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Background: Staphylococcus aureus bloodstream infection is treated with at least 14 days of intravenous antimicrobials. We assessed the efficacy and safety of an early switch to oral therapy in patients at low risk for complications related to S aureus bloodstream infection., Methods: In this international, open-label, randomised, controlled, non-inferiority trial done in 31 tertiary care hospitals in Germany, France, the Netherlands, and Spain, adult patients with low-risk S aureus bloodstream infection were randomly assigned after 5-7 days of intravenous antimicrobial therapy to oral antimicrobial therapy or to continue intravenous standard therapy. Randomisation was done via a central web-based system, using permuted blocks of varying length, and stratified by study centre. The main exclusion criteria were signs and symptoms of complicated S aureus bloodstream infection, non-removable foreign devices, and severe comorbidity. The composite primary endpoint was the occurrence of any complication related to S aureus bloodstream infection (relapsing S aureus bloodstream infection, deep-seated infection, and mortality attributable to infection) within 90 days, assessed in the intention-to-treat population by clinical assessors who were masked to treatment assignment. Adverse events were assessed in all participants who received at least one dose of study medication (safety population). Due to slow recruitment, the scientific advisory committee decided on Jan 15, 2018, to stop the trial after 215 participants were randomly assigned (planned sample size was 430 participants) and to convert the planned interim analysis into the final analysis. The decision was taken without knowledge of outcome data, at a time when 126 participants were enrolled. The new sample size accommodated a non-inferiority margin of 10%; to claim non-inferiority, the upper bound of the 95% CI for the treatment difference (stratified by centre) had to be below 10 percentage points. The trial is closed to recruitment and is registered with ClinicalTrials.gov (NCT01792804), the German Clinical trials register (DRKS00004741), and EudraCT (2013-000577-77)., Findings: Of 5063 patients with S aureus bloodstream infection assessed for eligibility, 213 were randomly assigned to switch to oral therapy (n=108) or to continue intravenous therapy (n=105). Mean age was 63·5 (SD 17·2) years and 148 (69%) participants were male and 65 (31%) were female. In the oral switch group, 14 (13%) participants met the primary endpoint versus 13 (12%) in the intravenous group, with a treatment difference of 0·7 percentage points (95% CI -7·8 to 9·1; p=0·013). In the oral switch group, 36 (34%) of 107 participants in the safety population had at least one serious adverse event compared with 27 (26%) of 103 participants in the intravenous group (p=0·29)., Interpretation: Oral switch antimicrobial therapy was non-inferior to intravenous standard therapy in participants with low-risk S aureus bloodstream infection. However, it is necessary to carefully assess patients for signs and symptoms of complicated S aureus bloodstream infection at the time of presentation and thereafter before considering early oral switch therapy., Funding: Deutsche Forschungsgemeinschaft., Translations: For the German, Spanish, French and Dutch translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests AJK received funding for this study from the Deutsche Forschungsgemeinschaft and is Chairperson of the German Sepsis Society. HSe received grants or research support from the Bundesministerium für Bildung und Forschung (BMBF) Germany and the German Center for Infection Research, and has been a consultant for Debiopharm, Gilead, MSD, and Shionogi. AS has received grants from Gilead Sciences (IN-ES-540–6089) and Pfizer, consulting fees and lecture honoraria from Pfizer, MSD, Angelini, Shionogi, Gilead, and Menarini, and travel support from Pfizer. JR-B has received grants or research support from the Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/00001) and Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC, CB21/13/00012), Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, which are co-financed by the European Development Regional Fund. SH received honoraria and travel support from Shionogi, Pfizer, Infectopharm, and AdvanzPharma. NJ reports receiving honoraria for lectures from AbbVie, Bayer, Infectopharm, and Medacta, travel support from Gilead, Pfizer, and Correvio, participation in paid advisory board meetings for MSD, and membership in the steering committee of the German Society of Internal Medicine. SRi received honoraria for lectures from Falk Foundation, Pfizer, bioMérieux, Akademie für Infektionsmedizin, Med Update, streamedup!, and Deutscher Apotheker-Verlag. TW reports receiving honoraria for presentations from AstraZeneca, Advanz, MSD, Pfizer, and Shionogi, grants or research support from BMBF Germany, and travel support from Pfizer. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Staphylococcus aureus persistent bacteraemia is only vaguely defined and the effect of different durations of bacteraemia on mortality is not well established. Our primary aim was to analyse mortality according to duration of bacteraemia and to derive a clinically relevant definition for persistent bacteraemia., Methods: We did a secondary analysis of a prospective observational cohort study at 17 European centres (nine in the UK, six in Spain, and two in Germany), with recruitment between Jan 1, 2013, and April 30, 2015. Adult patients who were consecutively hospitalised with monomicrobial S aureus bacteraemia were included. Patients were excluded if no follow-up blood culture was taken, if the first follow-up blood-culture was after 7 days, or if active antibiotic therapy was started more than 3 days after first blood culture. The primary outcome was 90-day mortality. Univariable and time-dependent multivariable Cox regression analysis were used to assess predictors of mortality. Duration of bacteraemia was defined as bacteraemic days under active antibiotic therapy counting the first day as day 1., Findings: Of 1588 individuals assessed for eligibility, 987 were included (median age 65 years [IQR 51-75]; 625 [63%] male). Death within 90 days occurred in 273 (28%) patients. Patients with more than 1 day of bacteraemia (315 [32%]) had higher Charlson comorbidity index and sequential organ failure assessment scores and a longer interval from first symptom to first blood culture. Crude 90-day mortality increased from 22% (148 of 672) with 1 day of bacteraemia, to 39% (85 of 218) with 2-4 days, 43% (30 of 69) with 5-7 days, and 36% (10 of 28) with more than 7 days of bacteraemia. Metastatic infections developed in 39 (6%) of 672 patients with 1 day of bacteraemia versus 40 (13%) of 315 patients if bacteraemia lasted for at least 2 days. The second day of bacteraemia had the highest HR and earliest cutoff significantly associated with mortality (adjusted hazard ratio 1·93, 95% CI 1·51-2·46; p<0·0001)., Interpretation: We suggest redefining the cutoff duration for persistent bacteraemia as 2 days or more despite active antibiotic therapy. Our results favour follow-up blood cultures after 24 h for early identification of all patients with increased risk of death and metastatic infection., Funding: None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Staphylococcus aureus is a major human pathogen causing a vast array of infections with significant mortality. Its versatile physiology enables it to adapt to various environments. Specific physiological changes are thought to underlie the frequent failure of antimicrobial therapy despite susceptibility in standard microbiological assays. Bacteria capable of surviving high antibiotic concentrations despite having a genetically susceptible background are described as 'antibiotic tolerant'. In this review, we put current knowledge on environmental triggers and molecular mechanisms of increased antibiotic survival of S. aureus into its clinical context. We discuss animal and clinical evidence of its significance and outline strategies to overcome infections with antibiotic-tolerant S. aureus., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The combination of a fluoroquinolone with rifampin is one of the cornerstones in the treatment of prosthetic joint infections (PJI) caused by staphylococci. Moxifloxacin is highly active against methicillin-susceptible Staphylococcus aureus (MSSA) and, therefore, is an attractive agent to use. However, several studies reported a lowering in serum moxifloxacin levels when combined with rifampin. The clinical relevance remains unclear. We determined the outcome of patients with early acute PJI caused by MSSA treated with either moxifloxacin/rifampin or levofloxacin/rifampin., Methods: Medical files of patients treated with moxifloxacin/rifampin (University Medical Centre Groningen) or levofloxacin/rifampin (Hospital Clinic Barcelona) were retrospectively reviewed (2005-2015). Treatment failure was defined as the need for revision surgery and/or suppressive therapy, death by infection or a relapse of infection during follow-up., Results: Differences in baseline characteristics between the two cohorts were observed, but prognostic parameters for failure, as defined by the KLIC-score (Kidney failure, Liver cirrhosis, Index surgery, C-reactive protein and Cemented prosthesis), were similar in the two groups (2.9 [1.5 SD] for the moxifloxacin group vs. 2.2 [1.2 SD] for the levofloxacin group [P = 0.16]). With a mean follow-up of 50 months (36 SD) in the moxifloxacin group, and 67 months (50 SD) in the levofloxacin group (P = 0.36), treatment was successful in 89% vs. 87.5%, respectively (P = 0.89). None of the failures in the moxifloxacin group were due to rifampin- or