Comparison of colistin–carbapenem, colistin–sulbactam, and colistin plus other antibacterial agents for the treatment of extremely drug-resistant Acinetobacter baumannii bloodstream infections

  • A. Batirel
  • I. I. Balkan
  • O. Karabay
  • C. Agalar
  • S. Akalin
  • O. Alici
  • E. Alp
  • F. A. Altay
  • N. Altin
  • F. Arslan
  • T. Aslan
  • N. Bekiroglu
  • S. Cesur
  • A. D. Celik
  • M. Dogan
  • B. Durdu
  • F. Duygu
  • A. Engin
  • D. O. Engin
  • I. Gonen
  • E. Guclu
  • T. Guven
  • C. A. Hatipoglu
  • S. Hosoglu
  • M. K. Karahocagil
  • A. U. Kilic
  • B. Ormen
  • D. Ozdemir
  • S. Ozer
  • N. Oztoprak
  • N. Sezak
  • V. Turhan
  • N. Turker
  • H. Yilmaz
Article

Abstract

The purpose of this investigation was to compare the efficacy of colistin-based therapies in extremely drug-resistant Acinetobacter spp. bloodstream infections (XDR-ABSI). A retrospective study was conducted in 27 tertiary-care centers from January 2009 to August 2012. The primary end-point was 14-day survival, and the secondary end-points were clinical and microbiological outcomes. Thirty-six and 214 patients [102 (47.7 %): colistin–carbapenem (CC), 69 (32.2 %): colistin–sulbactam (CS), and 43 (20.1 %: tigecycline): colistin with other agent (CO)] received colistin monotherapy and colistin-based combinations, respectively. Rates of complete response/cure and 14-day survival were relatively higher, and microbiological eradication was significantly higher in the combination group. Also, the in-hospital mortality rate was significantly lower in the combination group. No significant difference was found in the clinical (p = 0.97) and microbiological (p = 0.92) outcomes and 14-day survival rates (p = 0.79) between the three combination groups. Neither the timing of initial effective treatment nor the presence of any concomitant infection was significant between the three groups (p > 0.05) and also for 14-day survival (p > 0.05). Higher Pitt bacteremia score (PBS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Charlson comorbidity index (CCI), and prolonged hospital and intensive care unit (ICU) stay before XDR-ABSI were significant risk factors for 14-day mortality (p = 0.02, p = 0.0001, p = 0.0001, p = 0.02, and p = 0.01, respectively). In the multivariable analysis, PBS, age, and duration of ICU stay were independent risk factors for 14-day mortality (p < 0.0001, p < 0.0001, and p = 0.001, respectively). Colistin-based combination therapy resulted in significantly higher microbiological eradication rates, relatively higher cure and 14-day survival rates, and lower in-hospital mortality compared to colistin monotherapy. CC, CS, and CO combinations for XDR-ABSI did not reveal significant differences with respect to 14-day survival and clinical or microbiological outcome before and after propensity score matching (PSM). PBS, age, and length of ICU stay were independent risk factors for 14-day mortality.

Keywords

Intensive Care Unit Stay Colistin Charlson Comorbidity Index Propensity Score Match Combination Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Conflict of interest

None to declare.

Funding

None.

