Selective decontamination of the digestive tract (SDD) in critically ill patients: a narrative review.

Selective decontamination of the digestive tract (SDD) is an infection prevention measure for intensive care unit (ICU) patients that was proposed more than 30 years ago, and that is currently considered standard of care in the Netherlands, but only used sporadically in ICUs in other countries. In this narrative review, we first describe the rationale of the individual components of SDD and then review the evidence base for patient-centered outcomes, where we distinguish ICUs with low prevalence of antibiotic resistance from ICUs with moderate-high prevalence of resistance. In settings with low prevalence of antibiotic resistance, SDD has been associated with improved patient outcome in three cluster-randomized studies. These benefits were not confirmed in a large international cluster-randomized study in settings with moderate-to-high prevalence of antibiotic resistance. There is no evidence that SDD increases antibiotic resistance. We end with future directions for research.

Adjusting for Disease Severity Across ICUs in Multicenter Studies.

OBJECTIVES: To compare methods to adjust for confounding by disease severity during multicenter intervention studies in ICU, when different disease severity measures are collected across centers. DESIGN: In silico simulation study using national registry data. SETTING: Twenty mixed ICUs in The Netherlands. SUBJECTS: Fifty-five-thousand six-hundred fifty-five ICU admissions between January 1, 2011, and January 1, 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: To mimic an intervention study with confounding, a fictitious treatment variable was simulated whose effect on the outcome was confounded by Acute Physiology and Chronic Health Evaluation IV predicted mortality (a common measure for disease severity). Diverse, realistic scenarios were investigated where the availability of disease severity measures (i.e., Acute Physiology and Chronic Health Evaluation IV, Acute Physiology and Chronic Health Evaluation II, and Simplified Acute Physiology Score II scores) varied across centers. For each scenario, eight different methods to adjust for confounding were used to obtain an estimate of the (fictitious) treatment effect. These were compared in terms of relative (%) and absolute (odds ratio) bias to a reference scenario where the treatment effect was estimated following correction for the Acute Physiology and Chronic Health Evaluation IV scores from all centers. Complete neglect of differences in disease severity measures across centers resulted in bias ranging from 10.2% to 173.6% across scenarios, and no commonly used methodology-such as two-stage modeling or score standardization-was able to effectively eliminate bias. In scenarios where some of the included centers had (only) Acute Physiology and Chronic Health Evaluation II or Simplified Acute Physiology Score II available (and not Acute Physiology and Chronic Health Evaluation IV), either restriction of the analysis to Acute Physiology and Chronic Health Evaluation IV centers alone or multiple imputation of Acute Physiology and Chronic Health Evaluation IV scores resulted in the least amount of relative bias (0.0% and 5.1% for Acute Physiology and Chronic Health Evaluation II, respectively, and 0.0% and 4.6% for Simplified Acute Physiology Score II, respectively). In scenarios where some centers used Acute Physiology and Chronic Health Evaluation II, regression calibration yielded low relative bias too (relative bias, 12.4%); this was not true if these same centers only had Simplified Acute Physiology Score II available (relative bias, 54.8%). CONCLUSIONS: When different disease severity measures are available across centers, the performance of various methods to control for confounding by disease severity may show important differences. When planning multicenter studies, researchers should make contingency plans to limit the use of or properly incorporate different disease measures across centers in the statistical analysis.

Associations Between Enteral Colonization With Gram-Negative Bacteria and Intensive Care Unit-Acquired Infections and Colonization of the Respiratory Tract.

Background: Enteral and respiratory tract colonization with gram-negative bacteria may lead to subsequent infections in critically ill patients. We aimed to clarify the interdependence between gut and respiratory tract colonization and their associations with intensive care unit (ICU)-acquired infections in patients receiving selective digestive tract decontamination (SDD). Methods: Colonization status of the rectum and respiratory tract was determined using twice-weekly microbiological surveillance in mechanically ventilated subjects receiving SDD between May 2011 and June 2015 in a tertiary medical-surgical ICU in the Netherlands. Acquisition of infections was monitored daily by dedicated observers. Marginal structural models were used to determine the associations between gram-negative rectal colonization and respiratory tract colonization, ICU-acquired gram-negative infection, and ICU-acquired gram-negative bacteremia. Results: Among 2066 ICU admissions, 1157 (56.0%) ever had documented gram-negative carriage in the rectum during ICU stay. Cumulative incidences of ICU-acquired gram-negative infection and bacteremia were 6.0% (n = 124) and 2.1% (n = 44), respectively. Rectal colonization was an independent risk factor for both respiratory tract colonization (cause-specific hazard ratio [CSHR], 2.93 [95% confidence interval {CI}, 2.02-4.23]) and new gram-negative infection in the ICU (CSHR, 3.04 [95% CI, 1.99-4.65]). Both rectal and respiratory tract colonization were associated with bacteremia (CSHR, 7.37 [95% CI, 3.25-16.68] and 2.56 [95% CI, 1.09-6.03], respectively). Similar associations were observed when Enterobacteriaceae and glucose nonfermenting gram-negative bacteria were analyzed separately. Conclusions: Gram-negative rectal colonization tends to be stronger associated with subsequent ICU-acquired gram-negative infections than gram-negative respiratory tract colonization. Gram-negative rectal colonization seems hardly associated with subsequent ICU-acquired gram-negative respiratory tract colonization.