moxifloxacin-resistant S. aureus strains., Conclusion: Our data indicate that moxifloxacin combined with rifampin is as clinically effective as levofloxacin/rifampin for early acute PJI caused by MSSA., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Catheter-related bacteremia (CRB) is an important cause of morbidity and mortality among hospitalized patients, being staphylococci the main etiologic agents. The objective of this study was to assess the use of a PCR-based assay for detection of staphylococci directly from blood obtained through the catheter to diagnose CRB caused by these microorganisms and to perform a cost-effectiveness analysis. A total of 92 patients with suspected CRB were included in the study. Samples were obtained through the catheter. Paired blood cultures were processed by standard culture methods and 4 ml blood samples were processed by GeneXpert-MRSA assay for the detection of methicillin-susceptible (MSSA) or methicillin-resistant (MRSA) Staphylococcus aureus, and methicillin-resistant coagulase-negative staphylococci (MR-CoNS). Sixteen CRB caused by staphylococci were diagnosed among 92 suspected patients. GeneXpert detected 14 out of 16 cases (87.5%), including 4 MSSA and 10 MR-CoNS in approximately 1 hour after specimen receipt. The sensitivity and specificity of GeneXpert were 87.5% (CI 95%: 60.4-97.8) and 92.1% (CI 95%: 83-96.7), respectively, compared with standard culture methods. The sensitivity of GeneXpert for S. aureus was 100%. Regarding a cost-effectiveness analysis, the incremental cost of using GeneXpert was of 31.1€ per patient while the incremental cost-effectiveness ratio of GeneXpert compared with blood culture alones was about 180€ per life year gained. In conclusion, GeneXpert can be used directly with blood samples obtained through infected catheters to detect S. aureus and MR-CoNS in approximately 1h after sampling. In addition, it is cost-effective especially in areas with high prevalence of staphylococcal CRB., Competing Interests: We received funding from Cepheid, however, this does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: Staphylococcus aureus bacteraemia is a common, often fatal infection. Our aim was to describe how its clinical presentation varies between populations and to identify common determinants of outcome., Methods: We conducted a pooled analysis on 3395 consecutive adult patients with S. aureus bacteraemia. Patients were enrolled between 2006 and 2011 in five prospective studies in 20 tertiary care centres in Germany, Spain, United Kingdom, and United States., Results: The median age of participants was 64 years (interquartile range 50-75 years) and 63.8% were male. 25.4% of infections were associated with diabetes mellitus, 40.7% were nosocomial, 20.6% were caused by methicillin-resistant S. aureus (MRSA), although these proportions varied significantly across studies. Intravenous catheters were the commonest identified infective focus (27.7%); 8.3% had endocarditis. Crude 14 and 90-day mortality was 14.6% and 29.2%, respectively. Age, MRSA bacteraemia, nosocomial acquisition, endocarditis, and pneumonia were independently associated with death, but a strong association was with an unidentified infective focus (adjusted hazard ratio for 90-day mortality 2.92; 95% confidence interval 2.33 to 3.67, p < 0.0001)., Conclusion: The baseline demographic and clinical features of S. aureus bacteraemia vary significantly between populations. Mortality could be reduced by assiduous MRSA control and early identification of the infective focus., (Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: To compare the specific characteristics, the outcome and the predictors of failure of prosthetic joint infections (PJI) due to methicillin-resistant (MRS) and methicillin- susceptible staphylococci (MSS) treated with open debridement and retention of the implant., Material and Methods: PJI due to MRS or MRS prospectively registered in a database from 1999 to 2009 were retrospectively reviewed., Results: During the study period, 96 patients met the inclusion criteria of the study. The mean follow-up period was 3.9 years and at least 2 years in all patients. The failure rate was 25%. The only variable significantly associated with failure in the global cohort was polymicrobial infection (59.3% vs. 40.7%, p=0.036). Thirty-four (35.4%) patients had an infection due to MRS and 62 (63.6%) due to MSS. Among MSS infections, 95.2% corresponded to primary arthroplasties while 29.4% of PJI due to MRS were after revision arthroplasties (p=0.001). CRP was significantly higher in PJI due to MSS (5.2 mg/dl vs 9.1 mg/dL, p=0.02).The failure rate (20% vs 27%, p=0.62) was very similar in MSS and MRS groups., Conclusion: PJI due to MRS were mainly coagulase-negative staphylococci, more frequent after revision arthroplasties, had a lower inflammatory response, and had a similar failure rate than MSS infections.