References

  1. 1.
    Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ, Vatopoulos A, Weber JT, Monnet DL (2012) Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18(3):268–281PubMedCrossRefGoogle Scholar
  2. 2.
    Vila J, Pachón J (2008) Therapeutic options for Acinetobacter baumannii infections. Expert Opin Pharmacother 9(4):587–599PubMedCrossRefGoogle Scholar
  3. 3.
    Falagas ME, Karveli EA, Siempos II, Vardakas KZ (2008) Acinetobacter infections: a growing threat for critically ill patients. Epidemiol Infect 136(8):1009–1019PubMedCentralPubMedGoogle Scholar
  4. 4.
    Erbay A, Idil A, Gözel MG, Mumcuoğlu I, Balaban N (2009) Impact of early appropriate antimicrobial therapy on survival in Acinetobacter baumannii bloodstream infections. Int J Antimicrob Agents 34(6):575–579PubMedCrossRefGoogle Scholar
  5. 5.
    Kim YJ, Kim SI, Hong KW, Kim YR, Park YJ, Kang MW (2012) Risk factors for mortality in patients with carbapenem-resistant Acinetobacter baumannii bacteremia: impact of appropriate antimicrobial therapy. J Korean Med Sci 27(5):471–475PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Kallel H, Bahloul M, Hergafi L, Akrout M, Ketata W, Chelly H, Hamida CB, Rekik N, Hammami A, Bouaziz M (2006) Colistin as a salvage therapy for nosocomial infections caused by multidrug-resistant bacteria in the ICU. Int J Antimicrob Agents 28(4):366–369PubMedCrossRefGoogle Scholar
  7. 7.
    Li J, Rayner CR, Nation RL, Owen RJ, Spelman D, Tan KE, Liolios L (2006) Heteroresistance to colistin in multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother 50(9):2946–2950PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Rahal JJ (2006) Novel antibiotic combinations against infections with almost completely resistant Pseudomonas aeruginosa and Acinetobacter species. Clin Infect Dis 43(Suppl 2):S95–S99PubMedCrossRefGoogle Scholar
  9. 9.
    Petrosillo N, Chinello P, Proietti MF, Cecchini L, Masala M, Franchi C, Venditti M, Esposito S, Nicastri E (2005) Combined colistin and rifampicin therapy for carbapenem-resistant Acinetobacter baumannii infections: clinical outcome and adverse events. Clin Microbiol Infect 11(8):682–683PubMedCrossRefGoogle Scholar
  10. 10.
    Pantopoulou A, Giamarellos-Bourboulis EJ, Raftogannis M, Tsaganos T, Dontas I, Koutoukas P, Baziaka F, Giamarellou H, Perrea D (2007) Colistin offers prolonged survival in experimental infection by multidrug-resistant Acinetobacter baumannii: the significance of co-administration of rifampicin. Int J Antimicrob Agents 29(1):51–55PubMedCrossRefGoogle Scholar
  11. 11.
    Montero A, Ariza J, Corbella X, Doménech A, Cabellos C, Ayats J, Tubau F, Borraz C, Gudiol F (2004) Antibiotic combinations for serious infections caused by carbapenem-resistant Acinetobacter baumannii in a mouse pneumonia model. J Antimicrob Chemother 54(6):1085–1091PubMedCrossRefGoogle Scholar
  12. 12.
    Saballs M, Pujol M, Tubau F, Peña C, Montero A, Domínguez MA, Gudiol F, Ariza J (2006) Rifampicin/imipenem combination in the treatment of carbapenem-resistant Acinetobacter baumannii infections. J Antimicrob Chemother 58(3):697–700PubMedCrossRefGoogle Scholar
  13. 13.
    Rodríguez-Hernández MJ, Pachón J, Pichardo C, Cuberos L, Ibáñez-Martínez J, García-Curiel A, Caballero FJ, Moreno I, Jiménez-Mejías ME (2000) Imipenem, doxycycline and amikacin in monotherapy and in combination in Acinetobacter baumannii experimental pneumonia. J Antimicrob Chemother 45(4):493–501PubMedCrossRefGoogle Scholar
  14. 14.
    Bernabeu-Wittel M, Pichardo C, García-Curiel A, Pachón-Ibáñez ME, Ibáñez-Martínez J, Jiménez-Mejías ME, Pachón J (2005) Pharmacokinetic/pharmacodynamic assessment of the in-vivo efficacy of imipenem alone or in combination with amikacin for the treatment of experimental multiresistant Acinetobacter baumannii pneumonia. Clin Microbiol Infect 11(4):319–325PubMedCrossRefGoogle Scholar
