Stewardship / Resistance Scan for May 08, 2019

MCR-9 gene in Salmonella
Carbapenem de-escalation

MCR-9 gene discovered in Salmonella Typhimurium strain

Researchers from Cornell University have discovered another variant of the mobile colistin-resistance gene MCR, according to a study yesterday in mBio.

The MCR-9 gene was identified in a multidrug-resistant (MDR) Salmonella enterica serotype Typhimurium strain isolated from a patient in Washington state in 2010. The strain was tested for phenotypic resistance to colistin and was found to be sensitive at the 2-milligrams-per-liter (mg/L) European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint. However, when the MRR-9 gene was cloned and transferred to colistin-susceptible Escherichia coli, it conferred resistance to colistin at levels up to 5 mg/L.

Further analysis revealed that the amino acid sequence of MCR-9 most closely resembled that of the MCR-3 gene, and pairwise comparisons of the predicted protein structures of all MCR genes showed that MCR-9, MCR-3, MCR-4, and MCR-7 share a high degree of similarity at the structural level. A search of the National Center for Biotechnology Information's non-redundant protein sequence database found that MCR-9 was present in multiple genera of Enterobacteriaceae.

Colistin is considered a "last resort" drug for MDR infections.

"These results indicate that mcr-9 has the potential to reduce susceptibility to colistin, up to and beyond the EUCAST breakpoint, and can be found extrachromosomally in multiple species of Enterobacteriaceae, making it a relevant threat to public health," the authors of the study write. "Future studies querying the plasmids that harbor mcr-9 (e.g., transferability, stability, and copy number variation) will offer further insight into the potential role that mcr-9 plays in the dissemination of colistin resistance worldwide."
May 7 mBio study


Study: Carbapenem de-escalation doesn't compromise clinical outcomes

Researchers at a university hospital in Spain report that a carbapenem de-escalation strategy was safe in patients with severe infections, regardless of microbiological results. The findings appeared yesterday in the International Journal of Infectious Diseases.

In the prospective observational study, conducted from August 2013 through July 2014, researchers evaluated the de-escalation strategy in all patients who started treatment with carbapenems at admission for intra-abdominal, respiratory, urinary, skin, or soft-tissue infections. De-escalation was defined as the discontinuation of carbapenems, or substitution with narrower-spectrum agents, during the first 96 hours of treatment. The primary outcomes were in-hospital morality, mortality at 30 days after carbapenem prescription, and infection-related readmission within 30 days.

The study included 1,161 patients, and de-escalation was performed in 667 (57.5%) of these. In the de-escalation group, 54.9% of cultures were positive. After propensity score matching, 30-day mortality was lower (17.4 vs 25.7%, P = 0.036), carbapenem treatment was 4 days shorter (4 vs 8 days, P < 0.001), total antibiotic therapy duration was 2 days longer (12 vs 10 days, P = 0.003) and the length of hospital stay was 5 days shorter (8 vs 13 days, P = 0.008) in the de-escalated patients versus the not-de-escalated patients. In-hospital mortality and 30-day readmission rates did not significantly differ between these groups.

The authors conclude, "Carbapenem de-escalation is a safe strategy that does not compromise the prognosis of severely ill hospitalized patients. There appeared to be no increase in 30-day mortality, 30-day re-admission rate, or length of hospital stay in these patients."
May 7 Int J Infect Dis abstract

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