Background: Several series predicting the prognosis of staphylococcal prosthetic joint infection (PJI) managed with debridement, antibiotics, and implant retention (DAIR) have been published, but some of their conclusions are controversial. At present, little is known regarding the efficacy of the different antibiotics that are used or their ability to eliminate methicillin-resistant S. aureus (MRSA) infection., Methods: This was a retrospective, multicenter, observational study of cases of PJI by S. aureus that were managed with DAIR (2003-2010). Cases were classified as failures when infection persistence/relapse, death, need for salvage therapy, or prosthesis removal occurred. The parameters that predicted failure were analyzed with logistic and Cox regression., Results: Out of 345 episodes (41% men, 73 years), 81 episodes were caused by MRSA. Fifty-two were hematogenous, with poorer prognoses, and 88% were caused by methicillin-susceptible S. aureus (MSSA). Antibiotics were used for a median of 93 days, with similar use of rifampin-based combinations in MSSA- and MRSA-PJI. Failure occurred in 45% of episodes, often early after debridement. The median survival time was 1257 days. There were no overall prognostic differences between MSSA- and MRSA-PJI, but there was a higher incidence of MRSA-PJI treatment failure during the period of treatment (HR 2.34), while there was a higher incidence of MSSA-PJI treatment failure after therapy. Rifampin-based combinations exhibited an independent protective effect. Other independent predictors of outcome were polymicrobial, inflammatory, and bacteremic infections requiring more than 1 debridement, immunosuppressive therapy, and the exchange of removable components of the prosthesis., Conclusions: This is the largest series of PJI by S. aureus managed with DAIR reported to date. The success rate was 55%. The use of rifampin may have contributed to homogenizing MSSA and MRSA prognoses, although the specific rifampin combinations may have had different efficacies.

Purposes: To evaluate the specific characteristics, outcome, and predictors of failure of prosthetic joint infections (PJI) due to S. aureus and coagulase-negative staphylococci (CNS) treated with open debridement and retention of the implant., Methods: PJI due to S. aureus or CNS prospectively registered in a database from 1999 to 2009 were retrospectively reviewed. During the study period, 106 patients met the inclusion criteria. The mean follow-up period was 3.8 years and for at least 2 years in all patients. The failure rate was 23.6% (25 out of 106). The only variable significantly associated with failure in the global cohort was polymicrobial infection (38.7% vs. 17.3%, p = 0.024). Fifty-seven (53.8%) patients had an infection due to S. aureus and 49 (46.2%) due to CNS. Among S. aureus infections, 95% corresponded to primary arthroplasties while 98% of PJIs due to CNS were after revision arthroplasties (p<0.001). C-reactive protein was significantly higher in PJI due to S. aureus (9.5 mg/dl vs. 4.9 mg/dl, p = 0.007). The rate of methicillin-resistance (8.8% vs. 59.2%, p<0.001) and fluoroquinolone-resistance (15.8% vs. 34.7%, p = 0.005) was significantly higher in CNS infections. The global failure rate was higher in S. aureus infections (28% vs. 18.3. p = 0.26). In S. aureus infections, patients diagnosed within the first 15 days after joint arthroplasty (p = 0.031) and with bacteremia (p = 0.046) had poor pro-gnosis. In CNS infections only the location of the prosthesis (knee 27.6% vs. hip 5%, p = 0.045) was associated with failure., Conclusions: PJIs due to S. aureus were mainly in primary arthroplasties; they had a higher inflammatory response; and the strains were more susceptible to fluoroquinolones and methicillin than CNS infections. S. aureus infections had a higher failure rate than CNS infections, however, the difference was not statistically significant. There were few factors associated with failure and they were different in S. aureus and CNS infections.

