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Impact of nutrition route on fungal infections
ARTICLE IN PRESS Clinical Nutrition (2005) 24, 326–327
http://intl.elsevierhealth.com/journals/clnu
CORRESPONDENCE Impact of nutrition route on fungal infections
Dear Sir, We read with interest the article of Garbino et al. on the impact of enteral versus parenteral nutrition on fungal infections in patients requiring ventilation and selective digestive decontamination (SDD) on the intensive care unit (ICU).1 Although the fungal infection rate in the patients receiving enteral nutrition was about half that in the parenteral group, the difference was not statistically significant (9.9% vs. 17.3%, P ¼ 0:32), due to design and small sample size. Additionally, the two groups were not comparable as the 29 parenterally fed patients were iller with peritonitis and pancreatitis receiving broad spectrum antibiotics, hence increasing the risk of fungal infection. Remarkably, the Swiss investigators dismiss the high rates of fungal infection and lower airway colonisation in their study. A fungal infection rate of 12% is high in a population receiving SDD. The fungal infection rate was 1.4% in SDD patients versus 4.6% in the control in a recent meta-analysis of randomised controlled trials (RCTs) of SDD.2 The fungal infection rate is 10-fold higher in the Geneva study because the patients did not receive SDD.3 The features of SDD include surveillance cultures of throat and rectum for the detection of carriage of potential pathogens combined with the oropharyngeal and enteral administration of polymyxin, tobramycin and amphotericin B to eradicate the potential pathogens from throat and gut. This strategy selectively targets the potential pathogens including Candida species which contribute to morbidity and mortality. SDD is the only ICUintervention with a Grade A recommendation.4 The most recent meta-analysis of 36 RCTs shows SDD reduces the odds ratio for pneumonia to 0.35, and mortality to 0.78.4 Two large RCTs reported an absolute mortality reduction of 8%—corresponding to the treatment of 12 patients with SDD to save one life.5,6 The Geneva group modified the SDD
protocol by omitting an antifungal, and surveillance samples of the oropharynx were not obtained. Hence, their title is misleading as the patients were not treated with SDD despite their claims. However, their fungal infection rate of 12% is less than the 20% incidence in the German RCT on SDD.5 Again, the Munich investigators did not use an antifungal. The higher fungal incidence may be explained by the use of ciprofloxacin in the Munich study compared with neomycin in the Geneva study to cover aerobic Gram-negative bacilli (AGNB). Aminoglycosides have only minor effects on the indigenous anaerobic flora. Fluoroquinolones—albeit having limited activity against anaerobes—promote yeast overgrowth. Elimination of gut AGNB by intravenous ciprofloxacin lowers the rate of microbial oxygen consumption, permitting an increase in the intraluminal oxygen tension from 5 to 60 mm of mercury; under such conditions strictly anaerobic micro-organisms can no longer survive, even though they may not themselves be sensitive to ciprofloxacin, and yeast overgrowth may subsequently develop due to the impaired microbial factor of the carriage defence.7 The lower airways were colonised by yeasts in one-fifth of the study population, an abnormally high proportion not explained by the Swiss group. Although yeast colonisation of the lower airways rarely leads to pneumonia, colonisation of internal organs is non-physiological and causes inflammation as the physiological condition of an internal organ is sterility. Oropharyngeal overgrowth is a risk factor for colonisation of the lower airways implying that minimally one in five patients carried high yeast concentrations in the throat. However, the level of yeast carriage can only be detected by obtaining surveillance cultures of the oropharynx a manoeuvre omitted by the Geneva investigators. The 20% colonisation rate of the lower airways is in line with their original study3 showing a statistically significant higher colonisation rate with yeasts of the tracheobronchial tree in patients receiving the polymyxin, neomycin, vancomycin solution compared with placebo.
0261-5614/$ - see front matter & 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.clnu.2004.11.009
ARTICLE IN PRESS CORRESPONDENCE We were surprised by the superficial understanding of the process of Candida carriage, colonisation and infection. That is the only explanation for the omission of an antifungal agent from an antimicrobial prophylaxis that has nothing to do with SDD. The authors’ retrospective observation that enteral feeding does not reduce fungal infections is invalid as their study is fatally flawed.
