Effectiveness and safety of measures to prevent infections and other complications associated with peripheral intravenous catheters: A systematic review and meta-analysis.

BACKGROUND: Peripheral intravenous catheters (PIVCs) contribute substantially to the global burden of infections. This systematic review assessed 24 infection prevention and control (IPC) interventions to prevent PIVC-associated infections and other complications. METHODS: We searched Ovid MEDLINE, Embase, Cochrane Library, WHO Global Index Medicus, CINAHL and reference lists for controlled studies, from January 1, 1980-March 16, 2023. We dually selected studies, assessed risk of bias, extracted data, and rated the certainty of evidence (COE). For outcomes with three or more trials, we conducted Bayesian random-effects meta-analyses. RESULTS: 105 studies met our prespecified eligibility criteria, addressing 16 of the 24 research questions; no studies were identified for eight research questions.Based on findings of low to high COE, wearing gloves reduced the risk for overall adverse events related to insertion compared to no gloves (one non-randomised controlled trial [RCT]; adjusted risk ratio [RR]: 0.52, 95% confidence interval 0.33-0.85), and catheter removal based on defined schedules potentially resulted in a lower phlebitis/thrombophlebitis incidence (10 RCTs; RR: 0.74, 95% credible interval 0.49-1.01) compared to clinically indicated removal in adults. In neonates, chlorhexidine reduced the phlebitis score compared to non-chlorhexidine-containing disinfection (one RCT; 0.14 versus 0.68, p = 0.003). No statistically significant differences were found for other measures. CONCLUSIONS: Despite their frequent use and concern about PIVC-associated complications, this review underscores the urgent need for more high-quality studies on effective IPC methods regarding safe PIVC management. In the absence of valid evidence, adherence to standard precaution measures and documentation remain the most important principles to curb PIVC complications.

Australian Donation and Transplantation Biobank: A Research Biobank Integrated Within a Deceased Organ and Tissue Donation Program.

We aimed to facilitate the donation of tissue samples for research by establishing a centralized system integrated in the organ donation program for collection, storage, and distribution of samples (the Australian Donation and Transplantation Biobank [ADTB]). Methods: Feasibility of a research biobank integrated within the deceased organ and tissue donation program was assessed. DonateLife Victoria sought consent for ADTB donation after consent was received for organ donation for transplantation from the donor's senior available next of kin. ADTB samples were collected during donation surgery and distributed fresh to researchers or stored for future research. The main outcome measures were ADTB donation rates, ADTB sample collection, ADTB sample use, and to identify ethical considerations. Results: Over 2 y, samples were collected for the ADTB from 69 donors (28% of 249 donors). Samples were obtained from the spleen (n = 59, 86%), colon (n = 57, 83%), ileum (n = 56, 82%), duodenum (n = 55, 80%), blood (n = 55, 80%), bone marrow (n = 55, 80%), skin (n = 54, 78%), mesenteric lymph nodes (n = 56, 81%), liver (n = 21, 30%), lung (n = 29, 42%), and lung-draining lymph node (n = 29, 42%). Heart (n = 20), breast (n = 1), and lower urinary tract (n = 1) samples were obtained in the second year. Five hundred fifty-six samples were used in 19 ethics-approved research projects spanning the fields of immunology, microbiology, oncology, anatomy, physiology, and surgery. Conclusions: The integration of routine deceased donation and transplantation activities with a coordinated system for retrieval and allocation of donor samples for use in a range of research projects is feasible and valuable.

Multi-site implementation of whole genome sequencing for hospital infection control: A prospective genomic epidemiological analysis.

