Explore the vast range of titles available.

Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus   aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III–IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), –5.95–16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 . New treatments are essential for methicillin-susceptible Staphylococcus   aureus bacteremia, but progress is slow. In this phase III–IV trial, cloxacillin plus fosfomycin failed to show superiority over cloxacillin alone, underscoring the challenges to improving patient outcomes.

Abstract Background Information on outcomes of methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) bacteremia, particularly readmission, is scarce and requires further research to inform optimal patient care. Methods We performed a retrospective analysis using the 2014 Nationwide Readmissions Database, capturing 49.3% of US hospitalizations. We identified MSSA and MRSA bacteremia using International Classification of Diseases, Ninth Revision, Clinical Modification among patients aged ≥18 years. Thirty-day readmission, mortality, length of stay, and costs were assessed using Cox proportional hazards regression, logistic regression, Poisson regression, and generalized linear model with gamma distribution and log link, respectively. Results Of 92 089 (standard error [SE], 1905) patients with S. aureus bacteremia, 48.5% (SE, 0.4%) had MRSA bacteremia. Thirty-day readmission rate was 22% (SE, 0.3) overall with no difference between MRSA and MSSA, but MRSA bacteremia had more readmission for bacteremia recurrence (hazard ratio, 1.17 [95% confidence interval {CI}, 1.02–1.34]), higher in-hospital mortality (odds ratio, 1.15 [95% CI, 1.07–1.23]), and longer hospitalization (incidence rate ratio, 1.09 [95% CI, 1.06–1.11]). Readmission with bacteremia recurrence was particularly more common among patients with endocarditis, immunocompromising comorbidities, and drug abuse. The cost of readmission was $12 425 (SE, $174) per case overall, and $19 186 (SE, $623) in those with bacteremia recurrence. Conclusions Thirty-day readmission after S. aureus bacteremia is common and costly. MRSA bacteremia is associated with readmission for bacteremia recurrence, increased mortality, and longer hospitalization. Efforts should continue to optimize patient care, particularly for those with risk factors, to decrease readmission and associated morbidity and mortality in patients with S. aureus bacteremia. Thirty-day readmission after having Staphylococcus aureus bacteremia is common and costly. Methicillin-resistant S. aureus bacteremia is associated with readmission for recurrent bacteremia, mortality, and longer hospitalization. Identifying high-risk patients for readmission may help optimize care for S. aureus bacteremia.

This study was conducted to estimate the prevalence of Livestock-Associated Methicillin-Resistant Staphylococcus aureus (LA-MRSA) in retail chicken meat and broiler chickens from the Province of Quebec, Canada, and to characterize LA-MRSA isolates. A total of 309 chicken drumsticks and thighs were randomly selected in 2013 from 43 retail stores in the Monteregie. In addition, nasal swabs and caeca samples were collected in 2013-2014 from 200 broiler chickens of 38 different flocks. LA-MRSA was not detected in broiler chickens. Fifteen LA-MRSA isolates were recovered from four (1.3%) of the 309 chicken meat samples. Multi-Locus Sequence Typing (MLST) and SCCmec typing revealed two profiles (ST398-MRSA-V and ST8-MRSA-IVa), which were distinct using pulse-field gel electrophoresis (PFGE) and microarray (antimicrobial resistance and virulence genes) analyses. In addition to beta-lactam resistance, tetracycline and spectinomycin resistance was detected in all isolates from the 3 positive samples of the ST398 profile. Southern blot hybridization revealed that the resistance genes aad(D) and lnu(A), encoding resistances to aminoglycosides and lincosamides respectively, were located on plasmid. All isolates were able to produce biofilms, but biofilm production was not correlated with hld gene expression. Our results show the presence of two separate lineages of MRSA in retail chicken meat in Quebec, one of which is likely of human origin.

