Detection of vancomycin-resistant Enterococcus faecium hospital-adapted lineages in municipal wastewater treatment plants indicates widespread distribution and release into the environment.

Vancomycin-resistant Enterococcus faecium (VREfm) is a leading cause of healthcare-associated infection. Reservoirs of VREfm are largely assumed to be nosocomial although there is a paucity of data on alternative sources. Here, we describe an integrated epidemiological and genomic analysis of E. faecium associated with bloodstream infection and isolated from wastewater. Treated and untreated wastewater from 20 municipal treatment plants in the East of England, United Kingdom was obtained and cultured to isolate E. faecium, ampicillin-resistant E. faecium (AREfm), and VREfm. VREfm was isolated from all 20 treatment plants and was released into the environment by 17/20 plants, the exceptions using terminal ultraviolet light disinfection. Median log10 counts of AREfm and VREfm in untreated wastewater from 10 plants in direct receipt of hospital sewage were significantly higher than 10 plants that were not. We sequenced and compared the genomes of 423 isolates from wastewater with 187 isolates associated with bloodstream infection at five hospitals in the East of England. Among 481 E. faecium isolates belonging to the hospital-adapted clade, we observed genetic intermixing between wastewater and bloodstream infection, with highly related isolates shared between a major teaching hospital in the East of England and 9/20 plants. We detected 28 antibiotic resistance genes in the hospital-adapted clade, of which 23 were represented in bloodstream, hospital sewage, and municipal wastewater isolates. We conclude that our findings are consistent with widespread distribution of hospital-adapted VREfm beyond acute healthcare settings with extensive release of VREfm into the environment in the East of England.

Exploring temporal trends and risk factors for resistance in Escherichia coli-causing bacteraemia in England between 2013 and 2018: an ecological study.

BACKGROUND: Escherichia coli are Gram-negative bacteria associated with an increasing burden of antimicrobial resistance (AMR) in England. OBJECTIVES: To create a comprehensive epidemiological picture of E. coli bacteraemia resistance trends and risk factors in England by linking national microbiology data sources and performing a longitudinal analysis of rates. METHODS: A retrospective observational study was conducted on all national records for antimicrobial susceptibility testing on E. coli bacteraemia in England from 1 January 2013 to 31 December 2018 from the UK Health Security Agency (UKHSA) and the BSAC Resistance Surveillance Programme (BSAC-RSP). Trends in AMR and MDR were estimated using iterative sequential regression. Logistic regression analyses were performed on UKHSA data to estimate the relationship between risk factors and AMR or MDR in E. coli bacteraemia isolates. RESULTS: An increase in resistance rates was observed in community- and hospital-onset bacteraemia for third-generation cephalosporins, co-amoxiclav, gentamicin and ciprofloxacin. Among community-acquired cases, and after adjustment for other factors, patients aged >65 years were more likely to be infected by E. coli isolates resistant to at least one of 11 antibiotics than those aged 18-64 years (OR: 1.21, 95% CI: 1.18-1.25; P < 0.05). In hospital-onset cases, E. coli isolates from those aged 1-17 years were more likely to be resistant than those aged 18-64 years (OR: 1.33, 95% CI: 1.02-1.73; P < 0.05). CONCLUSIONS: Antibiotic resistance rates in E. coli-causing bacteraemia increased between 2013 and 2018 in England for key antimicrobial agents. Findings of this study have implications for guiding future policies on a prescribing of antimicrobial agents, for specific patient populations in particular.

Are resistance rates among bloodstream isolates a good proxy for other infections? Analysis from the BSAC Resistance Surveillance Programme.

