Skip to main content
Top
Published in: BMC Anesthesiology 1/2013

Open Access 01-12-2013 | Research article

Adjunctive aerosolized colistin for multi-drug resistant gram-negative pneumonia in the critically ill: a retrospective study

Authors: Neha M Doshi, Charles H Cook, Kari L Mount, Stanislaw P Stawicki, Erin N Frazee, Heather A Personett, Garrett E Schramm, Heather M Arnold, Claire V Murphy

Published in: BMC Anesthesiology | Issue 1/2013

Login to get access

Abstract

Background

The incidence of multi-drug resistant (MDR) gram-negative (GN) organisms including Pseudomonas and Acinetobacter spp has increased in the last decade, prompting re-evaluation of colistin for the management of these infections. Aerosolized colistin as an adjunct to intravenous therapy is a current option for the management of MDR-GN pneumonia, although data supporting this practice is limited. This study evaluates the efficacy of adjunctive aerosolized colistin in combination with intravenous colistin in critically ill patients with MDR-GN pneumonia.

Methods

A retrospective multi-center cohort analysis comparing critically ill patients with MDR-GN pneumonia who received intravenous colistin (IV) alone or in combination with adjunctive aerosolized colistin (IV/AER) with a primary endpoint of clinical cure at the end of colistin therapy. Secondary endpoints included microbiologic cure, duration of mechanical ventilation, length of stay, and hospital mortality. A post-hoc subgroup analysis was performed for patients with high quality cultures used for diagnosis of MDR-GN pneumonia. Dichotomous data were compared using Fisher’s exact test while the student’s t-test or Mann–Whitney U test were used for continuous variables.

Results

Ninety-five patients met criteria for evaluation with 51 patients receiving IV and 44 receiving IV/AER. Baseline characteristics were similar between the two groups. Twenty patients (39.2%) receiving IV and 24 (54.5%) receiving IV/AER achieved clinical cure (p = 0.135). There was no difference in microbiologic cure rates between the IV and IV/AER colistin groups (40.7vs. 44.4%, p = 0.805). The IV group demonstrated a trend towards higher pneumonia attributable mortality (70.4 vs. 40%, p = 0.055). In the subgroup analysis of patients with high quality respiratory cultures, there was a significantly lower clinical cure rate for those in the IV group as compared to the IV/AER group (31.3 vs. 57.1%, p = 0.033).