Bacterial resistance to antibiotics remains an imposing global public health challenge. Of the most serious pathogens, methicillin-resistant Staphylococcus aureus (MRSA) is problematic given strains have emerged that exhibit resistance to several antibiotic classes including β-lactams and agents of last resort such as vancomycin. New antibacterial agents composed of unique chemical scaffolds are needed to counter this public health challenge. The present study examines two synthetic diphenylurea compounds 1 and 2 that inhibit growth of clinically-relevant isolates of MRSA at concentrations as low as 4 µg/mL and are non-toxic to human colorectal cells at concentrations up to 128 μg/mL. Both compounds exhibit rapid bactericidal activity, completely eliminating a high inoculum of MRSA within four hours. MRSA mutants exhibiting resistance to 1 and 2 could not be isolated, indicating a low likelihood of rapid resistance emerging to these compounds. Bacterial cytological profiling revealed the diphenylureas exert their antibacterial activity by targeting bacterial cell wall synthesis. Both compounds demonstrate the ability to resensitize vancomycin-resistant Staphylococcus aureus to the effect of vancomycin. The present study lays the foundation for further investigation and development of diphenylurea compounds as a new class of antibacterial agents.

Methicillin-resistant Staphylococcus aureus (MRSA) is a primarily nosocomial pathogen that, in recent years, has increasingly spread to the general population. The rising prevalence of MRSA in the community implies more frequent introductions in healthcare settings that could jeopardize the effectiveness of infection-control procedures. To investigate the epidemiological dynamics of MRSA in a low-prevalence country, we developed an individual-based model (IBM) reproducing the population’s sociodemography, explicitly representing households, hospitals, and nursing homes. The model was calibrated to surveillance data from the Norwegian national registry (2008–2015) and to published household prevalence data. We estimated an effective reproductive number of 0.68 (95% CI 0.47–0.90), suggesting that the observed rise in MRSA infections is not due to an ongoing epidemic but driven by more frequent acquisitions abroad. As a result of MRSA importations, an almost twofold increase in the prevalence of carriage was estimated over the study period, in 2015 reaching a value of 0.37% (0.25–0.54%) in the community and 1.11% (0.79–1.59%) in hospitalized patients. Household transmission accounted for half of new MRSA acquisitions, indicating this setting as a potential target for preventive strategies. However, nosocomial acquisition was still the primary source of symptomatic disease, which reinforces the importance of hospital-based transmission control. Although our results indicate little reason for concern about MRSA transmission in low-prevalence settings in the immediate future, the increases in importation and global circulation highlight the need for coordinated initiatives to reduce the spread of antibiotic resistance worldwide.

Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia is associated with poor outcomes. Ceftriaxone offers logistical advantages over other standard therapies, though in vitro studies have questioned its efficacy and clinical studies of ceftriaxone in MSSA bacteremia are conflicting. We performed a multicenter, retrospective cohort study of adult patients who received ceftriaxone, cefazolin, or antistaphylococcal penicillins as definitive therapy for MSSA bacteremia from 2018 to 2019. Definitive therapy was defined as the antibiotic used in the outpatient setting. Patients were excluded if they received less than 7 days of outpatient therapy. Follow-up started on the date of definitive therapy completion. The primary outcome was 90-day treatment failure, defined as a composite of mortality and microbiologic recurrence. This was analyzed with multivariable Cox regression. A total of 223 patients were included, 37 (16.6%) of whom received ceftriaxone. The most common ceftriaxone dose was 2 g daily (83.8%). The most common primary site of infection was skin/soft tissue (37.2%), unknown (21.1%), and catheter-related (15.2%). Twenty-six (11.7%) developed infective endocarditis. Median total duration of treatment was 31.0 days, and median outpatient duration was 24.0 days. Twenty-six (11.7%) developed 90-day treatment failure. After adjusting for Charlson comorbidity index, duration of therapy, and use of transesophageal echocardiography, definitive treatment with ceftriaxone was associated with treatment failure (hazard ratio 2.66, 95% confidence interval 1.15–6.12; p =0.022). Among patients with MSSA bacteremia, definitive treatment with ceftriaxone was associated with a higher risk of treatment failure within 90 days as compared to cefazolin or antistaphylococcal penicillins.