BACKGROUND: Bacteraemia data are often used as a general measure of resistance prevalence but may poorly represent other infection types. We compared resistance prevalence between bloodstream infection (BSI) and lower respiratory tract infection (LRTI) isolates collected by the BSAC Resistance Surveillance Programme. METHODS: BSI isolates (n = 8912) were collected during 2014-18 inclusive and LRTI isolates (n = 6280) between October 2013 to September 2018 from participating laboratories in the UK and Ireland, to a fixed annual quota per species group. LRTI isolates, but not BSI, were selected by onset: community for Streptococcus pneumoniae; hospital for Staphylococcus aureus, Pseudomonas aeruginosa and Enterobacterales. MICs were determined centrally by agar dilution; statistical modelling adjusted for ICU location and possible clustering by collection centre. RESULTS: Resistance was more prevalent among the LRTI isolates, even after adjusting for a larger proportion of ICU patients. LRTI P. aeruginosa and S. pneumoniae were more often resistant than BSI isolates for most antibiotics, and the proportion of MRSA was higher in LRTI. For S. pneumoniae, the observation reflected different serotype distributions in LRTI and BSI. Relationships between LRTI and resistance were less marked for Enterobacterales, but LRTI E. coli were more often resistant to ß-lactams, particularly penicillin/ß-lactamase inhibitor combinations, and LRTI K. pneumoniae to piperacillin/tazobactam. For E. cloacae there was a weak association between LRTI, production of AmpC enzymes and cephalosporin resistance. CONCLUSIONS: Estimates of resistance prevalence based upon bloodstream isolates underestimate the extent of the problem in respiratory isolates, particularly for P. aeruginosa, S. pneumoniae, S. aureus and, less so, for Enterobacterales.

Activity of ceftaroline versus ceftobiprole against staphylococci and pneumococci in the UK and Ireland: analysis of BSAC surveillance data.

BACKGROUND: Ceftaroline and ceftobiprole inhibit most MRSA and MDR pneumococci. Few direct comparisons of their activity have been published, but in several years (2008, 2013, 2017 and 2018) both were tested in parallel in the BSAC Resistance Surveillance Programme, giving paired results. These are reviewed. METHODS: Isolates included were bloodstream Staphylococcus aureus [n = 1884 (MRSA, n = 234)], bloodstream CoNS (n = 813; 574 methicillin resistant), and bloodstream (n = 852) and respiratory (n = 670) Streptococcus pneumoniae. MICs were determined by BSAC agar dilution and reviewed against EUCAST breakpoints; S. aureus breakpoints were assumed for CoNS. RESULTS: Ceftaroline MICs were mostly 2-fold lower than those of ceftobiprole, but, for all groups, MICs of both agents were strongly inter-related. Methicillin-susceptible staphylococci were universally susceptible to both agents; all MRSA were susceptible to ceftobiprole, whereas 10/234 had intermediate/high-dose susceptibility to ceftaroline. Among methicillin-resistant CoNS, 88% were susceptible to both agents, but reduced ceftaroline susceptibility and ceftobiprole resistance were frequent (65%) among methicillin-resistant Staphylococcus haemolyticus. One S. pneumoniae was resistant to both ceftaroline (MIC 0.5 mg/L) and ceftobiprole (MIC 1 mg/L) and seven others were only resistant to ceftobiprole (MIC 1 mg/L); seven of these eight pneumococci belonged to serotype 19A or 19F. No time trend in susceptibility was seen for either cephalosporin. CONCLUSIONS: Ceftaroline and ceftobiprole have similarly good activity against staphylococci and pneumococci. Therapeutic choices between these agents should be predicated on other differentiating factors, including licensed indications, clinical experience and need for Gram-negative coverage.

Inherent colistin resistance in genogroups of the Enterobacter cloacae complex: epidemiological, genetic and biochemical analysis from the BSAC Resistance Surveillance Programme.