Purposes: To review patients with a hematogenous and early post-surgical prosthetic joint infection (PJI) due to S. aureus treated with debridement and retention of the implant and to compare their clinical characteristics and outcome., Methods: From January 2000 all patients with a prosthetic joint infection treated in a single-center were prospectively registered and followed-up. All potentially variables associated with outcome were recorded. For the present study, cases with a hematogenous or early post-surgical PJI due to S. aureus treated with debridement and at least 2 years of follow-up were reviewed. Cox regression model to identify factors associated with outcome were applied., Results: 12 hematogenous and 53 early post-surgical PJI due to S. aureus were included. Number of patients presenting with fever, leucocyte count, C-reactive protein concentration, and the number of bacteremic patients were significantly higher in hematogenous infections while the number of polymicrobial infections was lower in hematogenous than in early post-surgical infections. The global failure rate in hematogenous and early post-surgical PJI was 58.7% and 24.5%, respectively (p=0.02). The Cox regression model identified hematogenous infections (OR: 2.57, CI95%: 1.02-6.51, p=0.04) and the need of a second debridement (OR: 4.61, CI95%: 1.86-11.4, p=0.001) as independent predictors of failure., Conclusion: Hematogenous infections were monomicrobial and had more severe symptoms and signs of infection than early post-surgical PJI. Hematogenous PJI due to S. aureus, using debridement with implant retention, had a worse outcome than early post-surgical infections.

Background: Vancomycin treatment failure in methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is not uncommon, even when MRSA is susceptible to vancomycin. The aim of our study was to evaluate whether vancomycin minimum inhibitory concentration has any influence on the mortality associated with MRSA bacteremia., Methods: A total of 414 episodes of MRSA bacteremia were prospectively followed-up from 1991 through 2005. MIC of vancomycin for the first isolate was determined by E-test. Clinical variables recorded were age, comorbidity, prior administration of vancomycin, use of corticosteroids, prognosis of underlying disease, source of bacteremia, the need for mechanical ventilation, shock, and mortality. A "treatment group" variable was created and defined as follows: (1) receipt of empirical vancomycin and an isolate with a vancomycin MIC of 1 microg/mL (38 episodes), (2) receipt of empirical vancomycin and an isolate with a vancomycin MIC of 1.5 microg/mL (90 episodes), (3) receipt of empirical vancomycin and an isolate with a vancomycin MIC of 2 microg/mL (40 episodes), and (4) receipt of inappropriate empirical therapy (246 episodes). Univariate and multivariate analyses were performed., Results: Episodes caused by strains with a vancomycin MIC of 2 microg/mL were independently associated with a lower risk of shock (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.15-0.75). Multivariate analysis selected receipt of empirical vancomycin and an isolate with a vancomycin MIC of 2 microg/mL (OR, 6.39; 95% CI, 1.68-24.3), receipt of inappropriate empirical therapy (OR, 3.62; 95% CI, 1.20-10.9), increasing age (OR, 1.02; 95% CI, 1.00-1.04), use of corticosteroids (OR, 1.85; 95% CI, 1.04-3.29), an ultimately (OR, 10.2; 95% CI, 2.85-36.8) or rapidly (OR, 1.81; 95% CI, 1.06-3.10) fatal underlying disease, high-risk (OR, 3.60; 95% CI, 1.89-6.88) and intermediate-risk (OR, 2.18; 95% CI, 1.17-4.04) sources of bacteremia, and shock (OR, 7.38; 95% CI, 4.11-13.3) as the best predictors of mortality., Conclusions: Mortality associated with MRSA bacteremia was significantly higher when the empirical antibiotic was inappropriate and when vancomycin was empirically used for treatment of infection with strains with a high vancomycin MIC (>1 microg/mL).

