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Objective: Group B Streptococcus (GBS)-associated maternal, perinatal, and neonatal mortality and morbidity disproportionately affects Sub-Saharan Africa (SSA). This systematic review and meta-analysis aimed to address the estimated prevalence, antimicrobial susceptibility, and serotype distribution of GBS isolates in SSA., Methods: This study was done according to PRISMA guidelines. MEDLINE/PubMed, CINAHL (EBSCO), Embase, SCOPUS, Web of Sciences databases, and Google Scholar were used to retrieve both published and unpublished articles. STATA software version 17 was used for data analysis. Forest plots using the random-effect model were used to present the findings. Heterogeneity was assessed using Cochrane chi-square (I 2 ) statistics, while the Egger intercept was used to assess publication bias., Results: Fifty-eight studies that fulfilled the eligibility criteria were included for meta-analysis. The pooled prevalence of maternal rectovaginal colonization and vertical transmission of GBS were 16.06, 95% CI [13.94, 18.30] and 43.31%, 95% CI [30.75, 56.32], respectively. The highest pooled proportion of antibiotic resistance to GBS was observed in gentamicin (45.58%, 95% CI [4.12%, 91.23]), followed by erythromycin, (25.11%, 95% CI [16.70, 34.49]). The lowest antibiotic resistance was observed in vancomycin (3.84%, 95% CI [0.48, 9.22]). Our findings indicate that serotypes Ia/Ib/II/ III/and V cover almost 88.6% of serotypes in SSA., Conclusions: The estimated high prevalence and resistance to different antibiotic classes observed in GBS isolates from SSA suggests the need for implementation of effective intervention efforts., Competing Interests: Competing interests None declared., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Antimicrobial resistance is one of the major public health challenges in Ethiopia. However, there is no comprehensive summary of existing AMR data in the country., Aim: To determine the prevalence of antimicrobial resistance and its clinical implications in Ethiopia., Methods: A systematic literature search was performed on the PubMed/Medline database. Original studies on antimicrobial resistance conducted in Ethiopia between 1st January 2009 and 31st July 2019 were included. The outcome measure was the number of isolates resistant to antimicrobial agents in terms of specific pathogens, and disease condition. Data was calculated as total number of resistant isolates relative to the total number of isolates per specific pathogen and medication., Results: A total of 48,021 study participants enrolled from 131 original studies were included resulting in 15,845 isolates tested for antimicrobial resistance. The most common clinical sample sources were urine (28%), ear, nose, and throat discharge collectively (27%), and blood (21%). All the studies were cross-sectional and 83% were conducted in hospital settings. Among Gram-positive bacteria, the reported level of resistance to vancomycin ranged from 8% (Enterococcus species) to 20% (S. aureus). E. coli, K. pneumoniae and P. aeruginosa were the most common Gram-negative pathogens resistant to key antimicrobial agents described in the national standard treatment guideline and were associated with diverse clinical conditions: urinary tract infections, diarrhea, surgical site infections, pneumonia, ocular infections, and middle ear infections., Conclusion: Overall, there is a high prevalence of antimicrobial resistance in Ethiopia. Empirical treatment of bacterial infections needs to be guided by up-to-date national guidelines considering local antimicrobial susceptibility patterns. Equipping diagnostic laboratories with culture and drug susceptibility testing facilities, and establishing a strong antimicrobial stewardship program should be high priorities., (© 2021. The Author(s).)

Background: Bloodstream infection is common in the UK and has significant mortality depending on the pathogen involved, site of infection and other patient factors. Healthcare staffing and ward activity may also impact on outcomes in a range of conditions, however there is little specific National Health Service (NHS) data on the impact for patients with bloodstream infection. Bloodstream Infections - Focus on Outcomes is a multicentre cohort study with the primary aim of identifying modifiable risk factors for 28-day mortality in patients with bloodstream infection due to one of six key pathogens., Methods: Adults under the care of five NHS Trusts in England and Wales between November 2010 and May 2012 were included. Multivariable Cox regression was used to quantify the association between modifiable risk factors, including staffing levels and timing of appropriate therapy, and 28-day mortality, after adjusting for non-modifiable risk factors such as patient demographics and long-term comorbidities., Results: A total of 1676 patients were included in the analysis population. Overall, 348/1676 (20.8%) died within 28 days. Modifiable factors associated with 28-day mortality were ward speciality, ward activity (admissions and discharges), movement within ward speciality, movement from critical care, and time to receipt of appropriate antimicrobial therapy in the first 7 days. For each additional admission or discharge per 10 beds, the hazard increased by 4% (95% CI 1 to 6%) in medical wards and 11% (95% CI 4 to 19%) in critical care. Patients who had moved wards within speciality or who had moved out of a critical care ward had a reduction in hazard of mortality. In the first 7 days, hazard of death increased with increasing time to receipt of appropriate antimicrobial therapy., Conclusion: This study underlines the importance of appropriate antimicrobials within the first 7 days, and the potential for ward activity and ward movements to impact on survival in bloodstream infection.

Polyketide synthases assemble diverse natural products with numerous important applications. The thioester intermediates in polyketide assembly are covalently tethered to acyl carrier protein domains of the synthase. Several mechanisms for polyketide chain release are known, contributing to natural product structural diversification. Here, we report a dual transacylation mechanism for chain release from the enacyloxin polyketide synthase, which assembles an antibiotic with promising activity against Acinetobacter baumannii. A non-elongating ketosynthase domain transfers the polyketide chain from the final acyl carrier protein domain of the synthase to a separate carrier protein, and a non-ribosomal peptide synthetase condensation domain condenses it with (1S,3R,4S)-3,4-dihydroxycyclohexane carboxylic acid. Molecular dissection of this process reveals that non-elongating ketosynthase domain-mediated transacylation circumvents the inability of the condensation domain to recognize the acyl carrier protein domain. Several 3,4-dihydroxycyclohexane carboxylic acid analogues can be employed for chain release, suggesting a promising strategy for producing enacyloxin analogues.

Background: Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed an antibiotic, which may not always be appropriate and may cause harm. C-reactive protein (CRP) is an acute-phase biomarker that can be rapidly measured at the point of care and may predict benefit from antibiotic treatment in AECOPD. It is not clear whether the addition of a CRP point-of-care test (POCT) to clinical assessment leads to a reduction in antibiotic consumption without having a negative impact on COPD health status., Methods/design: This is a multicentre, individually randomised controlled trial (RCT) aiming to include 650 participants with a diagnosis of AECOPD in primary care. Participants will be randomised to be managed according to usual care (control) or with the addition of a CRP POCT to guide antibiotic prescribing. Antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status (total score) measured by the Clinical COPD Questionnaire (CCQ) at 2 weeks post randomisation will be co-primary outcomes. Primary analysis (by intention-to-treat) will determine differences in antibiotic consumption for superiority and COPD health status for non-inferiority. Secondary outcomes include: COPD health status, CCQ domain scores, use of other COPD treatments (weeks 1, 2 and 4), EQ-5D utility scores (weeks 1, 2 and 4 and month 6), disease-specific, health-related quality of life (HRQoL) at 6 months, all-cause antibiotic consumption (antibiotic use for any condition) during first 4 weeks post randomisation, total antibiotic consumption (number of days during first 4 weeks of antibiotic consumed for AECOPD/any reason), antibiotic prescribing at the index consultation and during following 4 weeks, adverse effects over the first 4 weeks, incidence of pneumonia (weeks 4 and 6 months), health care resource use and cost comparison over the 6 months following randomisation. Prevalence and resistance profiles of bacteria will be assessed using throat and sputum samples collected at baseline and 4-week follow-up. A health economic evaluation and qualitative process evaluation will be carried out., Discussion: If shown to be effective (i.e. leads to a reduction in antibiotic use with no worse COPD health status), the use of the CRP POCT could lead to better outcomes for patients with AECOPD and help reduce selective pressures driving the development of antimicrobial resistance. PACE will be one of the first studies to evaluate the cost-effectiveness of a POCT biomarker to guide clinical decision-making in primary care on patient-reported outcomes, antibiotic prescribing and antibiotic resistance for AECOPD., Trial Registration: ISRCTN registry, ID: ISRCTN24346473 . Registered on 20 August 2014.

Objectives: To monitor and compare trends in the non-susceptibility of bloodstream isolates of pathogens to key antibiotics in the constituent countries of the UK between 2010 and 2014., Methods: Routinely generated antibiotic susceptibility test results for bloodstream isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas spp., Streptococcus pneumoniae and Staphylococcus aureus were collected from hospital microbiology laboratories in each country., Results: With the exception of a decrease in the proportion of S. aureus that were MRSA, non-susceptibility to key antibiotics among the pathogens studied remained largely unchanged over the 5 year study period, with any increases in non-susceptibility being small. Although some intercountry variation in the proportions of non-susceptible isolates was seen, apart from MRSA, the differences were generally small (<5%) and fluctuated from year to year, with no country showing consistently higher or lower rates of resistance., Conclusions: Collaboration between the constituent countries of the UK allows an integrated approach to nationwide surveillance of antibiotic resistance., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Antibiotic treatment recommendations based on susceptibility data from routinely submitted urine samples may be biased because of variation in sampling, laboratory procedures and inclusion of repeat samples, leading to uncertainty about empirical treatment., Objective: To describe and compare susceptibilities of Escherichia coli cultured from routinely submitted samples, with E. coli causing urinary tract infection (UTI) from a cohort of systematically sampled, acutely unwell children., Methods: Susceptibilities of 1458 E. coli isolates submitted during the course of routine primary care for children <5 years (routine care samples), compared to susceptibilities of 79 E. coli isolates causing UTI from 5107 children <5 years presenting to primary care with an acute illness [systematic sampling: the Diagnosis of Urinary Tract infection in Young children (DUTY) cohort]., Results: The percentage of E. coli sensitive to antibiotics cultured from routinely submitted samples were as follows: amoxicillin 45.1% (95% confidence interval: 42.5-47.7%); co-amoxiclav using the lower systemic break point (BP) 86.6% (84.7-88.3%); cephalexin 95.1% (93.9-96.1%); trimethoprim 74.0% (71.7-76.2%) and nitrofurantoin 98.2% (97.4-98.8%). The percentage of E. coli sensitive to antibiotics cultured from systematically sampled DUTY urines considered to be positive for UTI were as follows: amoxicillin 50.6% (39.8-61.4%); co-amoxiclav using the systemic BP 83.5% (73.9-90.1%); co-amoxiclav using the urinary BP 94.9% (87.7-98.4%); cephalexin 98.7% (93.2-99.8%); trimethoprim 70.9% (60.1-80.0%); nitrofurantoin 100% (95.3-100.0%) and ciprofloxacin 96.2% (89.4-98.7%)., Conclusion: Escherichia coli susceptibilities from routine and systematically obtained samples were similar. Most UTIs in preschool children remain susceptible to nitrofurantoin, co-amoxiclav and cephalexin., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Secondary skin infection is common during eczema exacerbations and many children are treated with antibiotics when this is suspected, although there is little high-quality evidence to justify this practice., Objective: To determine the clinical effectiveness of oral and topical antibiotics, in addition to standard treatment with emollients and topical corticosteroids, in children with clinically infected eczema., Design: Multicentre randomised, double-blind, placebo-controlled trial., Setting: General practices and dermatology clinics in England, Wales and Scotland., Participants: Children (aged 3 months to < 8 years) with a diagnosis of eczema (according to U.K. Working Party definition) and clinical suspicion of infection., Interventions: (1) Oral flucloxacillin and topical placebo; (2) topical fusidic acid (Fucidin(®), Leo Laboratories Limited) and oral placebo; and (3) oral and topical placebos, all for 1 week., Main Outcome Measures: Patient-Orientated Eczema Measure (POEM) at 2 weeks (assessing subjective severity in the week following treatment)., Results: We randomised 113 children (36 to oral antibiotic, 37 to topical antibiotic and 40 to placebo), which was fewer than our revised target sample size of 282. A total of 103 (92.0%) children had one or more clinical features suggestive of infection and 78 (69.6%) children had Staphylococcus aureus cultured from a skin swab. Oral and topical antibiotics resulted in a 1.52 [95% confidence interval (CI) -1.35 to 4.40] and 1.49 (95% CI -1.55 to 4.53) increase (worse subjective severity) in POEM score at 2 weeks, relative to placebo and controlling for baseline POEM score. Eczema Area and Severity Index (objective severity) scores were also higher (worse) in the intervention groups, at 0.20 (95% CI -0.12 to 0.52) and 0.42 (95% CI 0.09 to 0.75) for oral and topical antibiotics, respectively, at 2 weeks. Analyses of impact on the family, quality of life, daily symptom scores, and longer-term outcomes were all consistent with the finding of no or limited difference and a trend towards worse outcomes in the intervention groups. Sensitivity analyses, including adjusting for compliance and imputation for missing data, were consistent with the main findings., Conclusions: Our data suggest that oral and topical antibiotics have no effect, or a harmful effect, on subjective eczema severity in children with clinically infected eczema in the community. The CIs around our estimates exclude a meaningful beneficial effect (published minimal clinically important difference for POEM is 3.4). Although most patients in this trial had features suggestive of infection and S. aureus on their skin, participants primarily had mild-moderate eczema and those with signs of more severe infection were often excluded. Clinicians should consider avoiding oral and topical antibiotic use in children with suspected infected eczema in the community who do not have signs of 'severe infection'. Further research should seek to understand how best to encourage the use of topical steroids and limit use of antibiotics in those with eczema flares without signs of severe infection, as well as developing tools to better phenotype eczema flares, in order to better define a population that may benefit from antibiotic treatment., Trial Registration: European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2011-003591-37 and Current Controlled Trials ISRCTN96705420., Funding: The National Institute for Health Research Health Technology Assessment programme.

Currently available point-of-care (POC) diagnostic tests for managing urinary tract infections (UTIs) in general practice are limited by poor performance characteristics, and laboratory culture generally provides results only after a few days. This laboratory evaluation compared the analytic performance of the POC UK Flexicult(™) (Statens Serum Institut) (SSI) urinary kit for quantification, identification and antibiotic susceptibility testing and routine UK National Health Service (NHS) urine processing to an advanced urine culture method. Two hundred urine samples routinely submitted to the Public Health Wales Microbiology Laboratory were divided and: (1) analysed by routine NHS microbiological tests as per local laboratory standard operating procedures, (2) inoculated onto the UK Flexicult(™) SSI urinary kit and (3) spiral plated onto Colorex Orientation UTI medium (E&O Laboratories Ltd). The results were evaluated between the NHS and Flexicult(™ )methods, and discordant results were compared to the spiral plating method. The UK Flexicult(™) SSI urinary kit was compared to routine NHS culture for identification of a pure or predominant uropathogen at ≥ 10(5) cfu/mL, with a positive discordancy rate of 13.5% and a negative discordancy rate of 3%. The sensitivity and specificity were 86.7% [95% confidence interval (CI) 73.8-93.7] and 82.6% (95% CI 75.8-87.7), respectively. The UK Flexicult(™) SSI urinary kit was comparable to routine NHS urine processing in identifying microbiologically positive UTIs in this laboratory evaluation. However, the number of false-positive samples could lead to over-prescribing of antibiotics in clinical practice. The Flexicult(™) SSI kit could be useful as a POC test for UTIs in primary care but further pragmatic evaluations are necessary.

Background: the risk factors for and frequency of antibiotic prescription and antibiotic-associated diarrhoea (AAD) among care home residents are unknown., Aim: to prospectively study frequency and risks for antibiotic prescribing and AAD for care home residents., Design and Setting: a 12-month prospective cohort study in care homes across South Wales., Method: antibiotic prescriptions and the development of AAD were recorded on case report forms. We defined AAD as three or more loose stools in a 24-h period occurring within 8 weeks of exposure to an antibiotic., Results: we recruited 279 residents from 10 care homes. The incidence of antibiotic prescriptions was 2.16 prescriptions per resident year (95% CI: 1.90-2.46). Antibiotics were less likely to be prescribed to residents from dual-registered homes (OR compared with nursing homes: 0.38, 95% CI: 0.18-0.79). For those who were prescribed antibiotics, the incidence of AAD was 0.57 episodes per resident year (95% CI: 0.41-0.81 episodes). AAD was more likely in residents who were prescribed co-amoxiclav (hazards ratio, HR = 2.08, 95% confidence interval, CI: 1.18-3.66) or routinely used incontinence pads (HR = 2.54, 95% CI: 1.26-5.13) and less likely in residents from residential homes (HR compared with nursing homes: 0.14, 95% CI: 0.06-0.32)., Conclusion: residents of care homes, particularly of nursing homes, are frequently prescribed antibiotics and often experience diarrhoea following such prescriptions. Co-amoxiclav is associated with greater risk of AAD., (© The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Urinary tract infections (UTI) are the most frequent bacterial infection affecting women and account for about 15% of antibiotics prescribed in primary care. However, some women with a UTI are not prescribed antibiotics or are prescribed the wrong antibiotics, while many women who do not have a microbiologically confirmed UTI are prescribed antibiotics. Inappropriate antibiotic prescribing unnecessarily increases the risk of side effects and the development of antibiotic resistance, and wastes resources., Methods/design: 614 adult female patients will be recruited from four primary care research networks (Wales, England, Spain, the Netherlands) and individually randomised to either POCT guided care or the guideline-informed 'standard care' arm. Urine and stool samples (where possible) will be obtained at presentation (day 1) and two weeks later for microbiological analysis. All participants will be followed up on the course of their illness and their quality of life, using a 2 week self-completed symptom diary. At 3 months, a primary care notes review will be conducted for evidence of further evidence of treatment failures, recurrence, complications, hospitalisations and health service costs., Discussion: Although the Flexicult™ POCT is used in some countries in routine primary care, it's clinical and cost effectiveness has never been evaluated in a randomised clinical trial. If shown to be effective, the use of this POCT could benefit individual sufferers and provide evidence for health care authorities to develop evidence based policies to combat the spread and impact of the unprecedented rise of infections caused by antibiotic resistant bacteria in Europe., Trial Registration Number: ISRCTN65200697 (Registered 10 September 2013).

Background: Antibiotic prescribing rates in care homes are higher than in the general population. Antibiotics disrupt the normal gut flora, sometimes causing antibiotic-associated diarrhoea (AAD). Clostridium difficile (Hall and O'Toole 1935) Prévot 1938 is the most commonly identified cause of AAD. Little is known either about the frequency or type of antibiotics prescribed in care homes or about the incidence and aetiology of AAD in this setting., Objectives: The Probiotics for Antibiotic-Associated Diarrhoea (PAAD) study was designed as a two-stage study. PAAD stage 1 aimed to (1) prospectively describe antibiotic prescribing in care homes; (2) determine the incidence of C. difficile carriage and AAD (including C. difficile-associated diarrhoea); and (3) to consider implementation challenges and establish the basis for a sample size estimation for a randomised controlled trial (RCT) of probiotic administration with antibiotics to prevent AAD in care homes. If justified by PAAD stage 1, the RCT would be implemented in PAAD stage 2. However, as a result of new evidence regarding the clinical effectiveness of probiotics on the incidence of AAD, a decision was taken not to proceed with PAAD stage 2., Design: PAAD stage 1 was a prospective observational cohort study in care homes in South Wales with up to 12 months' follow-up for each resident., Setting: Recruited care homes had management and owner's agreement to participate and three or more staff willing to take responsibility for implementing the study., Participants: Eleven care homes were recruited, but one withdrew before any residents were recruited. A total of 279 care home residents were recruited to the observational study and 19 withdrew, 16 (84%) because of moving to a non-participating care home., Main Outcome Measures: The primary outcomes were the rate of antibiotic prescribing, incidence of AAD, defined as three or more loose stools (type 5-7 on the Bristol Stool Chart) in a 24-hour period, and C. difficile carriage confirmed on stool culture., Results: Stool samples were obtained at study entry from 81% of participating residents. Over half of the samples contained antibiotic-resistant isolates, with Enterobacteriaceae resistant to ciprofloxacin in 47%. Residents were prescribed an average of 2.16 antibiotic prescriptions per year [95% confidence interval (CI) 1.90 to 2.46]. Antibiotics were less likely to be prescribed to residents from dual-registered homes. The incidence of AAD was 0.57 (95% CI 0.41 to 0.81) episodes per year among those residents who were prescribed antibiotics. AAD was more likely in residents who were prescribed co-amoxiclav than other antibiotics and in those residents who routinely used incontinence pads. AAD was less common in residents from residential homes., Conclusions: Care home residents, particularly in nursing homes, are frequently prescribed antibiotics and often experience AAD. Antibiotic resistance, including ciprofloxacin resistance, is common in Enterobacteriaceae isolated from the stool of care home residents. Co-amoxiclav is associated with greater risk of AAD than other commonly prescribed antibiotics., Trial Registration: Current Controlled Trials ISRCTN 7954844., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 63. See the NIHR Journals Library website for further project information.

Purpose: Cycloserine has been used previously in some areas of the world for the treatment of urinary tract infections. The emergence of multi-resistant strains of Enterobacteriaceae and the lack of new agents in the development pipeline has prompted a need to review the activity of older agents. Susceptibility testing of cycloserine has traditionally been problematic owing to testing in standard media, containing competitive alanine, thus presenting falsely elevated minimum inhibitory concentrations (MICs). This study tests urinary coliforms against cycloserine in both standard and minimal media., Methods: Susceptibilities were performed on 500 "wild type" UTI coliforms using Mueller-Hinton broth in the range 0.008-128 μg/ml in accordance with ISO guidelines. Cycloserine was also tested in Minimal Salts medium + 2 % 1 M glucose + 0.2 % 1 M magnesium sulphate. MICs were recorded after 18 h of incubation at 35 °C and interpreted with EUCAST breakpoints (where available)., Results: Cycloserine MIC50 for the "wild type" coliforms was 32 μg/ml in Mueller-Hinton broth compared with 2 μg/ml in Minimal Salts. Eighty-seven per cent of "wild type" UTI coliforms show cycloserine MICs < = 8 μg/ml in Minimal Salts. The epidemiological cut-off values for cycloserine for E. coli in this study were 64 μg/ml using Mueller-Hinton broth and 8 μg/ml using Minimal Salts medium. Ninety-four per cent of trimethoprim-resistant and 82 % of third generation cephalosporin-resistant E. coli had MICs in Minimal Salts ≤ 8 μg/ml., Conclusion: Cycloserine is still licensed in some countries for the treatment of urinary infections and the data presented here suggest that it may play a role in the management of infections resistant to trimethoprim and third generation cephalosporins.

This article highlights key amendments incorporated into version 11 of the BSAC standardized disc susceptibility testing method, available as Supplementary data at JAC Online (http://jac.oxfordjournals.org/) and on the BSAC web site (http://bsac.org.uk/susceptibility/guidelines-standardized-disc-susceptibility-testing-method/). The basic disc susceptibility testing method remains unchanged, but there have been a number of alterations to the interpretive criteria for certain organism/drug combinations due to continuing harmonization with the EUCAST MIC breakpoints and constant efforts to improve the reliability and clinical applicability of the guidance.

Objective: To evaluate the effectiveness and costs of a multifaceted flexible educational programme aimed at reducing antibiotic dispensing at the practice level in primary care., Design: Randomised controlled trial with general practices as the unit of randomisation and analysis. Clinicians and researchers were blinded to group allocation until after randomisation., Setting: 68 general practices with about 480,000 patients in Wales, United Kingdom., Participants: 34 practices were randomised to receive the educational programme and 34 practices to be controls. 139 clinicians from the intervention practices and 124 from control practices had agreed to participate before randomisation. Practice level data covering all the clinicians in the 68 practices were analysed., Interventions: Intervention practices followed the Stemming the Tide of Antibiotic Resistance (STAR) educational programme, which included a practice based seminar reflecting on the practices' own dispensing and resistance data, online educational elements, and practising consulting skills in routine care. Control practices provided usual care., Main Outcome Measures: Total numbers of oral antibiotic items dispensed for all causes per 1000 practice patients in the year after the intervention, adjusted for the previous year's dispensing. Secondary outcomes included reconsultations, admissions to hospital for selected causes, and costs., Results: The rate of oral antibiotic dispensing (items per 1000 registered patients) decreased by 14.1 in the intervention group but increased by 12.1 in the control group, a net difference of 26.1. After adjustment for baseline dispensing rate, this amounted to a 4.2% (95% confidence interval 0.6% to 7.7%) reduction in total oral antibiotic dispensing for the year in the intervention group relative to the control group (P=0.02). Reductions were found for all classes of antibiotics other than penicillinase-resistant penicillins but were largest and significant individually for phenoxymethylpenicillins (penicillin V) (7.3%, 0.4% to 13.7%) and macrolides (7.7%, 1.1% to 13.8%). There were no significant differences between intervention and control practices in the number of admissions to hospital or in reconsultations for a respiratory tract infection within seven days of an index consultation. The mean cost of the programme was £2923 (€3491, $4572) per practice (SD £1187). There was a 5.5% reduction in the cost of dispensed antibiotics in the intervention group compared with the control group (-0.4% to 11.4%), equivalent to a reduction of about £830 a year for an average intervention practice., Conclusion: The STAR educational programme led to reductions in all cause oral antibiotic dispensing over the subsequent year with no significant change in admissions to hospital, reconsultations, or costs. Trial registration ISRCT No 63355948.

The BSAC standardized disc susceptibility testing method remains unchanged, but there are considerable changes to the interpretative criteria due to continuing harmonization with the European Committee on Antimicrobial Susceptibility Testing (EUCAST) MIC breakpoints. There are a number of agents for which interpretative criteria have been removed. These MIC and/or zone diameter breakpoints will be published on the BSAC web site as a 'Legacy' table; they may be used for research or comparative purposes, but are not recommended for clinical management. Notably, testing of staphylococci for susceptibility to glycopeptides by disc diffusion has been removed because this method has been found to be unreliable, particularly for the detection of low-level resistance; low-level vancomycin resistance in staphylococci is increasingly deemed to be of clinical relevance. The tables for anaerobes have been expanded to include MIC breakpoints that have been determined by EUCAST. There are currently no zone diameter breakpoints for these organisms and an MIC method is recommended if susceptibility testing is required.

Objectives: This study aimed to investigate the origin of high-level azithromycin resistance that emerged in isolates of Neisseria gonorrhoeae in England and Wales in 2007, and to establish methods for identifying high-level azithromycin resistance., Methods: The Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) data from 2001-07 were examined for emerging trends in azithromycin susceptibility. Further to the identification of six high-level azithromycin-resistant isolates in GRASP 2007, an additional 102 isolates were selected on the basis of azithromycin susceptibility and geographic origin from the GRASP 2006 and 2007 collections. Susceptibility testing by Etest and disc diffusion was performed on all 108 isolates and 75 of these were typed by N. gonorrhoeae multiantigen sequence typing., Results: A slight drift towards higher MICs of azithromycin was observed in the gonococcal population since 2001. Of greater concern was the first example of a shift to high-level resistance observed in six isolates in 2007. All six isolates were sequence type 649, which was not observed in any of the lower-level azithromycin-resistant isolates from 2007 or in any isolates tested from the same geographical locations. Contact tracing data for one patient suggested a link with Scotland. Disc diffusion testing of all 108 isolates showed that azithromycin, but not erythromycin, discs can differentiate between low-level and high-level resistance., Conclusions: High-level azithromycin resistance has emerged in England and Wales. Contact tracing and typing data suggest this may have originated from Scotland. Surveillance of azithromycin resistance will be key in controlling its further dissemination.

Background: GPs are urged to prescribe antibiotics less frequently, despite lack of evidence linking reduced antibiotic prescribing with reductions in resistance at a local level., Aim: To investigate associations between changes in antibiotic dispensing and changes in antibiotic resistance at general-practice level., Design of Study: Seven-year study of dispensed antibiotics and antibiotic resistance in coliform isolates from urine samples routinely submitted from general practice., Setting: General practices in Wales., Method: Multilevel modelling of trends in resistance to ampicillin and trimethoprim, and changes in practice total antibiotic dispensing and amoxicillin and trimethoprim dispensing., Results: The primary analysis included data on 164 225 coliform isolates from urine samples submitted from 240 general practices over the 7-year study period. These practices served a population of 1.7 million patients. The quartile of practices that had the greatest decrease in total antibiotic dispensing demonstrated a 5.2% reduction in ampicillin resistance over the 7-year period with changes of 0.4%, 2.4%, and -0.3% in the other three quartiles. There was a statistically significant overall decrease in ampicillin resistance of 1.03% (95% confidence interval [CI] = 0.37 to 1.67%) per decrease of 50 amoxicillin items dispensed per 1000 patients per annum. There were also significant reductions in trimethoprim resistance in the two quartiles of practices that reduced total antibiotic dispensing most compared with those that reduced it least, with an overall decrease in trimethoprim resistance of 1.08% (95% CI = 0.065 to 2.10%) per decrease of 20 trimethoprim items dispensed per 1000 patients per annum. Main findings were confirmed by secondary analyses of 256 370 isolates from 527 practices that contributed data at some point during the study period., Conclusion: Reducing antibiotic dispensing at general-practice level is associated with reduced local antibiotic resistance. These findings should further encourage clinicians and patients to use antibiotics conservatively.

Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) may account for treatment failure with vancomycin and act as a precursor of vancomycin-intermediate or -resistant S. aureus. The activity of vancomycin was assessed against vancomycinsusceptible, hVISA and VISA strains in a dilutional pharmacokinetic model. Over a 48 h period, total bacteria and cells with a vancomycin-intermediate phenotype were quantified. Total counts of hVISA were reduced by vancomycin in a similar way to a vancomycin-susceptible control. The vancomycin-intermediate sub-population was eradicated from the model within one dose interval. Exposure to low vancomycin concentrations did not result in an increase in the proportion of cells which were vancomycin intermediate. Short-term exposure of hVISA to vancomycin at gradient concentrations did not increase the proportion of cells with vancomycin-intermediate phenotype.

The sensitivity and specificity of seven methods (agar dilution, broth microdilution, Etest at 0.5 and 2.0 McFarland (McF) inocula, two agar screening methods, and population studies [PS]) were evaluated in a double-blind study involving 284 methicillin-resistant Staphylococcus aureus (MRSA) strains and 45 Staphylococcus strains with reduced susceptibilities to vancomycin (SRSV). The results were compared to the population analysis profile-area under the curve ratio method (PAP-AUC ratio compared to that of Mu3) as described by Wootton et al. The agar screening method using brain heart infusion agar (6 microg of vancomycin per ml) gave a sensitivity of 22% and a specificity of 97%. A similar method using Mueller-Hinton agar (5 microg of vancomycin per ml) gave a sensitivity of 20% and a specificity of 99%. The PS method detected 34 false positives (12%) and gave a sensitivity of 71% and a specificity of 88%. Etest using 0.5 and 2.0 McF inocula gave sensitivities and specificities of 82 and 93% and of 96 and 97%, respectively. The best Etest interpretative criteria for the 2.0 McF inoculum was > or =8 mg of vancomycin per liter and > or =8 microg teicoplanin per ml or > or =12 microg of teicoplanin per ml. The direct colony suspension inoculum for this method was found to be equally accurate in detecting (hetero-)glycopeptide-intermediate S. aureus compared to the overnight broth inoculum preparation method. Agar dilution and broth microdilution using the NCCLS breakpoint criteria for vancomycin gave sensitivities and specificities of 20 and 100% and of 11 and 100%, respectively. Using the Etest with a 2.0 McF inoculum, six different media were assessed against a selection of SRSV (n = 48) and MRSA (n = 12). Brain heart infusion agar yielded the highest sensitivity and specificity values: 88 and 88%, respectively.

Vancomycin-sensitive, -intermediate, and -heterointermediate methicillin-resistant Staphylococcus aureus isolates were tested by using E-tests to explore the interaction of methicillin and vancomycin. For the vancomycin-intermediate and -heterointermediate strains both drugs showed antagonism at concentrations below their MICs but synergy at methicillin concentrations near the MIC. This property could be used to screen for heterointermediate S. aureus strains.

Background: Sore throat is a common symptom presented to general practitioners (GPs), and there remains controversy about the appropriate use of antibiotics., Aim: To compare, in a randomized controlled trial, the effectiveness of penicillin, cefixime and placebo on symptom resolution in patients presenting with a sore throat in general practice., Method: Twenty-two GPs in Avon recruited 154 patients, aged 16-60 years, presenting to their GP with a sore throat, and for whom the GP would normally prescribe an antibiotic. Patients were randomized to one of three groups: penicillin V 250 mg four times a day; cefixime 200 mg daily; and placebo. Each was prescribed for five days. The main outcome measures were a diary of symptom resolution over seven days and eradication of group A beta-haemolytic streptococcus (GABHS)., Results: Of the 103 (67%) patients who completed symptom diaries, 40 were allocated to receive penicillin, 29 cefixime and 34 placebo. In the analysis including all patients, symptom resolution was greater by day 3 in the cefixime group than in the placebo group. Penicillin did not improve symptom resolution by day 3 compared with placebo, and cefixime was not statistically significantly different from penicillin. There were significant differences in the proportion of patients using analgesia at day 3, with the proportion being lowest in the cefixime group. The results for the subgroup of patients without GABHS were similar to those for all patients; in particular, the only statistically significant difference was between cefixime and placebo. Although numbers were too small for statistical significance, among patients with GABHS the effects of penicillin and cefixime were similarly raised in relation to placebo., Conclusion: Compared with placebo, cefixime can improve the rate of resolution of symptoms in patients with a sore throat who are selected for antibiotic treatment by their GP. The unexpected finding that cefixime was of benefit compared with placebo for patients without GABHS suggests that bacteria other than GABHS may be important in the pathogenesis of sore throat.

One hundred patients, known to have been excreting Clostridium difficile cytotoxin in faeces, were reviewed retrospectively to determine the response time for treatment with oral metronidazole and vancomycin, and the effect of the additional administration of anti-motility agents. Records were available for 78 patients of whom 58 had received treatment with either metronidazole or vancomycin. Response and relapse rates were similar for the two treatment regimens. However, the mean duration of symptoms was significantly shorter in evaluable patients treated with vancomycin (3.0 days, n = 22) compared with those given metronidazole (4.6 days, n = 28) (Mann-Whitney-U, P < 0.01). No difference in the duration of symptoms, irrespective of antibiotic therapy, was associated with use of anti-motility agents. The increased cost of vancomycin compared with metronidazole for the treatment of C. difficile infection may be justifiable by reductions in the length of stay in hospital or in the need for nursing in isolation facilities, consequent upon a shorter symptomatic response time. Administration of anti-motility agents did not appear to impair response in patients with mild to moderate C. difficile infection.