Oral probiotic and prevention of Pseudomonas aeruginosa infections: a randomized, double-blind, placebo-controlled pilot study in intensive care unit patients

Christiane Forestier, Dominique Guelon, Valérie Cluytens, Thierry Gillart, Jacques Sirot, Christophe De Champs, Christiane Forestier, Dominique Guelon, Valérie Cluytens, Thierry Gillart, Jacques Sirot, Christophe De Champs

Abstract

Introduction: Preventing carriage of potentially pathogenic micro-organisms from the aerodigestive tract is an infection control strategy used to reduce the occurrence of ventilator-associated pneumonia in intensive care units. However, antibiotic use in selective decontamination protocols is controversial. The purpose of this study was to investigate the effect of oral administration of a probiotic, namely Lactobacillus, on gastric and respiratory tract colonization/infection with Pseudomonas aeruginosa strains. Our hypothesis was that an indigenous flora should exhibit a protective effect against secondary colonization.

Methods: We conducted a prospective, randomized, double-blind, placebo-controlled pilot study between March 2003 and October 2004 in a 17-bed intensive care unit of a teaching hospital in Clermont-Ferrand, France. Consecutive patients with a unit stay of longer than 48 hours were included, 106 in the placebo group and 102 in the probiotic group. Through a nasogastric feeding tube, patients received either 109 colony-forming units unity forming colony of Lactobacillus casei rhamnosus or placebo twice daily, from the third day after admission to discharge. Digestive tract carriage of P. aeruginosa was monitored by cultures of gastric aspirates at admission, once a week thereafter and on discharge. In addition, bacteriological analyses of respiratory tract specimens were conducted to determine patient infectious status.

Results: The occurrence of P. aeruginosa respiratory colonization and/or infection was significantly delayed in the probiotic group, with a difference in median delay to acquisition of 11 days versus 50 days (P = 0.01), and a nonacquisition expectancy mean of 69 days versus 77 days (P = 0.01). The occurrence of ventilator-associated pneumonia due to P. aeruginosa in the patients receiving the probiotic was less frequent, although not significantly reduced, in patients in the probiotic group (2.9%) compared with those in the placebo group (7.5%). After multivariate Cox proportional hazards modelling, the absence of probiotic treatment increased the risk for P. aeruginosa colonization in respiratory tract (adjusted hazard ratio = 3.2, 95% confidence interval - 1.1 to 9.1).

Conclusion: In this pilot study, oral administration of a probiotic delayed respiratory tract colonization/infection by P. aeruginosa.

Trial registration: The trial registration number for this study is NCT00604110.

Figures

Figure 1
Figure 1
Patient flowchart.
Figure 2
Figure 2
Actuarial representation of estimated probabilities of non-acquisition of Pseudomonas aeruginosa in the respiratory tract. The numbers of patients acquiring P. aeruginosa relative to the number of patients under study are indicated directly at each time point.