BACKGROUND: Polymyxins have re-entered use against problem Gram-negative bacteria. Resistance rates are uncertain, with estimates confounded by selective testing. METHODS: The BSAC Resistance Surveillance Programme has routinely tested colistin since 2010; we reviewed data up to 2017 for relevant Enterobacterales (n = 10 914). Unexpectedly frequent resistance was seen among the Enterobacter cloacae complex isolates (n = 1749); for these, we investigated relationships to species, genome, carbon source utilization and LPS structure. RESULTS: Annual colistin resistance rates among E. cloacae complex isolates were 4.4%-20%, with a rising trend among bloodstream organisms; in contrast, annual rates for Escherichia coli and Klebsiella spp. (including K. aerogenes) generally remained <2%. WGS split the E. cloacae complex isolates into seven genogroup clusters, designated A-G. Among isolates assigned to genogroups A-D, 47/50 sequenced were colistin resistant, and many of those belonging to genogroups A-C identified as E. asburiae. Isolates belonging to genogroups E-G consistently identified as E. cloacae and were rarely (only 3/45 representatives sequenced) colistin resistant. Genogroups F and G, the predominant colistin-susceptible clusters, were metabolically distinct from other clusters, notably regarding utilization or not of l-fucose, formic acid, d-serine, adonitol, myo-inositol, l-lyxose and polysorbates. LPS from resistant organisms grown without colistin pressure lacked substitutions with 4-amino-arabinose or ethanolamine but was more structurally complex, with more molecular species present. CONCLUSIONS: Colistin resistance is frequent in the E. cloacae complex and increasing among bloodstream isolates. It is associated with: (i) particular genomic and metabolic clusters; (ii) identification as E. asburiae; and (iii) with more complex LPS architectures.

Potentiation of imipenem by relebactam for Pseudomonas aeruginosa from bacteraemia and respiratory infections.

BACKGROUND: Imipenem resistance in Pseudomonas aeruginosa most often entails loss of the 'carbapenem-specific' porin OprD; more rarely it reflects acquired carbapenemases. Loss of OprD only confers resistance to imipenem if AmpC ß-lactamase is expressed, and we investigated whether this mechanism was overcome by relebactam, a developmental diazabicyclooctane ß-lactamase inhibitor. METHODS: Consecutive P. aeruginosa isolates causing bacteraemia or hospital-onset lower respiratory tract infections were collected between 2014 and 2016 under the aegis of the BSAC Resistance Surveillance Programme. Imipenem MICs were determined centrally by BSAC agar dilution, with relebactam at a fixed concentration (4 mg/L). RESULTS: For most imipenem-susceptible P. aeruginosa (726/759, 95.7%), the MICs of imipenem alone were 0.5-2 mg/L and were decreased 3- to 4-fold by addition of relebactam, as based on geometric means or modes. For most imipenem-resistant P. aeruginosa (82/92, 89%), imipenem MICs were 8-16 mg/L, and were reduced to 1-2 mg/L by relebactam. These patterns applied regardless of whether the isolates were susceptible to penicillins and cephalosporins or had phenotypes suggesting derepressed AmpC or up-regulated efflux. Imipenem MICs for five P. aeruginosa with MBLs remained high (≥16 mg/L) regardless of relebactam. CONCLUSIONS: Potentiation of imipenem by relebactam was almost universal, in accordance with the view that endogenous pseudomonal AmpC ordinarily protects against this carbapenem to a small degree. Imipenem MICs were reduced to the current breakpoint, or lower, except for MBL producers. Potentiation was not compromised by derepression of AmpC or up-regulation of efflux.

Outpatient parenteral antimicrobial therapy: updated recommendations from the UK.

Outpatient parenteral antimicrobial therapy (OPAT) offers safe, effective and patient-centred care for adults and children. The OPAT UK good practice recommendations for adults and children have recently been updated through a process of literature review, expert consensus and extensive stakeholder consultation. Here we discuss the key changes in the updated recommendations in the context of recent developments, including novel antimicrobial agents and delivery devices, the place of oral antimicrobials as an alternative to intravenous therapy, new OPAT service models and the broader antimicrobial stewardship agenda.

A survey of practice and opinions on the use of topical antibiotics to prevent surgical site infection: more confusion than consensus.