  15. 15.
    Haddad FA, Van Horn K, Carbonaro C, Aguero-Rosenfeld M, Wormser GP (2005) Evaluation of antibiotic combinations against multidrug-resistant Acinetobacter baumannii using the E-test. Eur J Clin Microbiol Infect Dis 24(8):577–579PubMedCrossRefGoogle Scholar
  16. 16.
    Ko WC, Lee HC, Chiang SR, Yan JJ, Wu JJ, Lu CL, Chuang YC (2004) In vitro and in vivo activity of meropenem and sulbactam against a multidrug-resistant Acinetobacter baumannii strain. J Antimicrob Chemother 53(2):393–395PubMedCrossRefGoogle Scholar
  17. 17.
    Kiffer CR, Sampaio JL, Sinto S, Oplustil CP, Koga PC, Arruda AC, Turner PJ, Mendes C (2005) In vitro synergy test of meropenem and sulbactam against clinical isolates of Acinetobacter baumannii. Diagn Microbiol Infect Dis 52(4):317–322PubMedCrossRefGoogle Scholar
  18. 18.
    Sobieszczyk ME, Furuya EY, Hay CM, Pancholi P, Della-Latta P, Hammer SM, Kubin CJ (2004) Combination therapy with polymyxin B for the treatment of multidrug-resistant Gram-negative respiratory tract infections. J Antimicrob Chemother 54(2):566–569PubMedCrossRefGoogle Scholar
  19. 19.
    Kasiakou SK, Michalopoulos A, Soteriades ES, Samonis G, Sermaides GJ, Falagas ME (2005) Combination therapy with intravenous colistin for management of infections due to multidrug-resistant Gram-negative bacteria in patients without cystic fibrosis. Antimicrob Agents Chemother 49(8):3136–3146PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Bassetti M, Repetto E, Righi E, Boni S, Diverio M, Molinari MP, Mussap M, Artioli S, Ansaldi F, Durando P, Orengo G, Bobbio Pallavicini F, Viscoli C (2008) Colistin and rifampicin in the treatment of multidrug-resistant Acinetobacter baumannii infections. J Antimicrob Chemother 61(2):417–420PubMedCrossRefGoogle Scholar
  21. 21.
    Horan TC, Andrus M, Dudeck MA (2008) CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 36(5):309–332PubMedCrossRefGoogle Scholar
  22. 22.
    Chow JW, Yu VL (1999) Combination antibiotic therapy versus monotherapy for gram-negative bacteraemia: a commentary. Int J Antimicrob Agents 11(1):7–12PubMedCrossRefGoogle Scholar
  23. 23.
    Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13(10):818–829PubMedCrossRefGoogle Scholar
  24. 24.
    Chen SJ, Chao TF, Chiang MC, Kuo SC, Chen LY, Yin T, Chen TL, Fung CP (2011) Prediction of patient outcome from Acinetobacter baumannii bacteremia with Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores. Intern Med 50(8):871–877PubMedCrossRefGoogle Scholar
  25. 25.
    Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40(5):373–383PubMedCrossRefGoogle Scholar
  26. 26.
    Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P; Acute Dialysis Quality Initiative workgroup (2004) Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 8(4):R204–R212PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Spapen H, Jacobs R, Van Gorp V, Troubleyn J, Honoré PM (2011) Renal and neurological side effects of colistin in critically ill patients. Ann Intensive Care 1(1):14PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Falagas ME, Koletsi PK, Bliziotis IA (2006) The diversity of definitions of multidrug-resistant (MDR) and pandrug-resistant (PDR) Acinetobacter baumannii and Pseudomonas aeruginosa. J Med Microbiol 55(Pt 12):1619–1629PubMedCrossRefGoogle Scholar
  29. 29.
    Fowler RA, Flavin KE, Barr J, Weinacker AB, Parsonnet J, Gould MK (2003) Variability in antibiotic prescribing patterns and outcomes in patients with clinically suspected ventilator-associated pneumonia. Chest 123(3):835–844PubMedCrossRefGoogle Scholar
  30. 30.
    Vouillamoz J, Moreillon P, Giddey M, Entenza JM (2008) In vitro activities of tigecycline combined with other antimicrobials against multiresistant gram-positive and gram-negative pathogens. J Antimicrob Chemother 61(2):371–374PubMedCrossRefGoogle Scholar
