ABSTRACT
The novel non-ß-lactam ß-lactamase inhibitor NXL104, in combination with cefepime, ceftazidime, ceftriaxone, amdinocillin, and meropenem, was tested against 190 extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolates, 94 AmpC-hyperproducing E. coli isolates, and 8 AmpC/ESBL-coexpressing E. coli isolates. NXL104 restored 100% susceptibility to the partner cephalosporins for all isolates tested. Amdinocillin and meropenem MICs were modestly improved (2 to 32 times lower) by NXL104. These results suggest that NXL104 may be useful in combination with ß-lactams for the treatment of infections caused by ESBL- and AmpC-producing Enterobacteriaceae.
Subject(s)
Azabicyclo Compounds/pharmacology , Escherichia coli/drug effects , Escherichia coli/enzymology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/enzymology , beta-Lactamases/metabolism , beta-Lactams/pharmacology , Escherichia coli/genetics , Klebsiella pneumoniae/genetics , beta-Lactamases/geneticsABSTRACT
The in vitro activity of ceftazidime in combination with NXL104 versus 470 Pseudomonas aeruginosa clinical isolates was evaluated using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methods. Ceftazidime had MIC90s of 8 µg/ml and 32 µg/ml in the presence and absence of NXL104, respectively. Of 25 multidrug-resistant P. aeruginosa isolates, the percentages with a ceftazidime MIC of ≤8 µg/ml with and without NXL104 were 60% and 4%, respectively. These data suggest that the ceftazidime-NXL104 combination may prove useful for treating many P. aeruginosa infections.
Subject(s)
Anti-Bacterial Agents/pharmacology , Azabicyclo Compounds/pharmacology , Ceftazidime/pharmacology , Pseudomonas aeruginosa/drug effects , beta-Lactamase Inhibitors , Humans , Microbial Sensitivity TestsABSTRACT
The in vitro activity of colistin was evaluated versus 3,480 isolates of gram-negative bacilli using CLSI broth microdilution methods. The MIC(90) of colistin was < or = 2 microg/ml against a variety of clinically important gram-negative bacilli, including Escherichia coli, Klebsiella spp., Enterobacter spp., Acinetobacter baumannii, and Pseudomonas aeruginosa. All multidrug-resistant (n = 76) P. aeruginosa isolates were susceptible to colistin (MIC, < or = 2 microg/ml). These data support a role for colistin in the treatment of infections caused by multidrug-resistant P. aeruginosa.
Subject(s)
Anti-Bacterial Agents/pharmacology , Colistin/pharmacology , Gram-Negative Bacteria/drug effects , Drug Resistance, Multiple, Bacterial , Humans , Microbial Sensitivity Tests , Time FactorsABSTRACT
OBJECTIVES: Multidrug-resistant (MDR) Acinetobacter baumannii is a growing concern in many countries. This report describes patient demographics, antimicrobial susceptibilities and molecular characteristics of A. baumannii cases identified through the Canadian Ward Surveillance Study (CANWARD). In addition, clinical cases involving MDR carbapenem-resistant A. baumannii are also detailed in this report. METHODS: From January to December 2007, 12 hospital centres across Canada submitted pathogens from clinics, emergency rooms, intensive care units and medical/surgical wards as part of the CANWARD study. MICs were determined using microbroth dilution (CLSI). PCR and sequence analysis identified OXA genes among carbapenem-resistant isolates. PFGE was used to determine genetic relatedness and compare representatives of the Midlands 2 strain, OXA-23 clone 1 or 2, T strains and isolates collected from military sources. RESULTS: This study identified A. baumannii in 0.33% (n = 26) of infections. The majority of isolates remained susceptible to the antimicrobials tested, however, 7.7% (n = 2) displayed an MDR phenotype, including resistance to carbapenems. In one isolate bla(OXA-58) was found to be the likely cause of carbapenem resistance while the other isolate had an insertion sequence element upstream of its intrinsic bla(OXA-51). The clinical data of these two isolates suggest that one is travel-related while the source of the other remains unknown. CONCLUSIONS: A. baumannii infections from Canadian hospitals were relatively low. Carbapenem-resistant MDR A. baumannii were also rare and unrelated to previously observed isolates from military sources. Continued surveillance in Canada is suggested in order to determine if such organisms will become a problem.
