Intensive Care Med (2014) 40:1611–1612 DOI 10.1007/s00134-014-3444-z
Damien Roux Jean-Damien Ricard
Ask the wrong question, you’ll the get the wrong answer
Accepted: 8 August 2014 Published online: 20 August 2014 Ó Springer-Verlag Berlin Heidelberg and ESICM 2014
Dear Editor We read with great interest the article by Albert et al. [1] studying the impact of an antifungal treatment in patients with respiratory tract Candida colonization and a clinically suspected ventilator-associated pneumonia (VAP). The authors did not observe any clinical or biological benefits using anidulafungin and concluded that there was no evidence to support a larger trial examining the efficacy of empiric antifungal treatment in patients with a clinical suspicion of VAP. The authors should be commended for having performed such a study. Unfortunately, theirs was biased right from the start since antifungal therapy was given only once VAP had already developed. It therefore cannot answer the question as to a potential benefit in administering antifungal therapy to patients with Candida in the respiratory tract, in order to reduce the incidence of VAP. Indeed, the whole pathophysiologic reasoning surrounding the possible pathogenic role of Candida colonization in VAP development [2, 3] lies in the sequence of events.
CO RRESPONDENCE
Experimentally, preexisting Candida colonization significantly increased the incidence of subsequent bacterial pneumonia [4, 5]. These observations were strengthened by the possible beneficial role of an antifungal therapy when the treatment was applied before the development of bacterial pneumonia [5, 6]. In ICU patients, Nseir et al. [6] observed a reduction in respiratory tract infection by Pseudomonas aeruginosa when patients with Candida colonization received an antifungal therapy. In our murine model of respiratory tract Candida colonization, treatment by amphotericin B applied 3 days before animals were challenged with P. aeruginosa allowed a significant reduction of fungal counts, of inflammatory status, and eventually of P. aeruginosa pneumonia [5]. These results highlight the impact of Candida colonization that impairs immune response allowing bacterial pneumonia development and the necessity of treating Candida colonization early to avoid its negative impact on innate immunity [4, 5]. Therefore, we are not surprised by the results of the present study since antifungal treatment was given only when a VAP was clinically suspected. If ever an antifungal treatment should prove beneficial for ventilated patients, we believe that this treatment should be initiated before the clinical suspicion of VAP, when Candida is recovered from the respiratory secretions. This requires a more systematic detection of Candida colonization in the respiratory tract of ventilated patients in order to randomize colonized patients to receive an antifungal therapy or a placebo and compare the rate of definite VAP in the two groups.
We therefore fully agree with De Pascale and Antonelli that a definite conclusion has not yet been reached [7] and believe that there is still evidence to support a larger trial, but one designed differently than the one envisaged by Albert et al. Conflicts of interest None.
References 1. Albert M, Williamson D, Muscedere J, Lauzier F, Roystein C, Kanji S, Jang X, Hall M, Heyland D (2014) Candida in the respiratory tract secretions of critically ill patients and the impact of antifungal treatment: a randomised placebo-controlled pilot trial (CANTREAT study). Intensive Care Med. doi:10.1007/s00134-014-3352-2 2. Azoulay E, Timsit JF, Tafflet M, de Lassence A, Darmon M, Zahar JR, Adrie C, Garrouste-Orgeas M, Cohen Y, Mourvillier B, Schlemmer B, Outcomerea Study Group (2006) Candida colonization of the respiratory tract and subsequent pseudomonas ventilator-associated pneumonia. Chest 129:110–117 3. Ricard JD, Roux D (2012) Candida colonization in ventilated ICU patients: no longer a bystander! Intensive Care Med 38:1243–1245 4. Roux D, Gaudry S, Dreyfuss D, ElBenna J, de Prost N, Denamur E, Saumon G, Ricard JD (2009) Candida albicans impairs macrophage function and facilitates Pseudomonas aeruginosa pneumonia in rat. Crit Care Med 37:1062–1067 5. Roux D, Gaudry S, Khoy-Ear L, Aloulou M, Phillips-Houlbracq M, Bex J, Skurnik D, Denamur E, Monteiro RC, Dreyfuss D, Ricard JD (2013) Airway fungal colonization compromises the immune system allowing bacterial pneumonia to prevail. Crit Care Med 41:e191–e199
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6. Nseir S, Jozefowicz E, Cavestri B, Sendid B, Di Pompeo C, Dewavrin F, Favory R, Roussel-Delvallez M, Durocher A (2007) Impact of antifungal treatment on Candida–Pseudomonas interaction: a preliminary retrospective case-control study. Intensive Care Med 33:137–142
7. De Pascale G, Antonelli M (2014) Candida colonization of respiratory tract: to treat or not to treat, will we ever get an answer? Intensive Care Med. doi: 10.1007/s00134-014-3364-y D. Roux J.-D. Ricard INSERM, IAME, UMR 1137, 75018 Paris, France D. Roux J.-D. Ricard Univ Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cite´, 75018 Paris, France
D. Roux J.-D. Ricard ()) AP-HP, Service de Re´animation Me´dicochirurgicale, Hoˆpital Louis Mourier, 178 rue des Renouillers, 92700 Colombes, France e-mail: [email protected] Tel.: ?33147606750
Damien Roux Jean-Damien Ricard
Ask the wrong question, you’ll the get the wrong answer
Accepted: 8 August 2014 Published online: 20 August 2014 Ó Springer-Verlag Berlin Heidelberg and ESICM 2014
Dear Editor We read with great interest the article by Albert et al. [1] studying the impact of an antifungal treatment in patients with respiratory tract Candida colonization and a clinically suspected ventilator-associated pneumonia (VAP). The authors did not observe any clinical or biological benefits using anidulafungin and concluded that there was no evidence to support a larger trial examining the efficacy of empiric antifungal treatment in patients with a clinical suspicion of VAP. The authors should be commended for having performed such a study. Unfortunately, theirs was biased right from the start since antifungal therapy was given only once VAP had already developed. It therefore cannot answer the question as to a potential benefit in administering antifungal therapy to patients with Candida in the respiratory tract, in order to reduce the incidence of VAP. Indeed, the whole pathophysiologic reasoning surrounding the possible pathogenic role of Candida colonization in VAP development [2, 3] lies in the sequence of events.