  31. 31.
    Principe L, D’Arezzo S, Capone A, Petrosillo N, Visca P (2009) In vitro activity of tigecycline in combination with various antimicrobials against multidrug resistant Acinetobacter baumannii. Ann Clin Microbiol Antimicrob 8:18PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Falagas ME, Rafailidis PI, Ioannidou E, Alexiou VG, Matthaiou DK, Karageorgopoulos DE, Kapaskelis A, Nikita D, Michalopoulos A (2010) Colistin therapy for microbiologically documented multidrug-resistant Gram-negative bacterial infections: a retrospective cohort study of 258 patients. Int J Antimicrob Agents 35(2):194–199PubMedCrossRefGoogle Scholar
  33. 33.
    Durante-Mangoni E, Signoriello G, Andini R, Mattei A, De Cristoforo M, Murino P, Bassetti M, Malacarne P, Petrosillo N, Galdieri N, Mocavero P, Corcione A, Viscoli C, Zarrilli R, Gallo C, Utili R (2013) Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial. Clin Infect Dis 57(3):349–358PubMedCrossRefGoogle Scholar
  34. 34.
    Pogue JM, Kaye KS (2013) Is there really no benefit to combination therapy with colistin? Expert Rev Anti Infect Ther 11(9):881–884PubMedCrossRefGoogle Scholar
  35. 35.
    Gauthier TP (2013) Editorial commentary: rifampicin plus colistin in the era of extensively drug-resistant Acinetobacter baumannii infections. Clin Infect Dis 57(3):359–361PubMedCrossRefGoogle Scholar
  36. 36.
    Song JY, Cheong HJ, Choi WS, Heo JY, Noh JY, Kim WJ (2011) Clinical and microbiological characterization of carbapenem-resistant Acinetobacter baumannii bloodstream infections. J Med Microbiol 60(Pt 5):605–611PubMedCrossRefGoogle Scholar
  37. 37.
    Kuo SC, Lee YT, Yang SP, Chiang MC, Lin YT, Tseng FC, Chen TL, Fung CP (2013) Evaluation of the effect of appropriate antimicrobial therapy on mortality associated with Acinetobacter nosocomialis bacteraemia. Clin Microbiol Infect 19(7):634–639PubMedCrossRefGoogle Scholar
  38. 38.
    Ogutlu A, Guclu E, Karabay O, Utku AC, Tuna N, Yahyaoglu M (2014) Effects of Carbapenem consumption on the prevalence of Acinetobacter infection in intensive care unit patients. Ann Clin Microbiol Antimicrob 13(1):7PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Deveci A, Coban AY, Acicbe O, Tanyel E, Yaman G, Durupinar B (2012) In vitro effects of sulbactam combinations with different antibiotic groups against clinical Acinetobacter baumannii isolates. J Chemother 24(5):247–252PubMedCrossRefGoogle Scholar
  40. 40.
    Cıkman A, Ceylan MR, Parlak M, Karahocagil MK, Berktaş M (2013) Evaluation of colistin–ampicillin/sulbactam combination efficacy in imipenem-resistant Acinetobacter baumannii strains. Mikrobiyol Bul 47(1):147–151PubMedGoogle Scholar
  41. 41.
    Dizbay M, Tozlu DK, Cirak MY, Isik Y, Ozdemir K, Arman D (2010) In vitro synergistic activity of tigecycline and colistin against XDR-Acinetobacter baumannii. J Antibiot (Tokyo) 63(2):51–53CrossRefGoogle Scholar
  42. 42.
    Michalopoulos A, Falagas ME, Karatza DC, Alexandropoulou P, Papadakis E, Gregorakos L, Chalevelakis G, Pappas G (2011) Epidemiologic, clinical characteristics, and risk factors for adverse outcome in multiresistant gram-negative primary bacteremia of critically ill patients. Am J Infect Control 39(5):396–400PubMedCrossRefGoogle Scholar
  43. 43.
    Tseng YC, Wang JT, Wu FL, Chen YC, Chie WC, Chang SC (2007) Prognosis of adult patients with bacteremia caused by extensively resistant Acinetobacter baumannii. Diagn Microbiol Infect Dis 59(2):181–190PubMedCrossRefGoogle Scholar
  44. 44.
    Sunenshine RH, Wright MO, Maragakis LL, Harris AD, Song X, Hebden J, Cosgrove SE, Anderson A, Carnell J, Jernigan DB, Kleinbaum DG, Perl TM, Standiford HC, Srinivasan A (2007) Multidrug-resistant Acinetobacter infection mortality rate and length of hospitalization. Emerg Infect Dis 13(1):97–103PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • A. Batirel
