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Published in: Critical Care 5/2013

Open Access 01-10-2013 | Research

Nebulised amphotericin B to eradicate Candida colonisation from the respiratory tract in critically ill patients receiving selective digestive decontamination: a cohort study

Authors: David SY Ong, Peter MC Klein Klouwenberg, Cristian Spitoni, Marc JM Bonten, Olaf L Cremer

Published in: Critical Care | Issue 5/2013

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Abstract

Introduction

Colonisation of the lower respiratory tract with Candida species occurs in 25% of mechanically ventilated critically ill patients, and is associated with increased morbidity. Nebulised amphotericin B has been used to eradicate Candida as part of selective decontamination of the digestive tract (SDD) protocols, but its effectiveness is unknown. We aimed to determine the effectiveness of nebulised amphotericin B in eradicating Candida respiratory tract colonisation in patients receiving SDD.

Methods

We included consecutive mechanically ventilated patients during a four-year period. Microbiological screening was performed upon admission and twice weekly thereafter according to a standardised protocol. A colonisation episode was defined as the presence of Candida species in two consecutive sputum samples taken at least one day apart. To correct for time-varying bias and possible confounding, we used a multistate approach and performed time-varying Cox regression with adjustment for age, disease severity, Candida load at baseline and concurrent corticosteroid use.

Results

Among 1,819 patients, colonisation with Candida occurred 401 times in 363 patients; 333 of these events were included for analysis. Decolonisation occurred in 51 of 59 episodes (86%) and in 170 of 274 episodes (62%) in patients receiving and not receiving nebulised amphotericin B, respectively. Nebulised amphotericin B was associated with an increased rate of Candida eradication (crude HR 2.0; 95% CI 1.4 to 2.7, adjusted HR 2.2; 95% CI 1.6 to 3.0). Median times to decolonisation were six and nine days, respectively. The incidence rate of ventilator-associated pneumonia, length of stay and mortality did not differ between both groups.