Community-acquired pneumonia (CAP) is one of the leading causes of admission to emergency departments. Ceftaroline is a fifth-generation cephalosporin with a potent In vitro activity against Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus, the three most important pathogens causing CAP. Three randomized and double-blind clinical trials compared the efficacy of ceftaroline versus ceftriaxone in patients with CAP and the results of each trial and a meta-analysis, concluded the superiority of ceftaroline in terms of clinical success. In particular, the major difference was observed among patients with CAP caused by S. aureus. Accordingly, ceftaroline has been included as a first-line option in the recent clinical guidelines for the management of CAP. [ABSTRACT FROM AUTHOR]

Summary Objectives To evaluate characteristics and prognostic factors of community-onset bloodstream infection (Co-BSI) in elderly patients (≥65 years). Methods Analysis of a prospective series of Co-BSI at a tertiary hospital (2005–2011). Predictors of 30-day mortality were established by logistic regression analysis. Results A total of 2605 episodes of Co-BSI were identified and empirical antibiotic treatment was inappropriate in 404 (15.5%). Thirty-day mortality was 11.4% and was independently associated with age (75–84 years OR 1.9, 1.37–2.67; ≥85 OR 2.85, 1.93–4.21), previous hospitalization (OR 1.45, 1.05–2.00), a fatal underlying disease (OR 2.81, 2.10–3.76), neutropenia (OR 2.62, 1.54–4.43), absence of fever (OR 1.99, 1.26–3.12), shock (OR 7.96, 5.83–10.89), inappropriate empirical treatment (OR 1.49, 1.03–2.16), isolation of Staphylococcus aureus (methicillin-resistant OR 2.83, 1.38–5.78; methicillin-susceptible OR 3.24, 1.98–5.32), enterococci (OR 2.02, 1.14–3.59) or Enterobacteriaceae resistant to third-generation cephalosporin (3GCR-E) (OR 1.96, 1.16–3.32) and having endovascular non-catheter (OR 4.64, 2.51–8.59), abdominal (OR 3.65, 2.12–6.27), skin/soft tissue (OR 3.48, 1.90–6.37), respiratory (OR 2.80, 1.75–4.50) or unknown (OR 1.83, 1.17–2.87) source. Conclusions Age is a prognostic factor and appropriateness of empirical treatment is the only modifiable variable. S. aureus , enterococci and 3GCR-E may be the microorganisms with major prognostic significance; hence efforts should be made to improve their management. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a common cause of serious infections. One of the main drawbacks in its treatment is the time required for a positive diagnosis, over 24 h, as most methods are still based in bacterial culture. Herein, a microfluidic optical device for the rapid and ultrasensitive quantification of S. aureus in real human fluids is designed. In this approach, the surface‐enhanced Raman scattering (SERS)‐encoded particles, functionalized with either an antibody or an aptamer, form a dense collection of electromagnetic hot spots on the surface of S. aureus. This allows for an exponentially increase of the SERS signal when particles accumulate on the microorganism as compared to their free condition in bulk solution. Quantification is achieved by passing the sample through a microfluidic device with a collection window where a laser interrogates and classifies each of the induced bacteria–nanoparticle aggregates in real time. Further, the advantages of using aptamers versus antibodies as biorecognition elements are extensively investigated. [ABSTRACT FROM AUTHOR]

Dalbavancin is a lipoglycopeptide with a very prolonged half-life enabling treatment with a single intravenous administration that has been approved to treat complicated skin and soft-tissue infections. Information on the efficacy and safety of dalbavancin in other situations is very scarce. This retrospective study included adult patients who received at least one dose of dalbavancin between 2016 and 2017 in 29 institutions in Spain. The primary objective was to report the use of dalbavancin in clinical practice, including its efficacy and tolerability. The potential impact of dalbavancin on reducing the length of hospital stay and hospital costs was also evaluated. A total of 69 patients received dalbavancin during the study period (58.0% male; median age 63.5 years). Dalbavancin was used to treat prosthetic joint infection (29.0%), acute bacterial skin and skin-structure infection (21.7%), osteomyelitis (17.4%) and catheter-related bacteraemia (11.6%). These infections were mainly caused by Staphylococcus aureus (27 isolates), coagulase-negative staphylococci (24 isolates) and Enterococcus spp. (11 isolates). All but two patients received previous antibiotics for a median of 18 days. Dalbavancin was administered for a median of 21 days (range 7–168 days), and concomitant antimicrobial therapy was prescribed to 25 patients (36.2%). The overall clinical success rate of dalbavancin was 84.1%. Adverse events, mainly mild in intensity, were reported in nine patients. Overall, dalbavancin was estimated to reduce hospitalisation by 1160 days, with an estimated overall cost reduction of €211 481 (€3064 per patient). Dalbavancin appears to be an effective therapy for many serious Gram-positive infections. [ABSTRACT FROM AUTHOR]

