Antibiotics or probiotics as preventive measures against ventilator-associated pneumonia: a literature review

Marcus J Schultz, Lenneke E Haas, Marcus J Schultz, Lenneke E Haas

Abstract

Introduction: Mechanically ventilated critically ill patients frequently develop ventilator-associated pneumonia (VAP), a life-threatening complication. Proposed preventive measures against VAP include, but are not restricted to, selective decontamination of the digestive tract (SDD), selective oropharyngeal decontamination (SOD) and the use of probiotics. Probiotics are live bacteria that could have beneficial effects on the host by altering gastrointestinal flora. Similar to SDD and SOD, a prescription of probiotics aims at the prevention of secondary colonization of the upper and/or lower digestive tract.

Methods: We performed a literature review to describe the differences and similarities between SDD/SOD and probiotic preventive strategies, focusing on (a) efficacy, (b) risks, and (c) the routing of these strategies.

Results: Reductions in the incidence of VAP have been achieved with SDD and SOD. Two large randomized controlled trials even showed reduced mortality with these preventive strategies. Randomized controlled trials of probiotic strategies also showed a reduction of the incidence of VAP, but trials were too small to draw firm conclusions. Preventive strategies with antibiotics and probiotics may be limited due to the risk of emerging resistance to the locally applied antibiotics and the risk of probiotic-related infections, respectively. The majority of trials of SDD and SOD did not exhaustively address the issue of emerging resistance. Likewise, trials of probiotic strategies did not adequately address the risk of colonization with probiotics and probiotic-related infection. In studies of SDD and SOD the preventive strategy aimed at decontamination of the oral cavity, throat, stomach and intestines, and the oral cavity and throat, respectively. In the vast majority of studies of probiotic therapy the preventive strategy aimed at decontamination of the stomach and intestines.

Conclusions: Prophylactic use of antibiotics in critically ill patients is effective in reducing the incidence of VAP. Probiotic strategies deserve consideration in future well-powered trials. Future studies are needed to determine if preventive antibiotic and probiotic strategies are safe with regard to development of antibiotic resistance and probiotic infections. It should be determined whether the efficacy of probiotics improves when these agents are provided to the mouth and the intestines simultaneously.

Figures

Figure 1
Figure 1
Route of administration of prophylactic agents. (A) no prophylaxis; (B) the concept of SDD, with the application of non-absorbable antibiotics in mouth and intestines; (C) the concept of SOD, with the application of non-absorbable antibiotics solely in the mouth (note that agents applied in the mouth could get into the stomach); (D) application of probiotics as in most trials in critically ill patients.

