On the basis of a systematic review and meta-analysis, Nick Daneman and colleagues, concluded that there was no evidence for increased colonisation or infection with antimicrobial-resistant bacteria in patients receiving selective digestive decontamination (SDD) or selective oropharyngeal decontamination (SOD). The investigators recommend future studies focus on long-term effects of these interventions on antibiotic resistance with a non-crossover cluster-randomised study design. Importantly, the only evidence of better survival with SDD or SOD comes from studies in intensive-care units (ICUs) where—among isolates causing ICU-acquired bacteraemia—less than 1% were resistant to meticillin for Staphylococcus aureus or vancomycin for enterococci, and less than 5% of Escherichia coli and Klebsiella spp were producing extended-spectrum β lactamases.2de Jonge E Schultz MJ Spanjaard L et al.Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial.Lancet. 2003; 362: 1011-1016Summary Full Text Full Text PDF PubMed Scopus (491) Google Scholar, 3de Smet AM Kluytmans JA Cooper BS et al.Decontamination of the digestive tract and oropharynx in ICU patients.N Engl J Med. 2009; 360: 20-31Crossref PubMed Scopus (594) Google Scholar, 4Krueger WA Lenhart FP Neeser G et al.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: 1029-1037Crossref PubMed Scopus (229) Google Scholar Whether these findings can be extrapolated to settings with higher levels of antimicrobial resistance is unknown. Unless future studies are (again) done in settings with low levels of antibiotic resistance, clinically significant benefits in unambiguous outcomes for patients, preferably survival, should be the primary focus. Therefore, such studies should include standard-of-care treatment (no SDD or SOD), and investigators should consider chlorhexidine oropharyngeal decontamination as a comparator because this intervention has also been association with prevention of ventilator-associated pneumonia,5Koeman M van der Ven AJ Hak E et al.Oral decontamination with chlorhexidine reduces the incidence of ventilator-associated pneumonia.Am J Respir Crit Care Med. 2006; 173: 1348-1355Crossref PubMed Scopus (308) Google Scholar but has never been compared with SDD or SOD. We fully agree that randomly assigning units instead of patients is the most appropriate design in view of the unit-wide ecological effect pursued. However, the inherent absence of individual randomisation in a cluster randomised study increases the risk of bias caused by systematic differences in baseline characteristics of patients between intervention groups, especially when the intervention is known at time of enrolment, as will be the case when trying to modify the unit-wide ecology. Adjustment for covariates is then needed, which reduces the precision of the effect estimate. Moreover, ICUs might differ in characteristics that are difficult to quantify, but could substantially change study outcomes, such as hand hygiene and antibiotic use. A crossover design would minimise effects of such variables. Therefore, we recommend a cluster-randomised crossover study comparing SDD, SOD, and chlorhexidine to standard care in contemporary settings of antimicrobial resistance. This approach will examine the effectiveness of decontamination strategies on patients' outcomes, before we focus on the long-term consequences of SDD and SOD on antibiotic resistance in such settings. BHJW is supported by funding from the European Community's Seventh Framework Programme ( FP7/2007-2013 ) under grant agreement 282512. MJMB is supported by The Netherlands Organization of Scientific Research ( NWO-VICI 918.76.611 ). Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysisWe detected no relation between the use of SDD or SOD and the development of antimicrobial-resistance in pathogens in patients in the ICU, suggesting that the perceived risk of long-term harm related to selective decontamination cannot be justified by available data. However, our study indicates that the effect of decontamination on ICU-level antimicrobial resistance rates is understudied. We recommend that future research includes a non-crossover, cluster randomised controlled trial to assess long-term ICU-level changes in resistance rates. Full-Text PDF Studies of selective decontamination – Authors' replyJames Hurley and Bastiaan Wittekamp and colleagues discuss some of the fascinating and controversial aspects of selective digestive decontamination (SDD) and sound the call for further research to clarify its benefits and risks in intensive care units (ICUs). We agree with Hurley that the greatest limitation of previous research is that it has largely involved patient-level randomisation in single ICUs. We share his concern that this could lead to cross-transmission of antimicrobial-resistant pathogens from intervention to control patients, and mask signals of increased antibiotic resistance. Full-Text PDF