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The intensive care medicine research agenda on multidrug-resistant bacteria, antibiotics, and stewardship.

ABSTRACT: PURPOSE:To concisely describe the current standards of care, major recent advances, common beliefs that have been contradicted by recent trials, areas of uncertainty, and clinical studies that need to be performed over the next decade and their expected outcomes with regard to the management of multidrug-resistant (MDR) bacteria, antibiotic use, and antimicrobial stewardship in the intensive care unit (ICU) setting. METHODS:Narrative review based on a systematic analysis of the medical literature, national and international guidelines, and expert opinion. RESULTS:The prevalence of infection of critically ill patients by MDR bacteria is rapidly evolving. Clinical studies aimed at improving understanding of the changing patterns of these infections in ICUs are urgently needed. Ideal antibiotic utilization is another area of uncertainty requiring additional investigations aimed at better understanding of dose optimization, duration of therapy, use of combination treatment, aerosolized antibiotics, and the integration of rapid diagnostics as a guide for treatment. Moreover, there is an imperative need to develop non-antibiotic approaches for the prevention and treatment of MDR infections in the ICU. Finally, clinical research aimed at demonstrating the beneficial impact of antimicrobial stewardship in the ICU setting is essential. CONCLUSIONS:These and other fundamental questions need to be addressed over the next decade in order to better understand how to prevent, diagnose, and treat MDR bacterial infections. Clinical studies described in this research agenda provide a template and set priorities for investigations that should be performed in this field.

SUBMITTER: Kollef MH

PROVIDER: S-EPMC6204331 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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The intensive care medicine research agenda on multidrug-resistant bacteria, antibiotics, and stewardship.

Kollef Marin H MH Bassetti Matteo M Francois Bruno B Burnham Jason J Dimopoulos George G Garnacho-Montero Jose J Lipman Jeffrey J Luyt Charles-Edouard CE Nicolau David P DP Postma Maarten J MJ Torres Antonio A Welte Tobias T Wunderink Richard G RG

Intensive care medicine 20170204 9

<h4>Purpose</h4>To concisely describe the current standards of care, major recent advances, common beliefs that have been contradicted by recent trials, areas of uncertainty, and clinical studies that need to be performed over the next decade and their expected outcomes with regard to the management of multidrug-resistant (MDR) bacteria, antibiotic use, and antimicrobial stewardship in the intensive care unit (ICU) setting.<h4>Methods</h4>Narrative review based on a systematic analysis of the me ...[more]

PMID: 28160023

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Project description:Contamination of hospital sinks with microbial pathogens presents a serious potential threat to patients, but our understanding of sink colonization dynamics is largely based on infection outbreaks. Here, we investigate the colonization patterns of multidrug-resistant organisms (MDROs) in intensive care unit sinks and water from two hospitals in the USA and Pakistan collected over 27 months of prospective sampling. Using culture-based methods, we recovered 822 bacterial isolates representing 104 unique species and genomospecies. Genomic analyses revealed long-term colonization by Pseudomonas spp. and Serratia marcescens strains across multiple rooms. Nanopore sequencing uncovered examples of long-term persistence of resistance-conferring plasmids in unrelated hosts. These data indicate that antibiotic resistance (AR) in Pseudomonas spp. is maintained both by strain colonization and horizontal gene transfer (HGT), while HGT maintains AR within Acinetobacter spp. and Enterobacterales, independent of colonization. These results emphasize the importance of proactive, genomic-focused surveillance of built environments to mitigate MDRO spread. IMPORTANCE Hospital sinks are frequently linked to outbreaks of antibiotic-resistant bacteria. Here, we used whole-genome sequencing to track the long-term colonization patterns in intensive care unit (ICU) sinks and water from two hospitals in the USA and Pakistan collected over 27 months of prospective sampling. We analyzed 822 bacterial genomes, representing over 100 different species. We identified long-term contamination by opportunistic pathogens, as well as transient appearance of other common pathogens. We found that bacteria recovered from the ICU had more antibiotic resistance genes (ARGs) in their genomes compared to matched community spaces. We also found that many of these ARGs are harbored on mobilizable plasmids, which were found shared in the genomes of unrelated bacteria. Overall, this study provides an in-depth view of contamination patterns for common nosocomial pathogens and identifies specific targets for surveillance.

Project description:BACKGROUND:Intensive care units (ICUs) are high-risk settings for the transmission of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE). METHODS:In a cluster-randomized trial, we evaluated the effect of surveillance for MRSA and VRE colonization and of the expanded use of barrier precautions (intervention) as compared with existing practice (control) on the incidence of MRSA or VRE colonization or infection in adult ICUs. Surveillance cultures were obtained from patients in all participating ICUs; the results were reported only to ICUs assigned to the intervention. In intervention ICUs, patients who were colonized or infected with MRSA or VRE were assigned to care with contact precautions; all the other patients were assigned to care with universal gloving until their discharge or until surveillance cultures obtained at admission were reported to be negative. RESULTS:During a 6-month intervention period, there were 5434 admissions to 10 intervention ICUs, and 3705 admissions to 8 control ICUs. Patients who were colonized or infected with MRSA or VRE were assigned to barrier precautions more frequently in intervention ICUs than in control ICUs (a median of 92% of ICU days with either contact precautions or universal gloving [51% with contact precautions and 43% with universal gloving] in intervention ICUs vs. a median of 38% of ICU days with contact precautions in control ICUs, P<0.001). In intervention ICUs, health care providers used clean gloves, gowns, and hand hygiene less frequently than required for contacts with patients assigned to barrier precautions; when contact precautions were specified, gloves were used for a median of 82% of contacts, gowns for 77% of contacts, and hand hygiene after 69% of contacts, and when universal gloving was specified, gloves were used for a median of 72% of contacts and hand hygiene after 62% of contacts. The mean (±SE) ICU-level incidence of events of colonization or infection with MRSA or VRE per 1000 patient-days at risk, adjusted for baseline incidence, did not differ significantly between the intervention and control ICUs (40.4±3.3 and 35.6±3.7 in the two groups, respectively; P=0.35). CONCLUSIONS:The intervention was not effective in reducing the transmission of MRSA or VRE, although the use of barrier precautions by providers was less than what was required. (Funded by the National Institute of Allergy and Infectious Diseases and others; STAR*ICU ClinicalTrials.gov number, NCT00100386.).

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The intensive care medicine research agenda on multidrug-resistant bacteria, antibiotics, and stewardship.

Publications

The intensive care medicine research agenda on multidrug-resistant bacteria, antibiotics, and stewardship.

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