References

    1. Fagon JY, Chastre J, Hance AJ, Montravers P, Novara A, Gibert C. Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay. Am J Med. 1993;94:281–288. doi: 10.1016/0002-9343(93)90060-3.
    1. Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med. 2002;165:867–903.
    1. Warren DK, Shukla SJ, Olsen MA, Kollef MH, Hollenbeak CS, Cox MJ, Cohen MM, Fraser VJ. Outcome and attributable cost of ventilator-associated pneumonia among intensive care unit patients in a suburban medical center. Crit Care Med. 2003;31:1312–1317. doi: 10.1097/01.CCM.0000063087.93157.06.
    1. Nguile-Makao M, Zahar JR, Français A, Tabah A, Garrouste-Orgeas M, Allaouchiche B, Goldgran-Toledano D, Azoulay E, Adrie C, Jamali S, Clec'h C, Souweine B, Timsit JF. Attributable mortality of ventilator-associated pneumonia: respective impact of main characteristics at ICU admission and VAP onset using conditional logistic regression and multi-state models. Intensive Care Med. 2010;36:781–789. doi: 10.1007/s00134-010-1824-6.
    1. Bonten MJ. Prevention of ventilator-associated pneumonia: bugs or drugs? Am J Respir Crit Care Med. 2010;182:993–994. doi: 10.1164/rccm.201007-1033ED.
    1. Melsen WG, Rovers MM, Bonten MJ. Ventilator-associated pneumonia and mortality: a systematic review of observational studies. Crit Care Med. 2009;37:2709–2718. doi: 10.1097/CCM.0b013e3181ab8655.
    1. Dodek P, Keenan S, Cook D, Heyland D, Jacka M, Hand L, Muscedere J, Foster D, Mehta N, Hall R, Brun-Buisson C. Canadian Critical Care Trials Group; Canadian Critical Care Society. Evidence-based clinical practice guideline for the prevention of ventilator-associated pneumonia. Ann Intern Med. 2004;141:305–313.
    1. American Thoracic Society; Infectious Diseases Society of America. 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. Rello J, Lode H, Cornaglia G, Masterton R. A European care bundle for prevention of ventilator-associated pneumonia. Intensive Care Med. 2010;36:773–780. doi: 10.1007/s00134-010-1841-5.
    1. Bouza E, Burillo A. Advances in the prevention and management of ventilator-associated pneumonia. Curr Opin Infect Dis. 2009;22:345–351. doi: 10.1097/QCO.0b013e32832d8910.
    1. van Saene HK, Damjanovic V, Murray AE, de la Cal MA. How to classify infections in intensive care units--the carrier state, a criterion whose time has come? J Hosp Infect. 1996;33:1–12. doi: 10.1016/S0195-6701(96)90025-0.
    1. van der Waaij D, Berghuis-de Vries JM, Lekkerkerk Lv. Colonization resistance of the digestive tract in conventional and antibiotic-treated mice. J Hyg (Lond) 1971;69:405–411. doi: 10.1017/S0022172400021653.
    1. Kerver AJ, Rommes JH, Mevissen-Verhage EA, Hulstaert PF, Vos A, Verhoef J, Wittebol P. Prevention of colonization and infection in critically ill patients: a prospective randomized study. Crit Care Med. 1988;16:1087–1093. doi: 10.1097/00003246-198811000-00001.
    1. Ledingham IM. Prevention and management of infections with gram-negative bacteria in intensive care units. Br J Clin Pract Suppl. 1988;57:45.
    1. Ulrich C, Harinck-de Weerd JE, Bakker NC, Jacz K, Doornbos L, de Ridder VA. Selective decontamination of the digestive tract with norfloxacin in the prevention of ICU-acquired infections: a prospective randomized study. Intensive Care Med. 1989;15:424–431. doi: 10.1007/BF00255597.
    1. Aerdts SJ, van Dalen R, Clasener HA, Festen J, van Lier HJ, Vollaard EJ. Antibiotic prophylaxis of respiratory tract infection in mechanically ventilated patients. A prospective, blinded, randomized trial of the effect of a novel regimen. Chest. 1991;100:783–791. doi: 10.1378/chest.100.3.783.
    1. Blair P, Rowlands BJ, Lowry K, Webb H, Armstrong P, Smilie J. Selective decontamination of the digestive tract: a stratified, randomized, prospective study in a mixed intensive care unit. Surgery. 1991;110:303–309. discussion 309-310.
    1. Hartenauer U, Thülig B, Diemer W, Lawin P, Fegeler W, Kehrel R, Ritzerfeld W. Effect of selective flora suppression on colonization, infection, and mortality in critically ill patients: a one-year, prospective consecutive study. Crit Care Med. 1991;19:463–473. doi: 10.1097/00003246-199104000-00003.