Conclusions

Nebulised amphotericin B reduces the duration of Candida colonisation in the lower respiratory tracts of mechanically ventilated critically ill patients receiving SDD, but data remain lacking that this is associated with a meaningful improvement in clinical outcomes. Until more evidence becomes available, nebulised amphotericin B should not be used routinely as part of the SDD protocol.
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Literature
1.
go back to reference Azoulay E, Timsit JF, Tafflet M, de Lassence A, Darmon M, Zahar JR, Adrie C, Garrouste-Orgeas M, Cohen Y, Mourvillier B, Schlemmer B: Candida colonization of the respiratory tract and subsequent pseudomonas ventilator-associated pneumonia. Chest 2006, 129: 110-117. 10.1378/chest.129.1.110CrossRefPubMed Azoulay E, Timsit JF, Tafflet M, de Lassence A, Darmon M, Zahar JR, Adrie C, Garrouste-Orgeas M, Cohen Y, Mourvillier B, Schlemmer B: Candida colonization of the respiratory tract and subsequent pseudomonas ventilator-associated pneumonia. Chest 2006, 129: 110-117. 10.1378/chest.129.1.110CrossRefPubMed
2.
go back to reference Delisle MS, Williamson DR, Perreault MM, Albert M, Jiang X, Heyland DK: The clinical significance of Candida colonization of respiratory tract secretions in critically ill patients. J Crit Care 2008, 23: 11-17. 10.1016/j.jcrc.2008.01.005CrossRefPubMed Delisle MS, Williamson DR, Perreault MM, Albert M, Jiang X, Heyland DK: The clinical significance of Candida colonization of respiratory tract secretions in critically ill patients. J Crit Care 2008, 23: 11-17. 10.1016/j.jcrc.2008.01.005CrossRefPubMed
3.
go back to reference Hamet M, Pavon A, Dalle F, Pechinot A, Prin S, Quenot JP, Charles PE: Candida spp. airway colonization could promote antibiotic-resistant bacteria selection in patients with suspected ventilator-associated pneumonia. Intensive Care Med 2012, 38: 1272-1279. 10.1007/s00134-012-2584-2CrossRefPubMed Hamet M, Pavon A, Dalle F, Pechinot A, Prin S, Quenot JP, Charles PE: Candida spp. airway colonization could promote antibiotic-resistant bacteria selection in patients with suspected ventilator-associated pneumonia. Intensive Care Med 2012, 38: 1272-1279. 10.1007/s00134-012-2584-2CrossRefPubMed
4.
go back to reference Olaechea PM, Palomar M, Leon-Gil C, Alvarez-Lerma F, Jorda R, Nolla-Salas J, León-Regidor MA, et al.: Economic impact of Candida colonization and Candida infection in the critically ill patient. Eur J Clin Microbiol Infect Dis 2004, 23: 323-330. 10.1007/s10096-004-1104-xCrossRefPubMed Olaechea PM, Palomar M, Leon-Gil C, Alvarez-Lerma F, Jorda R, Nolla-Salas J, León-Regidor MA, et al.: Economic impact of Candida colonization and Candida infection in the critically ill patient. Eur J Clin Microbiol Infect Dis 2004, 23: 323-330. 10.1007/s10096-004-1104-xCrossRefPubMed
5.
go back to reference Ricard JD, Roux D: Candida pneumonia in the ICU: myth or reality? Intensive Care Med 2009, 35: 1500-1502. 10.1007/s00134-009-1563-8CrossRefPubMed Ricard JD, Roux D: Candida pneumonia in the ICU: myth or reality? Intensive Care Med 2009, 35: 1500-1502. 10.1007/s00134-009-1563-8CrossRefPubMed
6.
go back to reference Meersseman W, Lagrou K, Spriet I, Maertens J, Verbeken E, Peetermans WE, Van Wijngaerden E: Significance of the isolation of Candida species from airway samples in critically ill patients: a prospective, autopsy study. Intensive Care Med 2009, 35: 1526-1531. 10.1007/s00134-009-1482-8CrossRefPubMed Meersseman W, Lagrou K, Spriet I, Maertens J, Verbeken E, Peetermans WE, Van Wijngaerden E: Significance of the isolation of Candida species from airway samples in critically ill patients: a prospective, autopsy study. Intensive Care Med 2009, 35: 1526-1531. 10.1007/s00134-009-1482-8CrossRefPubMed
7.
go back to reference El-Azizi MA, Starks SE, Khardori N: Interactions of Candida albicans with other Candida spp. and bacteria in the biofilms. J Appl Microbiol 2004, 96: 1067-1073. 10.1111/j.1365-2672.2004.02213.xCrossRefPubMed El-Azizi MA, Starks SE, Khardori N: Interactions of Candida albicans with other Candida spp. and bacteria in the biofilms. J Appl Microbiol 2004, 96: 1067-1073. 10.1111/j.1365-2672.2004.02213.xCrossRefPubMed
