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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.Copyright © 2018 The Authors, some rights reserved;.

Background: Vancomycin-resistant Enterococcus faecium (VRE) is a leading cause of hospital-acquired infections. New, presumably better-adapted strains of VRE appear unpredictably; it is uncertain how they spread despite improved infection control. We aimed to investigate the relatedness of a novel sequence type (ST) of vanB E. faecium - ST796 - very near its time of origin from hospitals in three Australian states and New Zealand. Method(s): Following near-simultaneous outbreaks of ST796 in multiple institutions, we gathered then tested colonization and bloodstream infection isolates' antimicrobial resistance (AMR) phenotypes, and phylogenomic relationships using whole genome sequencing (WGS). Patient meta-data was explored to trace the spread of ST796. Result(s): A novel clone of vanB E. faecium (ST796) was first detected at one Australian hospital in late 2011, then in two New Zealand hospitals linked by inter-hospital transfers from separate Melbourne hospitals. ST796 also appeared in hospitals in South Australia and New South Wales and was responsible for at least one major colonization outbreak in a Neonatal Intensive Care Unit without identifiable links between centers. No exceptional AMR was detected in the isolates. While WGS analysis showed very limited diversity at the core genome, consistent with recent emergence of the clone, clustering by institution was observed. Conclusion(s): Evolution of new E. faecium clones, followed by recognized or unrecognized movement of colonized individuals then rapid intra-institutional cross-transmission best explain the multi-center, multistate and international outbreak we observed.Copyright © 2018 The Author(s).

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.

Background: Vancomycin-resistant Enterococcus faecium (VRE) is a leading cause of hospital-acquired infections. New, presumably better-adapted strains of VRE appear unpredictably; it is uncertain how they spread despite improved infection control. We aimed to investigate the relatedness of a novel sequence type (ST) of vanB E. faecium - ST796 - very near its time of origin from hospitals in three Australian states and New Zealand. Methods: Following near-simultaneous outbreaks of ST796 in multiple institutions, we gathered then tested colonization and bloodstream infection isolates' antimicrobial resistance (AMR) phenotypes, and phylogenomic relationships using whole genome sequencing (WGS). Patient meta-data was explored to trace the spread of ST796. Results: A novel clone of vanB E. faecium (ST796) was first detected at one Australian hospital in late 2011, then in two New Zealand hospitals linked by inter-hospital transfers from separate Melbourne hospitals. ST796 also appeared in hospitals in South Australia and New South Wales and was responsible for at least one major colonization outbreak in a Neonatal Intensive Care Unit without identifiable links between centers. No exceptional AMR was detected in the isolates. While WGS analysis showed very limited diversity at the core genome, consistent with recent emergence of the clone, clustering by institution was observed. Conclusions: Evolution of new E. faecium clones, followed by recognized or unrecognized movement of colonized individuals then rapid intra-institutional cross-transmission best explain the multi-center, multistate and international outbreak we observed.

From early 2012, a novel clone of vancomycin resistant Enterococcus faecium (assigned the multi locus sequence type ST796) was simultaneously isolated from geographically separate hospitals in south eastern Australia and New Zealand. Here we describe the complete genome sequence of Ef_aus0233, a representative ST796 E. faecium isolate. We used PacBio single molecule real-time sequencing to establish a high quality, fully assembled genome comprising a circular chromosome of 2,888,087 bp and five plasmids. Comparison of Ef_aus0233 to other E. faecium genomes shows Ef_aus0233 is a member of the epidemic hospital-adapted lineage and has evolved from an ST555- like ancestral progenitor by the accumulation or modification of five mosaic plasmids and five putative prophage, acquisition of two cryptic genomic islands, accrued chromosomal single nucleotide polymorphisms and a 80 kb region of recombination, also gaining Tn1549 and Tn916, transposons conferring resistance to vancomycin and tetracycline respectively. The genomic dissection of this new clone presented here underscores the propensity of the hospital E. faecium lineage to change, presumably in response to the specific conditions of hospital and healthcare environments.

Objective: To screen for faecal colonisation with vancomycin-resistant enterococci (VRE) among potentially at-risk patients. Design(s): Infection control screening program. Setting(s): Monash Medical Centre (a tertiary care hospital), Melbourne, Victoria, in the seven months from June 1997. Patient(s): Patients in the Renal, Oncology and Intensive Care (ICU) Units. Main Outcome Measure(s): Presence of VRE in a rectal swab or faecal specimen taken at admission and at regular intervals during inpatient stay; presence of vancomycin-resistance genes (vanA, vanB and vanC) assessed by polymerase chain reaction (PCR); genetic clonality of isolates assessed by pulsed-field gel electrophoresis (PFGE). Result(s): 574 patients (356 renal, 134 ICU and 84 oncology) were screened; 12 were colonised with VRE - nine renal inpatients, two having peritoneal dialysis or in-centre haemodialysis, and one ICU patient. Nine isolates were Enterococcus faecalis (seven positive for vanB and two negative for all three resistance genes) and three were Enterococcus faecium (all positive for vanB). Eight were high-level gentamicin resistant. PFGE suggested genetic clonality between the index isolate and five other isolates from renal patients. No specific clinical practice was associated with VRE colonisation. Attempts to clear rectal carriage with oral ampicillin/amoxyciliin or bacitracin were of limited success. Although antibiotic prescribing in the Renal Unit was generally consistent with defined protocols, use of vancomycin and third-generation cephalosporins has been further restricted. Conclusion(s): Renal inpatients in our institution appear most at risk of VRE colonisation (4.6% overall) and thereore of VRE infection. Routine screening, especially of potentially high-risk patients, should be considered in major Australian hospitals.