References

    1. Bengmark S. Ecological control of the gastrointestinal tract. The role of probiotic flora. Gut. 1998;42:2–7.
    1. Bengmark S. Symbiotics to strengthen gut barrier function and reduce morbidity in critically ill patients. Clin Nutr. 2004;23:441–445. doi: 10.1016/j.clnu.2004.01.005.
    1. Bert F, Lambert-Zechovsky N. Bacteria isolated from protected bronchopulmonary samples: variation as a function of the previous length of stay in the recovery room. Pathol Biol. 1998;46:380–384.
    1. Bonten MJ, Gaillard CA, Hulst R van der, de Leeuw PW, Geest S van der, Stobberingh EE, Soeters PB. Intermittent enteral feeding: the influence on respiratory and digestive tract colonization in mechanically ventilated intensive-care-unit patients. Am J Respir Crit Care Med. 1996;154:394–399.
    1. Bergmans DC, Bonten MJ, Gaillard CA, Paling JC, Geest S van der, 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.
    1. Bonten MJ, Gaillard CA, de Leeuw PW, Stobberingh EE. Role of colonization of the upper intestinal tract in the pathogenesis of ventilator-associated pneumonia. Clin Infect Dis. 1997;24:309–319.
    1. Bonten MJ, Gaillard CA, Geest S van der, van Tiel FH, Beysens AJ, Smeets HG, Stobberingh EE. The role of intragastric acidity and stress ulcus prophylaxis on colonization and infection in mechanically ventilated ICU patients. A stratified, randomized, double-blind study of sucralfate versus antacids. Am J Respir Crit Care Med. 1995;152:1825–1834.
    1. Brun-Buisson C, Legrand P, Rauss A, Richard C, Montravers F, Besbes M, Meakins JL, Soussy CJ, Lemaire F. Intestinal decontamination for control of nosocomial multiresistant gram-negative bacilli. Study of an outbreak in an intensive care unit. Ann Intern Med. 1989;110:873–881.
    1. de Latorre FJ, Pont T, Ferrer A, Rossello J, Palomar M, Planas M. Pattern of tracheal colonization during mechanical ventilation. Am J Respir Crit Care Med. 1995;152:1028–1033.
    1. Bonten MJ, Brun-Buisson C, Weinstein RA. Selective decontamination of the digestive tract: to stimulate or stifle? Intensive Care Med. 2003;29:672–676.
    1. Leone M, Albanese J, Antonini F, Nguyen-Michel A, Martin C. Long-term (6-year) effect of selective digestive decontamination on antimicrobial resistance in intensive care, multiple-trauma patients. Crit Care Med. 2003;31:2090–2095. doi: 10.1097/01.CCM.0000079606.16776.C5.
    1. Stoutenbeek CP, van Saene HK, Miranda DR, Zandstra DF. The effect of selective decontamination of the digestive tract on colonisation and infection rate in multiple trauma patients. Intensive Care Med. 1984;10:185–192. doi: 10.1007/BF00259435.
    1. van Saene HKF, Petros AJ, Ramsay G, Baxby D. All great truths iconoclastic: selective decontamination of the digestive tract moves from heresy to level 1 truth. Intensive Care Med. 2003;29:677–690. doi: 10.1007/s00134-003-1770-7.
    1. 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. The Cochrane Collaboration. 2006;1:1–54.
    1. Silvestri L, van Saene HKF, Milanese M, Duri D, Gregori D, Gullo A. Selective decontamination of the digestive tract reduces blood stream infections and mortality in critically ill patients. Systematic review of randomized, controlled trials. J Hosp Infect. 2007;65:187–203. doi: 10.1016/j.jhin.2006.10.014.
    1. Stoutenbeek CP, van Saene HKF, Little RA, Whitehead RA, for the Working Group on Selective Decontamination of the Digestive Tract The effect of selective decontamination of the digestive tract on mortality in multiple trauma patients: a multicenter randomized controlled trial. Intensive Care Med. 2007;33:261–270. doi: 10.1007/s00134-006-0455-4.
    1. Bonten MJ, Kullberg BJ, van Dalen R, Girbes AR, Hoepelman IM, Hustinx W, Meer JW van der, Speelman P, Stobberingh EE, Verbrugh HA, Verhoef J, Zwaveling JH. Selective digestive decontamination in patients in intensive care. The Dutch Working Group on Antibiotic Policy. J Antimicrob Chemother. 2000;46:351–362. doi: 10.1093/jac/46.3.351.
    1. Kollef MH. Ventilator-associated pneumonia. A multivariate analysis. Jama. 1993;270:1965–1970. doi: 10.1001/jama.270.16.1965.
    1. Kollef MH. Private attending physician status and the withdrawal of life-sustaining interventions in a medical intensive care unit population. Crit Care Med. 1996;24:968–975. doi: 10.1097/00003246-199606000-00016.
    1. Rello J, Ausina V, Ricart M, Castella J, Prats G. Impact of previous antimicrobial therapy on the etiology and outcome of ventilator-associated pneumonia. Chest. 1993;104:1230–1235. doi: 10.1378/chest.104.4.1230.
    1. Silvestri L, van Saene HKF, Thomann C, Peric M. Selective decontamination of the digestive tract reduces pneumonia and mortality without resistance emerging. Am J Infect Control. 2007;35:354–357. doi: 10.1016/j.ajic.2006.07.003.
    1. de Jonge E, Schultz MJ, Spanjaard L, Bossuyt PMM, 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;362:1011–1015. doi: 10.1016/S0140-6736(03)14409-1.