Conclusions

Addition of aerosolized colistin to IV colistin may improve clinical cure and mortality for patients with MDR-GN pneumonia. Larger, prospective trials are warranted to confirm the benefit of adjunctive aerosolized colistin in critically ill patients with MDR-GN pneumonia.
Appendix
Available only for authorised users
Literature
1.
go back to reference Michalopoulos A, Kasiakou SK, Mastora Z, et al: Aerosolized colistin for the treatment of nosocomial pneumonia due to multidrug-resistant gram-negative bacteria in patients without cystic fibrosis. Crit Care. 2005, 9: R53-R59. 10.1186/cc3020.CrossRefPubMedPubMedCentral Michalopoulos A, Kasiakou SK, Mastora Z, et al: Aerosolized colistin for the treatment of nosocomial pneumonia due to multidrug-resistant gram-negative bacteria in patients without cystic fibrosis. Crit Care. 2005, 9: R53-R59. 10.1186/cc3020.CrossRefPubMedPubMedCentral
2.
go back to reference Laessig KA: End points in hospital-acquired pneumonia and/or ventilator-associated pneumonia in clinical trials: food and drug administration perspective. Clin Inf Dis. 2010, 51: S117-S119. 10.1086/653059.CrossRef Laessig KA: End points in hospital-acquired pneumonia and/or ventilator-associated pneumonia in clinical trials: food and drug administration perspective. Clin Inf Dis. 2010, 51: S117-S119. 10.1086/653059.CrossRef
3.
go back to reference Jones ME, Draghi DC, Thornsberry C, et al: Emerging resistance among bacterial pathogens in the intensive care unit–a European and North American surveillance study (2000–2002). Ann Clin Microbiol Antimicrob. 2004, 3: 14-10.1186/1476-0711-3-14.CrossRefPubMedPubMedCentral Jones ME, Draghi DC, Thornsberry C, et al: Emerging resistance among bacterial pathogens in the intensive care unit–a European and North American surveillance study (2000–2002). Ann Clin Microbiol Antimicrob. 2004, 3: 14-10.1186/1476-0711-3-14.CrossRefPubMedPubMedCentral
4.
go back to reference Li J, Nationa RL, Turnidge JD, et al: Colistin: The re-emerging antibiotic for multi-drug resistant gram-negative bacterial infections. Lancet Infect Dis. 2006, 6: 589-601. 10.1016/S1473-3099(06)70580-1.CrossRefPubMed Li J, Nationa RL, Turnidge JD, et al: Colistin: The re-emerging antibiotic for multi-drug resistant gram-negative bacterial infections. Lancet Infect Dis. 2006, 6: 589-601. 10.1016/S1473-3099(06)70580-1.CrossRefPubMed
5.
go back to reference Evans ME, Feola DJ, Rapp RP: Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant gram-negative bacteria. Ann Pharmacother. 1999, 33: 960-967. 10.1345/aph.18426.CrossRefPubMed Evans ME, Feola DJ, Rapp RP: Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant gram-negative bacteria. Ann Pharmacother. 1999, 33: 960-967. 10.1345/aph.18426.CrossRefPubMed
6.
go back to reference Lu Q, Girardi C, Zhang M, et al: Nebulized and intravenous colistin in experimental pneumonia caused by pseudomonas aeruginosa. Int Care Med. 2010, 36: 1147-1155. 10.1007/s00134-010-1879-4.CrossRef Lu Q, Girardi C, Zhang M, et al: Nebulized and intravenous colistin in experimental pneumonia caused by pseudomonas aeruginosa. Int Care Med. 2010, 36: 1147-1155. 10.1007/s00134-010-1879-4.CrossRef
7.
go back to reference Kofteridis DP, Alexopoulou C, Valachis A, et al: Aerosolized plus intravenous colistin versus intravenous colistin alone for the treatment of ventilator-associated pneumonia: a matched case–control study. Clin Infect Dis. 2010, 51: 1238-1244. 10.1086/657242.CrossRefPubMed Kofteridis DP, Alexopoulou C, Valachis A, et al: Aerosolized plus intravenous colistin versus intravenous colistin alone for the treatment of ventilator-associated pneumonia: a matched case–control study. Clin Infect Dis. 2010, 51: 1238-1244. 10.1086/657242.CrossRefPubMed
8.
go back to reference Korbila IP, Michalopoulos A, Rafailidis PI, et al: Inhaled colistin as adjunctive therapy to intravenous colistin for the treatment of microbiologically documented ventilator-associated pneumonia: a comparative cohort study. Clin Microbiol Infect. 2010, 16: 1230-1236.CrossRefPubMed Korbila IP, Michalopoulos A, Rafailidis PI, et al: Inhaled colistin as adjunctive therapy to intravenous colistin for the treatment of microbiologically documented ventilator-associated pneumonia: a comparative cohort study. Clin Microbiol Infect. 2010, 16: 1230-1236.CrossRefPubMed
9.
go back to reference Horan TC, Andrus M, Dudeck MA: 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. 2008, 36: 309-322. 10.1016/j.ajic.2008.03.002.CrossRefPubMed Horan TC, Andrus M, Dudeck MA: 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. 2008, 36: 309-322. 10.1016/j.ajic.2008.03.002.CrossRefPubMed
10.
go back to reference Le F, Ashley ED, Neuhauser MM, et al: Consensus summary of aerosolized antimicrobial agents: application of guideline criteria: insights from the society of infectious diseases pharmacists. Pharmacotherapy. 2010, 30: 562-584. 10.1592/phco.30.6.562.CrossRefPubMed Le F, Ashley ED, Neuhauser MM, et al: Consensus summary of aerosolized antimicrobial agents: application of guideline criteria: insights from the society of infectious diseases pharmacists. Pharmacotherapy. 2010, 30: 562-584. 10.1592/phco.30.6.562.CrossRefPubMed
11.
