This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Li, J.
Right arrow Articles by Liolios, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, J.
Right arrow Articles by Liolios, L.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, September 2006, p. 2946-2950, Vol. 50, No. 9
0066-4804/06/$08.00+0     doi:10.1128/AAC.00103-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Heteroresistance to Colistin in Multidrug-Resistant Acinetobacter baumannii

Jian Li,1* Craig R. Rayner,1 Roger L. Nation,1 Roxanne J. Owen,1 Denis Spelman,2 Kar Eng Tan,1 and Lisa Liolios2

Facility for Anti-infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia,1 Department of Microbiology and Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria, Australia2

Received 25 January 2006/ Returned for modification 3 May 2006/ Accepted 13 June 2006

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 108 to 109 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.

* Corresponding author. Mailing address: Facility for Anti-infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia. Phone: 61 3 9903 9702. Fax: 61 3 9903 9629. E-mail: Jian.Li{at}vcp.monash.edu.au.

Antimicrobial Agents and Chemotherapy, September 2006, p. 2946-2950, Vol. 50, No. 9
0066-4804/06/$08.00+0     doi:10.1128/AAC.00103-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Adams, M. D., Nickel, G. C., Bajaksouzian, S., Lavender, H., Murthy, A. R., Jacobs, M. R., Bonomo, R. A. (2009). Resistance to Colistin in Acinetobacter baumannii Associated with Mutations in the PmrAB Two-Component System. Antimicrob. Agents Chemother. 53: 3628-3634 [Abstract] [Full Text]  
  • Gordon, N. C., Wareham, D. W. (2009). Failure of the MicroScan WalkAway System To Detect Heteroresistance to Carbapenems in a Patient with Enterobacter aerogenes Bacteremia. J. Clin. Microbiol. 47: 3024-3025 [Abstract] [Full Text]  
  • Cummins, J., Reen, F. J., Baysse, C., Mooij, M. J., O'Gara, F. (2009). Subinhibitory concentrations of the cationic antimicrobial peptide colistin induce the pseudomonas quinolone signal in Pseudomonas aeruginosa. Microbiology 155: 2826-2837 [Abstract] [Full Text]  
  • Poudyal, A., Howden, B. P., Bell, J. M., Gao, W., Owen, R. J., Turnidge, J. D., Nation, R. L., Li, J. (2008). In vitro pharmacodynamics of colistin against multidrug-resistant Klebsiella pneumoniae. J Antimicrob Chemother 62: 1311-1318 [Abstract] [Full Text]  
  • Cao, G., Ali, F. E. A., Chiu, F., Zavascki, A. P., Nation, R. L., Li, J. (2008). Development and validation of a reversed-phase high-performance liquid chromatography assay for polymyxin B in human plasma. J Antimicrob Chemother 62: 1009-1014 [Abstract] [Full Text]  
  • Valentine, S. C., Contreras, D., Tan, S., Real, L. J., Chu, S., Xu, H. H. (2008). Phenotypic and Molecular Characterization of Acinetobacter baumannii Clinical Isolates from Nosocomial Outbreaks in Los Angeles County, California. J. Clin. Microbiol. 46: 2499-2507 [Abstract] [Full Text]  
  • Landman, D., Georgescu, C., Martin, D. A., Quale, J. (2008). Polymyxins Revisited. Clin. Microbiol. Rev. 21: 449-465 [Abstract] [Full Text]  
  • Peleg, A. Y., Seifert, H., Paterson, D. L. (2008). Acinetobacter baumannii: Emergence of a Successful Pathogen. Clin. Microbiol. Rev. 21: 538-582 [Abstract] [Full Text]  
  • Karageorgopoulos, D. E., Kelesidis, T., Kelesidis, I., Falagas, M. E. (2008). Tigecycline for the treatment of multidrug-resistant (including carbapenem-resistant) Acinetobacter infections: a review of the scientific evidence. J Antimicrob Chemother 62: 45-55 [Abstract] [Full Text]  
  • Burgess, D. S., Rapp, R. P. (2008). Bugs versus drugs: Addressing the pharmacist's challenge. Am J Health Syst Pharm 65: S4-S15 [Abstract] [Full Text]  
  • Munoz-Price, L. S., Weinstein, R. A. (2008). Acinetobacter Infection. NEJM 358: 1271-1281 [Full Text]  
  • Hawley, J. S., Murray, C. K., Jorgensen, J. H. (2008). Colistin Heteroresistance in Acinetobacter and Its Association with Previous Colistin Therapy. Antimicrob. Agents Chemother. 52: 351-352 [Abstract] [Full Text]  
  • Zavascki, A. P., Goldani, L. Z., Li, J., Nation, R. L. (2007). Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review. J Antimicrob Chemother 60: 1206-1215 [Abstract] [Full Text]  
  • Hawley, J. S., Murray, C. K., Jorgensen, J. H. (2007). Development of Colistin-Dependent Acinetobacter baumannii-Acinetobacter calcoaceticus Complex. Antimicrob. Agents Chemother. 51: 4529-4530 [Full Text]  
  • Perez, F., Hujer, A. M., Hujer, K. M., Decker, B. K., Rather, P. N., Bonomo, R. A. (2007). Global Challenge of Multidrug-Resistant Acinetobacter baumannii. Antimicrob. Agents Chemother. 51: 3471-3484 [Full Text]  
  • Lo-Ten-Foe, J. R., de Smet, A. M. G. A., Diederen, B. M. W., Kluytmans, J. A. J. W., van Keulen, P. H. J. (2007). Comparative Evaluation of the VITEK 2, Disk Diffusion, Etest, Broth Microdilution, and Agar Dilution Susceptibility Testing Methods for Colistin in Clinical Isolates, Including Heteroresistant Enterobacter cloacae and Acinetobacter baumannii Strains. Antimicrob. Agents Chemother. 51: 3726-3730 [Abstract] [Full Text]  
  • Tan, C.-H., Li, J., Nation, R. L. (2007). Activity of Colistin against Heteroresistant Acinetobacter baumannii and Emergence of Resistance in an In Vitro Pharmacokinetic/Pharmacodynamic Model. Antimicrob. Agents Chemother. 51: 3413-3415 [Abstract] [Full Text]  
  • Morand, B., Muhlemann, K. (2007). Heteroresistance to penicillin in Streptococcus pneumoniae. Proc. Natl. Acad. Sci. USA 104: 14098-14103 [Abstract] [Full Text]  
  • Tan, T. Y., Ng, L. S. Y., Tan, E., Huang, G. (2007). In vitro effect of minocycline and colistin combinations on imipenem-resistant Acinetobacter baumannii clinical isolates. J Antimicrob Chemother 60: 421-423 [Abstract] [Full Text]  
  • Song, J. Y., Kee, S. Y., Hwang, I. S., Seo, Y. B., Jeong, H. W., Kim, W. J., Cheong, H. J. (2007). In vitro activities of carbapenem/sulbactam combination, colistin, colistin/rifampicin combination and tigecycline against carbapenem-resistant Acinetobacter baumannii. J Antimicrob Chemother 60: 317-322 [Abstract] [Full Text]  
  • Owen, R. J., Li, J., Nation, R. L., Spelman, D. (2007). In vitro pharmacodynamics of colistin against Acinetobacter baumannii clinical isolates. J Antimicrob Chemother 59: 473-477 [Abstract] [Full Text]  
  • Hawley, J. S., Murray, C. K., Griffith, M. E., McElmeel, M. L., Fulcher, L. C., Hospenthal, D. R., Jorgensen, J. H. (2007). Susceptibility of Acinetobacter Strains Isolated from Deployed U.S. Military Personnel. Antimicrob. Agents Chemother. 51: 376-378 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»