Interest in the combination of antimicrobial therapy for orthopaedic device-related infections due to Enterococcus spp.

INTRODUCTION: The objective of this study was to evaluate the management of orthopaedic device-related infections (ODRIs) due to Enterococcus spp. MATERIALS AND METHODS: We performed a retrospective cohort study in a French tertiary university hospital. Patients with prosthetic joint- or osteosynthesis-associated infections caused by enterococci from 2013 to 2020 were included. Patients who died within 5 days after surgery; who were in palliative care; or who had osteosynthesis of the hand, foot or vertebra were excluded. RESULTS: Thirty-six patients were included, with 24 in the arthroplasty group and 12 in the osteosynthesis material group. Most infections were polymicrobial (63.9%, n = 23). Debridement, antibiotics and implant retention (DAIR) was performed in 30.6% (n = 11), withdrawal of material in 16.7% (n = 6), one-stage exchange in 30.6% (n = 11) and two-stage exchange in 22.2% of cases (n = 8). The antibiotic regimen was amoxicillin in 41.6% (n = 15), rifampicin in 27.8% (n = 10), linezolid in 25% (n = 9) and/or fluoroquinolones in 30.6% (n = 11). Clinical success at 1 year was 67% (18/27). The only variable statistically associated with a decreased risk of clinical failure was a duration of antibiotic therapy of 12 weeks (p = 0.04). Patients with a lower body mass index and age tended to decrease the risk of clinical failure (p = 0.05 and 0.06 respectively). CONCLUSIONS: The management of enterococcal ODRIs is complex, and ODRI patients are at high risk for relapse. In our small study, a better outcome was not demonstrated for patients with combination therapy and rifampicin use. Further studies are needed to improve the medico-surgical strategy for treating these infections.

Impact of vaccination on the presence and severity of symptoms in hospitalized patients with an infection of the Omicron variant (B.1.1.529) of the SARS-CoV-2 (subvariant BA.1).

OBJECTIVES: The emergence of SARS-CoV-2 variants raised questions about the extent to which vaccines designed in 2020 have remained effective. We aimed to assess whether vaccine status was associated with the severity of Omicron SARS-CoV-2 infection in hospitalized patients. METHODS: We conducted an international, multi-centric, retrospective study in 14 centres (Bulgaria, Croatia, France, and Turkey). We collected data on patients hospitalized for ≥24 hours between 1 December 2021 and 3 March 2022 with PCR-confirmed infection at a time of exclusive Omicron circulation and hospitalization related or not related to the infection. Patients who had received prophylaxis by monoclonal antibodies were excluded. Patients were considered fully vaccinated if they had received at least two injections of either mRNA and/or ChAdOx1-S or one injection of Ad26.CoV2-S vaccines. RESULTS: Among 1215 patients (median age, 73.0 years; interquartile range, 57.0-84.0; 51.3% men), 746 (61.4%) were fully vaccinated. In multivariate analysis, being vaccinated was associated with lower 28-day mortality (Odds Ratio [95% Confidence Interval] (OR [95CI]) = 0.50 [0.32-0.77]), intensive care unit admission (OR [95CI] = 0.40 [0.26-0.62]), and oxygen requirement (OR [95CI] = 0.34 [0.25-0.46]), independent of age and comorbidities. When co-analysing these patients with Omicron infection with 948 patients with Delta infection from a study we recently conducted, Omicron infection was associated with lower 28-day mortality (OR [95CI] = 0.53 [0.37-0.76]), intensive care unit admission (OR [95CI] = 0.19 [0.12-0.28]), and oxygen requirements (OR [95CI] = 0.50 [0.38-0.67]), independent of age, comorbidities, and vaccination status. DISCUSSION: Originally designed vaccines have remained effective on the severity of Omicron SARS-CoV-2 infection. Omicron is associated with a lower risk of severe forms, independent of vaccination and patient characteristics.

Improvement of patient care through hirudotherapy and the management of leeches from their reception to their disposal in France.