Background: Current microbiological methods lack the resolution to accurately identify multidrug-resistant organism (MDRO) transmission, however, whole genome sequencing can identify highly-related patient isolates providing opportunities for precision infection control interventions. We investigated the feasibility and potential impact of a prospective multi-centre genomics workflow for hospital infection control. Methods: We conducted a prospective genomics implementation study across eight Australian hospitals over 15 months (2017,2018), collecting all clinical and screening isolates from inpatients with vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec), or ESBL Klebsiella pneumoniae (ESBL-Kp). Genomic and epidemiologic data were integrated to assess MDRO transmission. Findings: In total, 2275 isolates were included from 1970 patients, predominantly ESBL-Ec (40·8%) followed by MRSA (35·6%), vanA VRE (15·2%), and ESBL-Kp (8·3%).Overall, hospital and genomic epidemiology showed 607 patients (30·8%) acquired their MDRO in hospital, including the majority of vanA VRE (266 patients, 86·4%), with lower proportions of ESBL-Ec (186 patients, 23·0%), ESBL-Kp (42 patients, 26·3%), and MRSA (113 patients, 16·3%). Complex patient movements meant the majority of MDRO transmissions would remain undetected without genomic data.The genomics implementation had major impacts, identifying unexpected MDRO transmissions prompting new infection control interventions, and contributing to vanA VRE becoming a notifiable condition. We identified barriers to implementation and recommend strategies for mitigation. Interpretation: Implementation of a multi-centre genomics-informed infection control workflow is feasible and identifies many unrecognised MDRO transmissions. This provides critical opportunities for interventions to improve patient safety in hospitals. Funding: Melbourne Genomics Health Alliance (supported by State Government of Victoria, Australia), and National Health and Medical Research Council (Australia).

Lung-resident memory B cells established after pulmonary influenza infection display distinct transcriptional and phenotypic profiles.

Recent studies have established that memory B cells, largely thought to be circulatory in the blood, can take up long-term residency in inflamed tissues, analogous to widely described tissue-resident T cells. The dynamics of recruitment and retention of memory B cells to tissues and their immunological purpose remains unclear. Here, we characterized tissue-resident memory B cells (BRM) that are stably maintained in the lungs of mice after pulmonary influenza infection. Influenza-specific BRM were localized within inducible bronchus-associated lymphoid tissues (iBALTs) and displayed transcriptional signatures distinct from classical memory B cells in the blood or spleen while showing partial overlap with memory B cells in lung-draining lymph nodes. We identified lung-resident markers, including elevated expression of CXCR3, CCR6, and CD69, on hemagglutinin (HA)- and nucleoprotein (NP)-specific lung BRM. We found that CCR6 facilitates increased recruitment and/or retention of BRM in lungs and differentiation into antibody-secreting cells upon recall. Although expression of CXCR3 and CCR6 was comparable in total and influenza-specific memory B cells isolated across tissues of human donors, CD69 expression was higher in memory B cells from lung and draining lymph nodes of human organ donors relative to splenic and PBMC-derived populations, indicating that mechanisms underpinning BRM localization may be evolutionarily conserved. Last, we demonstrate that human memory B cells in lungs are transcriptionally distinct to populations in lung-draining lymph nodes or PBMCs. These data suggest that BRM may constitute a discrete component of B cell immunity, positioned at the lung mucosa for rapid humoral response against respiratory viral infections.

Optimising genomic approaches for identifying vancomycin-resistant Enterococcus faecium transmission in healthcare settings.

Vancomycin-resistant Enterococcus faecium (VREfm) is a major nosocomial pathogen. Identifying VREfm transmission dynamics permits targeted interventions, and while genomics is increasingly being utilised, methods are not yet standardised or optimised for accuracy. We aimed to develop a standardized genomic method for identifying putative VREfm transmission links. Using comprehensive genomic and epidemiological data from a cohort of 308 VREfm infection or colonization cases, we compared multiple approaches for quantifying genetic relatedness. We showed that clustering by core genome multilocus sequence type (cgMLST) was more informative of population structure than traditional MLST. Pairwise genome comparisons using split k-mer analysis (SKA) provided the high-level resolution needed to infer patient-to-patient transmission. The more common mapping to a reference genome was not sufficiently discriminatory, defining more than three times more genomic transmission events than SKA (3729 compared to 1079 events). Here, we show a standardized genomic framework for inferring VREfm transmission that can be the basis for global deployment of VREfm genomics into routine outbreak detection and investigation.

Staff to staff transmission as a driver of healthcare worker infections with COVID-19.