Background: Surgical site infection (SSI) is one of the most common causes of healthcare-associated infection. Although the use of topical antibiotics to prevent SSI is not recommended by current guidelines, published studies document conflicting results and conclusions. Objectives: The objectives of this survey were to: (i) determine the extent of the use of topical antibiotics to prevent SSI in clinical practice; and (ii) gather the opinions of healthcare professionals most likely to be involved in their use. Methods: A questionnaire was circulated to members of BSAC and the European Wound Management Association (EWMA). Results: The questionnaire received 160 responses from a variety of healthcare professionals around the world. Most respondents (70%) did not have guidelines for the use of topical antibiotics for the prevention of SSI in their institution; if present, local guidance was based on national guidelines (20/31, 65%). Most respondents did not use or recommend topical antibiotics to prevent SSI; of those that did, gentamicin collagen sponges were most commonly used (24/96 responses, 25%). Over half of the surgeons (18/33, 55%) who responded to the survey did not use topical antibiotics for the prevention of SSI but, when used, contaminated surgery (8/33, 24%) was the most commonly stated indication. Conclusions: There are diverse opinions and practices among healthcare professionals about the use of topical antibiotics for the prevention of SSI. This considerable, and possibly inappropriate, variation in clinical practice needs to be addressed as part of antibiotic stewardship.

Impact of long-term care facility residence on the antibiotic resistance of urinary tract Escherichia coli and Klebsiella.

Background: Long-term care facilities (LTCFs) are thought to be important reservoirs of antimicrobial-resistant (AMR) bacteria; however, there is no routine surveillance of resistance in LTCF residents, or large population-based studies comparing AMR in LTCFs with the community, so the relative burden of AMR in LTCFs remains unknown. Objectives: To compare the frequency of antibiotic resistance of urinary tract bacteria from residents of LTCFs for the elderly and adults aged 70 years or older living in the community. Methods: Positive urine specimens reported to any diagnostic microbiology laboratory in the West Midlands region (England) from 1 April 2010 to 31 March 2014 collected from individuals aged 70 years or older were analysed. The resistance of Escherichia coli and Klebsiella to trimethoprim, nitrofurantoin, third-generation cephalosporins and ciprofloxacin and the rate of laboratory-confirmed E. coli and Klebsiella urinary tract infection (UTI) were assessed in LTCF residents and in the community. Results: LTCF residents had a laboratory-confirmed E. coli and Klebsiella UTI rate of 21 per 100 person years compared with 8 per 100 person years in the elderly living in the community [rate ratio (RR)=2.66, 95% CI = 2.58-2.73] and a higher rate of developing E. coli and Klebsiella UTIs caused by bacteria resistant to trimethoprim (RR = 4.41, 95% CI = 4.25-4.57), nitrofurantoin (RR = 4.38, 95% CI = 3.98-4.83), ciprofloxacin (RR = 5.18, 95% CI = 4.82-5.57) and third-generation cephalosporins (RR = 4.49, 95% CI = 4.08-4.94). Conclusions: Residents of LTCFs for the elderly had more than double the rate of E. coli and Klebsiella UTI and more than four times the rate of E. coli and Klebsiella UTI caused by antibiotic-resistant bacteria compared with those living in the community.

Carbapenemase-producing Enterobacteriaceae in the UK: a national study (EuSCAPE-UK) on prevalence, incidence, laboratory detection methods and infection control measures.

