I ncreased prevalence of infections caused by Gram-negative pathogens that are multidrug resistant has prompted the reconsideration of polymyxins as therapeutic options. Resistance to polymyxins is due to mutations in the lipid A synthesis (1) that can be caused by the acquisition of mcr (2). Genes mcr-1 through mcr-8 (3, 4) and multiple subtypes have been reported to encode proteins that share 30 to 70% amino acid identity.We previously reported the prevalence of mcr-1 among Escherichia coli and Klebsiella pneumoniae isolates collected worldwide during 2014 and 2015 by the SENTRY Program (5). As an ongoing effort, colistin-resistant E. coli and K. pneumoniae clinical isolates collected in 2016 were screened for the presence of mcr, and a new mcr-1 variant was characterized.Among 11,493 E. coli and K. pneumoniae isolates tested, 199 (1.7%) were resistant to colistin per EUCAST criteria (6) and considered non-wild type by the CLSI (7) epidemiological cutoff value. Isolates displaying colistin MIC values of Ն4 mg/liter (resistant/ non-wild type) were screened for the mcr-1 and mcr-2 genes by PCR. All isolates carrying mcr were submitted to whole-genome sequencing.A total of 12 isolates were mcr-1 positive, including 10 E. coli isolates (2 in the United States, 3 [clonal] in Venezuela, 3 in Peru, 1 in Colombia, and 1 in Poland) and 2 K. pneumoniae isolates (1 each in Spain and Italy) (Table 1) recovered from invasive infections (Table 1). Colistin MIC values ranged from 4 to Ͼ8 mg/liter. No isolate yielded positive results for mcr-2.One E. coli isolate from Peru (sequence type 95 [ST95]) carried mcr-1 displaying an insertion of valine in amino acid position 6 and was designated mcr-1.11. This isolate showed susceptible phenotypes to ␤-lactams, aminoglycosides, tigecycline, and trimethoprim-sulfamethoxazole but resistance to tetracycline and quinolones ( Table 1). The mcr-1.11 gene was located on a 63-kb IncI2 plasmid carrying no other resistance genes (GenBank accession number KY853650). Two genetically unrelated E. coli isolates (ST7954 and ST1485) from the same hospital that carried mcr-1 displayed the same plasmid structure (Table 1; Fig. 1).The mcr-1.11 gene cloned in an E. coli background exhibited colistin and polymyxin B MIC results (2 to 8 mg/liter) similar to those of mcr-1 (2 to 4 mg/liter). The mcr-1.11 gene likely emerged via spontaneous mutation within a plasmid structure that is endemic to the medical center in Peru, as seems common among mcr-like genes (1).Unlike the vast majority of reports of mcr-like genes from animal-based sources, our results show a global prevalence of colistin resistance and mcr-1 among isolates collected from important human infections. Similar to the 2014 to 2015 survey, isolates carrying mcr-1 were identified in only 0.1% of the isolates tested; however, this study emphasizes its worldwide dissemination. Furthermore, our results and others (8,9) Citation Deshpande LM, Hubler C, Davis AP, Castanheira M. 2019. Updated prevalence of mcr-like genes among Escherichia coli and Kle...

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BackgroundPlazomicin (PLZ) is a next-generation aminoglycoside (AMG) stable against aminoglycoside-modifying enzymes (AME) that completed Phase 3 studies for complicated urinary tract infections and serious infections due to carbapenem-resistant Enterobacteriaceae (ENT). We evaluated the activity of PLZ and AMGs against ENT collected in US hospitals during 2016.MethodsA total of 2,097 ENT were susceptibility (S) tested by CLSI reference broth microdilution methods. E. coli, Klebsiella spp. Enterobacter spp., and P. mirabilis isolates displaying non-S MICs (CLSI criteria) for gentamicin (GEN), amikacin (AMK), and/or tobramycin (TOB) were submitted to WGS, de novo assembly and screening for AME genes.ResultsAgainst ENT, PLZ was more active than all 3 clinically available AMGs (Table). PLZ and AMK activities were stable regardless of the infection type; however, differences were observed for GEN and TOB. Bloodstream isolates displayed higher GEN MICs when compared with the other infection sites. TOB activity varied 4-fold, being higher for bloodstream and pneumonia infections and lower for skin/soft tissue and other/unknown specimens. Against 198 isolates carrying 1 or more AME-encoding genes detected among 208 AMG-non-S isolates, the activity of PLZ was 8- to 16-fold greater when compared with the activity of AMK and at least 16-fold higher than the activity of GEN or TOB.ConclusionPLZ was active against ENT isolates from US hospitals regardless of infection type. PLZ displayed activity against isolates carrying AME genes that represent 12.0% of selected species. AME-carrying isolates were considerably more resistant to AMK, GEN, and TOB, highlighting the potential value of PLZ to treat infections caused by these organisms.This project has been funded under BARDA Contract No. HHSO100201000046C.Disclosures M. Castanheira, Achaogen: Research Contractor, Research grant; L. M. Deshpande, Achaogen: Research Contractor, Research grant; C. M. Hubler, Achaogen: Research Contractor, Research grant; R. E. Mendes, Achaogen: Research Contractor, Research grant; A. W. Serio, Achaogen: Employee, Salary; K. M. Krause, Achaogen: Employee, Salary; R. K. Flamm, Achaogen: Research Contractor, Research grant

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This study investigated the activity of an oral carbapenem, tebipenem, against various molecularly characterized subsets of Escherichia coli . A total of 15.0% of E. coli isolates (360/2,035 isolates) met the MIC criteria for screening for β-lactamases.