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In Vitro Synergistic Effects of Antimicrobial Combinations on Extensively Drug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Isolates

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Background: Extensively drug-resistant (XDR) Pseudomonas aeruginosa and Acinetobacter baumannii are a threat to hospitalized patients. We evaluated the effects of antimicrobial combinations on XDR P. aeruginosa and A. baumannii isolates. Methods: P. aeruginosa and A. baumannii isolates, which were resistant to all antibiotics except colistin (CL), were collected from eight hospitals in Korea. Genes encoding metallo-β-lactamases (MBLs) and OXA carbapenemases were detected by PCR in eight P. aeruginosa and 30 A. baumannii isolates. In vitro synergy of antimicrobial combinations was tested by using the checkerboard method. Results: Minimum inhibitory concentrations of β-lactams, aminoglycosides, and fluoroquinolones were very high, while that of CL was low for majority of XDR P. aeruginosa and A. baumannii isolates. Antimicrobial combinations including Imipenem (IPM)-CL, ceftazidime (CAZ)-CL, and rifampin (RIF)-CL exerted only additive/indifferent effects on majority of XDR P. aeruginosa isolates. Proportions of XDR A. baumannii isolates that showed synergistic and additive/indifferent inhibition after treatment with antimicrobial combinations used are as follows: IPM-ampicillin-sulbactam (AMS), 17% and 80% isolates, respectively; IPM-rifampin (RIF), 13% and 81% isolates, respectively; IPM-CL, 13% and 87% isolates, respectively; and RIF-COL, 20% and 73% isolates, respectively. Significant proportion (19%) of XDR P. aeruginosa isolates produced MBLs, and majority (82%) of A. baumannii isolates produced either MBLs or OXA-23. Conclusions: Our results suggest that combinations of IPM-AMS, IPM-RIF, IPM-CL, and RIF-CL are more useful than individual drugs for treating 13-20% of XDR A. baumannii infections.

Abstract

Background: Extensively drug-resistant (XDR) Pseudomonas aeruginosa and Acinetobacter baumannii are a threat to hospitalized patients. We evaluated the effects of antimicrobial combinations on XDR P. aeruginosa and A. baumannii isolates. Methods: P. aeruginosa and A. baumannii isolates, which were resistant to all antibiotics except colistin (CL), were collected from eight hospitals in Korea. Genes encoding metallo-β-lactamases (MBLs) and OXA carbapenemases were detected by PCR in eight P. aeruginosa and 30 A. baumannii isolates. In vitro synergy of antimicrobial combinations was tested by using the checkerboard method. Results: Minimum inhibitory concentrations of β-lactams, aminoglycosides, and fluoroquinolones were very high, while that of CL was low for majority of XDR P. aeruginosa and A. baumannii isolates. Antimicrobial combinations including Imipenem (IPM)-CL, ceftazidime (CAZ)-CL, and rifampin (RIF)-CL exerted only additive/indifferent effects on majority of XDR P. aeruginosa isolates. Proportions of XDR A. baumannii isolates that showed synergistic and additive/indifferent inhibition after treatment with antimicrobial combinations used are as follows: IPM-ampicillin-sulbactam (AMS), 17% and 80% isolates, respectively; IPM-rifampin (RIF), 13% and 81% isolates, respectively; IPM-CL, 13% and 87% isolates, respectively; and RIF-COL, 20% and 73% isolates, respectively. Significant proportion (19%) of XDR P. aeruginosa isolates produced MBLs, and majority (82%) of A. baumannii isolates produced either MBLs or OXA-23. Conclusions: Our results suggest that combinations of IPM-AMS, IPM-RIF, IPM-CL, and RIF-CL are more useful than individual drugs for treating 13-20% of XDR A. baumannii infections.