    • 1
  • I. I. Balkan
    • 2
  • O. Karabay
    • 3
  • C. Agalar
    • 4
  • S. Akalin
    • 5
  • O. Alici
    • 4
  • E. Alp
    • 6
  • F. A. Altay
    • 7
  • N. Altin
    • 8
  • F. Arslan
    • 9
  • T. Aslan
    • 10
  • N. Bekiroglu
    • 11
  • S. Cesur
    • 8
  • A. D. Celik
    • 12
  • M. Dogan
    • 13
  • B. Durdu
    • 14
  • F. Duygu
    • 15
  • A. Engin
    • 16
  • D. O. Engin
    • 17
  • I. Gonen
    • 18
  • E. Guclu
    • 3
  • T. Guven
    • 19
  • C. A. Hatipoglu
    • 20
  • S. Hosoglu
    • 21
  • M. K. Karahocagil
    • 22
  • A. U. Kilic
    • 6
  • B. Ormen
    • 23
  • D. Ozdemir
    • 24
  • S. Ozer
    • 1
  • N. Oztoprak
    • 25
  • N. Sezak
    • 24
  • V. Turhan
    • 26
  • N. Turker
    • 24
  • H. Yilmaz
    • 27
  1. 1.Infectious Diseases and Clinical MicrobiologyKartal Dr. Lutfi Kirdar Education and Research HospitalKartal, IstanbulTurkey
  2. 2.Infectious Diseases and Clinical Microbiology, Cerrahpasa Medical FacultyIstanbul UniversityIstanbulTurkey
  3. 3.Infectious Diseases and Clinical Microbiology, Medical FacultySakarya UniversitySakaryaTurkey
  4. 4.Infectious Diseases and Clinical MicrobiologyFatih Sultan Mehmet Education and Research HospitalIstanbulTurkey
  5. 5.Infectious Diseases and Clinical Microbiology, Medical FacultyPamukkale UniversityDenizliTurkey
  6. 6.Infectious Diseases and Clinical Microbiology, Medical FacultyErciyes UniversityKayseriTurkey
  7. 7.Infectious Diseases and Clinical MicrobiologyDiskapi Education and Research HospitalAnkaraTurkey
  8. 8.Infectious Diseases and Clinical MicrobiologyAnkara Etlik Education and Research HospitalAnkaraTurkey
  9. 9.Infectious Diseases, Medical FacultyIstanbul Medipol UniversityIstanbulTurkey
  10. 10.Infectious Diseases, Medical FacultyBezmi Alem UniversityIstanbulTurkey
  11. 11.Biostatistics, Medical FacultyMarmara UniversityIstanbulTurkey
  12. 12.Infectious Diseases, Medical FacultyTrakya UniversityEdirneTurkey
  13. 13.Infectious Diseases and Clinical Microbiology, Medical FacultyNamik Kemal UniversityTekirdagTurkey
  14. 14.Infectious Diseases and Clinical MicrobiologyBakirkoy Sadi Konuk Education and Research HospitalIstanbulTurkey
  15. 15.Infectious Diseases and Clinical Microbiology, Medical FacultyGaziosmanpasa UniversityTokatTurkey
  16. 16.Infectious Diseases and Clinical Microbiology, Medical FacultyCumhuriyet UniversitySivasTurkey
  17. 17.Infectious Diseases and Clinical MicrobiologyHaydarpasa Numune Education and Research HospitalIstanbulTurkey
  18. 18.Infectious Diseases and Clinical Microbiology, Medical FacultySuleyman Demirel UniversityIspartaTurkey
  19. 19.Infectious Diseases and Clinical MicrobiologyAnkara Ataturk Education and Research HospitalAnkaraTurkey
  20. 20.Infectious Diseases and Clinical MicrobiologyAnkara Education and Research HospitalAnkaraTurkey
  21. 21.Infectious Diseases and Clinical Microbiology, Medical FacultyDicle UniversityDiyarbakırTurkey
  22. 22.Infectious Diseases and Clinical Microbiology, Medical FacultyYuzuncu Yil UniversityVanTurkey
  23. 23.Infectious Diseases and Clinical MicrobiologyIzmir Ataturk Education and Research HospitalIzmirTurkey
  24. 24.Infectious Diseases and Clinical Microbiology, Education and Research HospitalDuzce UniversityDüzceTurkey
  25. 25.Infectious Diseases and Clinical MicrobiologyAntalya Education and Research HospitalAntalyaTurkey
  26. 26.Infectious Diseases and Clinical MicrobiologyGATA Haydarpasa Education and Research HospitalIstanbulTurkey
  27. 27.Infectious Diseases and Clinical Microbiology, Medical FacultyOndokuz Mayıs UniversitySamsunTurkey

Personalised recommendations