go back to reference Michalopoulos A, Papadakis E: Inhaled anti-infective agents: emphasis on colistin. Infection. 2010, 38: 81-88. 10.1007/s15010-009-9148-6.CrossRefPubMed Michalopoulos A, Papadakis E: Inhaled anti-infective agents: emphasis on colistin. Infection. 2010, 38: 81-88. 10.1007/s15010-009-9148-6.CrossRefPubMed
12.
go back to reference Kwa ALH, Loh C, Low JGH, et al: Nebulized colistin in the treatment of pneumonia due to multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Clin Inf Dis. 2005, 41: 754-757. 10.1086/432583.CrossRef Kwa ALH, Loh C, Low JGH, et al: Nebulized colistin in the treatment of pneumonia due to multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Clin Inf Dis. 2005, 41: 754-757. 10.1086/432583.CrossRef
13.
go back to reference Lin CC, Liu TC, Kuo CF, et al: Aerosolized colistin for the treatment of multi-drug resistant Acinetobacter baumannii pneumonia: experience in a tertiary care hospital in northern Taiwan. J Microbiol Immunol Infect. 2010, 43: 323-331. 10.1016/S1684-1182(10)60050-3.CrossRefPubMed Lin CC, Liu TC, Kuo CF, et al: Aerosolized colistin for the treatment of multi-drug resistant Acinetobacter baumannii pneumonia: experience in a tertiary care hospital in northern Taiwan. J Microbiol Immunol Infect. 2010, 43: 323-331. 10.1016/S1684-1182(10)60050-3.CrossRefPubMed
14.
go back to reference Falagas ME, Siempos II, Rafailidis PI, et al: Inhaled colistin as monotherapy for multidrug-resistant gram(-) nosocomial pneumonia: a case series. Resp Med. 2009, 103: 707-713. 10.1016/j.rmed.2008.11.018.CrossRef Falagas ME, Siempos II, Rafailidis PI, et al: Inhaled colistin as monotherapy for multidrug-resistant gram(-) nosocomial pneumonia: a case series. Resp Med. 2009, 103: 707-713. 10.1016/j.rmed.2008.11.018.CrossRef
15.
go back to reference Fagon JY, Chastre J, Domart Y, et al: Mortality due to ventilator-associated pneumonia or colonization with Pseudomonas or Acinetobacter species: assessment by quantitative culture of samples obtained by a protected specimen brush. Clin Infect Dis. 1996, 23: 538-542. 10.1093/clinids/23.3.538.CrossRefPubMed Fagon JY, Chastre J, Domart Y, et al: Mortality due to ventilator-associated pneumonia or colonization with Pseudomonas or Acinetobacter species: assessment by quantitative culture of samples obtained by a protected specimen brush. Clin Infect Dis. 1996, 23: 538-542. 10.1093/clinids/23.3.538.CrossRefPubMed
16.
go back to reference Visscher S, Schruink CA, Melsen WG, et al: Effects of systemic antibiotic therapy on bacterial persistence in the respiratory tract of mechanically ventilated patients. Int Care Med. 2008, 34: 692-699. 10.1007/s00134-007-0984-5.CrossRef Visscher S, Schruink CA, Melsen WG, et al: Effects of systemic antibiotic therapy on bacterial persistence in the respiratory tract of mechanically ventilated patients. Int Care Med. 2008, 34: 692-699. 10.1007/s00134-007-0984-5.CrossRef
17.
go back to reference Vakil N: Acid inhibition and infections outside the gastrointestinal tract. Am J Gastroenterol. 2009, 104: S16-S20.CrossRef Vakil N: Acid inhibition and infections outside the gastrointestinal tract. Am J Gastroenterol. 2009, 104: S16-S20.CrossRef
18.
go back to reference Dennesen PJW, van de Ven JAM, Kessels AGH, Ramsay G, Bonten MJM: Resolution of infectious parameters after antimicrobial therapy in patients with ventilator-associated pneumonia. Am J Respir Crit Care Med. 2001, 163: 1371-1375. 10.1164/ajrccm.163.6.2007020.CrossRefPubMed Dennesen PJW, van de Ven JAM, Kessels AGH, Ramsay G, Bonten MJM: Resolution of infectious parameters after antimicrobial therapy in patients with ventilator-associated pneumonia. Am J Respir Crit Care Med. 2001, 163: 1371-1375. 10.1164/ajrccm.163.6.2007020.CrossRefPubMed
19.
go back to reference Petrosillo N, Ioannidou E, Falagas ME: Colistin monotherapy vs. combination therapy: evidence from microbiological, animal and clinical studies. Clin Microbiol Infect. 2008, 14: 216-227.CrossRef Petrosillo N, Ioannidou E, Falagas ME: Colistin monotherapy vs. combination therapy: evidence from microbiological, animal and clinical studies. Clin Microbiol Infect. 2008, 14: 216-227.CrossRef
20.
go back to reference Rynn C, Wootton M, Bowker KE, et al: In vitro assessment of colistin’s antipseudomonal antimicrobial interactions with other antibiotics. Clin Microbiol Infect. 1999, 5: 32-36.PubMed Rynn C, Wootton M, Bowker KE, et al: In vitro assessment of colistin’s antipseudomonal antimicrobial interactions with other antibiotics. Clin Microbiol Infect. 1999, 5: 32-36.PubMed
21.
go back to reference Timurkaynak F, Can F, Azap OK, et al: 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. 2006, 27: 224-228. 10.1016/j.ijantimicag.2005.10.012.CrossRefPubMed Timurkaynak F, Can F, Azap OK, et al: 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. 2006, 27: 224-228. 10.1016/j.ijantimicag.2005.10.012.CrossRefPubMed
Metadata
Title
Adjunctive aerosolized colistin for multi-drug resistant gram-negative pneumonia in the critically ill: a retrospective study
Authors
Neha M Doshi
Charles H Cook
Kari L Mount
Stanislaw P Stawicki
Erin N Frazee
Heather A Personett
Garrett E Schramm
Heather M Arnold
Claire V Murphy
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Anesthesiology / Issue 1/2013
Electronic ISSN: 1471-2253
DOI
https://doi.org/10.1186/1471-2253-13-45

Other articles of this Issue 1/2013

BMC Anesthesiology 1/2013 Go to the issue