrobial therapy constituting most interventions pre-EAM and post-EAM (46.8% and 54.3%), followed by safety/monitoring (37.2% and 28.2%). Interventions were accepted more than 96% of the time.

Analysis of secondary outcomes showed that days of therapy (DOT) for all target antimicrobials per 1,000 patient-days per group decreased from 5,338.5 pre-EAM to 4,753.2 post-EAM (P = 0.4), while the percentage of antimicrobial drug expenditures relative to overall drug expenditures did not change significantly (7.14% pre-EAM and 8.32% post-EAM, P > .05). The average length of stay was similar between both groups (9.2 days vs. 9.0 days, P > .05), but the overall inpatient all-cause mortality rate was higher in the pre-EAM group (0.39 vs. 0.20, P < .01).

"The improved process for identification of patients requiring ASP review and/or intervention as well as streamlined documentation resulting from the EAM have broadened our ability to ensure optimal, safe, and judicious use of antimicrobials," the authors write. "Based on our experience, hospitals looking to establish or improve upon existing ASP practices should consider investing in a comprehensive clinical decision support system to improve efficiency and document value."
Jun 28 Infect Control Hosp Epidemiol abstract 


Dutch report shows small increase in animal antibiotic use

Originally published by CIDRAP News Jul 2

A new report by Dutch public health, veterinary, and food safety officials shows that sales of antibiotics for animals in the Netherlands in 2017 rose slightly compared to 2016, while the presence of antibiotic-resistant bacteria in chickens fell.

The MARAN 2018 report (Monitoring of Antimicrobial Resistance and Antibiotic Usage in Animals in the Netherlands) shows an increase of 3% in sales of antimicrobial veterinary medicinal products in 2017 (181 tonnes) compared to 2016 (176 tonnes), with significant reductions in antibiotic use observed in broilers and turkeys, smaller reductions observed in pigs, and veal calves, and a small increase observed in dairy cattle. The use of antibiotics of critical importance to human healthcare (fluoroquinolones, 3rd and 4th generation cephalosporins, polymixins, and trimethoprim/sulfonamides) continued to drop, with steep declines noted in comparison with 2011 sales.

Analysis of antimicrobial resistance data found that resistance in indicator E coli from fecal samples to most antibiotics tested decreased in broilers from 2016 to 2017, stabilized in pigs, and showed a slight increase in veal calves. The proportion of resistant E coli remained low in dairy cattle. As in previous years, levels of resistant E coli were substantially higher in chicken and turkey meat than in pork and beef. The proportion of E coli isolates resistant to 3rd generation cephalosporins was low in fecal samples from broilers and pigs and not detected in dairy cattle and veal calves.

Selective culturing of fecal samples found that 22.6% were positive for ESBL/AmpC-producing E coli, with a sharp decrease noted in broilers (from 56.5-50.3% in 2015-2016 to 32.6% in 2017); the prevalence in pigs and dairy cows also decreased and stabilized at around 10%. For the second year in a row, an increase was observed in white and rose veal calves carrying ESBL/AmpC-producing E coli,and 2017 was the first year a higher prevalence was recorded in veal calves than in broilers (36.7% vs. 32.6%). The overall presence of ESBL/AmpC-producing E coli in meat samples in 2017 was 9.6%.

No carbapenemase-producing Enterobacteriaceae were detected in active surveillance of livestock, and the colistin-resistance gene MCR-1 was detected in 1.2% of E coli from livestock 7.7% of E colifrom chicken meat. The authors of the report say the higher prevalence of MCR-1 in chicken meat compared to fecal broiler samples could be explained by the fact that some retail chicken meat in Dutch supermarkets comes from countries where colistin is used in livestock production.
Jun 27 MARAN 2018 report

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