References 1. Garbino J, Pichard C, Pichna P, Pittet D, Lew D, Romand JA. Impact of enteral versus parenteral nutrition on the incidence of fungal infections: a retrospective study in ICU patients on mechanical ventilation with selective digestive decontamination. Clin Nutr 2004;23:705–10. 2. Silvestri L, Milanese M, Gregori D, van Saene HKF. Impact of selective decontamination of the digestive tract on fungal carriage and infection: systematic review of randomised controlled studies. Intens Care Med 2003;29(Suppl. 1):S128. 3. Pugin S, Auckenthaler R, Lew DP, Suter PM. Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia. A randomised, placebo-controlled, double-blind clinical trial. J Am Med Assoc 1991;265:2704–10. 4. Liberati A, D’Amico R, Pifferi S, Torri V, Brazzi L. Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care (Cochrane Review). In: The Cochrane Library, Issue 1. Chichester, UK: Wiley; 2004.
327 5. Krueger WA, Lenhart FP, Neeser G, Ruckdeschel G, Schreckhase H, Eisnner HJ, et al. Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections, organ dysfunctions and mortality in critically ill surgical patients. Am J Respir Crit Care Med 2002;166: 1029–37. 6. de Jonge E, Schultz MJ, Spanjaard L, Bossuyt PMM, Vroom BM, Dankert J, Kesecioglu J. Effects of selective decontamination of the digestive tract on mortality and acquisition of resistant bacteria in intensive care. A randomized controlled trial. Lancet 2003;362:1011–8. 7. van Saene HKF, Zandstra DF. Selective decontamination of the digestive tract: rationale behind evidence-based use in liver transplantation. Liver Transplant 2004;10: 826–33.
H.K.F. van Saene Department Medical Microbiology, University of Liverpool, Duncan Building, Daulby Street, PO Box 147, Liverpool L 69 3BX, UK E-mail address: [email protected] L. Silvestri Regional Hospital, Gorizia, Italy M.A. de la Cal University Hospital of Getafe, Madrid, Spain
http://intl.elsevierhealth.com/journals/clnu
CORRESPONDENCE Impact of nutrition route on fungal infections
Dear Sir, We read with interest the article of Garbino et al. on the impact of enteral versus parenteral nutrition on fungal infections in patients requiring ventilation and selective digestive decontamination (SDD) on the intensive care unit (ICU).1 Although the fungal infection rate in the patients receiving enteral nutrition was about half that in the parenteral group, the difference was not statistically significant (9.9% vs. 17.3%, P ¼ 0:32), due to design and small sample size. Additionally, the two groups were not comparable as the 29 parenterally fed patients were iller with peritonitis and pancreatitis receiving broad spectrum antibiotics, hence increasing the risk of fungal infection. Remarkably, the Swiss investigators dismiss the high rates of fungal infection and lower airway colonisation in their study. A fungal infection rate of 12% is high in a population receiving SDD. The fungal infection rate was 1.4% in SDD patients versus 4.6% in the control in a recent meta-analysis of randomised controlled trials (RCTs) of SDD.2 The fungal infection rate is 10-fold higher in the Geneva study because the patients did not receive SDD.3 The features of SDD include surveillance cultures of throat and rectum for the detection of carriage of potential pathogens combined with the oropharyngeal and enteral administration of polymyxin, tobramycin and amphotericin B to eradicate the potential pathogens from throat and gut. This strategy selectively targets the potential pathogens including Candida species which contribute to morbidity and mortality. SDD is the only ICUintervention with a Grade A recommendation.4 The most recent meta-analysis of 36 RCTs shows SDD reduces the odds ratio for pneumonia to 0.35, and mortality to 0.78.4 Two large RCTs reported an absolute mortality reduction of 8%—corresponding to the treatment of 12 patients with SDD to save one life.5,6 The Geneva group modified the SDD
