In vitro evaluation of dual carbapenem combinations against carbapenemase-producing Enterobacteriaceae

Objectives: This study aimed to analyse the in vitro activity of dual combinations of carbapenems against Klebsiella pneumoniae producing the main carbapenemase types.Methods: MIC values of the carbapenems, imipenem, meropenem, ertapenem and doripenem were determined alone and in dual combinations for 20 clinical K. pneumoniae isolates producing representative carbapenemases, i.e. OXA-48 (n = 6), NDM-1 (n = 4), NDM-1 + OXA-48 (n = 2) and KPC-2 (n = 8). MICs were also determined for Escherichia coli recombinant strains with or without permeability defects producing NDM-1, OXA-48 or KPC-2. In vitro synergy combination testing was performed using the microdilution and chequerboard techniques. Fractional inhibitory concentration indexes were calculated to determine whether the combinations were synergistic, indifferent or antagonistic.Results: All carbapenemase producers were resistant to the tested carbapenems, with most isolates showing MICs of carbapenems >32 mg/L. None of the combinations was antagonistic. For KPC producers, synergistic combinations were observed with imipenem/ertapenem (5/8 isolates), imipenem/doripenem (4/8), imipenem/doripenem (4/8), meropenem/doripenem (3/8) and ertapenem/doripenem (3/8), while no synergy was observed with meropenem/ertapenem. For OXA-48 producers, synergies were observed with imipenem/ertapenem and with imipenem/meropenem for both isolates tested. Notably, combining imipenem with a non-carbapenem β-lactam (cefalotin) did not give any synergistic result. No synergy was observed for all NDM-1 and NDM-1+OXA-48 producers. Time–kill assays confirmed most of the data obtained by chequerboard testing.Conclusions: The data strongly support the hypothesis that dual carbapenem combinations might be effective against serine-β-lactamase producers (KPC, OXA-48). The imipenem-containing combinations appeared to be the most efficient

In-vitro study of ISApl1-mediated mobilization of the colistin resistance gene mcr-1

The plasmid-mediated mcr-1 gene encodes a phosphoethanolamine transferase conferring resistance to polymyxins. The mcr-1 gene is associated with insertion sequence ISApl1 (IS30 family). In-vitro mobilization assays demonstrated the functionality of the composite transposon structure ISApl1-mcr-1-ISApl1. Transposition generated a 2-bp duplication and occurred in AT-rich DNA regions. This is the first report demonstrating the mobility of the mcr-1 gene by transposition

Co-production of MCR-1 and extended-spectrum β-lactamase in Escherichia coli recovered from urinary tract infections in Switzerland

International audienc

High prevalence of carbapenemase-producing enterobacteriaceae among hospitalized children in luanda, angola

This study aimed to evaluate the prevalence of carbapenemase-producing Enterobacteriaceae in Luanda, Angola. A total of 157 rectal samples were collected from children visiting a pediatric hospital in Luanda in March 2015. Fifty-seven imipenem-nonsusceptible enterobacterial isolates were recovered, most of which were non-clonally related. The blaOXA-181 (50/57) and blaNDM-1 (7/57) carbapenemase genes were identified. Notably, OXA-181-producing Escherichia coli isolates rarely coproduced extended-spectrum β-lactamases and consequently remained susceptible to broad-spectrum cephalosporins. The blaOXA-181 gene was always located on an IncX3 plasmid, while the blaNDM-1 gene was located on either IncFIA or IncA/C plasmids. The study identified a high prevalence of OXA-181 among hospitalized children in Angola

About the usefulness of contact precautions for carriers of extended-spectrum beta-lactamase-producing Escherichia coli

Extended-spectrum β-lactamases producing Escherichia coli (ESBL-E) are increasingly identified in health care facilities. As previously done for the control of methicillin-resistant Staphylococcus aureus, many hospitals have established screening strategies for early identification of patients being carriers of ESBL producers in general and ESBL-E in particular, and have implemented contact precautions (CP) for infected and colonized patients.Methods: The incidence of ESBL-E has been compared retrospectively between two French university hospitals (A and B) with different infection control policies over a 5-year long period of time (2006–2010).Results: While hospital A only implemented standard precautions after identification of patients colonized with ESBL-E, hospital B recommended additional CP. During the period of the study, the ESBL-E incidence rate significantly increased in both hospitals, but no significant difference was observed between the two hospitals.Conclusions: This observational study did not reveal that additional CP measures had a greater impact on the incidence of ESBL-E in hospital settings