8.
go back to reference Ricard JD, Roux D: Candida colonization in ventilated ICU patients: no longer a bystander! Intensive Care Med 2012, 38: 1243-1245. 10.1007/s00134-012-2587-zCrossRefPubMed Ricard JD, Roux D: Candida colonization in ventilated ICU patients: no longer a bystander! Intensive Care Med 2012, 38: 1243-1245. 10.1007/s00134-012-2587-zCrossRefPubMed
9.
go back to reference Nseir S, Jozefowicz E, Cavestri B, Sendid B, Di PC, Dewavrin F, Favory R, Roussel-Delvallez M, Durocher A: Impact of antifungal treatment on Candida-Pseudomonas interaction: a preliminary retrospective case-control study. Intensive Care Med 2007, 33: 137-142. 10.1007/s00134-006-0422-0CrossRefPubMed Nseir S, Jozefowicz E, Cavestri B, Sendid B, Di PC, Dewavrin F, Favory R, Roussel-Delvallez M, Durocher A: Impact of antifungal treatment on Candida-Pseudomonas interaction: a preliminary retrospective case-control study. Intensive Care Med 2007, 33: 137-142. 10.1007/s00134-006-0422-0CrossRefPubMed
10.
go back to reference Roux D, Gaudry S, Dreyfuss D, El-Benna J, de Prost N, Denamur E, Saumon G, Ricard JD: Candida albicans impairs macrophage function and facilitates Pseudomonas aeruginosa pneumonia in rat. Crit Care Med 2009, 37: 1062-1067. 10.1097/CCM.0b013e31819629d2CrossRefPubMed Roux D, Gaudry S, Dreyfuss D, El-Benna J, de Prost N, Denamur E, Saumon G, Ricard JD: Candida albicans impairs macrophage function and facilitates Pseudomonas aeruginosa pneumonia in rat. Crit Care Med 2009, 37: 1062-1067. 10.1097/CCM.0b013e31819629d2CrossRefPubMed
11.
go back to reference Lam SW, Eschenauer GA, Carver PL: Evolving role of early antifungals in the adult intensive care unit. Crit Care Med 2009, 37: 1580-1593. 10.1097/CCM.0b013e31819dec9bCrossRefPubMed Lam SW, Eschenauer GA, Carver PL: Evolving role of early antifungals in the adult intensive care unit. Crit Care Med 2009, 37: 1580-1593. 10.1097/CCM.0b013e31819dec9bCrossRefPubMed
12.
go back to reference de Smet AM, Kluytmans JA, Cooper BS, Mascini EM, Benus RF, van der Werf TS, van der Hoeven JG, Pickkers P, Bogaers-Hofman D, van der Meer NJ, Bernards AT, Kuijper EJ, Joore JC, Leverstein-van Hall MA, Bindels AJ, Jansz AR, Wesselink RM, de Jongh BM, Dennesen PJ, van Asselt GJ, te Velde LF, Frenay IH, Kaasjager K, Bosch FH, van Iterson M, Thijsen SF, Kluge GH, Pauw W, de Vries JW, Kaan JA, et al.: Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med 2009, 360: 20-31. 10.1056/NEJMoa0800394CrossRefPubMed de Smet AM, Kluytmans JA, Cooper BS, Mascini EM, Benus RF, van der Werf TS, van der Hoeven JG, Pickkers P, Bogaers-Hofman D, van der Meer NJ, Bernards AT, Kuijper EJ, Joore JC, Leverstein-van Hall MA, Bindels AJ, Jansz AR, Wesselink RM, de Jongh BM, Dennesen PJ, van Asselt GJ, te Velde LF, Frenay IH, Kaasjager K, Bosch FH, van Iterson M, Thijsen SF, Kluge GH, Pauw W, de Vries JW, Kaan JA, et al.: Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med 2009, 360: 20-31. 10.1056/NEJMoa0800394CrossRefPubMed
13.
go back to reference Shintani AK, Girard TD, Eden SK, Arbogast PG, Moons KG, Ely EW: Immortal time bias in critical care research: application of time-varying Cox regression for observational cohort studies. Crit Care Med 2009, 37: 2939-2945. 10.1097/CCM.0b013e3181b7fbbbPubMedCentralCrossRefPubMed Shintani AK, Girard TD, Eden SK, Arbogast PG, Moons KG, Ely EW: Immortal time bias in critical care research: application of time-varying Cox regression for observational cohort studies. Crit Care Med 2009, 37: 2939-2945. 10.1097/CCM.0b013e3181b7fbbbPubMedCentralCrossRefPubMed
14.
go back to reference Suissa S: Effectiveness of inhaled corticosteroids in chronic obstructive pulmonary disease: immortal time bias in observational studies. Am J Respir Crit Care Med 2003, 168: 49-53. 10.1164/rccm.200210-1231OCCrossRefPubMed Suissa S: Effectiveness of inhaled corticosteroids in chronic obstructive pulmonary disease: immortal time bias in observational studies. Am J Respir Crit Care Med 2003, 168: 49-53. 10.1164/rccm.200210-1231OCCrossRefPubMed
15.