OBJECTIVES: To estimate UK prevalence and incidence of clinically significant carbapenemase-producing Enterobacteriaceae (CPE), and to determine epidemiological characteristics, laboratory methods and infection prevention and control (IPC) measures in acute care facilities. METHODS: A 6 month survey was undertaken in November 2013-April 2014 in 21 sentinel UK laboratories as part of the European Survey on Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) project. Up to 10 consecutive, non-duplicate, clinically significant and carbapenem-non-susceptible isolates of Escherichia coli or Klebsiella pneumoniae were submitted to a reference laboratory. Participants answered a questionnaire on relevant laboratory methods and IPC measures. RESULTS: Of 102 isolates submitted, 89 (87%) were non-susceptible to ≥1 carbapenem, and 32 (36%) were confirmed as CPE. CPE were resistant to most antibiotics, except colistin (94% susceptible), gentamicin (63%), tigecycline (56%) and amikacin (53%). The prevalence of CPE was 0.02% (95% CI = 0.01%-0.03%). The incidence of CPE was 0.007 per 1000 patient-days (95% CI = 0.005-0.010), with north-west England the most affected region at 0.033 per 1000 patient-days (95% CI = 0.012-0.072). Recommended IPC measures were not universally followed, notably screening high-risk patients on admission (applied by 86%), using a CPE 'flag' on patients' records (70%) and alerting neighbouring hospitals when transferring affected patients (only 30%). Most sites (86%) had a laboratory protocol for CPE screening, most frequently using chromogenic agar (52%) or MacConkey/CLED agars with carbapenem discs (38%). CONCLUSIONS: The UK prevalence and incidence of clinically significant CPE is currently low, but these MDR bacteria affect most UK regions. Improved IPC measures, vigilance and monitoring are required.

Living conditions are associated with increased antibiotic resistance in community isolates of Escherichia coli.

OBJECTIVES: The objective of this study was to measure the associations between domains of deprivation and antibiotic resistance of Escherichia coli. METHODS: Routine surveillance data for antibiotic susceptibility of E. coli isolates were obtained from urine specimens taken from patients presenting with suspected urinary tract infection in 2010-12 to healthcare practitioners based in the community in Leeds and Bradford. Eight antibiotics were included in the analyses. Postcodes were linked to lower super output areas (average populations of 1500). The 2010 Indices of Deprivation were used as neighbourhood characteristics for each lower super output area. Multilevel logistic regression models were used to estimate the independent effect of structural components on the odds of resistance to each antibiotic. RESULTS: With respect to living conditions, residence in the most-deprived areas compared with the least-deprived areas was associated with increased odds of antibiotic resistance for all eight antibiotics analysed. The magnitude of these associations included an OR of 2.04 (95% CI 1.03-3.07) for cefalexin, 2.16 (95% CI 1.16-4.05) for ciprofloxacin, 2.47 (95% CI 1.08-5.66) for nitrofurantoin and 1.33 (95% CI 1.07-1.75) for trimethoprim. CONCLUSIONS: Social deprivation in the form of living conditions is associated with increased antibiotic resistance for E. coli. This evidence suggests there is a need for further individual-level studies to explore the potential mechanism for these associations.

Antibiotic resistance determination using Enterococcus faecium whole-genome sequences: a diagnostic accuracy study using genotypic and phenotypic data.