    1. Gastinne H, Wolff M, Delatour F, Faurisson F, Chevret S. A controlled trial in intensive care units of selective decontamination of the digestive tract with nonabsorbable antibiotics. The French Study Group on Selective Decontamination of the Digestive Tract. N Engl J Med. 1992;326:594–599. doi: 10.1056/NEJM199202273260903.
    1. Cockerill FR, Muller SR, Anhalt JP, Marsh HM, Farnell MB, Mucha P, Gillespie DJ, Ilstrup DM, Larson-Keller JJ, Thompson RL. Prevention of infection in critically ill patients by selective decontamination of the digestive tract. Ann Intern Med. 1992;117:545–553.
    1. Hammond JM, Potgieter PD, Saunders GL, Forder AA. Double-blind study of selective decontamination of the digestive tract in intensive care. Lancet. 1992;340:5–9. doi: 10.1016/0140-6736(92)92422-C.
    1. Jacobs S, Foweraker JE, Roberts SE. Effectiveness of selective decontamination of the digestive tract in an ICU with a policy encouraging a low gastric pH. Clinical Intensive Care. 1992;3:52–58.
    1. Rocha LA, Martín MJ, Pita S, Paz J, Seco C, Margusino L, Villanueva R, Durán MT. Prevention of nosocomial infection in critically ill patients by selective decontamination of the digestive tract. A randomized, double blind, placebo-controlled study. Intensive Care Med. 1992;18:398–404. doi: 10.1007/BF01694341.
    1. Winter R, Humphreys H, Pick A, MacGowan AP, Willatts SM, Speller DC. A controlled trial of selective decontamination of the digestive tract in intensive care and its effect on nosocomial infection. J Antimicrob Chemother. 1992;30:73–87. doi: 10.1093/jac/30.1.73.
    1. Ferrer M, Torres A, González J, Puig de la Bellacasa J, el-Ebiary M, Roca M, Gatell JM, Rodriguez-Roisin R. Utility of selective digestive decontamination in mechanically ventilated patients. Ann Intern Med. 1994;120:389–395.
    1. Palomar M, Alvarez-Lerma F, Jorda R, Bermejo B. Prevention of nosocomial infection in mechanically ventilated patients: selective digestive decontamination versus sucralfate. Clinical Intensive Care. 1997;8:228–235. doi: 10.1080/714029035.
    1. Verwaest C, Verhaegen J, Ferdinande P, Schetz M, Van den Berghe G, Verbist L, Lauwers P. Randomized, controlled trial of selective digestive decontamination in 600 mechanically ventilated patients in a multidisciplinary intensive care unit. Crit Care Med. 1997;25:63–71. doi: 10.1097/00003246-199701000-00014.
    1. Sánchez García M, Cambronero Galache JA, López Diaz J, Cerdá Cerdá E, Rubio Blasco J, Gómez Aguinaga MA, Núnez Reiz A, Rogero Marín S, Onoro Canaveral JJ, Sacristán del Castillo JA. Effectiveness and cost of selective decontamination of the digestive tract in critically ill intubated patients. A randomized, double-blind, placebo-controlled, multicenter trial. Am J Respir Crit Care Med. 1998;158:908–916.
    1. Krueger WA, Lenhart FP, Neeser G, Ruckdeschel G, Schreckhase H, Eissner HJ, Forst H, Eckart J, Peter K, Unertl KE. Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections, organ dysfunctions, and mortality in critically ill surgical patients a prospective, stratified, randomized, double-blind, placebo-controlled clinical trial. Am J Respir Crit Care Med. 2002;166:1029–1037. doi: 10.1164/rccm.2105141.
    1. Rodríguez-Roldán JM, Altuna-Cuesta A, López A, Carrillo A, Garcia J, León J, Martínez-Pellús AJ. Prevention of nosocomial lung infection in ventilated patients: use of an antimicrobial pharyngeal nonabsorbable paste. Crit Care Med. 1990;18:1239–1242.
    1. Pugin J, Auckenthaler R, Lew DP, Suter PM. Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia. A randomized, placebo-controlled, double-blind clinical trial. JAMA. 1991;265:2704–2710. doi: 10.1001/jama.265.20.2704.
    1. Laggner AN, Tryba M, Georgopoulos A, Lenz K, Grimm G, Graninger W, Schneeweiss B, Druml W. Oropharyngeal decontamination with gentamicin for long-term ventilated patients on stress ulcer prophylaxis with sucralfate? Wien Klin Wochenschr. 1994;106:15–19.
