title: In vitro activity of avibactam (NXL104) in combination with β-lactams against Gram-negative bacteria, including OXA-48 β-lactamase-producing Klebsiella pneumoniae.
abstract: The objective of this study was to investigate the in vitro antibacterial activity of avibactam (formerly NXL104) in combination with imipenem, cefepime or ceftazidime against Gram-negative bacteria. Bacterial isolates included: Pseudomonas aeruginosa harbouring PER-1 β-lactamase (n=14); Acinetobacter baumannii harbouring PER-1, OXA-51 and OXA-58 (n=20); carbapenem-non-susceptible Klebsiella pneumoniae (n=25) and Escherichia coli (n=1) harbouring OXA-48; carbapenem-non-susceptible E. coli (n=1) harbouring both IMP-1 metallo-β-lactamase and extended-spectrum β-lactamase (ESBL); carbapenem-non-susceptible Serratia marcescens (n=1); and carbapenem-susceptible E. coli (n=20) and K. pneumoniae isolates (n=12) with CTX-M-15 ESBL. Minimum inhibitory concentrations (MICs) of imipenem, cefepime and ceftazidime were determined in combination with 4 mg/L avibactam by the Clinical and Laboratory Standards Institute (CLSI) method on Mueller-Hinton agar. Imipenem/avibactam and ceftazidime/avibactam displayed limited potency against A. baumannii isolates, whereas cefepime/avibactam and ceftazidime/avibactam were active against P. aeruginosa. Klebsiella pneumoniae isolates with OXA-48 β-lactamase were resistant to imipenem [MIC for 90% of the organisms (MIC(90)) ≥4 mg/L]. MIC(90) values for the combination of avibactam 4 mg/L with imipenem, cefepime and ceftazidime were in the susceptible range for all strains (MIC(90)≤0.5mg/L). All E. coli and K. pneumoniae isolates with CTX-M-15 β-lactamase were inhibited at ≤1 mg/L for combinations with avibactam and 100% were susceptible by CLSI breakpoint criteria to imipenem, cefepime and ceftazidime. In conclusion, combinations of imipenem, cefepime and ceftazidime with avibactam may present a promising therapeutic strategy to treat infections due to K. pneumoniae with OXA-48 enzyme as well as K. pneumoniae and E. coli with CTX-M-15 enzyme.
authors: Department of Clinical Microbiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey. aktaszerrin@yahoo.com
authors: Z
authors: Z
authors: Aktaş
authors: C
authors: C
authors: Kayacan
authors: O
authors: O
authors: Oncul
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology; D008826:Microbial Sensitivity Tests / Q000592:standards; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D047090:beta-Lactams; C543519:avibactam; C473109:beta-lactamase CTX-M-15; D001618:beta-Lactamases; C108449:oxacillinase