BACKGROUND: DNA sequencing could become an alternative to in vitro antibiotic susceptibility testing (AST) methods for determining antibiotic resistance by detecting genetic determinants associated with decreased antibiotic susceptibility. Here, we aimed to assess and improve the accuracy of antibiotic resistance determination from Enterococcus faecium genomes for diagnosis and surveillance purposes. METHODS: In this retrospective diagnostic accuracy study, we first conducted a literature search in PubMed on Jan 14, 2021, to compile a catalogue of genes and mutations predictive of antibiotic resistance in E faecium. We then evaluated the diagnostic accuracy of this database to determine susceptibility to 12 different, clinically relevant antibiotics using a diverse population of 4382 E faecium isolates with available whole-genome sequences and in vitro culture-based AST phenotypes. Isolates were obtained from various sources in 11 countries worldwide between 2000 and 2018. We included isolates tested with broth microdilution, Vitek 2, and disc diffusion, and antibiotics with at least 50 susceptible and 50 resistant isolates. Phenotypic resistance was derived from raw minimum inhibitory concentrations and measured inhibition diameters, and harmonised primarily using the breakpoints set by the European Committee on Antimicrobial Susceptibility Testing. A bioinformatics pipeline was developed to process raw sequencing reads, identify antibiotic resistance genetic determinants, and report genotypic resistance. We used our curated database, as well as ResFinder, AMRFinderPlus, and LRE-Finder, to assess the accuracy of genotypic predictions against phenotypic resistance. FINDINGS: We curated a catalogue of 228 genetic markers involved in resistance to 12 antibiotics in E faecium. Very accurate genotypic predictions were obtained for ampicillin (sensitivity 99·7% [95% CI 99·5-99·9] and specificity 97·9% [95·8-99·0]), ciprofloxacin (98·0% [96·4-98·9] and 98·8% [95·9-99·7]), vancomycin (98·8% [98·3-99·2] and 98·8% [98·0-99·3]), and linezolid resistance (after re-testing false negatives: 100·0% [90·8-100·0] and 98·3% [97·8-98·7]). High sensitivity was obtained for tetracycline (99·5% [99·1-99·7]), teicoplanin (98·9% [98·4-99·3]), and high-level resistance to aminoglycosides (97·7% [96·6-98·4] for streptomycin and 96·8% [95·8-97·5] for gentamicin), although at lower specificity (60-90%). Sensitivity was expectedly low for daptomycin (73·6% [65·1-80·6]) and tigecycline (38·3% [27·1-51·0]), for which the genetic basis of resistance is not fully characterised. Compared with other antibiotic resistance databases and bioinformatic tools, our curated database was similarly accurate at detecting resistance to ciprofloxacin and linezolid and high-level resistance to streptomycin and gentamicin, but had better sensitivity for detecting resistance to ampicillin, tigecycline, daptomycin, and quinupristin-dalfopristin, and better specificity for ampicillin, vancomycin, teicoplanin, and tetracycline resistance. In a validation dataset of 382 isolates, similar or improved diagnostic accuracies were also achieved. INTERPRETATION: To our knowledge, this work represents the largest published evaluation to date of the accuracy of antibiotic susceptibility predictions from E faecium genomes. The results and resources will facilitate the adoption of whole-genome sequencing as a tool for the diagnosis and surveillance of antimicrobial resistance in E faecium. A complete characterisation of the genetic basis of resistance to last-line antibiotics, and the mechanisms mediating antibiotic resistance silencing, are needed to close the remaining sensitivity and specificity gaps in genotypic predictions. FUNDING: Wellcome Trust, UK Department of Health, British Society for Antimicrobial Chemotherapy, Academy of Medical Sciences and the Health Foundation, Medical Research Council Newton Fund, Vietnamese Ministry of Science and Technology, and European Society of Clinical Microbiology and Infectious Disease.

Expert consensus recommendations for the provision of infective endocarditis services: updated guidance from the Joint British Societies.

Infective endocarditis (IE) remains a difficult condition to diagnose and treat and is an infection of high consequence for patients, causing long hospital stays, life-changing complications and high mortality. A new multidisciplinary, multiprofessional, British Society for Antimicrobial Chemotherapy (BSAC)-ledWorking Party was convened to undertake a focused systematical review of the literature and to update the previous BSAC guidelines relating delivery of services for patients with IE. A scoping exercise identified new questions concerning optimal delivery of care, and the systematic review identified 16 231 papers of which 20 met the inclusion criteria. Recommendations relating to endocarditis teams, infrastructure and support, endocarditis referral processes, patient follow-up and patient information, and governance are made as well as research recommendations. This is a report of a joint Working Party of the BSAC, British Cardiovascular Society, British Heart Valve Society, British Society of Echocardiography, Society of Cardiothoracic Surgeons of Great Britain and Ireland, British Congenital Cardiac Association and British Infection Association.

Evolutionary and functional history of the Escherichia coli K1 capsule.

