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Antimicrobial Agents and Chemotherapy, May 2007, p. 1621-1626, Vol. 51, No. 5
0066-4804/07/$08.00+0     doi:10.1128/AAC.01099-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

In Vitro Activities of Various Antimicrobials Alone and in Combination with Tigecycline against Carbapenem-Intermediate or -Resistant Acinetobacter baumannii{triangledown}

Marc H. Scheetz,1* Chao Qi,2 John R. Warren,2 Michael J. Postelnick,1 Teresa Zembower,3 Arlene Obias,2 and Gary A. Noskin3

Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois,1 Department of Pathology, Clinical Microbiology Division, Northwestern Memorial Hospital, Chicago, Illinois,2 Department of Medicine, Division of Infectious Diseases, Northwestern University, Feinberg School of Medicine, Chicago, Illinois3

Received 30 August 2006/ Returned for modification 17 October 2006/ Accepted 12 February 2007

The activities of tigecycline alone and in combination with other antimicrobials are not well defined for carbapenem-intermediate or -resistant Acinetobacter baumannii (CIRA). Pharmacodynamic activity is even less well defined when clinically achievable serum concentrations are considered. Antimicrobial susceptibility testing of clinical CIRA isolates from 2001 to 2005 was performed by broth or agar dilution, as appropriate. Tigecycline concentrations were serially increased in time-kill studies with a representative of the most prevalent carbapenem-resistant clone (strain AA557; imipenem MIC, 64 mg/liter). The in vitro susceptibility of the strain was tested by time-kill studies in duplicate against the average free serum steady-state concentrations of tigecycline alone and in combination with various antimicrobials. Ninety-three CIRA isolates were tested and were found to have the following antimicrobial susceptibility profiles: tigecycline, MIC50 of 1 mg/liter and MIC90 of 2 mg/liter; minocycline, MIC50 of 0.5 mg/liter and MIC90 of 8 mg/liter; doxycycline, MIC50 of 2 mg/liter and MIC90 of ≥32 mg/liter; ampicillin-sulbactam, MIC50 of 48 mg/liter and MIC90 of 96 mg/liter; ciprofloxacin, MIC50 of ≥16 mg/liter and MIC90 of ≥16 mg/liter; rifampin, MIC50 of 4 mg/liter and MIC90 of 8 mg/liter; polymyxin B, MIC50 of 1 mg/liter and MIC90 of 1 mg/liter; amikacin, MIC50 of 32 mg/liter and MIC90 of ≥32 mg/liter; meropenem, MIC50 of 16 mg/liter and MIC90 of ≥128 mg/liter; and imipenem, MIC50 of 4 mg/liter and MIC90 of 64 mg/liter. Among the tetracyclines, the isolates were more susceptible to tigecycline than minocycline and doxycycline, according to FDA breakpoints (95%, 88%, and 71% of the isolates were susceptible to tigecycline, minocycline, and doxycycline, respectively). Concentration escalation studies with tigecycline revealed a maximal killing effect near the MIC, with no additional extent or rate of killing at concentrations 2x to 4x the MIC for tigecycline. Time-kill studies demonstrated indifference for tigecycline in combination with the antimicrobials tested. Polymyxin B, minocycline, and tigecycline are the most active antimicrobials in vitro against CIRA. Concentration escalation studies demonstrate that tigecycline may need to approach concentrations higher than those currently achieved in the bloodstream to adequately treat CIRA bloodstream infections. Future studies should evaluate these findings in vivo.

* Corresponding author. Mailing address: Department of Pharmacy, Northwestern Memorial Hospital, 251 East Huron Street, Feinberg Pavilion LC-700, Chicago, IL 60611. Phone: (312) 926-2546. Fax: (312) 926-7956. E-mail: mscheetz{at}nmh.org

{triangledown} Published ahead of print on 16 February 2007.

Antimicrobial Agents and Chemotherapy, May 2007, p. 1621-1626, Vol. 51, No. 5
0066-4804/07/$08.00+0     doi:10.1128/AAC.01099-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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