BACKGROUND: High rates of healthcare worker (HCW) infections due to COVID-19 have been attributed to several factors, including inadequate personal protective equipment (PPE), exposure to a high density of patients with COVID-19, and poor building ventilation. We investigated an increase in the number of staff COVID-19 infections at our hospital to determine the factors contributing to infection and to implement the interventions required to prevent subsequent infections. METHODS: We conducted a single-centre retrospective cohort study of staff working at a tertiary referral hospital who tested positive for SARS-CoV-2 between 25 January 2020 and 25 November 2020. The primary outcome was the source of COVID-19 infection. RESULTS: Of 45 staff who returned a positive test result for SARS-CoV-2, 19 were determined to be acquired at our hospital. Fifteen (15/19; 79% [95% CI: 54-94%]) of these were identified through contact tracing and testing following exposures to other infected staff and were presumed to be staff-to-staff transmission, including an outbreak in 10 healthcare workers (HCWs) linked to a single ward that cared for COVID-19 patients. The staff tearoom was identified as the likely location for transmission, with subsequent reduction in HCW infections and resolution of the outbreak following implementation of enhanced control measures in tearoom facilities. No HCW contacts (0/204; 0% [95% CI: 0-2%]) developed COVID-19 infection following exposure to unrecognised patients with COVID-19. CONCLUSION: Unrecognised infections among staff may be a significant driver of HCW infections in healthcare settings. Control measures should be implemented to prevent acquisition from other staff as well as patient-staff transmission.

Pilot study of a combined genomic and epidemiologic surveillance program for hospital-acquired multidrug-resistant pathogens across multiple hospital networks in Australia.

OBJECTIVES: To conduct a pilot study implementing combined genomic and epidemiologic surveillance for hospital-acquired multidrug-resistant organisms (MDROs) to predict transmission between patients and to estimate the local burden of MDRO transmission. DESIGN: Pilot prospective multicenter surveillance study. SETTING: The study was conducted in 8 university hospitals (2,800 beds total) in Melbourne, Australia (population 4.8 million), including 4 acute-care, 1 specialist cancer care, and 3 subacute-care hospitals. METHODS: All clinical and screening isolates from hospital inpatients (April 24 to June 18, 2017) were collected for 6 MDROs: vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) and Acinetobacter baumannii (CRAb). Isolates were analyzed and reported as routine by hospital laboratories, underwent whole-genome sequencing at the central laboratory, and were analyzed using open-source bioinformatic tools. MDRO burden and transmission were assessed using combined genomic and epidemiologic data. RESULTS: In total, 408 isolates were collected from 358 patients; 47.5% were screening isolates. ESBL-Ec was most common (52.5%), then MRSA (21.6%), vanA VRE (15.7%), and ESBL-Kp (7.6%). Most MDROs (88.3%) were isolated from patients with recent healthcare exposure.Combining genomics and epidemiology identified that at least 27.1% of MDROs were likely acquired in a hospital; most of these transmission events would not have been detected without genomics. The highest proportion of transmission occurred with vanA VRE (88.4% of patients). CONCLUSIONS: Genomic and epidemiologic data from multiple institutions can feasibly be combined prospectively, providing substantial insights into the burden and distribution of MDROs, including in-hospital transmission. This analysis enables infection control teams to target interventions more effectively.

Cure of Limb-Threatening XDR Pseudomonas aeruginosa Infection: Combining Genome Sequencing, Therapeutic Drug Level Monitoring, and Surgical Debridement.

We describe a case of limb-threatening osteomyelitis and metalware infection with carbapenemase-producing extensively drug-resistant Pseudomonas aeruginosa successfully cured with aggressive surgical debridement and combined intravenous fosfomycin and colistin. Real-time therapeutic drug monitoring was used to maximize probability of efficacy and minimize potential for toxicity.

Key parameters for genomics-based real-time detection and tracking of multidrug-resistant bacteria: a systematic analysis.