protocol by omitting an antifungal, and surveillance samples of the oropharynx were not obtained. Hence, their title is misleading as the patients were not treated with SDD despite their claims. However, their fungal infection rate of 12% is less than the 20% incidence in the German RCT on SDD.5 Again, the Munich investigators did not use an antifungal. The higher fungal incidence may be explained by the use of ciprofloxacin in the Munich study compared with neomycin in the Geneva study to cover aerobic Gram-negative bacilli (AGNB). Aminoglycosides have only minor effects on the indigenous anaerobic flora. Fluoroquinolones—albeit having limited activity against anaerobes—promote yeast overgrowth. Elimination of gut AGNB by intravenous ciprofloxacin lowers the rate of microbial oxygen consumption, permitting an increase in the intraluminal oxygen tension from 5 to 60 mm of mercury; under such conditions strictly anaerobic micro-organisms can no longer survive, even though they may not themselves be sensitive to ciprofloxacin, and yeast overgrowth may subsequently develop due to the impaired microbial factor of the carriage defence.7 The lower airways were colonised by yeasts in one-fifth of the study population, an abnormally high proportion not explained by the Swiss group. Although yeast colonisation of the lower airways rarely leads to pneumonia, colonisation of internal organs is non-physiological and causes inflammation as the physiological condition of an internal organ is sterility. Oropharyngeal overgrowth is a risk factor for colonisation of the lower airways implying that minimally one in five patients carried high yeast concentrations in the throat. However, the level of yeast carriage can only be detected by obtaining surveillance cultures of the oropharynx a manoeuvre omitted by the Geneva investigators. The 20% colonisation rate of the lower airways is in line with their original study3 showing a statistically significant higher colonisation rate with yeasts of the tracheobronchial tree in patients receiving the polymyxin, neomycin, vancomycin solution compared with placebo.
0261-5614/$ - see front matter & 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.clnu.2004.11.009
ARTICLE IN PRESS CORRESPONDENCE We were surprised by the superficial understanding of the process of Candida carriage, colonisation and infection. That is the only explanation for the omission of an antifungal agent from an antimicrobial prophylaxis that has nothing to do with SDD. The authors’ retrospective observation that enteral feeding does not reduce fungal infections is invalid as their study is fatally flawed.
References 1. Garbino J, Pichard C, Pichna P, Pittet D, Lew D, Romand JA. Impact of enteral versus parenteral nutrition on the incidence of fungal infections: a retrospective study in ICU patients on mechanical ventilation with selective digestive decontamination. Clin Nutr 2004;23:705–10. 2. Silvestri L, Milanese M, Gregori D, van Saene HKF. Impact of selective decontamination of the digestive tract on fungal carriage and infection: systematic review of randomised controlled studies. Intens Care Med 2003;29(Suppl. 1):S128. 3. Pugin S, Auckenthaler R, Lew DP, Suter PM. Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia. A randomised, placebo-controlled, double-blind clinical trial. J Am Med Assoc 1991;265:2704–10. 4. Liberati A, D’Amico R, Pifferi S, Torri V, Brazzi L. Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care (Cochrane Review). In: The Cochrane Library, Issue 1. Chichester, UK: Wiley; 2004.
327 5. Krueger WA, Lenhart FP, Neeser G, Ruckdeschel G, Schreckhase H, Eisnner HJ, et al. Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections, organ dysfunctions and mortality in critically ill surgical patients. Am J Respir Crit Care Med 2002;166: 1029–37. 6. de Jonge E, Schultz MJ, Spanjaard L, Bossuyt PMM, Vroom BM, Dankert J, Kesecioglu J. Effects of selective decontamination of the digestive tract on mortality and acquisition of resistant bacteria in intensive care. A randomized controlled trial. Lancet 2003;362:1011–8. 7. van Saene HKF, Zandstra DF. Selective decontamination of the digestive tract: rationale behind evidence-based use in liver transplantation. Liver Transplant 2004;10: 826–33.
H.K.F. van Saene Department Medical Microbiology, University of Liverpool, Duncan Building, Daulby Street, PO Box 147, Liverpool L 69 3BX, UK E-mail address: [email protected] L. Silvestri Regional Hospital, Gorizia, Italy M.A. de la Cal University Hospital of Getafe, Madrid, Spain