Heteroresistance to Colistin in Multidrug-Resistant <i>Acinetobacter baumannii</i>

Antimicrobial Agents and Chemotherapy - Tập 50 Số 9 - Trang 2946-2950 - 2006
Jian Li1, Craig R. Rayner2, Roger L. Nation2, Roxanne J. Owen2, Denis Spelman3, Kar Eng Tan2, Lisa Liolios3
1Facility for Anti-infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, Parkville, Victoria 3052, Australia.
2Facility for Anti-infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia
3Department of Microbiology and Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria, Australia

Tóm tắt

ABSTRACT Multidrug-resistant Acinetobacter baumannii has emerged as a significant clinical problem worldwide and colistin is being used increasingly as “salvage” therapy. MICs of colistin against A. baumannii indicate its significant activity. However, resistance to colistin in A. baumannii has been reported recently. Clonotypes of 16 clinical A. baumannii isolates and ATCC 19606 were determined by pulsed-field gel electrophoresis (PFGE), and colistin MICs were measured. The time-kill kinetics of colistin against A. baumannii ATCC 19606 and clinical isolate 6 were investigated, and population analysis profiles (PAPs) were conducted. Resistance development was investigated by serial passaging with or without exposure to colistin. Five different PFGE banding patterns were found in the clinical isolates. MICs of colistin against all isolates were within 0.25 to 2 μg/ml. Colistin showed early concentration-dependent killing, but bacterial regrowth was observed at 24 h. PAPs revealed that heteroresistance to colistin occurred in 15 of the 16 clinical isolates. Subpopulations (<0.1% from inocula of 10 8 to 10 9 CFU/ml) of ATCC 19606, and most clinical isolates grew in the presence of colistin 3 to 10 μg/ml. Four successive passages of ATCC 19606 in broth containing colistin (up to 200 μg/ml) substantially increased the proportion of the resistant subpopulations able to grow in the presence of colistin at 10 μg/ml from 0.000023 to 100%; even after 16 passages in colistin-free broth, the proportion only decreased to 2.1%. This represents the first demonstration of heterogeneous colistin-resistant A. baumannii in “colistin-susceptible” clinical isolates. Our findings give a strong warning that colistin-resistant A. baumannii may be observed more frequently due to potential suboptimal dosage regimens recommended in the product information of some products of colistin methanesulfonate.

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Tài liệu tham khảo

10.1128/JCM.43.2.903-905.2005

10.1128/AAC.00035-06

10.1046/j.1469-0691.2002.00487.x

Clinical and Laboratory Standards Institute. 2005. Performance standards for antimicrobial susceptibility testing; 15th information supplement M100-S15. Clinical and Laboratory Standards Institute Wayne Pa.

10.1128/JCM.38.11.4086-4095.2000

10.1016/j.ijantimicag.2003.09.026

10.1345/aph.18426

10.1086/429323

10.1097/00003246-199909000-00015

Gerber, A. U., and W. A. Craig. 1982. Aminoglycoside-selected subpopulations of Pseudomonas aeruginosa: characterization and virulence in normal and leukopenic mice. J. Lab. Clin. Med.100:671-681.

10.1093/infdis/146.5.691

10.1093/jac/dkh500

10.1016/S1473-3099(01)00091-3

10.1093/jac/40.1.135

Infectious Diseases Society of America. 2004. Bad bugs no drugs. [Online.] http://www.idsociety.org/pa/IDSA_Paper4_final_web.pdf . Infectious Diseases Society of America Alexandria Va.

10.1345/aph.1D592

10.1378/chest.119.2_suppl.397S

10.2307/30141136

10.1093/jac/dkg468

10.1128/AAC.47.4.1364-1370.2003

10.1093/jac/dkh167

10.1128/AAC.47.5.1766-1770.2003

10.1016/j.ijantimicag.2004.10.001

10.1128/AAC.49.11.4814-4815.2005

10.1128/AAC.45.3.781-785.2001

10.1111/j.1465-0691.2004.1004.x

10.1080/07853890310001609

Lopez-Hernandez, S., T. Alarcon, and M. Lopez-Brea. 1998. Carbapenem resistance mediated by beta-lactamases in clinical isolates of Acinetobacter baumannii in Spain. Eur. J. Clin. Microbiol. Infect. Dis.17:282-285.

10.1080/00365540410020776-1

10.1111/j.1469-0691.2004.01043.x

National Committee for Clinical Laboratory Standards. 2003. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7-A6 6th ed. National Committee for Clinical Laboratory Standards Wayne Pa.

10.1093/jac/dki115

10.1099/0022-1317-50-12-1018

10.1128/JCM.43.9.4328-4335.2005

10.1128/jcm.32.11.2677-2681.1994

10.1128/JCM.33.9.2233-2239.1995

Waterer, G. W., and R. G. Wunderink. 2001. Increasing threat of gram-negative bacteria. Crit. Care Med.29:N75-N81.

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Antimicrobial Agents and Chemotherapy

Tập 50 Số 9

2946-2950

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