Background: Although full surgical scrubs are performed prior to each case on an operating list, optimum regimens for hand cleaning have yet to be determined, and in-use efficacy evaluations are very limited. Method(s): A crossover study was undertaken comparing a chlorhexidine in detergent/alcohol regimen with povidine-iodine detergent scrub, within an orthopaedic operating environment. Depending on the skin asepsis regimen used, five surgical team members scrubbed or rubbed prior to each case for a complete operating list. Bactericidal efficacy was measured using the 'glove-juice' technique before and after hand asepsis, and at the completion of each case. Result(s): The chlorhexidine regimen caused substantial and sustained reductions in hand bacterial counts (>50-fold prior to case 1) during surgical cases. Application of alcoholic chlorhexidine prior to each subsequent case reduced bacterial counts to the same level as the original scrub. In contrast, the povidine-iodine scrub reduced counts <3-fold prior to the first case and <2-fold in subsequent cases. The chlorhexidine regimen also resulted in persistent bactericidal effects between cases, as counts prior to application of cases 2 and higher were significantly lower than prior to case 1 (>7-fold for case 2 vs case 1). Conclusion(s): The chlorhexidine regimen demonstrated excellent bactericidal efficacy throughout an operating list, and was superior to povidine-iodine scrubbing in all aspects. The alcoholic chlorhexidine regimen is simpler and should have wide surgical application.

Although infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility (SA-RVS) have been reported from a number of countries, including Australia, the optimal therapy is unknown. We reviewed the clinical features, therapy, and outcome of 25 patients with serious infections due to SA-RVS in Australia and New Zealand. Eight patients had endocarditis, 9 had bacteremia associated with deep-seated infection, 6 had osteomyelitis or septic arthritis, and 2 had empyema. All patients had received vancomycin before the isolation of SA-RVS, and glycopeptide treatment had failed for 19 patients (76%). Twenty-one patients subsequently received active treatment, which was effective for 16 patients (76%). Eighteen patients received linezolid, which was effective in 14 (78%), including 4 patients with endocarditis. Twelve patients received a combination of rifampicin and fusidic acid. Surgical intervention was required for 15 patients (60%). Antibiotic therapy, especially linezolid with or without rifampicin and fusidic acid, in conjunction with surgical debulking is effective therapy for the majority of patients with serious infections (including endocarditis) caused by SA-RVS.

To assess the rate of fecal vancomycin-resistant enterococci (VRE) colonization in Australia, we examined specimens from 1,085 healthy volunteers. VRE was cultured from 2 (0.2%) of 1,085 specimens; both were vanB Enterococcus faecium, identical by pulsed-field get electrophoresis, but with a pattern rare in Melbourne hospitals.

Accurate assessment of the risk factors for colonization with vancomycin-resistant enterococci (VRE) among high-risk patients is often confounded by nosocomial VRE transmission. We undertook a 15-month prospective cohort study of adults admitted to high-risk units (hematology, renal, transplant, and intensive care) in three teaching hospitals that used identical strict infection control and isolation procedures for VRE to minimize nosocomial spread. Rectal swab specimens for culture were regularly obtained, and the results were compared with patient demographic factors and antibiotic exposure data. Compliance with screening was defined as "optimal" (100% compliance) or "acceptable" (minor protocol violations were allowed, but a negative rectal swab specimen culture was required within 1 week of becoming colonized with VRE). Colonization with VRE was detected in 1.56% (66 of 4,215) of admissions (0.45% at admission and 0.83% after admission; the acquisition time was uncertain for 0.28%), representing 1.91% of patients. No patients developed infection with VRE. The subsequent rate of new acquisition of VRE was 1.4/1,000 patient days. Renal units had the highest rate (3.23/1,000 patient days; 95% confidence interval [CI], 1.54 to 6.77/1,000 patient days). vanB Enterococcus faecium was the most common species (71%), but other species included vanB Enterococcusfaecalis (21%), vana E. faecium (6%), and vana E. faecalis (2%). The majority of isolates were nonclonal by pulsed-field gel electrophoresis analysis. Multivariate analysis of risk factors in patients with an acceptable screening suggested that being managed by a renal unit (hazard ratio [HR] compared to the results for patients managed in an intensive care unit, 4.6; 95% CI, 1.2 to 17.0 [P = 0.02]) and recent administration of either ticarcillin-clavulanic acid (HR, 3.6; 95% CI, 1.1 to 11.6 [P = 0.03]) or carbapenems (HR, 2.8; 95% CI, 1.0, 8.0 [P = 0.05]), but not vancomycin or broad-spectrum cephalosporins, were

Spontaneous reporting of adverse drug reactions continues to be the principal method used for monitoring the safety of marketed drugs. Despite the many successes attributed to these schemes, they can reliably detect only a small fraction of the range of possible drug-related events and provide virtually no useful quantitative data. Some of the limitations of spontaneous reporting were demonstrated recently in relation to flucloxacillin. Reports in Australia suggested the likelihood of an unacceptable risk of flucloxacillin-associated jaundice, but the data from spontaneous reporting in countries with apparently similar use of the drug, such as New Zealand and the UK, were insufficient to confirm or refute this proposition. Spontaneous monitoring should be supplemented by the systematic monitoring of cohorts of users of new drugs, using record-linkage to track their subsequent health. Although several impediments exist to the introduction of such a scheme in Australia, consideration should be given to addressing how such a system might be implemented.