    1. Abele-Horn M, Dauber A, Bauernfeind A, Russwurm W, Seyfarth-Metzger I, Gleich P, Ruckdeschel G. Decrease in nosocomial pneumonia in ventilated patients by selective oropharyngeal decontamination (SOD) Intensive Care Med. 1997;23:187–195. doi: 10.1007/s001340050314.
    1. 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.
    1. Kotzampassi K, Giamarellos-Bourboulis EJ, Voudouris A, Kazamias P, Eleftheriadis E. Benefits of a synbiotic formula (Synbiotic 2000Forte) in critically Ill trauma patients: early results of a randomized controlled trial. World J Surg. 2006;30:1848–1855. doi: 10.1007/s00268-005-0653-1.
    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. JPEN J Parenter Enteral Nutr. 2007;31:119–126. doi: 10.1177/0148607107031002119.
    1. Forestier C, Guelon D, Cluytens V, Gillart T, Sirot J, De Champs C. Oral probiotic and prevention of Pseudomonas aeruginosa infections: a randomized, double-blind, placebo-controlled pilot study in intensive care unit patients. Crit Care. 2008;12:R69. doi: 10.1186/cc6907.
    1. Klarin B, Molin G, Jeppsson B, Larsson A. Use of the probiotic Lactobacillus plantarum 299 to reduce pathogenic bacteria in the oropharynx of intubated patients: a randomised controlled open pilot study. Crit Care. 2008;12:R136. doi: 10.1186/cc7109.
    1. Knight DJ, Gardiner D, Banks A, Snape SE, Weston VC, Bengmark S, Girling KJ. Effect of synbiotic therapy on the incidence of ventilator associated pneumonia in critically ill patients: a randomised, double-blind, placebo-controlled trial. Intensive Care Med. 2009;35:854–861. doi: 10.1007/s00134-008-1368-1.
    1. Morrow LE, Kollef MH, Casale TB. Probiotic prophylaxis of ventilator-associated pneumonia: a blinded, randomized, controlled trial. Am J Respir Crit Care Med. 2010;182:1058–1064. doi: 10.1164/rccm.200912-1853OC.
    1. Oudhuis GJ, Bergmans DC, Dormans T, Zwaveling JH, Kessels A, Prins MH, Stobberingh EE, Verbon A. Probiotics versus antibiotic decontamination of the digestive tract: infection and mortality. Intensive Care Med. 2011;37:110–117. doi: 10.1007/s00134-010-2002-6.
    1. Barraud D, Blard C, Hein F, Marçon O, Cravoisy A, Nace L, Alla F, Bollaert PE, Gibot S. Probiotics in the critically ill patient: a double blind, randomized, placebo-controlled trial. Intensive Care Med. 2010;36:1540–1547. doi: 10.1007/s00134-010-1927-0.
    1. Silvestri L, van Saene HK, Casarin A, Berlot G, Gullo A. Impact of selective decontamination of the digestive tract on carriage and infection due to Gram-negative and Gram-positive bacteria: a systematic review of randomised controlled trials. Anaesth Intensive Care. 2008;36:324–338.
    1. Silvestri L, van Saene HK, Weir I, Gullo A. Survival benefit of the full selective digestive decontamination regimen. J Crit Care. 2009;24:474. doi: 10.1016/j.jcrc.2008.11.005.
    1. Liberati A, D'Amico R, Pifferi S, Torri V, Brazzi L, Parmelli E. Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care. Cochrane Database Syst Rev. 2009. p. CD000022.
    1. Chan EY, Ruest A, Meade MO, Cook DJ. Oral decontamination for prevention of pneumonia in mechanically ventilated adults: systematic review and meta-analysis. BMJ. 2007;334:889. doi: 10.1136/.
    1. Besselink MG, Timmerman HM, Buskens E, Nieuwenhuijs VB, Akkermans LM, Gooszen HG. Probiotic prophylaxis in patients with predicted severe acute pancreatitis (PROPATRIA): design and rationale of a double-blind, placebo-controlled randomised multicenter trial [ISRCTN38327949] BMC Surg. 2004;4:12. doi: 10.1186/1471-2482-4-12.
    1. Siempos II, Ntaidou TK, Falagas ME. Impact of the administration of probiotics on the incidence of ventilator-associated pneumonia: A meta-analysis of randomized controlled trials. Crit Care Med. 2010;38:954–962. doi: 10.1097/CCM.0b013e3181c8fe4b.
    1. Watkinson PJ, Barber VS, Dark P, Young JD. The use of pre- pro- and synbiotics in adult intensive care unit patients: systematic review. Clin Nutr. 2007;26:182–192. doi: 10.1016/j.clnu.2006.07.010.