참고문헌 (40)

  1. Lister PD, "Antibacterial-resistant Pseudomonas aeruginosa: clinical impact and complex regulation of chromosomally encoded resistance mechanisms", Clin Microbiol Rev, 22, pp.582~610 (2009)
  2. Peleg AY, "Acinetobacter baumannii: emergence of a successful pathogen", Clin Microbiol Rev, 21, pp.538~582 (2008)
  3. 이경원, "Further Increases in Carbapenem-, Amikacin-, and Fluoroquinolone-Resistant Isolates of Acinetobacter spp. and P. aeruginosa in Korea: KONSAR Study 2009", Yonsei Medical Journal, 52(5), pp.793~802 (2011), 연세대학교의과대학
  4. Huh K, "Continuous increase of the antimicrobial resistance among gram-negative pathogens causing bacteremia: a nationwide surveillance study by the Korean Network for Study on Infectious Diseases (KONSID)", Diagn Microbiol Infect Dis, 76, pp.477~482 (2013)
  5. Koch-Weser J, "Adverse effects of sodium colistimethate. Manifestations and specific rates during 317 courses of therapy", Ann Intern Med, 72, pp.857~868 (1970)
  6. Li J, "Old polymyxins are back: is resistance close?", Clin Infect Dis, 43, pp.663~664 (2006)
  7. Bergen PJ, "Dosing of colistin-back to basic PK", PD, 2011, pp.11, 464~469
  8. Taccone FS, "Successful treatment of septic shock due to pan-resistant Acinetobacter baumannii using combined antimicrobial therapy including tigecycline", Eur J Clin Microbiol Infect Dis, 25, pp.257~260 (2006)
  9. Dean CR, "Efflux-mediated resistance to tigecycline (GAR-936) in Pseudomonas aeruginosa PAO1", Antimicrob Agents Chemother, 47, pp.972~978 (2003)
  10. Navon-Venezia S, "High tigecycline resistance in multidrug-resistant Acinetobacter baumannii", J Antimicrob Chemother, 59, pp.772~774 (2007)
  11. Peleg AY, "Tigecycline efflux as a mechanism for nonsusceptibility in Acinetobacter baumannii", Antimicrob Agents Chemother, 51, pp.2065~2069 (2007)
  12. Petrosillo N, "Colistin monotherapy vs. combination therapy: evidence from microbiological, animal and clinical studies", Clin Microbiol Infect, 14, pp.816~827 (2008)
  13. Tamma PD, "Combination therapy for treatment of infections with gram-negative bacteria", Clin Microbiol Rev, 25, pp.450~470 (2012)
  14. Zavascki AP, "Combination therapy for carbapenem-resistant Gram-negative bacteria", Expert Rev Anti Infect Ther, 11, pp.1333~1353 (2013)
  15. Zusman O, "Systematic review and meta-analysis of in vitro synergy of polymyxins and carbapenems", Antimicrob Agents Chemother, 57, pp.5104~5111 (2013)
  16. Clinical and Laboratory Standards Institute, "Performance standard for antimicrobial susceptibility testing", Clinical and Laboratory Standards Institute, ~ (2013)
  17. Lee K, "Improved performance of the modified Hodge test with MacConkey agar for screening carbapenemase-producing Gram-negative bacilli", J Microbiol Methods, 83, pp.149~152 (2010)
  18. Lee K, "Evaluation of the Hodge test and the imipenem-EDTA double-disk synergy test for differentiating metallo-beta-lactamase-producing isolates of Pseudomonas spp. and Acinetobacter spp", J Clin Microbiol, 41, pp.4623~4629 (2003)
  19. Lee K, "Wide dissemination of OXA-type carbapenemases in clinical Acinetobacter spp. isolates from South Korea", Int J Antimicrob Agents, 33, pp.520~524 (2009)
  20. Hindler JF, "Clinical microbiology procedures handbook", pp.5.0.1~5.18.2.1 (2010), ASM Press
  21. Biswas S, "Colistin: an update on the antibiotic of the 21st century", Expert Rev Anti Infect Ther, 10, pp.917~934 (2012)
  22. Dhariwal AK, "Colistin: re-emergence of the ‘forgotten’ antimicrobial agent", J Postgrad Med, 59, pp.208~215 (2013)