BACKGROUND: Pairwise single nucleotide polymorphisms (SNPs) are a cornerstone of genomic approaches to the inference of transmission of multidrug-resistant (MDR) organisms in hospitals. However, the impact of many key analytical approaches on these inferences has not yet been systematically assessed. This study aims to make such a systematic assessment. METHODS: We conducted a 15-month prospective study (2-month pilot phase, 13-month implementation phase), across four hospital networks including eight hospitals in Melbourne, VIC, Australia. Patient clinical and screening samples containing one or more isolates of meticillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae were collected and underwent whole genome sequencing. Using the genome data from the top four most numerous sequence types from each species, 16 in total, we systematically assessed the: (1) impact of sample and reference genome diversity through multiple core genome alignments using different data subsets and reference genomes, (2) effect of masking of prophage and regions of recombination in the core genome alignments by assessing SNP distances before and after masking, (3) differences between a cumulative versus a 3-month sliding-window approach to sample genome inclusion in the dataset over time, and (4) the comparative effects each of these approaches had when applying a previously defined SNP threshold for inferring likely transmission. FINDINGS: 2275 samples were collected (397 during the pilot phase from April 4 to June 18, 2017; 1878 during the implementation phase from Oct 30, 2017, to Nov 30, 2018) from 1870 patients. Of these 2275 samples, 1537 were identified as arising from the four most numerous sequence types from each of the four target species of MDR organisms in this dataset (16 sequence types in total: S aureus ST5, ST22, ST45, and ST93; E faecium ST80, ST203, ST1421, and ST1424; K pneumoniae ST15, ST17, ST307, and ST323; and E coli ST38, ST131, ST648, and ST1193). Across the species, using a reference genome of the same sequence type provided a greater degree of pairwise SNP resolution, compared with species and outgroup-reference alignments that mostly resulted in inflated SNP distances and the possibility of missed transmission events. Omitting prophage regions had minimal effect; however, omitting recombination regions had a highly variable effect, often inflating the number of closely related pairs. Estimated SNP distances between isolate pairs over time were more consistent using a sliding-window than a cumulative approach. INTERPRETATION: We propose that the use of a closely related reference genome, without masking of prophage or recombination regions, and of a sliding-window approach for isolate inclusion is best for accurate and consistent MDR organism transmission inference, when using core genome alignments and SNP thresholds. These approaches provide increased stability and resolution, so SNP thresholds can be more reliably applied for putative transmission inference among diverse MDR organisms, reducing the chance of incorrectly inferring the presence or absence of close genetic relatedness and, therefore, transmission. The establishment of a broadly applicable and standardised approach, as proposed here, is necessary to implement widespread prospective genomic surveillance for MDR organism transmission. FUNDING: Melbourne Genomics Health Alliance, and National Health and Medical Research Council of Australia.

The Penicillin Allergy Delabeling Program: A Multicenter Whole-of-Hospital Health Services Intervention and Comparative Effectiveness Study.

BACKGROUND: Penicillin allergies are associated with inferior patient and antimicrobial stewardship outcomes. We implemented a whole-of-hospital program to assess the efficacy of inpatient delabeling for low-risk penicillin allergies in hospitalized inpatients. METHODS: Patients ≥ 18 years of age with a low-risk penicillin allergy were offered a single-dose oral penicillin challenge or direct label removal based on history (direct delabeling). The primary endpoint was the proportion of patients delabeled. Key secondary endpoints were antibiotic utilization pre- (index admission) and post-delabeling (index admission and 90 days). RESULTS: Between 21 January 2019 and 31 August 2019, we assessed 1791 patients reporting 2315 antibiotic allergies, 1225 with a penicillin allergy. Three hundred fifty-five patients were delabeled: 161 by direct delabeling and 194 via oral penicillin challenge. Ninety-seven percent (194/200) of patients were negative upon oral penicillin challenge. In the delabeled patients, we observed an increase in narrow-spectrum penicillin usage (adjusted odds ratio [OR], 10.51 [95% confidence interval {CI}, 5.39-20.48]), improved appropriate antibiotic prescribing (adjusted OR, 2.13 [95% CI, 1.45-3.13]), and a reduction in restricted antibiotic usage (adjusted OR, 0.38 [95% CI, .27-.54]). In the propensity score analysis, there was an increase in narrow-spectrum penicillins (OR, 10.89 [95% CI, 5.09-23.31]) and ß-lactam/ß-lactamase inhibitors (OR, 6.68 [95% CI, 3.94-11.35]) and a reduction in restricted antibiotic use (OR, 0.52 [95% CI, .36-.74]) and inappropriate prescriptions (relative risk ratio, 0.43 [95% CI, .26-.72]) in the delabeled group compared with the group who retained their allergy label. CONCLUSIONS: This health services program using a combination of direct delabeling and oral penicillin challenge resulted in significant impacts on the use of preferred antibiotics and appropriate prescribing.

A multi-institutional outbreak of New Delhi metallo-ß-lactamase-producing Escherichia coli with subsequent acquisition of the Klebsiella pneumoniae carbapenemase gene.

We characterized 57 isolates from a 2-phase clonal outbreak of New Delhi metallo-ß-lactamase-producing Eschericha coli, involving 9 Israeli hospitals; all but 1 isolate belonged to sequence-type (ST) 410. Most isolates in the second phase harbored blaKPC-2 in addition to blaNDM-5. Genetic sequencing revealed most dual-carbapenemase-producing isolates to be monophyletically derived from a common ancestor.