Escherichia coli is a leading cause of invasive bacterial infections in humans. Capsule polysaccharide has an important role in bacterial pathogenesis, and the K1 capsule has been firmly established as one of the most potent capsule types in E. coli through its association with severe infections. However, little is known about its distribution, evolution and functions across the E. coli phylogeny, which is fundamental to elucidating its role in the expansion of successful lineages. Using systematic surveys of invasive E. coli isolates, we show that the K1-cps locus is present in a quarter of bloodstream infection isolates and has emerged in at least four different extraintestinal pathogenic E. coli (ExPEC) phylogroups independently in the last 500 years. Phenotypic assessment demonstrates that K1 capsule synthesis enhances E. coli survival in human serum independent of genetic background, and that therapeutic targeting of the K1 capsule re-sensitizes E. coli from distinct genetic backgrounds to human serum. Our study highlights that assessing the evolutionary and functional properties of bacterial virulence factors at population levels is important to better monitor and predict the emergence of virulent clones, and to also inform therapies and preventive medicine to effectively control bacterial infections whilst significantly lowering antibiotic usage.

Reduced susceptibility to chlorhexidine in staphylococci: is it increasing and does it matter?

Antiseptic agents are increasingly used for hand hygiene and skin decolonization as key tools for the prevention of healthcare-associated infections. Chlorhexidine, a divalent, cationic biguanide, has a broad spectrum of activity and is one of the most frequently used topical antiseptic agents. Notably, there are an increasing number of prevalence studies that report reduced levels of susceptibility to chlorhexidine. In contrast to bacterial resistance to antibiotics, using parameters such as the MIC to define resistance to antiseptics, including chlorhexidine, is not straightforward. A range of methods have been used for the detection of reduced susceptibility to chlorhexidine, but, importantly, there is no standardized method and no consensus on the definition of chlorhexidine 'resistance'. In this review we have assessed the methods available for the detection of reduced susceptibility to chlorhexidine and the prevalence of coresistance to other antimicrobial agents. We have focused on the development of reduced susceptibility to chlorhexidine and the presence of efflux-mediated resistance genes in staphylococci, and have reviewed the clinical significance of this phenomenon. Lastly, we have identified unanswered questions to further our understanding of this emergent threat. We anticipate that clinical use of chlorhexidine will continue to increase, and it will be important to be alert to the possibility that this may lead to the emergence of new clones with reduced susceptibility. Indiscriminate chlorhexidine use in the absence of efficacy data should be discouraged.

Treatment of methicillin-resistant Staphylococcus aureus (MRSA): updated guidelines from the UK.

These evidence-based guidelines are an updated version of those issued in 2008. They have been produced following a review of the published literature (2007-18) pertaining to the treatment of infections caused by MRSA. The guidelines update, where appropriate, previous recommendations, taking into account changes in the UK epidemiology of MRSA, ongoing national surveillance data and the efficacy of novel anti-staphylococcal agents licensed for use in the UK. Emerging therapies that have not been licensed for use in the UK at the time of the review have also been assessed.

Paediatric Common Infections Pathways: improving antimicrobial stewardship and promoting ambulation for children presenting with common infections to hospitals in the UK and Ireland.

Paediatric common infection pathways have been developed in collaboration between the BSAC and national paediatric groups, addressing the management of cellulitis, lymphadenitis/lymph node abscess, pneumonia/pleural empyema, pyelonephritis, tonsillitis/peritonsillar abscess, otitis media/mastoiditis, pre-septal/post-septal (orbital) cellulitis, and meningitis. Guidance for the management of a child presenting with a petechial/purpuric rash and the infant under 3 months of age with fever is also provided. The aim of these pathways is to support the delivery of high-quality infection management in children presenting to a hospital. The pathways focus on diagnostic approaches, including the recognition of red flags suggesting complex or severe infection requiring urgent intervention, approaches to antimicrobial stewardship (AMS) principles and guidance on safe and timely ambulation aligned with good practice of outpatient parenteral antimicrobial therapy (OPAT).