The effects of selective decontamination in Dutch Intensive Care Units

Infections are an important complication in the treatment of critical ill patients in Intensive Care Units (ICUs) and are associated with increased mortality, morbidity and health care costs. Selective Decontamination of the Digestive Tract (SDD) and Selective Oropharyngeal Decontamination (SOD) are powerful strategies to reduce the incidence of ICU-acquired infections. SDD consists of a mouth paste and suspension consisting of tobramycin, colistin and amphoterine B that are applied every six hours from ICU-admission until ICU-discharge. In addition, SDD-patients receive systemic antibiotics, usually a third generation cephalosporin, during the first four days in ICU. SOD only consists of the mouth paste. Previous studies have found that both SDD and SOD significantly reduce ICU mortality as compared to no-SDD/SOD use. Controversy still exists which regimen should be preferred and on the effects on antibiotic resistance. In this thesis, the effects of SDD and SOD on patient outcome and antibiotic resistance are studied by conducting a randomized multi-center trial in 16 Dutch ICUs. In this head-to-head comparison between SOD (12months) and SDD (12months) nearly 12,000 patients were included. Regarding their effect on patient outcome, this trial did not show a significant difference between SOD and SDD for mortality (day-28, ICU- and hospital mortality) nor for length of stay. Yet, the incidence of bacteremias was significantly lower during SDD as compared to SOD (

Decontamination of cephalosporin-resistant Enterobacteriaceae during selective digestive tract decontamination in intensive care units

Molecular basis of bacterial pathogenesis, virulence factors and antibiotic resistanc

Effects of selective digestive decontamination (SDD) on the gut resistome

Objectives Selective digestive decontamination (SDD) is an infection prevention measure for critically ill patients in intensive care units (ICUs) that aims to eradicate opportunistic pathogens from the oropharynx and intestines, while sparing the anaerobic flora, by the application of non-absorbable antibiotics. Selection for antibiotic-resistant bacteria is still a major concern for SDD. We therefore studied the impact of SDD on the reservoir of antibiotic resistance genes (i.e. the resistome) by culture-independent approaches. Methods We evaluated the impact of SDD on the gut microbiota and resistome in a single ICU patient during and after an ICU stay by several metagenomic approaches. We also determined by quantitative PCR the relative abundance of two common aminoglycoside resistance genes in longitudinally collected samples from 12 additional ICU patients who received SDD. Results The patient microbiota was highly dynamic during the hospital stay. The abundance of antibiotic resistance genes more than doubled during SDD use, mainly due to a 6.7-fold increase in aminoglycoside resistance genes, in particular aph(2¿)-Ib and an aadE-like gene. We show that aph(2¿)-Ib is harboured by anaerobic gut commensals and is associated with mobile genetic elements. In longitudinal samples of 12 ICU patients, the dynamics of these two genes ranged from a ~104 fold increase to a ~10-10 fold decrease in relative abundance during SDD. Conclusions ICU hospitalization and the simultaneous application of SDD has large, but highly individualized, effects on the gut resistome of ICU patients. Selection for transferable antibiotic resistance genes in anaerobic commensal bacteria could impact the risk of transfer of antibiotic resistance genes to opportunistic pathogens

Notice of Retraction and Replacement: Oostdijk et al. Effects of Decontamination of the Oropharynx and Intestinal Tract on Antibiotic Resistance in ICUs: A Randomized Clinical Trial. JAMA. 2014;312(14):1429-1437

Medical Microbiolog

Effects of Decontamination of the Oropharynx and Intestinal Tract on Antibiotic Resistance in ICUs: A Randomized Clinical Trial

IMPORTANCE\nSelective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) are prophylactic antibiotic regimens used in intensive care units (ICUs) and associated with improved patient outcome. Controversy exists regarding the relative effects of both measures on patient outcome and antibiotic resistance.\nOBJECTIVE\nTo compare the effects of SDD and SOD, applied as unit-wide interventions, on antibiotic resistance and patient outcome.\nDESIGN, SETTING, AND PARTICIPANTS\nPragmatic, cluster randomized crossover trial comparing 12 months of SOD with 12 months of SDD in 16 Dutch ICUs between August 1, 2009, and February 1, 2013. Patients with an expected length of ICU stay longer than 48 hours were eligible to receive the regimens, and 5881 and 6116 patients were included in the clinical outcome analysis for SOD and SDD, respectively.\nINTERVENTIONS\nIntensive care units were randomized to administer either SDD or SOD.\nMAIN OUTCOMES AND MEASURES\nUnit-wide prevalence of antibiotic-resistant gram-negative bacteria. Secondary outcomes were day-28 mortality, ICU-acquired bacteremia, and length of ICU stay.\nRESULTS\nIn point-prevalence surveys, prevalences of antibiotic-resistant gram-negative bacteria in perianal swabs were significantly lower during SDD compared with SOD; for aminoglycoside resistance, average prevalence was 5.6% (95% CI, 4.6%-6.7%) during SDD and 11.8% (95% CI, 10.3%-13.2%) during SOD (P < .001). During both interventions the prevalence of rectal carriage of aminoglycoside-resistant gram-negative bacteria increased 7% per month (95% CI, 1%-13%) during SDD (P = .02) and 4% per month (95% CI, 0%-8%) during SOD (P = .046; P = .40 for difference). Day 28-mortality was 25.4% and 24.1% during SOD and SDD, respectively (adjusted odds ratio, 0.96 [95% CI, 0.88-1.06]; P = .42), and there were no statistically significant differences in other outcome parameters or between surgical and nonsurgical patients. Intensive care unit-acquired bacteremia occurred in 5.9% and 4.6% of the patients during SOD and SDD, respectively (odds ratio, 0.77 [95% CI, 0.65-0.91]; P = .002; number needed to treat, 77).\nCONCLUSIONS AND RELEVANCE\nUnit-wide application of SDD and SOD was associated with low levels of antibiotic resistance and no differences in day-28 mortality. Compared with SOD, SDD was associated with lower rectal carriage of antibiotic-resistant gram-negative bacteria and ICU-acquired bacteremia but a more pronounced gradual increase in aminoglycoside-resistant gram-negative bacteria.\nTRIAL REGISTRATION\ntrialregister.nlIdentifier: NTR1780.Perioperative Medicine: Efficacy, Safety and Outcom