JAC Advance Access originally published online on January 16, 2004
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Journal of Antimicrobial Chemotherapy (2004) 53, 393-395
© 2004 The British Society for Antimicrobial Chemotherapy
In vitro and in vivo activity of meropenem and sulbactam against a multidrug-resistant Acinetobacter baumannii strain
Departments of 1 Medicine and 2 Medical Technology, National Cheng Kung University Medical College; Departments of 3 Medicine and 4 Medical Research, Chi Mei Medical Center; 5 Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
Received 19 August 2003; returned 13 October 2003; revised 17 November 2003; accepted 18 November 2003
Objectives: The potential therapeutic role of meropenem combined with sulbactam against a clinical endemic isolate of multidrug-resistant Acinetobacter baumannii, Ab-153, was investigated.
Methods: The antimicrobial susceptibility of Ab-153 to various drugs was studied by the agar dilution method and Etest strips. The antibacterial activity of meropenem and sulbactam were investigated by a time–kill study in vitro and further examined for therapeutic efficacy in vivo in a murine model.
Results: In the time–kill study, at a concentration of 0.5 x MIC (4 mg/L) of meropenem, 1 x MIC (8 mg/L) of sulbactam and both in combination, only the combination demonstrated bactericidal effects and there was at least a 5 log10 reduction in bacterial colony counts after 48 h, compared with either drug alone. BALB/c mice infected with 2.1–2.6 x 107 cfu of Ab-153 were treated with 20 mg/kg meropenem every 8 h, 40 mg/kg sulbactam every 8 h or both in combination. The survival rate of mice in the combination group was significantly higher than that in the meropenem-treated or sulbactam-treated group (87% versus 35%, P = 0.0004; 87% versus 30%, P = 0.0002).
Conclusions: Meropenem in conjunction with sulbactam can exhibit more potent antimicrobial activity against Ab-153 than meropenem or sulbactam alone.
Keywords: synergy, combination therapy, time–kill curves
* Correspondence address. Department of Medical Research, Chi Mei Medical Center, 901 Chung-Hwa Road, Yung-Kang City, Tainan, Taiwan 710. Tel: +886-6-281-2811, extension 2612; Fax: +886-6-251-7849; E-mail: chuangkenneth{at}hotmail.com
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