In vitro activity of BAL30072 against Burkholderia pseudomallei

Takehiko Mima, Brian H. Kvitko, Drew A. Rholl, Malcolm G P Page, Eric Desarbre, Herbert P. Schweizer

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)157-159
Number of pages3
JournalInternational Journal of Antimicrobial Agents
Volume38
Issue number2
DOIs
Publication statusPublished - Aug 2011
Externally publishedYes

Fingerprint

Burkholderia pseudomallei
meropenem
Ceftazidime
Imipenem
Burkholderia Infections
Melioidosis
Carbapenems
Thailand
Cephalosporins
Chronic Disease
BAL 30072
In Vitro Techniques
Anti-Bacterial Agents
Bacteria

Keywords

  • Burkholderia pseudomallei
  • Efflux
  • Melioidosis
  • Monosulfactam
  • Siderophore
  • Therapy

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

Cite this

In vitro activity of BAL30072 against Burkholderia pseudomallei. / Mima, Takehiko; Kvitko, Brian H.; Rholl, Drew A.; Page, Malcolm G P; Desarbre, Eric; Schweizer, Herbert P.

In: International Journal of Antimicrobial Agents, Vol. 38, No. 2, 08.2011, p. 157-159.

Research output: Contribution to journalArticle

Mima, Takehiko ; Kvitko, Brian H. ; Rholl, Drew A. ; Page, Malcolm G P ; Desarbre, Eric ; Schweizer, Herbert P. / In vitro activity of BAL30072 against Burkholderia pseudomallei. In: International Journal of Antimicrobial Agents. 2011 ; Vol. 38, No. 2. pp. 157-159.
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