Colistin and tobramycin resistance during long- term use of selective decontamination strategies in the intensive care unit: a post hoc analysis.

INTRODUCTION: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) have been shown to improve intensive care unit (ICU) patients' outcomes. The aim of this study was to determine the effects of long-term use of SDD and SOD on colistin and tobramycin resistance among gram-negative bacteria. METHODS: We performed a post hoc analysis of two consecutive multicentre cluster-randomised trials with crossover of interventions. SDD and SOD were alternately but continuously used during 7 years in five Dutch ICUs participating in two consecutive cluster-randomised trials. In both trials, to measure colistin and tobramycin resistance among gram-negative bacteria, rectal and respiratory samples were obtained monthly from all patients present in the ICU. RESULTS: The prevalence of tobramycin resistance in respiratory and rectal samples decreased significantly during long-term use of SOD and SDD. (rectal samples risk ratio (RR) 0.35 (0.23 to 0.53); respiratory samples RR 0.48 (0.32 to 0.73), SDD compared to standard care). Colistin resistance in rectal and respiratory samples did not change (rectal samples RR 0.63 (0.29 to 1.38); respiratory samples RR 1.26 (0.35 to 4.57), SDD compared to standard care). CONCLUSIONS: In this study, in a setting with low antimicrobial resistance rates, the prevalence of resistance against colistin and tobramycin among gram-negative isolates did not increase during a mean of 7 years of SDD or SOD use.

Fighting antibiotic resistance in the intensive care unit using antibiotics.

Antibiotic resistance is a global and increasing problem that is not counterbalanced by the development of new therapeutic agents. The prevalence of antibiotic resistance is especially high in intensive care units with frequently reported outbreaks of multidrug-resistant organisms. In addition to classical infection prevention protocols and surveillance programs, counterintuitive interventions, such as selective decontamination with antibiotics and antibiotic rotation have been applied and investigated to control the emergence of antibiotic resistance. This review provides an overview of selective oropharyngeal and digestive tract decontamination, decolonization of methicillin-resistant Staphylococcus aureus and antibiotic rotation as strategies to modulate antibiotic resistance in the intensive care unit.

Antibiotic prophylaxis in the era of multidrug-resistant bacteria.

The prophylactic use of antibiotics can only be justified when clinical benefits on relevant patient outcomes, such as morbidity or mortality, cost-effectiveness, and absence of immediate emergence of antibiotic resistance have been unequivocally demonstrated. In some intensive care unit (ICU) patients, antibiotic prophylaxis is used as part of selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD). Recent trials in ICUs with low levels of antibiotic resistance strongly suggest that both regimens reduce the incidence of ICU-acquired infections and improve patient survival. Naturally, the unique microbial ecology of such settings reduce generalizability of results. Therefore, the routine use of SOD and SDD remains highly controversial, especially in ICUs with higher levels of antibiotic resistance. Moreover, convincing evidence is still missing on several important aspects related to efficacy and safety. Despite numerous trials, effects of SDD and SOD on antibiotic resistance during and after decolonization treatment have still been insufficiently investigated, and existing results are contradicting. Furthermore, the effects of both regimens on the non-culturable part of the intestinal flora remain unknown. Finally, cost-effectiveness has not been thoroughly investigated, and prices of the antimicrobial agents that have been used have increased dramatically in recent years. In this review, important knowledge gaps that so far prevent the widespread use of SDD and SOD will be addressed.

Clinical review: post-extubation laryngeal edema and extubation failure in critically ill adult patients.

Laryngeal edema is a frequent complication of intubation. It often presents shortly after extubation as post-extubation stridor and results from damage to the mucosa of the larynx. Mucosal damage is caused by pressure and ischemia resulting in an inflammatory response. Laryngeal edema may compromise the airway necessitating reintubation. Several studies show that a positive cuff leak test combined with the presence of risk factors can identify patients with increased risk for laryngeal edema. Meta-analyses show that pre-emptive administration of a multiple-dose regimen of glucocorticosteroids can reduce the incidence of laryngeal edema and subsequent reintubation. If post-extubation edema occurs this may necessitate medical intervention. Parenteral administration of corticosteroids, epinephrine nebulization and inhalation of a helium/oxygen mixture are potentially effective, although this has not been confirmed by randomized controlled trials. The use of non-invasive positive pressure ventilation is not indicated since this will delay reintubation. Reintubation should be considered early after onset of laryngeal edema to adequately secure an airway. Reintubation leads to increased cost, morbidity and mortality.