go back to reference Simon R, Makuch RW: A non-parametric graphical representation of the relationship between survival and the occurrence of an event: application to responder versus non-responder bias. Stat Med 1984, 3: 35-44. 10.1002/sim.4780030106CrossRefPubMed Simon R, Makuch RW: A non-parametric graphical representation of the relationship between survival and the occurrence of an event: application to responder versus non-responder bias. Stat Med 1984, 3: 35-44. 10.1002/sim.4780030106CrossRefPubMed
16.
go back to reference Putter H, Fiocco M, Geskus RB: Tutorial in biostatistics: competing risks and multi-state models. Stat Med 2007, 26: 2389-2430. 10.1002/sim.2712CrossRefPubMed Putter H, Fiocco M, Geskus RB: Tutorial in biostatistics: competing risks and multi-state models. Stat Med 2007, 26: 2389-2430. 10.1002/sim.2712CrossRefPubMed
17.
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: 309-332. 10.1016/j.ajic.2008.03.002CrossRefPubMed 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: 309-332. 10.1016/j.ajic.2008.03.002CrossRefPubMed
18.
go back to reference Klein Klouwenberg PM, Ong DS, Bos LD, de Beer FM, van Hooijdonk RT, Huson MA, Straat M, van Vught LA, Wieske L, Horn J, Schultz MJ, van der Poll T, Bonten MJ, Cremer OL: Interobserver agreement of centers for disease control and prevention criteria for classifying infections in critically Ill patients. Crit Care Med 2013, 41: 2373-2378. 10.1097/CCM.0b013e3182923712CrossRefPubMed Klein Klouwenberg PM, Ong DS, Bos LD, de Beer FM, van Hooijdonk RT, Huson MA, Straat M, van Vught LA, Wieske L, Horn J, Schultz MJ, van der Poll T, Bonten MJ, Cremer OL: Interobserver agreement of centers for disease control and prevention criteria for classifying infections in critically Ill patients. Crit Care Med 2013, 41: 2373-2378. 10.1097/CCM.0b013e3182923712CrossRefPubMed
19.
go back to reference de Jonge E, Schultz MJ, Spanjaard L, Bossuyt PM, Vroom MB, Dankert J, Kesecioglu J: Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. Lancet 2003, 362: 1011-1016. 10.1016/S0140-6736(03)14409-1CrossRefPubMed de Jonge E, Schultz MJ, Spanjaard L, Bossuyt PM, Vroom MB, Dankert J, Kesecioglu J: Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. Lancet 2003, 362: 1011-1016. 10.1016/S0140-6736(03)14409-1CrossRefPubMed
20.
go back to reference Dummer JS, Lazariashvilli N, Barnes J, Ninan M, Milstone AP: A survey of anti-fungal management in lung transplantation. J Heart Lung Transplant 2004, 23: 1376-1381. 10.1016/j.healun.2003.09.028CrossRefPubMed Dummer JS, Lazariashvilli N, Barnes J, Ninan M, Milstone AP: A survey of anti-fungal management in lung transplantation. J Heart Lung Transplant 2004, 23: 1376-1381. 10.1016/j.healun.2003.09.028CrossRefPubMed
21.
go back to reference Koo S, Kubiak DW, Issa NC, Dietzek A, Boukedes S, Camp PC, Goldberg HJ, Baden LR, Fuhlbrigge AL, Marty FM: A targeted peritransplant antifungal strategy for the prevention of invasive fungal disease after lung transplantation: a sequential cohort analysis. Transplantation 2012, 94: 281-286.CrossRefPubMed Koo S, Kubiak DW, Issa NC, Dietzek A, Boukedes S, Camp PC, Goldberg HJ, Baden LR, Fuhlbrigge AL, Marty FM: A targeted peritransplant antifungal strategy for the prevention of invasive fungal disease after lung transplantation: a sequential cohort analysis. Transplantation 2012, 94: 281-286.CrossRefPubMed
22.
go back to reference Monforte V, Ussetti P, Lopez R, Gavalda J, Bravo C, de Pablo A, Pou L, Pahissa A, Morell F, Román A: Nebulized liposomal amphotericin B prophylaxis for Aspergillus infection in lung transplantation: pharmacokinetics and safety. J Heart Lung Transplant 2009, 28: 170-175. 10.1016/j.healun.2008.11.004CrossRefPubMed Monforte V, Ussetti P, Lopez R, Gavalda J, Bravo C, de Pablo A, Pou L, Pahissa A, Morell F, Román A: Nebulized liposomal amphotericin B prophylaxis for Aspergillus infection in lung transplantation: pharmacokinetics and safety. J Heart Lung Transplant 2009, 28: 170-175. 10.1016/j.healun.2008.11.004CrossRefPubMed
23.
go back to reference Dhand R: The role of aerosolized antimicrobials in the treatment of ventilator-associated pneumonia. Respir Care 2007, 52: 866-884.PubMed Dhand R: The role of aerosolized antimicrobials in the treatment of ventilator-associated pneumonia. Respir Care 2007, 52: 866-884.PubMed
24.
