Stewardship / Resistance Scan for Jul 03, 2018

Rising gram-negative resistance in Europe
MCR-1 in hospital-associated E coli
Audit and feedback in the ICU

ECDC report shows rising resistance in gram-negative bacteria

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 Escherichia 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 

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 Escherichia 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

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

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