  23. García-Quintanilla M, "Activity of host antimicrobials against multidrug-resistant Acinetobacter baumannii acquiring colistin resistance through loss of lipopolysaccharide", Antimicrob Agents Chemother, 58, pp.2972~2975 (2014)
  24. Lee JY, "Genomic variations between colistin-susceptible and -resistant Pseudomonas aeruginosa clinical isolates and their effects on colistin resistance", J Antimicrob Chemother, 69, pp.1248~1256 (2014)
  25. Matthaiou DK, "Risk factors associated with the isolation of colistin-resistant gram-negative bacteria: a matched case-control study", Crit Care Med, 36, pp.807~811 (2008)
  26. Kim Y, "In vivo emergence of colistin resistance in Acinetobacter baumannii clinical isolates of sequence type 357 during colistin treatment", Diagn Microbiol Infect Dis, 79, pp.362~366 (2014)
  27. Galani I, "Colistin susceptibility testing by Etest and disk diffusion methods", Int J Antimicrob Agents, 31, pp.434~439 (2008)
  28. Hindler JA, "Colistin MIC variability by method for contemporary clinical isolates of multidrug-resistant Gram-negative bacilli", J Clin Microbiol, 51, pp.1678~1684 (2013)
  29. Landman D, "Citywide emergence of Pseudomonas aeruginosa strains with reduced susceptibility to polymyxin B", J Antimicrob Chemother, 55, pp.954~957 (2005)
  30. Gunderson BW, "Synergistic activity of colistin and ceftazidime against multiantibiotic-resistant Pseudomonas aeruginosa in an in vitro pharmacodynamic model", Antimicrob Agents Chemother, 47, pp.905~909 (2003)
  31. Timurkaynak F, "In vitro activities of non-traditional antimicrobials alone or in combination against multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii isolated from intensive care units", Int J Antimicrob Agents, 27, pp.224~228 (2006)
  32. Cirioni O, "Efficacy of tachyplesin III, colistin, and imipenem against a multiresistant Pseudomonas aeruginosa strain", Antimicrob Agents Chemother, 51, pp.2005~2010 (2007)
  33. Tascini C, "Microbiological activity and clinical efficacy of a colistin and rifampin combination in multidrug-resistant Pseudomonas aeruginosa infections", J Chemother, 16, pp.282~287 (2004)
  34. Choi JY, "Synergic in-vitro activity of imipenem and sulbactam against Acinetobacter baumannii", Clin Microbiol Infect, 10, pp.1098~1101 (2004)
  35. Song JY, "Efficacy of monotherapy and combined antibiotic therapy for carbapenem-resistant Acinetobacter baumannii pneumonia in an immunosuppressed mouse model", Int J Antimicrob Agents, 33, pp.33~39 (2009)
  36. Pachón-Ibáñez ME, "Efficacy of rifampin, in monotherapy and in combinations, in an experimental murine pneumonia model caused by panresistant Acinetobacter baumannii strains", Eur J Clin Microbiol Infect Dis, 30, pp.895~901 (2011)
  37. Liang W, "Activities of colistin- and minocycline-based combinations against extensive drug resistant Acinetobacter baumannii isolates from intensive care unit patients", BMC Infect Dis, 11, pp.109~ (2011)
  38. Lee HJ, "Synergistic activity of colistin and rifampin combination against multidrug-resistant Acinetobacter baumannii in an in vitro pharmacokinetic", pharmacodynamic model, 2013, pp.57, 3738~3745
  39. Wareham DW, "In-vitro activity of polymyxin B in combination with imipenem, rifampicin and azithromycin versus multidrug resistant strains of Acinetobacter baumannii producing OXA-23 carbapenemases", Ann Clin Microbiol Antimicrob, 5, pp.10~ (2006)
  40. Khawcharoenporn T, "Colistin-based treatment for extensively drug-resistant Acinetobacter baumannii pneumonia", Int J Antimicrob Agents, 43, pp.378~382 (2014)

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