TY - JOUR
T1 - In vitro activity of BAL30072 against Burkholderia pseudomallei
AU - Mima, Takehiko
AU - Kvitko, Brian H.
AU - Rholl, Drew A.
AU - Page, Malcolm G.P.
AU - Desarbre, Eric
AU - Schweizer, Herbert P.
N1 - Funding Information:
Competing interests : HPS was supported by a grant-in-aid of research by Basilea Pharmaceutica International Ltd. MGPP and ED are employees of Basilea Pharmaceutica Ltd. All other authors declare no competing interests.
Funding Information:
Funding : This work was supported by a grant (U54 AI065357) from the National Institute of Allergy and Infectious Diseases , National Institutes of Health , and a grant-in-aid of research by Basilea Pharmaceutica International Ltd. to HPS.
PY - 2011/8
Y1 - 2011/8
N2 - Burkholderia pseudomallei is an intrinsically antibiotic-resistant Category B priority pathogen and the aetiological agent of melioidosis. Treatment of B. pseudomallei infection is biphasic and lengthy in order to combat the acute and chronic phases of the disease. Acute-phase treatment preferably involves an intravenous cephalosporin (ceftazidime) or a carbapenem (imipenem or meropenem). In this study, the anti-B. pseudomallei efficacy of a new monosulfactam, BAL30072, was tested against laboratory strains 1026b and 1710b and several isogenic mutant derivatives as well as a collection of clinical and environmental B. pseudomallei strains from Thailand. More than 93% of the isolates had minimal inhibitory concentrations (MICs) in the range 0.004-0.016 μg/mL. For the laboratory strain 1026b, the MIC of BAL30072 was 0.008 μg/mL, comparable with the MICs of 1.5 μg/mL for ceftazidime, 0.5 μg/mL for imipenem and 1 μg/mL for meropenem. Time-kill curves revealed that BAL30072 was rapidly bactericidal, killing >99% of bacteria in 2 h. BAL30072 activity was not significantly affected by efflux, it was only a marginal substrate of PenA β-lactamase, and activity was independent of malleobactin production and transport and the ability to transport pyochelin. In summary, BAL30072 has superior in vitro activity against B. pseudomallei compared with ceftazidime, meropenem or imipenem and it is rapidly bactericidal.
AB - Burkholderia pseudomallei is an intrinsically antibiotic-resistant Category B priority pathogen and the aetiological agent of melioidosis. Treatment of B. pseudomallei infection is biphasic and lengthy in order to combat the acute and chronic phases of the disease. Acute-phase treatment preferably involves an intravenous cephalosporin (ceftazidime) or a carbapenem (imipenem or meropenem). In this study, the anti-B. pseudomallei efficacy of a new monosulfactam, BAL30072, was tested against laboratory strains 1026b and 1710b and several isogenic mutant derivatives as well as a collection of clinical and environmental B. pseudomallei strains from Thailand. More than 93% of the isolates had minimal inhibitory concentrations (MICs) in the range 0.004-0.016 μg/mL. For the laboratory strain 1026b, the MIC of BAL30072 was 0.008 μg/mL, comparable with the MICs of 1.5 μg/mL for ceftazidime, 0.5 μg/mL for imipenem and 1 μg/mL for meropenem. Time-kill curves revealed that BAL30072 was rapidly bactericidal, killing >99% of bacteria in 2 h. BAL30072 activity was not significantly affected by efflux, it was only a marginal substrate of PenA β-lactamase, and activity was independent of malleobactin production and transport and the ability to transport pyochelin. In summary, BAL30072 has superior in vitro activity against B. pseudomallei compared with ceftazidime, meropenem or imipenem and it is rapidly bactericidal.
KW - Burkholderia pseudomallei
KW - Efflux
KW - Melioidosis
KW - Monosulfactam
KW - Siderophore
KW - Therapy
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U2 - 10.1016/j.ijantimicag.2011.03.019
DO - 10.1016/j.ijantimicag.2011.03.019
M3 - Article
C2 - 21596528
AN - SCOPUS:79959735594
SN - 0924-8579
VL - 38
SP - 157
EP - 159
JO - International Journal of Antimicrobial Agents
JF - International Journal of Antimicrobial Agents
IS - 2
ER -