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- Title
In vivo and in vitro activity of the siderophore monosulfactam BAL30072 against Acinetobacter baumannii.
- Authors
Russo, Thomas A.; Page, Malcolm G. P.; Beanan, Janet M.; Olson, Ruth; Hujer, Andrea M.; Hujer, Kristine M.; Jacobs, Michael; Bajaksouzian, Saralee; Endimiani, Andrea; Bonomo, Robert A.
- Abstract
<bold>Objectives: </bold>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.<bold>Methods: </bold>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).<bold>Results: </bold>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.<bold>Conclusions: </bold>These data support the continued evaluation of BAL30072 for use in the treatment of infections caused by MDR A. baumannii.
- Subjects
ACINETOBACTER infections; DRUG resistance in microorganisms; DRUG efficacy; ANTIBIOTICS; BETA lactamases; MULTIDRUG resistance; THERAPEUTICS; MICROBIAL genetics
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2011, Vol 66, Issue 4, p867
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkr013