Tuberc Respir Dis.  2009 Sep;67(3):212-220.

The Comparative Efficacy of Colistin Monotherapy and Combination Therapy Based on in vitro Antimicrobial Synergy in Ventilator-associated Pneumonia Caused by Multi-drug Resistant Acinetobacter baumannii

• Jang HJ
• Kim MN
• Lee K
• Hong SB
• Lim CM
• Koh Y

Abstract

BACKGROUND
Ventilator-associated pneumonia caused by multi-drug resistant Acinetobacter baumannii has been increasing and growing as a threat in intensive care units. Limited therapeutic options have forced clinicians to choose colistin with or without combination of other antibiotics. We tried to compare the effectiveness between colistin monotherapy and combination therapy based on in vitro synergistic tests. METHODS: From January 2006 to December 2007 in medical ICU of a tertiary care hospital in Korea, We reviewed the medical records of patients treated with intravenous colistin due to ventilator-associated pneumonia caused by multi-drug resistant Acinetobacter baumannii. RESULTS: A total of 41 patients were analyzed. 22 patients had been treated with colistin monotherapy and 19 patients with colistin and combination antibiotics that were found to have in vitro synergistic effects. Baseline characteristics were similar in both groups but the mean duration of colistin administration was significantly longer in the combination group (19.1+/-11.2 days vs. 12.3+/-6.8 days, p=0.042). There were no significant differences in outcome variables between the two groups. CONCLUSION: Combination treatment based on the in vitro antimicrobial synergy test did not show better outcomes compared with colistin monotherapy in VAP caused by multi-drug resistant A. baumannii.

Keyword

Colistin; Acinetobacter baumannii; Multi-drug Resistance; Ventilator associated pneumonia; in vitro antimicrobial synergy

MeSH Terms

Acinetobacter
Acinetobacter baumannii
Anti-Bacterial Agents
Colistin
Drug Resistance, Multiple
Humans
Intensive Care Units
Korea
Medical Records
Pneumonia, Ventilator-Associated
Tertiary Healthcare
Anti-Bacterial Agents
Colistin

Reference

1. Pournaras S, Markogiannakis A, Ikonomidis A, Kondyli L, Bethimouti K, Maniatis AN, et al. Outbreak of multiple clones of imipenem-resistant Acinetobacter baumannii isolates expressing OXA-58 carbapenemase in an intensive care unit. J Antimicrob Chemother. 2006. 57:557–561.

2. Wilks M, Wilson A, Warwick S, Price E, Kennedy D, Ely A, et al. Control of an outbreak of multidrug-resistant Acinetobacter baumannii-calcoaceticus colonization and infection in an intensive care unit (ICU) without closing the ICU or placing patients in isolation. Infect Control Hosp Epidemiol. 2006. 27:654–658.

3. Garnacho-Montero J, Ortiz-Leyba C, Jiménez-Jiménez FJ, Barrero-Almodóvar AE, García-Garmendia JL, Bernabeu-WittelI M, et al. Treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP) with intravenous colistin: a comparison with imipenem-susceptible VAP. Clin Infect Dis. 2003. 36:1111–1118.

4. Garnacho-Montero J, Ortiz-Leyba C, Fernández-Hinojosa E, Aldabó-Pallás T, Cayuela A, Marquez-Vácaro JA, et al. Acinetobacter baumannii ventilator-associated pneumonia: epidemiological and clinical findings. Intensive Care Med. 2005. 31:649–655.

5. Lortholary O, Fagon JY, Hoi AB, Slama MA, Pierre J, Giral P, et al. Nosocomial acquisition of multiresistant Acinetobacter baumannii: risk factors and prognosis. Clin Infect Dis. 1995. 20:790–796.

6. Oh SJ, Lee SU, Hwang HY, Bae IK, Jo HS, Lee BH, et al. Prevalence of class A extended-spectrum beta-lactamases in clinical isolates of acinetobacter baumannii and pseudomonas aeruginosa. Korean J Lab Med. 2006. 26:14–20.

7. Park AJ, Hong HR. Evaluation of methods for detection of antimicrobial resistance of Acinetobacter baumannii to Imipenem. Korean J Lab Med. 2003. 23:388–394.

8. Lee K, Lee HS, Jang SJ, Park AJ, Lee MH, Song WK, et al. Antimicrobial resistance surveillance of bacteria in 1999 in Korea with a special reference to resistance of enterococci to vancomycin and gram-negative bacilli to third generation cephalosporin, imipenem, and fluoroquinolone. J Korean Med Sci. 2001. 16:262–270.

9. Hong SG, Lee J, Yong D, Kim EC, Jeong SH, Park YJ, et al. Antimicrobial resistance of clinically important bacteria isolated from 12 hospitals in Korea. Korean J Clin Microbiol. 2004. 7:171–177.

10. Lee H, Kim CK, Lee J, Lee SH, Ahn JY, Hong SG, et al. Antimicrobial resistance of clinically important bacteria isolated from 12 hospitals in Korea in 2005 and 2006. Korean J Clin Microbiol. 2007. 10:59–69.

11. Rios FG, Luna CM, Maskin B, Saenz Valiente A, Lloria M, Gando S, et al. Ventilator-associated pneumonia due to colistin susceptible-only microorganisms. Eur Respir J. 2007. 30:307–313.

12. Yoon J, Urban C, Terzian C, Mariano N, Rahal JJ. In vitro double and triple synergistic activities of Polymyxin B, imipenem, and rifampin against multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2004. 48:753–757.

13. Song JY, Kee SY, Hwang IS, Seo YB, Jeong HW, Kim WJ, et al. In vitro activities of carbapenem/sulbactam combination, colistin, colistin/rifampicin combination and tigecycline against carbapenem-resistant Acinetobacter baumannii. J Antimicrob Chemother. 2007. 60:317–322.

14. Tan TY, Ng LS, Tan E, Huang G. In vitro effect of minocycline and colistin combinations on imipenem-resistant Acinetobacter baumannii clinical isolates. J Antimicrob Chemother. 2007. 60:421–423.

15. Motaouakkil S, Charra B, Hachimi A, Benslama A. Nosocomial pneumonia caused by multiresistant Acinetobacter baumanii treated by colistin and rifampicin. Ann Fr Anesth Reanim. 2006. 25:543–544.

16. Sung H, Choi SJ, Yoo S, Kim MN. In vitro antimicrobial synergy against imipenem-resistant Acinetobacter baumannii. Korean J Lab Med. 2007. 27:111–117.

17. National Committee for Clinical Laboratory Standards.Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard-sixth edition, M7-A6. 2003. Wayne: National Committee for Clinical Laboratory Standards.

18. National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard-sixth edition, M2-M8. 2003. Wayne: National Committee for Clinical Laboratory Standards.

19. Levin AS, Barone AA, Penco J, Santos MV, Marinho IS, Arruda EA, et al. Intravenous colistin as therapy for nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Clin Infect Dis. 1999. 28:1008–1011.

20. Markou N, Apostolakos H, Koumoudiou C, Athanasiou M, Koutsoukou A, Alamanos I, et al. Intravenous colistin in the treatment of sepsis from multiresistant Gram-negative bacilli in critically ill patients. Crit Care. 2003. 7:R78–R83.

21. Kasiakou SK, Michalopoulos A, Soteriades ES, Samonis G, Sermaides GJ, Falagas ME. Combination therapy with intravenous colistin for management of infections due to multidrug-resistant Gram-negative bacteria in patients without cystic fibrosis. Antimicrob Agents Chemother. 2005. 49:3136–3146.

22. Wood GC, Hanes SD, Boucher BA, Croce MA, Fabian TC. Tetracyclines for treating multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia. Intensive Care Med. 2003. 29:2072–2076.

23. Holloway KP, Rouphael NG, Wells JB, King MD, Blumberg HM. Polymyxin B and doxycycline use in patients with multidrug-resistant Acinetobacter baumannii infections in the intensive care unit. Ann Pharmacother. 2006. 40:1939–1945.

24. Falagas ME, Rafailidis PI, Kasiakou SK, Hatzopoulou P, Michalopoulos A. Effectiveness and nephrotoxicity of colistin monotherapy vs. colistin-meropenem combination therapy for multidrug-resistant Gram-negative bacterial infections. Clin Microbiol Infect. 2006. 12:1227–1230.