Methicillin-resistant Staphylococcus aureus (MRSA) are a major cause of healthcare and community- associated infections due to their ability to express a variety of virulence factors. We investigated 209 MRSA isolates obtained from 1 January to 31 December 2016 using a combination of phenotypic and genotypic methods to understand the genetic backgrounds of MRSA strains obtained in a General hospital in Kuwait. Antibiotics susceptibility was performed with disk diffusion, and MIC was measured with Etest strips. Molecular typing was performed using SCC mec typing, spa typing, and DNA microarray for antibiotic resistance and virulence genes. The isolates were susceptible to vancomycin, teicoplanin, rifampicin, ceftaroline, and linezolid but were resistant to gentamicin, tetracycline, erythromycin, fusidic acid, chloramphenicol and ciprofloxacin. Molecular typing revealed six SCC mec types, 56 spa types and 16 clonal complexes (CC). The common SCC mec types were type IV (39.5%), type III (34.4%), type V (25.8%) and type VI (3.8%). The dominant spa types were t860 (23.9%), t945 (8.6%), t127 (6.7%), t688 (6.7%), t304 (6.2) and t044 (5.7%). The other spa types occurred sporadically. Genes for PVL was detected in 59 (28.2%) of the isolates. CC8-ST239-MRSA-III + SCCmer (23.3%) was the most prevalent clone, followed by CC6-MRSA-IV (8.3%), CC80-MRSA-IV [PVL+] (5.8%), CC5-MRSA-VI + SCCfus (5.0%), CC30-MRSA-IV[PVL+] (4.1%), CC1-MRSA-V + SCCfus [PVL+] (4.1%), CC5-MRSA-V + SCCfus (4.1%) and CC22-MRSA-IV[PVL+] (4.1%). The study revealed that despite the emergence of MRSA with diverse genetic backgrounds over the years, ST239-MRSA-III remained the dominant clone in the hospital. This warrants reassessment of infection prevention and control procedures at this hospital.

Devising effective, targeted approaches to prevent recurrent meticillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infection requires an understanding of factors driving MRSA acquisition. We comprehensively defined household longitudinal, strain-level S aureus transmission dynamics in households of children with community-associated MRSA skin and soft tissue infection. From 2012–15, otherwise healthy paediatric patients with culture-confirmed, community-onset MRSA infections were recruited for the Household Observation of MRSA in the Environment (HOME) prospective cohort study from hospitals and community practices in metropolitan St Louis (MO, USA). Children with health-care-related risk factors were excluded, as determined by evidence of recent hospital admission, an invasive medical device, or residence in a long-term care facility. Household contacts (individuals sleeping in the home ≥four nights per week) and indoor dogs and cats were also enrolled. A baseline visit took place at the index patient's primary home, followed by four quarterly visits over 12 months. At each visit, interviews were done and serial cultures were collected, to detect S aureus from three anatomic sites of household members, two anatomic sites on dogs and cats, and 21 environmental surfaces. Molecular typing was done by repetitive-sequence PCR to define distinct S aureus strains within each household. Longitudinal, multivariable generalised mixed-effects logistic regression models identified factors associated with S aureus acquisition. Across household members, pets, and environmental surfaces, 1267 strain acquisition events were observed. Acquisitions were driven equally by 510 introductions of novel strains into households and 602 transmissions within households, each associated with distinct factors. Frequent handwashing decreased the likelihood of novel strain introduction into the household (odds ratio [OR] 0·86, credible interval [CrI] 0·74–1·01). Transmission recipients were less likely to own their homes (OR 0·77, CrI 0·63–0·94) and were more likely to share bedrooms with strain-colonised individuals (OR 1·33, CrI 1·12–1·58), live in homes with higher environmental S aureus contamination burden (OR 3·97, CrI 1·96–8·20), and report interval skin and soft tissue infection (OR 1·32, CrI 1·07–1·64). Transmission sources were more likely to share bath towels (OR 1·25, CrI 1·01–1·57). Pets were often transmission recipients, but rarely the sole transmission source. The household environment plays a key role in transmission, a factor associated with skin and soft tissue infection. Future interventions should inclusively target household members and the environment, focusing on straightforward changes in hand hygiene and household sharing behaviours. National Institutes of Health, Agency for Healthcare Research and Quality, Children's Discovery Institute, Burroughs Wellcome Foundation, Defense Advanced Research Projects Agency.