go back to reference Dolovich MB, Dhand R: Aerosol drug delivery: developments in device design and clinical use. Lancet 2011, 377: 1032-1045. 10.1016/S0140-6736(10)60926-9CrossRefPubMed Dolovich MB, Dhand R: Aerosol drug delivery: developments in device design and clinical use. Lancet 2011, 377: 1032-1045. 10.1016/S0140-6736(10)60926-9CrossRefPubMed
25.
go back to reference Kuiper L, Ruijgrok EJ: A review on the clinical use of inhaled amphotericin B. J Aerosol Med Pulm Drug Deliv 2009, 22: 213-227. 10.1089/jamp.2008.0715CrossRefPubMed Kuiper L, Ruijgrok EJ: A review on the clinical use of inhaled amphotericin B. J Aerosol Med Pulm Drug Deliv 2009, 22: 213-227. 10.1089/jamp.2008.0715CrossRefPubMed
26.
go back to reference Drew RH, Dodds AE, Benjamin DK Jr, Duane DR, Palmer SM, Perfect JR: Comparative safety of amphotericin B lipid complex and amphotericin B deoxycholate as aerosolized antifungal prophylaxis in lung-transplant recipients. Transplantation 2004, 77: 232-237. 10.1097/01.TP.0000101516.08327.A9CrossRefPubMed Drew RH, Dodds AE, Benjamin DK Jr, Duane DR, Palmer SM, Perfect JR: Comparative safety of amphotericin B lipid complex and amphotericin B deoxycholate as aerosolized antifungal prophylaxis in lung-transplant recipients. Transplantation 2004, 77: 232-237. 10.1097/01.TP.0000101516.08327.A9CrossRefPubMed
27.
go back to reference Dubois J, Bartter T, Gryn J, Pratter MR: The physiologic effects of inhaled amphotericin B. Chest 1995, 108: 750-753. 10.1378/chest.108.3.750CrossRefPubMed Dubois J, Bartter T, Gryn J, Pratter MR: The physiologic effects of inhaled amphotericin B. Chest 1995, 108: 750-753. 10.1378/chest.108.3.750CrossRefPubMed
28.
go back to reference Lowry CM, Marty FM, Vargas SO, Lee JT, Fiumara K, Deykin A, et al.: Safety of aerosolized liposomal versus deoxycholate amphotericin B formulations for prevention of invasive fungal infections following lung transplantation: a retrospective study. Transpl Infect Dis 2007, 9: 121-125. 10.1111/j.1399-3062.2007.00209.xCrossRefPubMed Lowry CM, Marty FM, Vargas SO, Lee JT, Fiumara K, Deykin A, et al.: Safety of aerosolized liposomal versus deoxycholate amphotericin B formulations for prevention of invasive fungal infections following lung transplantation: a retrospective study. Transpl Infect Dis 2007, 9: 121-125. 10.1111/j.1399-3062.2007.00209.xCrossRefPubMed
29.
go back to reference Myers SE, Devine SM, Topper RL, Ondrey M, Chandler C, O’Toole K, Williams SF, Larson RA, Geller RB: A pilot study of prophylactic aerosolized amphotericin B in patients at risk for prolonged neutropenia. Leuk Lymphoma 1992, 8: 229-233. 10.3109/10428199209054909CrossRefPubMed Myers SE, Devine SM, Topper RL, Ondrey M, Chandler C, O’Toole K, Williams SF, Larson RA, Geller RB: A pilot study of prophylactic aerosolized amphotericin B in patients at risk for prolonged neutropenia. Leuk Lymphoma 1992, 8: 229-233. 10.3109/10428199209054909CrossRefPubMed
30.
go back to reference Bergmans DC, Bonten MJ, Gaillard CA, Paling JC, van der Geest S, van Tiel FH, Beysens AJ, de Leeuw PW, Stobberingh EE: Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med 2001, 164: 382-388. 10.1164/ajrccm.164.3.2005003CrossRefPubMed Bergmans DC, Bonten MJ, Gaillard CA, Paling JC, van der Geest S, van Tiel FH, Beysens AJ, de Leeuw PW, Stobberingh EE: Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med 2001, 164: 382-388. 10.1164/ajrccm.164.3.2005003CrossRefPubMed
31.
go back to reference Levesque LE, Hanley JA, Kezouh A, Suissa S: Problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes. BMJ 2010, 340: b5087. 10.1136/bmj.b5087CrossRefPubMed Levesque LE, Hanley JA, Kezouh A, Suissa S: Problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes. BMJ 2010, 340: b5087. 10.1136/bmj.b5087CrossRefPubMed
Metadata
Title
Nebulised amphotericin B to eradicate Candida colonisation from the respiratory tract in critically ill patients receiving selective digestive decontamination: a cohort study
Authors
David SY Ong
Peter MC Klein Klouwenberg
Cristian Spitoni
Marc JM Bonten
Olaf L Cremer
Publication date
01-10-2013
Publisher
BioMed Central
Published in
Critical Care / Issue 5/2013
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc13056

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