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In vivo and in vitro activity of the siderophore monosulfactam BAL30072 against Acinetobacter baumannii.
- Source :
-
The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2011 Apr; Vol. 66 (4), pp. 867-73. Date of Electronic Publication: 2011 Feb 13. - Publication Year :
- 2011
-
Abstract
- Objectives: New antibiotics that are active against multidrug-resistant (MDR) Acinetobacter baumannii are urgently needed. BAL30072, a siderophore monosulfactam antibiotic that rapidly penetrates the outer membrane of A. baumannii and has potent activity against most isolates, including those harbouring AmpC β-lactamases and metallo- (class B) or OXA- (class D) carbapenemases, is being developed to meet that need.<br />Methods: We assessed the in vitro activity of BAL30072, meropenem and the combination of BAL30072 and meropenem (2:1 and 1:1 ratios) by MIC and time-kill studies. Proof-of-principle in vivo efficacy was determined using a rat soft-tissue infection model. Five diverse strains with defined phenotypic and genetic profiles were tested (AB307-0294, AB8407, AB1697, AB3340 and AB0057).<br />Results: In microdilution assays, combining BAL30072 with meropenem lowered meropenem MICs 2-8-fold. In time-kill studies, the BAL30072 and meropenem combinations resulted in bactericidal concentrations 2-8-fold lower than those of meropenem or BAL30072 alone. In the rat model, BAL30072 was active against four of five strains (AB307-0294, AB8407, AB1697 and AB3340), including meropenem-susceptible and -non-susceptible strains. AB0057 was the only strain resistant to BAL30072 in vivo and in vitro (MIC >64 mg/L). Meropenem was active in vivo against two of the five strains tested (AB307-0294 and AB3340). Both BAL30072 and BAL30072 with meropenem were equally effective in vivo.<br />Conclusions: These data support the continued evaluation of BAL30072 for use in the treatment of infections caused by MDR A. baumannii.
- Subjects :
- Acinetobacter Infections drug therapy
Animals
Anti-Bacterial Agents administration & dosage
Disease Models, Animal
Drug Interactions
Meropenem
Microbial Sensitivity Tests
Monobactams administration & dosage
Rats
Rodent Diseases drug therapy
Siderophores administration & dosage
Siderophores pharmacology
Thiazoles administration & dosage
Thienamycins administration & dosage
Thienamycins pharmacology
Treatment Outcome
Acinetobacter baumannii drug effects
Anti-Bacterial Agents pharmacology
Monobactams pharmacology
Thiazoles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2091
- Volume :
- 66
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of antimicrobial chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 21393224
- Full Text :
- https://doi.org/10.1093/jac/dkr013