Background & objectives: Methicillin resistant Staphylococcus aureus (MRSA) is endemic in India and is a dangerous pathogen for hospital acquired infections. This study was conducted in 15 Indian tertiary care centres during a two year period from January 2008 to December 2009 to determine the prevalence of MRSA and susceptibility pattern of S. aureus isolates in India. Methods: All S. aureus isolates obtained during the study period in the participating centres were included in the study. Each centre compiled their data in a predefined template which included data of the antimicrobial susceptibility pattern, location of the patient and specimen type. The data in the submitted templates were collated and analysed. Results: A total of 26310 isolates were included in the study. The overall prevalence of methicillin resistance during the study period was 41 per cent. Isolation rates for MRSA from outpatients, ward inpatients and ICU were 28, 42 and 43 per cent, respectively in 2008 and 27, 49 and 47 per cent, respectively in 2009. The majority of S. aureus isolates was obtained from patients with skin and soft tissue infections followed by those suffering from blood stream infections and respiratory infections. Susceptibility to ciprofloxacin was low in both MSSA (53%) and MRSA (21%). MSSA isolates showed a higher susceptibility to gentamicin, co-trimoxazole, erythromycin and clindamycin as compared to MRSA isolates. No isolate was found resistant to vancomycin or linezolid. Interpretation & conclusions: The study showed a high level of MRSA in our country. There is a need to study epidemiology of such infections. Robust antimicrobial stewardship and strengthened infection control measures are required to prevent spread and reduce emergence of resistance.

Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a morbid infection with mortality benefit from receipt of parenteral β-lactam therapy. A substantial portion of MSSA bacteremia patients report penicillin allergy, but infrequently have true allergy. To determine the frequency and predictors of optimal and adequate therapy in patients with MSSA bacteremia. Retrospective cohort. Adult inpatients with MSSA bacteremia, January 2009 through October 2013. The primary measure was a trial of optimal therapy (OT), defined as ≥3 inpatient days or discharge on any first-line agents (nafcillin, oxacillin, cefazolin, or penicillin G, if susceptible). The secondary measure was completion of adequate therapy (AT), defined as ≥10 inpatient days or discharge on an agent appropriate for MSSA bacteremia. Data were electronically gathered with key variables manually validated through chart review. Log-binomial regression models were used to determine the frequency and predictors of outcomes. Of 456 patients, 346 (76%) received a trial of OT. Patients reporting penicillin allergy (13%) were less likely to receive OT trial than those without penicillin allergy (47% vs. 80%, p <0.001). Adjusting for other factors, penicillin allergy was the largest negative predictor of OT trial (RR 0.64 [0.49, 0.83]). Infectious Disease (ID) consultation was the largest positive predictor of OT trial across all patients (RR 1.34 [1.14, 1.57]). Allergy/Immunology consultation was the single most important predictor of OT trial among patients reporting penicillin allergy (RR 2.33 [1.44, 3.77]). Of 440 patients, 391 (89%) completed AT, with ID consultation the largest positive predictor of the outcome (RR 1.28 [1.15, 1.43]). Nearly 25% of patients with MSSA bacteremia did not receive OT trial and about 10% did not receive AT completion. Reported penicillin allergy reduced, and ID consult increased, the likelihood of OT. Allergy evaluation, coupled with ID consultation, may improve outcomes in MSSA bacteremic patients.