Outcomes of an electronic medical record (EMR)-driven intensive care unit (ICU)-antimicrobial stewardship (AMS) ward round: Assessing the "Five Moments of Antimicrobial Prescribing".

OBJECTIVE: The primary objective of this study was to examine the impact of an electronic medical record (EMR)-driven intensive care unit (ICU) antimicrobial stewardship (AMS) service on clinician compliance with face-to-face AMS recommendations. AMS recommendations were defined by an internally developed "5 Moments of Antimicrobial Prescribing" metric: (1) escalation, (2) de-escalation, (3) discontinuation, (4) switch, and (5) optimization. The secondary objectives included measuring the impact of this service on (1) antibiotic appropriateness, and (2) use of high-priority target antimicrobials. METHODS: A prospective review was undertaken of the implementation and compliance with a new ICU-AMS service that utilized EMR data coupled with face-to-face recommendations. Additional patient data were collected when an AMS recommendation was made. The impact of the ICU-AMS round on antimicrobial appropriateness was evaluated using point-prevalence survey data. RESULTS: For the 202 patients, 412 recommendations were made in accordance with the "5 Moments" metric. The most common recommendation made by the ICU-AMS team was moment 3 (discontinuation), which comprised 173 of 412 recommendations (42.0%), with an acceptance rate of 83.8% (145 of 173). Data collected for point-prevalence surveys showed an increase in prescribing appropriateness from 21 of 45 (46.7%) preintervention (October 2016) to 30 of 39 (76.9%) during the study period (September 2017). CONCLUSIONS: The integration of EMR with an ICU-AMS program allowed us to implement a new AMS service, which was associated with high clinician compliance with recommendations and improved antibiotic appropriateness. Our "5 Moments of Antimicrobial Prescribing" metric provides a framework for measuring AMS recommendation compliance.

Beta-Lactam and Sulfonamide Allergy Testing Should Be a Standard of Care in Immunocompromised Hosts.

Antibiotic allergies are reported in up to 1 in 4 immunocompromised hosts with significant impacts on antibiotic utilization and patient outcomes. Health services programs focused on de-labeling beta-lactam and sulfonamide allergy labels should be a standard of care in immunocompromised hosts.

Broadening the infection prevention and control network globally; 2017 Geneva IPC-think tank (part 3).

Background: Healthcare-associated infection (HAI) is a major challenge for patient safety worldwide, and is further complicated by antimicrobial resistance (AMR) due to excessive antimicrobial use in both humans and animals. Existing infection prevention and control (IPC) networks must be strengthened and adapted to better address the global challenges presented by emerging AMR. Methods: In June 2017, 42 international experts convened in Geneva, Switzerland, to discuss two key areas for strengthening the global IPC network: 1) broadening collaboration in IPC; and 2) how to bring the fields IPC and AMR control together. Results: The US Centers for Disease Prevention and Control, the European Centre for Disease Prevention and Control, and the World Health Organization (WHO) convened together with international experts to discuss collaboration and networks, demonstrating the participating organizations' commitment to close collaboration in IPC. The challenge of emerging AMR can only be addressed by strengthening this collaboration across international organisations and between public health and academia. The WHO SAVE LIVES: Clean Your Hands initiative is an example of a successful collaboration between multiple global stakeholders including academia and international public health organisations; it can be used as a model. IPC-strategies are included within the four pillars to combat AMR: surveillance, IPC, antimicrobial and diagnostic stewardship, research and development. The prevention of transmission of multidrug-resistant microorganisms is a patient safety issue, and must be strengthened in the fight against AMR. Conclusions: The working group determined that international organisations should take the lead in creating new networks, which will in turn attract academia and other stakeholders to join. At the same time, they should invest in bringing existing IPC and AMR networks under one umbrella. Transmission of multidrug-resistant microorganisms in hospitals and in the community threatens the success of antimicrobial stewardship programmes, and thus, research and development in IPC should be addressed as an enhanced global priority.

Control of Carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa in Healthcare Facilities: A Systematic Review and Reanalysis of Quasi-experimental Studies.