    1. Salgado CD, O'Grady N, Farr BM. Prevention and control of antimicrobial-resistant infections in intensive care patients. Crit Care Med. 2005;33:2373–2382. doi: 10.1097/01.CCM.0000181727.04501.F3.
    1. Bastin AJ, Ryanna KB. Use of selective decontamination of the digestive tract in United Kingdom intensive care units. Anaesthesia. 2009;64:46–49. doi: 10.1111/j.1365-2044.2008.05676.x.
    1. Heininger A, Meyer E, Schwab F, Marschal M, Unertl K, Krueger WA. Effects of long-term routine use of selective digestive decontamination on antimicrobial resistance. Intensive Care Med. 2006;32:1569–1576. doi: 10.1007/s00134-006-0304-5.
    1. 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. doi: 10.1016/S0140-6736(03)14409-1.
    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. Brun-Buisson C, van Saene HK. SDD and the novel extended-broad-spectrum beta-lactamases. J Antimicrob Chemother. 1991;28:145–147. doi: 10.1093/jac/28.1.145.
    1. Taylor ME, Oppenheim BA. Selective decontamination of the gastrointestinal tract as an infection control measure. J Hosp Infect. 1991;17:271–278. doi: 10.1016/0195-6701(91)90271-9.
    1. Oostdijk EA, de Smet AM, Blok HE, Thieme Groen ES, van Asselt GJ, Benus RF, Bernards SA, Frénay IH, Jansz AR, de Jongh BM, Kaan JA, Leverstein-van Hall MA, Mascini EM, Pauw W, Sturm PD, Thijsen SF, Kluytmans JA, Bonten MJ. Ecological effects of selective decontamination on resistant gram-negative bacterial colonization. Am J Respir Crit Care Med. 2010;181:452–457. doi: 10.1164/rccm.200908-1210OC.
    1. Hammond JM, Potgieter PD. Long-term effects of selective decontamination on antimicrobial resistance. Crit Care Med. 1995;23:637–645. doi: 10.1097/00003246-199504000-00010.
    1. Lingnau W, Berger J, Javorsky F, Fille M, Allerberger F, Benzer H. Changing bacterial ecology during a five-year period of selective intestinal decontamination. J Hosp Infect. 1998;39:195–206. doi: 10.1016/S0195-6701(98)90258-4.
    1. de la Cal MA, Cerdá E, van Saene HK, García-Hierro P, Negro E, Parra ML, Arias S, Ballesteros D. Effectiveness and safety of enteral vancomycin to control endemicity of methicillin-resistant Staphylococcus aureus in a medical/surgical intensive care unit. J Hosp Infect. 2004;56:175–183. doi: 10.1016/j.jhin.2003.09.021.
    1. Besselink MG, van Santvoort HC, Renooij W, de Smet MB, Boermeester MA, Fischer K, Timmerman HM, Ahmed Ali U, Cirkel GA, Bollen TL, van Ramshorst B, Schaapherder AF, Witteman BJ, Ploeg RJ, van Goor H, van Laarhoven CJ, Tan AC, Brink MA, van der Harst E, Wahab PJ, van Eijck CH, Dejong CH, van Erpecum KJ, Akkermans LM, Gooszen HG. Dutch Acute Pancreatitis Study Group. Intestinal barrier dysfunction in a randomized trial of a specific probiotic composition in acute pancreatitis. Ann Surg. 2009;250:712–719. doi: 10.1097/SLA.0b013e3181bce5bd.
    1. 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. doi: 10.1056/NEJMoa0800394.
    1. Babcock HM, Zack JE, Garrison T, Trovillion E, Jones M, Fraser VJ, Kollef MH. An educational intervention to reduce ventilator-associated pneumonia in an integrated health system: a comparison of effects. Chest. 2004;125:2224–2231. doi: 10.1378/chest.125.6.2224.
    1. Walker WA. Mechanisms of action of probiotics. Clin Infect Dis. 2008;46:S87–91. doi: 10.1086/523335. discussion S144-151.
    1. Rayes N, Hansen S, Seehofer D, Müller AR, Serke S, Bengmark S, Neuhaus P. Early enteral supply of fiber and Lactobacilli versus conventional nutrition: a controlled trial in patients with major abdominal surgery. Nutrition. 2002;18:609–615. doi: 10.1016/S0899-9007(02)00811-0.
    1. Snydman DR. The safety of probiotics. Clin Infect Dis. 2008;46:S104–111. doi: 10.1086/523331. discussion S144-151.
    1. Wood GC, Boucher BA, Croce MA, Fabian TC. Lactobacillus species as a cause of ventilator-associated pneumonia in a critically ill trauma patient. Pharmacotherapy. 2002;22:1180–1182. doi: 10.1592/phco.22.13.1180.33530.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться