Objective To systematically review the literature and, where appropriate, meta-analyse studies investigating subsequent antibiotic resistance in individuals prescribed antibiotics in primary care. Design Systematic review with meta-analysis.Data sources Observational and experimental studies identified through Medline, Embase, and Cochrane searches.Review methods Electronic searches using MeSH terms and text words identified 4373 papers. Two independent reviewers assessed quality of eligible studies and extracted data. Meta-analyses were conducted for studies presenting similar outcomes.

Prosthetic joint infection (PJI) still remains a significant problem. In line with the forecasted rise in joint replacement procedures, the number of cases of PJI is also anticipated to rise. The formation of biofilm by causative pathogens is central to the occurrence and the recalcitrance of PJI. The subject of microbial biofilms is receiving increasing attention, probably as a result of the wide acknowledgement of the ubiquity of biofilms in the natural, industrial, and clinical contexts, as well as the notorious difficulty in eradicating them. In this review, we discuss the pertinent issues surrounding PJI and the challenges posed by biofilms regarding diagnosis and treatment. In addition, we discuss novel strategies of prevention and treatment of biofilm-related PJI.

These results provide direct evidence that linezolid inhibits mitochondrial protein synthesis with potentially severe clinical consequences. Prolonged courses of linezolid should be avoided if alternative treatment options are available.

SummaryBackgroundAntimicrobial resistance is a serious threat to public health, with most antibiotics prescribed in primary care. General practitioners (GPs) report defensive antibiotic prescribing to mitigate perceived risk of future hospital admission in children with respiratory tract infections. We developed a clinical rule aimed to reduce clinical uncertainty by stratifying risk of future hospital admission.Methods8394 children aged between 3 months and 16 years presenting with acute cough (for ≤28 days) and respiratory tract infection were recruited to a prognostic cohort study from 247 general practitioner practices in England. Exposure variables included demographic characteristics, parent-reported symptoms, and physical examination signs. The outcome was hospital admission for respiratory tract infection within 30 days, collected using a structured, blinded review of medical records.Findings8394 (100%) children were included in the analysis, with 78 (0·9%, 95% CI 0·7%–1·2%) admitted to hospital: 15 (19%) were admitted on the day of recruitment (day 1), 33 (42%) on days 2–7; and 30 (39%) on days 8–30. Seven characteristics were independently associated (p<0·01) with hospital admission: age <2 years, current asthma, illness duration of 3 days or less, parent-reported moderate or severe vomiting in the previous 24 h, parent-reported severe fever in the previous 24 h or a body temperature of 37·8°C or more at presentation, clinician-reported intercostal or subcostal recession, and clinician-reported wheeze on auscultation. The area under the receiver operating characteristic (AUROC) curve for the coefficient-based clinical rule was 0·82 (95% CI 0·77–0·87, bootstrap validated 0·81). Assigning one point per characteristic, a points-based clinical rule consisting of short illness, temperature, age, recession, wheeze, asthma, and vomiting (mnemonic STARWAVe; AUROC 0·81, 0·76–0·85) distinguished three hospital admission risk strata: very low (0·3%, 0·2–0·4%) with 1 point or less, normal (1·5%, 1·0–1·9%) with 2 or 3 points, and high (11·8%, 7·3–16·2%) with 4 points or more.InterpretationClinical characteristics can distinguish children at very low, normal, and high risk of future hospital admission for respiratory tract infection and could be used to reduce antibiotic prescriptions in primary care for children at very low risk.FundingNational Institute for Health Research (NIHR).

Background Enhanced methods of drug monitoring are required to support the individualisation of antibiotic dosing. We report the first-in-human evaluation of real-time phenoxymethylpenicillin monitoring using a minimally invasive microneedle-based β-lactam biosensor in healthy volunteers.

BackgroundProsthetic joint infection is an uncommon but serious complication of hip replacement. There are two main surgical treatment options, with the choice largely based on the preference of the surgeon. Evidence is required regarding the comparative effectiveness of one-stage and two-stage revision to prevent reinfection after prosthetic joint infection.MethodsWe conducted a systematic review to identify randomised controlled trials, systematic reviews and longitudinal studies in unselected patients with infection treated exclusively by one- or two-stage methods or by any method. The Embase, MEDLINE and Cochrane databases were searched up to March 2011. Reference lists were checked, and citations of key articles were identified by using the ISI Web of Science portal. Classification of studies and data extraction were performed independently by two reviewers. The outcome measure studied was reinfection within 2 years. Data were combined to produce pooled random-effects estimates using the Freeman-Tukey arc-sine transformation.ResultsWe identified 62 relevant studies comprising 4,197 patients. Regardless of treatment, the overall rate of reinfection after any treatment was 10.1% (95% CI = 8.2 to 12.0). In 11 studies comprising 1,225 patients with infected hip prostheses who underwent exclusively one-stage revision, the rate of reinfection was 8.6% (95% CI = 4.5 to 13.9). After two-stage revision exclusively in 28 studies comprising 1,188 patients, the rate of reinfection was 10.2% (95% CI = 7.7 to 12.9).ConclusionEvidence of the relative effectiveness of one- and two-stage revision in preventing reinfection of hip prostheses is largely based on interpretation of longitudinal studies. There is no suggestion in the published studies that one- or two stage methods have different reinfection outcomes. Randomised trials are needed to establish optimum management strategies.

Twelve patients undergoing total hip replacement were given 600 mg of linezolid as a 20 min iv infusion along with conventional prophylaxis of 1 g of cefamandole immediately before surgery. Routine total hip arthroplasty was carried out, and at timed intervals during surgery samples of bone, fat, muscle and blood were collected for assay by high-performance liquid chromatography analysis. Samples of the haematoma fluid that formed around the operation site and further blood samples for assay were also collected at timed intervals following the operation. The penetration of linezolid into bone was rapid, with mean concentrations of 9.1 mg/L (95% CI 7.7-10.6 mg/L) achieved at 10 min after the infusion, decreasing to 6.3 mg/L (95% CI 3.9-8.6 mg/L) at 30 min. Correction for the simultaneous blood concentrations gave mean values for bone penetration of 51% at 10 min, 60% at 20 min and 47% at 30 min. Although the penetration of linezolid into fat was also rapid, mean concentrations and degree of penetration were c. 60% of those in bone; at 10 min they were 4.5 mg/L (95% CI 3.0-6.1 mg/L; penetration 27%); at 20 min they were 5.2 mg/L (95% CI 4.0-6.4 mg/L; penetration 37%); and at 30 min, 4.1 mg/L (95% CI 3.3-4.8 mg/L; penetration 31%). For muscle the corresponding values were 10.4 mg/L (95% CI 8.1-12.7 mg/L; penetration 58%) at 10 min, 13.4 mg/L (95% CI 10.2-16.5 mg/L; penetration 94%) at 20 min and 12.0 mg/L (95% CI 9.2-14.8 mg/L; penetration 93%) at 30 min. Mean concentrations of linezolid in the haematoma fluid drained from around the operation site were 8.2 mg/L at 6-8 h and 5.6 mg/L at 10-12 h after the infusion, and 7.0 mg/L at 2-4 h following a second 600 mg infusion given 12 h post-operatively. We conclude that linezolid exhibits rapid penetration into bone, fat and muscle of patients undergoing hip arthroplasty, to achieve levels in excess of its MIC for susceptible organisms (< or=4 mg/L); therapeutic concentrations were maintained in the haematoma fluid that surrounds the operation site for >16 h.

Diabetes has major implications for public health, with diabetic foot ulcers (DFUs) being responsible for significant morbidity and mortality. A key factor in the development of nonhealing ulcers is infection, which often leads to the development of biofilm, gangrene, and amputation. A novel approach to treating DFUs is the local release of antibiotics from calcium sulfate beads. We have developed a novel model system to study and compare the release and efficacy of antibiotics released locally, using collagen as a substrate for biofilm growth and incorporating serum to mimic the biochemical complexity of the wound environment. We found that our soft-tissue model supports the growth of a robust Pseudomonas aeruginosa biofilm, and that this was completely eradicated by the introduction of calcium sulfate beads loaded with tobramycin or gentamicin. The model also enabled us to measure the concentration of these antibiotics at different distances from the beads and in simulated wound fluid bathing the collagen matrix. We additionally found that a multidrug-resistant Staphylococcus aureus biofilm, nonsusceptible to antibiotics, nonetheless showed an almost 1-log drop in viable counts when exposed to calcium sulfate beads combined with antibiotics. Together, these data suggest that locally applied antibiotics combined with calcium sulfate provide surprising efficacy in diabetic foot infections and offer an effective alternative approach to infection management. Our study additionally establishes our new system as a biochemically and histologically relevant model that may be used to study the effectiveness of a range of therapies locally or systemically for infected DFUs.