CO RRESPONDENCE
Experimentally, preexisting Candida colonization significantly increased the incidence of subsequent bacterial pneumonia [4, 5]. These observations were strengthened by the possible beneficial role of an antifungal therapy when the treatment was applied before the development of bacterial pneumonia [5, 6]. In ICU patients, Nseir et al. [6] observed a reduction in respiratory tract infection by Pseudomonas aeruginosa when patients with Candida colonization received an antifungal therapy. In our murine model of respiratory tract Candida colonization, treatment by amphotericin B applied 3 days before animals were challenged with P. aeruginosa allowed a significant reduction of fungal counts, of inflammatory status, and eventually of P. aeruginosa pneumonia [5]. These results highlight the impact of Candida colonization that impairs immune response allowing bacterial pneumonia development and the necessity of treating Candida colonization early to avoid its negative impact on innate immunity [4, 5]. Therefore, we are not surprised by the results of the present study since antifungal treatment was given only when a VAP was clinically suspected. If ever an antifungal treatment should prove beneficial for ventilated patients, we believe that this treatment should be initiated before the clinical suspicion of VAP, when Candida is recovered from the respiratory secretions. This requires a more systematic detection of Candida colonization in the respiratory tract of ventilated patients in order to randomize colonized patients to receive an antifungal therapy or a placebo and compare the rate of definite VAP in the two groups.
We therefore fully agree with De Pascale and Antonelli that a definite conclusion has not yet been reached [7] and believe that there is still evidence to support a larger trial, but one designed differently than the one envisaged by Albert et al. Conflicts of interest None.
References 1. Albert M, Williamson D, Muscedere J, Lauzier F, Roystein C, Kanji S, Jang X, Hall M, Heyland D (2014) Candida in the respiratory tract secretions of critically ill patients and the impact of antifungal treatment: a randomised placebo-controlled pilot trial (CANTREAT study). Intensive Care Med. doi:10.1007/s00134-014-3352-2 2. Azoulay E, Timsit JF, Tafflet M, de Lassence A, Darmon M, Zahar JR, Adrie C, Garrouste-Orgeas M, Cohen Y, Mourvillier B, Schlemmer B, Outcomerea Study Group (2006) Candida colonization of the respiratory tract and subsequent pseudomonas ventilator-associated pneumonia. Chest 129:110–117 3. Ricard JD, Roux D (2012) Candida colonization in ventilated ICU patients: no longer a bystander! Intensive Care Med 38:1243–1245 4. Roux D, Gaudry S, Dreyfuss D, ElBenna J, de Prost N, Denamur E, Saumon G, Ricard JD (2009) Candida albicans impairs macrophage function and facilitates Pseudomonas aeruginosa pneumonia in rat. Crit Care Med 37:1062–1067 5. Roux D, Gaudry S, Khoy-Ear L, Aloulou M, Phillips-Houlbracq M, Bex J, Skurnik D, Denamur E, Monteiro RC, Dreyfuss D, Ricard JD (2013) Airway fungal colonization compromises the immune system allowing bacterial pneumonia to prevail. Crit Care Med 41:e191–e199
1612
6. Nseir S, Jozefowicz E, Cavestri B, Sendid B, Di Pompeo C, Dewavrin F, Favory R, Roussel-Delvallez M, Durocher A (2007) Impact of antifungal treatment on Candida–Pseudomonas interaction: a preliminary retrospective case-control study. Intensive Care Med 33:137–142
7. De Pascale G, Antonelli M (2014) Candida colonization of respiratory tract: to treat or not to treat, will we ever get an answer? Intensive Care Med. doi: 10.1007/s00134-014-3364-y D. Roux J.-D. Ricard INSERM, IAME, UMR 1137, 75018 Paris, France D. Roux J.-D. Ricard Univ Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cite´, 75018 Paris, France
D. Roux J.-D. Ricard ()) AP-HP, Service de Re´animation Me´dicochirurgicale, Hoˆpital Louis Mourier, 178 rue des Renouillers, 92700 Colombes, France e-mail: [email protected] Tel.: ?33147606750