    1. Tenover FC, Hughes JM. WHO Scientific Working Group on monitoring and management of bacterial resistance to antimicrobial agents. Emerg Infect Dis. 1995;1:37.
    1. de Champs C, Maroncle N, Balestrino D, Rich C, Forestier C. Persistence of colonization of intestinal mucosa by a probiotic strain, Lactobacillus casei subsp. rhamnosus Lcr35, after oral consumption. J Clin Microbiol. 2003;41:1270–1273. doi: 10.1128/JCM.41.3.1270-1273.2003.
    1. Forestier C, De Champs C, Vatoux C, Joly B. Probiotic activities of Lactobacillus casei rhamnosus: in vitro adherence to intestinal cells and antimicrobial properties. Res Microbiol. 2001;152:167–173. doi: 10.1016/S0923-2508(01)01188-3.
    1. Alcon A, Fabregas N, Torres A. Hospital-acquired pneumonia: etiologic considerations. Infect Dis Clin North Am. 2003;17:679–695. doi: 10.1016/S0891-5520(03)00074-6.
    1. American Thoracic Society Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171:388–416. doi: 10.1164/rccm.200405-644ST.
    1. Anderson AD, McNaught CE, Jain PK, MacFie J. Randomised clinical trial of synbiotic therapy in elective surgical patients. Gut. 2004;53:241–245. doi: 10.1136/gut.2003.024620.
    1. Trouillet JL, Chastre J, Vuagnat A, Joly-Guillou ML, Combaux D, Dombret MC, Gibert C. Ventilator-associated pneumonia caused by potentially drug-resistant bacteria. Am J Respir Crit Care Med. 1998;157:531–539.
    1. Trouillet JL, Vuagnat A, Combes A, Kassis N, Chastre J, Gibert C. Pseudomonas aeruginosa ventilator-associated pneumonia: comparison of episodes due to piperacillin-resistant versus piperacillin-susceptible organisms. Clin Infect Dis. 2002;34:1047–1054. doi: 10.1086/339488.
    1. Andrews P, Azoulay E, Antonelli M, Brochard L, Brun-Buisson C, Dobb G, Fagon JY, Gerlach H, Groeneveld J, Mancebo J, Metnitz P, Nava S, Pugin J, Pinsky M, Radermacher P, Richard C, Tasker R. Year in review in intensive care medecine, 2005. II. Infection and sepsis, ventilator-associated pneumonia, ethics, haematology and haemostasis, ICU organisation and scoring, brain injury. Intensive Care Med. 2006;32:380–390. doi: 10.1007/s00134-005-0060-y.
    1. Concato J, Feinstein AR, Holford TR. The risk of determinating risk with multivariable models. Ann Intern Med. 1993;118:201–210.
    1. Harbarth S, Liassine N, Dharan S, Herrault P, Auckenthaler R, Pittet D. Risk factors for persistent carriage of methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2000;31:1380–1385. doi: 10.1086/317484.
    1. Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. Jama. 1993;270:2957–2963. doi: 10.1001/jama.270.24.2957.
    1. Horan T, Gaynes R. Surveillance of nosocomial infections. In: Mayhall C, editor. Hospital Epidemiology and Infection Control. 3. Philadelphia, PA: Lippincott Williams & Wilkins; 2004. pp. 1650–1702.
    1. Sirvent JM, Vidaur L, Gonzalez S, Castro P, de Batlle J, Castro A, Bonet A. Microscopic examination of intracellular organisms in protected bronchoalveolar mini-lavage fluid for the diagnosis of ventilator-associated pneumonia. Chest. 2003;123:518–523. doi: 10.1378/chest.123.2.518.
    1. Peduzzi P, Concato J, Feinstein AR, Holford TR. Importance of events per independent variable in proportional hazards regression analysis II. accuracy and precision of regression estimates. J Clin Epidemiol. 1995;12:1503–1510. doi: 10.1016/0895-4356(95)00048-8.
    1. Isakow W, Morrow LE, Kollef MH. Probiotics for preventing and treating nosocomial infections: review of current evidence and recommandations. Chest. 2007;132:286–294. doi: 10.1378/chest.06-2156.
    1. Fedorak RN, Madsen KL. Probiotics and the management of inflammatory bowel disease. Inflamm Bowel Dis. 2004;10:286–299. doi: 10.1097/00054725-200405000-00018.
    1. Guarner F, Malagelada JR. Gut flora in health and disease. Lancet. 2003;361:512–519. doi: 10.1016/S0140-6736(03)12489-0.
    1. Kruis W. Review article: antibiotics and probiotics in inflammatory bowel disease. Aliment Pharmacol Ther. 2004;20(suppl 4):75–78. doi: 10.1111/j.1365-2036.2004.02051.x.
    1. Reid G, Jass J, Sebulsky MT, McCormick JK. Potential uses of probiotics in clinical practice. Clin Microbiol Rev. 2003;16:658–672. doi: 10.1128/CMR.16.4.658-672.2003.
    1. Sartor RB. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics. Gastroenterology. 2004;126:1620–1633. doi: 10.1053/j.gastro.2004.03.024.
    1. Spindler-Vesel A, Bengmark S, Vovk I, Cerovic O, Kompan L. Synbiotics, prebiotics, Glutamine, or peptide in early enteral nutrition: a randomized study in trauma patients. J Parenter Enteral Nutr. 2007;31:119–126. doi: 10.1177/0148607107031002119.
    1. Ishibashi N, Yamazaki S. Probiotics and safety. Am J Clin Nutr. 2001;73:465S–470S.
    1. Boyle RJ, Robins-Browne RM, Tang ML. Probiotic use in clinical practice: what are the risks? Am J Clin Nutr. 2006;83:1256–1264. quiz 1446-1257.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel