The Journal of antimicrobial chemotherapy · 2013
Activity of BAL30072 alone or combined with β-lactamase inhibitors or with meropenem against carbapenem-resistant Enterobacteriaceae and non-fermenters.
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Mushtaq Shazad, Woodford Neil, Hope Russell, Adkin Rachael, Livermore David M
Аннотация
OBJECTIVES: We investigated the activity of BAL30072, a dihydroxypyridone monosulfactam, against carbapenem-resistant Enterobacteriaceae and non-fermenters (i) alone, (ii) combined with BAL29880 (to inhibit AmpC) and/or clavulanate [to inhibit extended-spectrum β-lactamases (ESBLs)] and (iii) combined 1:1 with meropenem.
METHODS: Isolates were from multiple UK hospitals. MICs were determined by CLSI agar dilution. Carbapenemases were identified by PCR and sequencing.
RESULTS: BAL30072 inhibited 69% of the carbapenem-resistant Enterobacteriaceae at ≤4 mg/L, including 60%-87% with OXA-48, IMP, NDM and VIM enzymes or combinations of impermeability with AmpC or ESBL, and 40% with KPC enzymes. The proportions susceptible exceeded 90% for BAL30072+BAL29880+clavulanate, except for isolates with KPC carbapenemases, where members of the international sequence type (ST) 258 Klebsiella pneumoniae clone remained resistant. At 4 mg/L, BAL30072 was active against all OprD-deficient Pseudomonas aeruginosa, against 8/12 with efflux-type β-lactam resistance and 19/25 with metallo-carbapenemases; these proportions were little increased if inhibitors were added. Most Acinetobacter baumannii with OXA or NDM carbapenemases were susceptible to BAL30072 alone at ≤4 mg/L, but those with OXA-58 were resistant, probably for reasons other than their β-lactamase. Addition of meropenem to BAL30072 increased activity against some individual isolates, but with little clear relationship to the resistance mechanism, except for consistent potentiation against OprD-deficient P. aeruginosa.
CONCLUSIONS: BAL30072 had good activity against many diverse carbapenem resistance types. Adding clavulanate and/or BAL29880 extended activity against carbapenem-resistant Enterobacteriaceae, but not non-fermenters. Adding meropenem resulted in small increases in activity against individual isolates. Resistance remained common in the K. pneumoniae ST258 KPC clone, even with both inhibitors or meropenem added.
METHODS: Isolates were from multiple UK hospitals. MICs were determined by CLSI agar dilution. Carbapenemases were identified by PCR and sequencing.
RESULTS: BAL30072 inhibited 69% of the carbapenem-resistant Enterobacteriaceae at ≤4 mg/L, including 60%-87% with OXA-48, IMP, NDM and VIM enzymes or combinations of impermeability with AmpC or ESBL, and 40% with KPC enzymes. The proportions susceptible exceeded 90% for BAL30072+BAL29880+clavulanate, except for isolates with KPC carbapenemases, where members of the international sequence type (ST) 258 Klebsiella pneumoniae clone remained resistant. At 4 mg/L, BAL30072 was active against all OprD-deficient Pseudomonas aeruginosa, against 8/12 with efflux-type β-lactam resistance and 19/25 with metallo-carbapenemases; these proportions were little increased if inhibitors were added. Most Acinetobacter baumannii with OXA or NDM carbapenemases were susceptible to BAL30072 alone at ≤4 mg/L, but those with OXA-58 were resistant, probably for reasons other than their β-lactamase. Addition of meropenem to BAL30072 increased activity against some individual isolates, but with little clear relationship to the resistance mechanism, except for consistent potentiation against OprD-deficient P. aeruginosa.
CONCLUSIONS: BAL30072 had good activity against many diverse carbapenem resistance types. Adding clavulanate and/or BAL29880 extended activity against carbapenem-resistant Enterobacteriaceae, but not non-fermenters. Adding meropenem resulted in small increases in activity against individual isolates. Resistance remained common in the K. pneumoniae ST258 KPC clone, even with both inhibitors or meropenem added.
Предметные рубрики MeSH
Anti-Bacterial AgentsBacterial ProteinsDNA, BacterialDrug SynergismEnterobacteriaceaeEnterobacteriaceae InfectionsEnzyme InhibitorsHospitalsHumansMeropenemMicrobial Sensitivity TestsMonobactamsPolymerase Chain ReactionSequence Analysis, DNAThiazolesThienamycinsUnited Kingdombeta-Lactam Resistancebeta-Lactamases