In Vitro Activity and In Vivo Efficacy of Clavulanic Acid against Acinetobacter baumannii

Servicio de Microbiología-Unidad de Investigación, Complejo Hospitalario Universitario Juan Canalejo, 15006 La Coruña, Spain.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 07/2009; 53(10):4298-304. DOI: 10.1128/AAC.00320-09
Source: PubMed


Clavulanic acid (CLA) exhibits low MICs against some Acinetobacter baumannii strains. The present study evaluates the efficacy of CLA in a murine model of A. baumannii pneumonia. For this purpose, two clinical strains, Ab11 and Ab51, were used; CLA MICs for these strains were 2 and 4 mg/liter, respectively, and the imipenem (IPM) MIC was 0.5 mg/liter for both. A pneumonia model in C57BL/6 mice was used. The CLA dosage (13 mg/kg of body weight given intraperitoneally) was chosen to reach a maximum concentration of the drug in serum similar to that in humans and a time during which the serum CLA concentration remained above the MIC equivalent to 40% of the interval between doses. Six groups (n = 15) were inoculated with Ab11 or Ab51 and were allocated to IPM or CLA therapy or to the untreated control group. In time-kill experiments, CLA was bactericidal only against Ab11 whereas IPM was bactericidal against both strains. CLA and IPM both decreased bacterial concentrations in lungs, 1.78 and 2.47 log10 CFU/g (P < or = 0.001), respectively, in the experiments with Ab11 and 2.42 and 2.28 log10 CFU/g (P < or = 0.001), respectively, with Ab51. IPM significantly increased the sterility of blood cultures over that for the controls with both strains (P < or = 0.005); CLA had the same effect with Ab51 (P < 0.005) but not with Ab11 (P = 0.07). For the first time, we suggest that CLA may be used for the treatment of experimental severe A. baumannii infections.

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Available from: Rafael López-Rojas, Mar 28, 2014
  • X. Zhang · Y. Xu · Y. Yu · Q. Yang · F. Wang · D. Zhu · Y. Ni · J. Sun · Z. Sun · C. Jian · [...] · L. Wei · L. Wu · C. Zhuo · D. Su · Z. Zhang · P. Ji · Z. Xiong · J. Shen · B. Shan · Y. Du ·
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    ABSTRACT: Objective To investigate the antimicrobial resistance of A. baumanii strains isolated from patients in 14 hospitals (12 general hospitals and 2 children's hospitals) in several regions of china during 2009. Methods A total of 4 163 clinical isolates of A. baumanii were collected from 14 teaching hospitals in China. Antimicrobial susceptibility testing was carried out by means of Kirby-Bauer method according to the unified protocol. The data were analyzed by WHONET 5. 4 software according to CLSI 2009 breakpoints. Results A. baumanii isolates showed the lowest resistant rates (26.3% and 26.1% respectively) to cefoperazone-sulbactam and minocycline. The resistant rates to other antimicrobial agents were higher than 53. 3%. The resistant rates to imipenem and meropenem were 54. 8% and 57. 2% , respectively. The antimicrobial resistant pattern varied in different hospital in china. The resistance of A. baumanii varied from one department to another. A number of pandrug-resistant (PDR) (17.0%, 709/4 163) and multidrug-resistant (MDR) (44.4%, 1 848/4 163) A. baumanii were found. Conclusions The antibiotic resistance of A. baumanii is still increasing, especially the MDR and PDR strains of A. baumanii. Cefoperazone-sulbactam remains the most active agent against A. baumanii.
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    ABSTRACT: Acinetobacter baumannii is a nosocomial pathogen with a high prevalence of multiple-drug-resistant strains, causing pneumonia and sepsis. The current studies further develop a systemic mouse model of this infection and characterize selected innate immune responses to the organism. Five clinical isolates, with various degrees of antibiotic resistance, were assessed for virulence in two mouse strains, and between male and female mice, using intraperitoneal infection. A nearly 1,000-fold difference in virulence was found between bacterial strains, but no significant differences between sexes or mouse strains were observed. It was found that microbes disseminated rapidly from the peritoneal cavity to the lung and spleen, where they replicated. A persistent septic state was observed. The infection progressed rapidly, with mortality between 36 and 48 h. Depletion of neutrophils with antibody to Ly-6G decreased mean time to death and increased mortality. Interleukin-17 (IL-17) promotes the response of neutrophils by inducing production of the chemokine keratinocyte-derived chemoattractant (KC/CXCL1), the mouse homolog of human IL-8. Acinetobacter infection resulted in biphasic increases in both IL-17 and KC/CXCL1. Depletion of neither IL-17 nor KC/CXCL1, using specific antibodies, resulted in a difference in bacterial burdens in organs of infected mice at 10 h postinfection. Comparison of bacterial burdens between IL-17a(-/-) and wild-type mice confirmed that the absence of this cytokine did not sensitize mice to Acinetobacter infection. These studies definitely demonstrate the importance of neutrophils in resistance to systemic Acinetobacter infection. However, neither IL-17 nor KC/CXCL1 alone is required for effective host defense to systemic infection with this organism.
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