To analyse the adherence and impact of quality-of-care indicators (QCIs) in the management of Staphylococcus aureus bloodstream infection in a prospective and multicentre cohort. Analysis of the prospective, multicentre international S. Aureus Collaboration cohort of S. Aureus bloodstream infection cases observed between January 2013 and April 2015. Multivariable analysis was performed to evaluate the impact of adherence to QCIs on 90-day mortality. A total of 1784 cases were included. Overall, 90-day mortality was 29.9% and mean follow-up period was 118 days. Adherence was 67% (n = 1180/1762) for follow-up blood cultures, 31% (n = 416/1342) for early focus control, 77.6% (n = 546/704) for performance of echocardiography, 75.5% (n = 1348/1784) for adequacy of targeted antimicrobial therapy, 88.6% (n = 851/960) for adequacy of treatment duration in non-complicated bloodstream infections and 61.2% (n = 366/598) in complicated bloodstream infections. Full bundle adherence was 18.4% (n = 328/1784). After controlling for immortal time bias and potential confounders, focus control (adjusted hazard ratio = 0.76; 95% CI, 0.59–0.99; p 0.038) and adequate targeted antimicrobial therapy (adjusted hazard ratio = 0.75; 95% CI, 0.61–0.91; p 0.004) were associated with low 90-day mortality. Adherence to QCIs in S. Aureus bloodstream infection did not reach expected rates. Apart from the benefits of application as a bundle, focus control and adequate targeted therapy were independently associated with low mortality. [ABSTRACT FROM AUTHOR]

• Outcomes of patients with severe community-acquired pneumonia (SCAP) treated with ceftaroline were assessed in a two-center study. • Thirty-day mortality and clinical failure were 20% (18 of 89) and 36% (32 of 89), respectively. • In a subgroup of patients with Streptococcus pneumoniae infection, clinical success was 83%. • In a subgroup of patients with methicillin-resistance Staphylococcus aureus (MRSA) infection, clinical success was 56%. • Considering its spectrum of activity, ceftaroline could represent an important option for SCAP. • Further studies are needed to delineate the precise clinical success rate against MRSA. Ceftaroline is one of latest additions to the armamentarium for treating community-acquired pneumonia (CAP). This study aimed to describe the outcome of severe CAP (SCAP) in a cohort of hospitalised patients treated with ceftaroline. A retrospective, observational study of patients with SCAP treated with ceftaroline in two hospitals in Spain and Italy. The primary objective was to explore 30-day mortality after diagnosis of SCAP. During the study period the following were observed: there were 89 cases of SCAP treated with ceftaroline and 53 cases used in combination with other antibiotics (60%). Overall, 30-day mortality and clinical failure were 20% (18 of 89) and 36% (32 of 89), respectively. Independent predictors of 30-day mortality were: increasing age (OR for 1 year increase 1.0, 95% CI 1.0–1.1, P 0.043), presence of solid neoplasm (OR 4.0, 95% CI 1.0–15.1, P 0.044) and concomitant therapy with oseltamivir (OR 8.5, 95% CI 1.2°57.3, P 0.029). The only independent predictor of clinical failure was the time elapsing from SCAP diagnosis to ceftaroline therapy (OR for each passing day 1.5, 95% CI 1.1–1.9, P 0.003). The clinical success rate was 64% (57 of 89). In the subgroups of patients with proven Streptococcus pneumoniae , methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) infection, clinical success was 83% (10 of 12), 75% (three of four) and 56% (five of nine), respectively. Considering its spectrum of activity, ceftaroline could represent an important therapeutic option for SCAP. Further studies are needed to identify the precise clinical success rate against MRSA in a larger cohort of patients with SCAP. [ABSTRACT FROM AUTHOR]