In vitro activity of avibactam (NXL104) in combination with beta-lactams against Gram-negative bacteria, including OXA-48 beta-lactamase-producing Klebsiella pneumoniae.

Article Details

Citation

Aktas Z, Kayacan C, Oncul O

In vitro activity of avibactam (NXL104) in combination with beta-lactams against Gram-negative bacteria, including OXA-48 beta-lactamase-producing Klebsiella pneumoniae.

Int J Antimicrob Agents. 2012 Jan;39(1):86-9. doi: 10.1016/j.ijantimicag.2011.09.012. Epub 2011 Oct 29.

PubMed ID
22041508 [ View in PubMed
]
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 beta-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-beta-lactamase and extended-spectrum beta-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 beta-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)

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
AvibactamBeta-lactamaseProteinEnterobacter cloacae
Yes
Inhibitor
Details
AvibactamBeta-lactamase CTX-M (Protein Group)Protein groupEscherichia coli
Yes
Inhibitor
Details
AvibactamBeta-lactamase CTX-M-15ProteinEscherichia coli
Yes
Inhibitor
Details
AvibactamBeta-lactamase SHV-1ProteinEscherichia coli
Yes
Inhibitor
Details
AvibactamBeta-lactamase SHV-1ProteinKlebsiella pneumoniae
Yes
Inhibitor
Details
AvibactamBeta-lactamase SHV-2ProteinEscherichia coli
Yes
Inhibitor
Details
AvibactamCarbapenem-hydrolyzing beta-lactamase KPCProteinKlebsiella pneumoniae
Yes
Inhibitor
Details
AvibactamClass D OXA-48 carbapenemaseProteinKlebsiella pneumoniae
Yes
Inhibitor
Details
AvibactamExtended-spectrum beta-lactamase PER-1ProteinPseudomonas aeruginosa
Yes
Inhibitor
Details