Carbapenem-resistant Enterobacteriaceae (CRE), Acinetobacter baumannii (CRAB), and Pseudomonas aeruginosa (CRPsA) are a serious cause of healthcare-associated infections, although the evidence for their control remains uncertain. We conducted a systematic review and reanalysis to assess infection prevention and control (IPC) interventions on CRE-CRAB-CRPsA in inpatient healthcare facilities to inform World Health Organization guidelines. Six major databases and conference abstracts were searched. Before-and-after studies were reanalyzed as interrupted time series if possible. Effective practice and organization of care (EPOC) quality criteria were used. Seventy-six studies were identified, of which 17 (22%) were EPOC-compatible and interrupted time series analyses, assessing CRE (n = 11; 65%), CRAB (n = 5; 29%) and CRPsA (n = 3; 18%). IPC measures were often implemented using a multimodal approach (CRE: 10/11; CRAB: 4/5; CRPsA: 3/3). Among all CRE-CRAB-CRPsA EPOC studies, the most frequent intervention components included contact precautions (90%), active surveillance cultures (80%), monitoring, audit and feedback of measures (80%), patient isolation or cohorting (70%), hand hygiene (50%), and environmental cleaning (40%); nearly all studies with these interventions reported a significant reduction in slope and/or level. The quality of EPOC studies was very low to low.

Effects of the Australian National Hand Hygiene Initiative after 8 years on infection control practices, health-care worker education, and clinical outcomes: a longitudinal study.

BACKGROUND: The National Hand Hygiene Initiative (NHHI) is a standardised culture-change programme based on the WHO My 5 Moments for Hand Hygiene approach to improve hand hygiene compliance among Australian health-care workers and reduce the risk of health-care-associated infections. We analysed its effectiveness. METHODS: In this longitudinal study, we assessed outcomes of the NHHI for the 8 years after implementation (between Jan 1, 2009, and June 30, 2017), including hospital participation, hand hygiene compliance (measured as the proportion of observed Moments) three times per year, educational engagement, cost, and association with the incidence of health-care-associated Staphylococcus aureus bacteraemia (HA-SAB). FINDINGS: Between 2009 and 2017, increases were observed in national health-care facility participation (105 hospitals [103 public and two private] in 2009 vs 937 hospitals [598 public and 339 private] in 2017) and overall hand hygiene compliance (36 213 [63·6%] of 56 978 Moments [95% CI 63·2-63·9] in 2009 vs 494 673 [84·3%] of 586 559 Moments [84·2-84·4] in 2017; p<0·0001). Compliance also increased for each Moment type and for each health-care worker occupational group, including for medical staff (4377 [50·5%] of 8669 Moments [95% CI 49·4-51·5] in 2009 vs 53 620 [71·7%] of 74 788 Moments [71·4-72·0]; p<0·0001). 1 989 713 NHHI online learning credential programmes were completed. The 2016 NHHI budget was equivalent to AUD$0·06 per inpatient admission nationally. Among Australia's major public hospitals (n=132), improved hand hygiene compliance was associated with declines in the incidence of HA-SAB (incidence rate ratio 0·85; 95% CI 0·79-0·93; p≤0·0001): for every 10% increase in hand hygiene compliance, the incidence of HA-SAB decreased by 15%. INTERPRETATION: The NHHI has been associated with significant sustained improvement in hand hygiene compliance and a decline in the incidence of HA-SAB. Key features include sustained central coordination of a standardised approach and incorporation into hospital accreditation standards. The NHHI could be emulated in other national culture-change programmes. FUNDING: Australian Commission on Safety and Quality in Health Care.

Increasing tolerance of hospital Enterococcus faecium to handwash alcohols.

Alcohol-based disinfectants and particularly hand rubs are a key way to control hospital infections worldwide. Such disinfectants restrict transmission of pathogens, such as multidrug-resistant Staphylococcus aureus and Enterococcus faecium Despite this success, health care infections caused by E. faecium are increasing. We tested alcohol tolerance of 139 hospital isolates of E. faecium obtained between 1997 and 2015 and found that E. faecium isolates after 2010 were 10-fold more tolerant to killing by alcohol than were older isolates. Using a mouse gut colonization model of E. faecium transmission, we showed that alcohol-tolerant E. faecium resisted standard 70% isopropanol surface disinfection, resulting in greater mouse gut colonization compared to alcohol-sensitive E. faecium We next looked for bacterial genomic signatures of adaptation. Alcohol-tolerant E. faecium accumulated mutations in genes involved in carbohydrate uptake and metabolism. Mutagenesis confirmed the roles of these genes in the tolerance of E. faecium to isopropanol. These findings suggest that bacterial adaptation is complicating infection control recommendations, necessitating additional procedures to prevent E. faecium from spreading in hospital settings.