The addition of enteral to parenteral antimicrobials may prolong antibiotic era

Resistance to parenteral antimicrobials generally occurs within two years after introduction into general use. The site where de novo resistance develops has been acknowledged to be the gut. Overgrowth of abnormal flora, defined as 105 potential pathogens per g of faeces is a risk factor for resistance following increased spontaneous mutation leading to polyclonality and antimicrobial resistance. As parenteral antimicrobials generally fail to eradicate the abnormal carrier state in overgrowth concentrations due to sub-lethal concentrations in bile and mucus the enteral antimicrobials polymyxin/tobramycin aiming at converting the abnormal carrier state into normal carriage, are the essential component of selective decontamination of the digestive tract (SDD), because they eradicate carriage and overgrowth including resistant mutants, maintaining the usefulness of parenteral antimicrobials.

normal carriage, abnor-mal carriage, overgrowth, mutation, polyclonality, resistance, selective decontamination of the digestive tract, parenteral antimicrobials, ente-ral antimicrobials

1. van Saene HKF, Zandstra DF. Selective decontamination of the digestive tract: rationale behind evidence-based use in liver transplantation. Liver Transpl 2004;10:828-33.

2. van Saene HKF, Taylor N, Damjanovic V, Sarginson RE. Microbial gut overgrowth guarantees increased spontaneous mutation leading to polyclonality and antibiotic resistance in the critically ill. Curr Drug Targ 2008;9:419-21.

3. Silvestri L, van Saene HKF, 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 Inten Care 2008;36:324-38.

4. Silvestri L, van Saene HKF. Selective decontamination of the digestive tract does not increase resistance in critically ill patients: evidence from randomized controlled trials. Crit Care Med 2006;34:2027-30.

5. Rocha LA, Martin MJ, Pita S, Paz J, Seco C, Margusino L, et al. Prevention of nosocomial infection in critically ill patients by selective decontamination of the digestive tract. Inten Care Med 1992;18:398-404.

6. Verwaest C, Verhaegen J, Ferdinande P, Schetz M, Van den Berghe G, Verbist L, et al. Randomized controlled trial of selective digestive decontamination in 600 mechanically ventilated patients in a multi-disciplinary intensive care unit. Crit Care Med 1997;25:63-71.

7. Brun-Buisson C, Legrand P, Rauss AA, Richard C, Montravers F, Besbes M, et al. Intestinal decontamination for control of nosocomial multi-resistant Gram-negative bacilli. Ann Intern Med 1989;110:873-81.

8. de Jonge E, Schultz M, Spanjaard L, Bossuyt PM, Vroom MB, Dankert J, et al. Effects of selective decontamination of the digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised, controlled trial. Lancet 2003;363:1101-16.

9. de Smet AMGA, Kluytmans JAJW, Cooper BS, Mascini EM, Benus RF, van der Werf TS, et al. Decontamination of the digestive tract and oropharynx in ICU-patients. N Engl J Med 2009;360:20-31.

10. O’Grady NP, Salgado CD, Farr BM. Selective decontamination of the digestive tract does not increase resistance in critically ill patients: Evidence from randomized controlled trials. Crit Care Med 2006;34:2027-38.

11. Rangel Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP. The natural history of the systemic inflammatory response syndrome (SIRS): a prospective study. JAMA 1995;273:117-23.

12. Cook D, Guyatt G, Marshall J, Leasa D, Fuller H, Hall R, et al. A comparison of sucralfate and ranitidine for the prevention of upper gastro-intestinal bleeding in patients requiring mechanical ventilation. N Engl J Med 1998;338: 791-7.

13. Fagon JY, Chastre J, Wolff M, Gervais C, Parer Aubas S, Stéphan F, et al. Invasive and non-invasive strategies for management of sus-pected ventilator-associated pneumonia. A randomised trial. Ann Intern Med 2000;132:621-30.

14. Ruiz M, Torres A, Ewig S, Marcos MA, Alcón A, Lledó R, et al. Non-invasive versus invasive microbial investigation in ventilator-associated pneumonia: evaluation of outcome. Am J Respir Crit Care Med 2000;162:119-25.

15. Kollef MH, Vlasnik J, Sharpless L, Pasque C, Murphy D, Fraser V. Scheduled changes of antibiotic classes. A strategy to decrease the incidence of ventilator-associated pneumonia. Am J Respir Crit Care Med 1997;156:1040-8.

16. Toltzis P, Dul MJ, Hoyen C, Salvator A, Walsh M, Zetts L, et al. The effect of antibiotic rotation on colonization with antibiotic-resistant bacilli in a neonatal intensive care unit. Pediatrics 2002;110:707-11.

17. Cepeda JA, Whitehouse T, Cooper B, Hails J, Jones K, Kwaku F, et al. Isolation of patients in single rooms or cohorts to reduce spread of MRSA in intensive care units: prospective two-centre study. Lancet 2005;365:295-304.

18. Silvestri L, Petros AJ, Sarginson RE, de la Cal MA, Murray AE, van Saene HK. Hand washing in the intensive care unit: a big measure with modest effects. J Hosp Infect 2005;59:172-9.

19. Huskins WC, Goldmann DA. Controlling methicillin-resistant Staphylococcus aureus, aka ‘Superbug’. Lancet 2005;365:273-5.

20. de Man P, Verhoeven BA, Verburgh HA, Vos MC, van den Anker JN. An antibiotic policy to prevent emergence of resistant bacilli. Lancet 2000;355:973-8.

21. Sompolinsky D, Yaron V, Alkan WJ. Microbiological changes in the human fecal flora following the administration of tetracyclines and chloramphenicol. The Am J Proctol 1967;18:471-8.

22. Stoutenbeek CP, van Saene HKF, Zandstra DF. The effect of oral non-absorbable antibiotics on the emergence of resistant bacteria in patients in an intensive care unit. J Antimicrob Chemother 1987;19:513-20.

23. Leone M, Albanese J, Antonini F, Nguyen-Michel A, Martin C. Long-term (6 year) effect of selective digestive decontamination on antimi-crobial resistance in intensive care, multiple-trauma patients. Crit Care Med 2003;31:2090-5.

24. Sarginson RE, Taylor N, Reilly N, Baines PB, van Saene HKF. Infection in prolonged paediatric critical illness: A prospective four-year study based on knowledge of the carrier state. Crit Care Med 2004;32:839-47.

25. Heininger A, Meyer E, Schwab F, Marschal M, Unertl K, Krueger WA. Effects of long-term routine use of selective decontamination on antimicrobial resistance. Inten Care Med 2006;32:1569-76.