OBJECTIVE: Medicinal leech therapy - known as hirudotherapy (HT) - is an empirical medical technique that has become popular again in reconstructive surgery. However, at each step of leech management there are risks for blood contamination of the caregivers and severe infections for patients. This reduces the success of the treatment. The aim of this study was to improve the management of leeches from ordering to disposal to improve patient care. METHODS: First, a review of the literature was performed. Second, we conducted a retrospective study of patients' antibiotic prophylaxis from January 2018 to December 2019. The data we collected were patient characteristics, the specific care unit at the hospital, indication, contra-indication, posology, duration of HT, number of leeches delivered, antibiotic prophylaxis prescribed and microbial organism, if identified. Third, an interdisciplinary meeting was organised to review the entire leech circuit: ordering, maintenance, prescription, dispensing, application and disposal. RESULTS: At the end of the literature review, six articles based on practices implemented in France were selected for inclusion. These articles discussed antibiotic prophylaxis, iron supplementation, and leech storage, application and disposal. On the retrospective study performed, antibiotic prophylaxis for HT was performed for 60% (30/50) of patients, 77% (23/30) of the prescriptions followed the recommendations for antibiotic prophylaxis, and 20 patients did not receive antibiotic prophylaxis. The interdisciplinary meeting made it possible to define a collegially validated protocol, containing a computerised antibiotic prophylaxis prescription, including per os ciprofloxacin antibiotic prophylaxis, intravenous iron supplementation and biological monitoring. A leech application protocol was created, and the method of leech disposal was revised. CONCLUSION: Despite the absence of clear guidelines and heterogeneous practices, this study reveals the importance of a standard procedure including leech management practices before use, antibiotic prophylaxis and application and disposal guides. The interdisciplinary protocol allows improved patient care management and makes leech management safer for caregivers.

Mycobacterium genavense Infections in Immunocompromised Patients Without HIV: Case Series of Solid Organ Transplant Patients and Literature Review.

Background: Mycobacterium genavense infection is rare and can occur in immunocompromised patients without human immunodeficiency virus (HIV). Methods: We describe 2 cases of M genavense infection in solid organ transplant (SOT) recipients, and we performed a literature review of immunocompromised patients without HIV. Results: Fifty-two cases are reported. Predisposing factors were receipt of SOT (40.4%) and autoimmune disease (36.5%). Infection was disseminated in 86.5% of cases. Organs involved were lymph nodes (72.3%), gastrointestinal tract (56.5%), lung (35.5%), and bone marrow (28.8%). Most patients were treated with at least 3 antimycobacterial agents (98%), with a clinical cure achieved in 54.9%. In multivariate analysis, lack for cure was associated with age of the time infection (odds ratio [OR], 15.81 [95% confidence interval {CI}, 2.92-152.93]; P = .011) and positive bone marrow culture (OR, 1.05 [95% CI, 1.01-1.12]; P = .042). Conclusions: Mycobacterium genavense infection is a rare and generally disseminated disease with a poor prognosis. Optimal treatment regimen and its duration remain to be defined.

Impact of vaccination on the symptoms of hospitalised patients with SARS-CoV-2 Delta variant (B.1.617.1) infection.

OBJECTIVES: The diffusion of the SARS-CoV-2 Delta (B.1.617.2) variant and the waning of immune response after primary Covid-19 vaccination favoured the breakthrough SARS-CoV-2 infections in vaccinated subjects. To assess the impact of vaccination, we determined the severity of infection in hospitalised patients according to vaccine status. METHODS: We performed a retrospective observational study on patients hospitalised in 10 centres with a SARS-CoV-2 infection (Delta variant) from July to November 2021 by including all patients who had completed their primary vaccination at least 14 days before hospital admission and the same number of completely unvaccinated patients. We assessed the impact of vaccination and other risk factors through logistic regression. RESULTS: We included 955 patients (474 vaccinated and 481 unvaccinated). Vaccinated patients were significantly older (75.0 [63.25-84.0] vs. 55.0 [38.0-73.0]; p < 0.001), more frequently males (55.1% (261/474) vs. 46.4% (223/481); p = 0.009), and had more comorbidities (2.0 [1.0-3.0] vs. 1.0 [0.0-2.0]; p < 0.001). Vaccinated patients were less often admitted for Covid-19 (59.3% (281/474) vs. 75.1% (361/481); p < 0.001), had less extended lung lesions (≤25%: 64.3% (117/182) vs. 38.4% (88/229); p < 0.001), required oxygen less frequently (57.5% (229/398) vs. 73.0% (270/370); p < 0.001), at a lower flow (3.0 [0.0-8.7] vs. 6.0 [2.0-50.0] L/min, p < 0.001), and for a shorter duration (3 [0.0-8.0] vs. 6 [2.0-12.0] days, p < 0.001)., and required less frequently intensive care unit admission (16.2% (60/370) vs. 36.0% (133/369); p < 0.001) but had comparable mortality in bivariate analysis (16.7% (74/443) vs. 12.2% (53/433); p = 0.075). Multivariate logistic regression showed that vaccination significantly decreased the risk of death (0.38 [0.20-0.70](p = 0.002), ICU admission (0.31 [0.21-0.47](p < 0.001) and oxygen requirement (0.16 [0.10-0.26](p < 0.001), even among older patients or with comorbidities. CONCLUSIONS: Among patients hospitalised with a delta variant SARS-CoV-2 infection, vaccination was associated with less severe forms, even in the presence of comorbidities.

Immunogenicity and reactogenicity of heterologous and homologous mRNA-1273 and BNT162b2 vaccination: A multicenter non-inferiority randomized trial.

Background: Although effective mRNA vaccines for SARS-CoV-2 infection have been deployed worldwide, their interchangeability could facilitate the scale-up of vaccination programs. The objective of the trial was to assess whether the immune response induced by a heterologous SARS-CoV-2 mRNA primo vaccination is non-inferior to that of a homologous mRNA vaccination. Methods: We conducted a multicenter, randomized, open-label trial in adults 18 years of age and older who received a first dose of SARS-CoV-2 mRNA vaccine. Participants were randomly assigned in a 1:1 ratio to receive a second dose of BNT162b2 or mRNA-1273, 28 to 49 days after the first dose. Randomization was stratified on the vaccine received at the first vaccination. The primary endpoint was the anti-spike IgG antibodies titer measured 28 days after the second vaccine dose. This study is registered with ClinicalTrials.gov, Trial, NCT04900467. Findings: Of the 414 randomized participants recruited from May 28 to July 2, 2021, 390 were included in the per protocol analysis: 94 participants in group 1 (BNT162b2/BNT162b2), 96 in group 2 (BNT162b2/mRNA-1273), 97 in group 3 (mRNA-1273/mRNA-1273), and 103 in group 4 (mRNA-1273/BNT162b2). The geometric mean titers ratios of anti-spike IgG antibodies for each heterologous regimen relative to the corresponding homologous regimen were 1·37 (two-sided 95% CI, 1·10 to 1·72) in the groups 1 and 2 and 0·67 (two-sided 95% CI, 0·55 to 0·82) in the groups 3 and 4. Levels of neutralizing antibodies to the main circulating SARS-Cov-2 viral strains were higher with the vaccine regimen containing mRNA-1273. Participants who received mRNA-1273 as a second dose experienced a higher rate of local adverse reactions and general symptoms than those who received BNT162b2 (p < 0·0001). Interpretation: The two SARS-CoV-2 mRNA vaccines could be used with flexibility for the second dose of COVID-19 primo vaccination. Tolerance remains good regardless of vaccine sequence although mRNA-1273 was more reactogenic. Funding: French Ministries of Solidarity and Health and Research. BNT162b2 was provided by Pfizer/BioNTech. mRNA-1273 was provided by Moderna.

Reactogenicity among health care workers following a BNT162b2 or mRNA-1273 second dose after priming with a ChAdOx1 nCOV-19 vaccine.

OBJECTIVES: In March 2021, French authorities recommended a heterologous second dose of the mRNA vaccine for persons aged <55 years, with administration 9 to 12 weeks after the first dose of ChAdOx1 nCoV-19. This recommendation was despite a lack of data on the reactogenicity and safety of the regimen. Since then, several studies have shown an acceptable short-term safety profile of ChAdOx1 nCoV-19 and BNT162b2 heterologous vaccination, although some transient increased reactogenicity has been described. METHODS: We performed a single-centre prospective observational cohort study among health care workers (HCWs) at a tertiary care hospital to assess the reactogenicity of the BNT162b2 and mRNA-1273 vaccines administered as a second dose in participants primed with ChAdOx1 nCoV-19. RESULTS: Among 1184 HCWs, 356 (30%) agreed to participate. Of the participants, 32.3% were male, and the mean age was 35 years (standard deviation: 10.1 years). Of the participants, 229 received BNT162b2 and 127 received mRNA-1273. A systemic reaction was observed in 130 of 229 (56.8%) and 100 of 127 (78.7%) HCWs, respectively. Injection site reactions were generally limited (grade 1 or 2 in 163 of 229 (97.6%) and 90 of 127 (85.7 %) HCWs, respectively). After adjustment for age, sex, and HCW role, receiving the mRNA-1273 vaccine was associated with higher reactogenicity with more grade 3 side effects (adjusted OR (aOR): 3.34; 95% CI, 1.91-5.85), more systemic symptoms (aOR: 2.82; 95% CI, 1.69-4.7), and not being able to work (aOR: 8.35; 95% CI, 3.78-18.44) compared with receiving the BNT162b2 vaccine. DISCUSSION: Among patients receiving the mRNA1273 vaccine as a second dose, our study confirms good tolerance of the heterologous schedule with a higher risk of short-term side effects in comparison with patients receiving the BNT162b2 vaccine.

Medicosurgical management of deep wound infections after thoracolumbar instrumentation: risk factors of poor outcomes.

BACKGROUND: Surgical site infection (SSI) after thoracolumbar osteosynthesis is a common complication. Its management relies on surgical revision and antibiotic therapy, but treatment failure is not uncommon. The aim of our study was to assess the frequency of SSI management failure and its risk factors. METHODS: A retrospective study of patients hospitalized from 2011 to 2019 at the University Hospital of Caen was carried out. The infection rate and the time to onset of failure were assessed over a minimum follow-up of 1 year. Treatment failure was defined as the occurrence of a new intervention in the spine in the year following the end of antibiotic therapy, the establishment of long-term suppressive antibiotic therapy, or death from any cause within 1 year of the end of antibiotic therapy. We compared the treatment failure group with the treatment success group to determine risk factors for treatment failure. RESULTS: A total of 2881 patients underwent surgery during the study period, and 92 developed an SSI, corresponding to an SSI rate of 3.19%. Thirty-six percent of the patients with an SSI presented treatment failure. The median time to failure was 31 days. On multivariate analysis, diabetes mellitus was identified as a risk factor for treatment failure, whereas prolonged postoperative drainage for 4 to 5 days was a protective factor. CONCLUSIONS: The number of failures was significant, and failure occurred mainly during the early phase. To decrease the risk of treatment failure, prolonged duration of postoperative drainage seems to be helpful. Additionally, as diabetes is a risk factor for treatment failure, good control of glycemia in these patients might impact their outcomes.

Valvular and infection-associated risk factors as criteria to guide the use of echocardiography in patients with native joint infections.

BACKGROUND: Native joint and bone infections (NJBI) are associated with infective endocarditis (IE) in 15% of cases. There are no studies analyzing the use of cardiac imaging in cases of NJBI. The objective of this study was to identify factors associated with echocardiography suggestive of IE in patients with NJBI. METHODS: This medical records review was conducted in patients hospitalized for NJBI between 2007 and 2017 in Rheumatology and Infectious Diseases departments of 2 university hospitals. Patients included had a microbiologically proven NJBI during their hospitalization. RESULTS: In this cohort of 546 patients, median age 66 years, echocardiography was suggestive of IE in 66 (12%). In multivariate analysis, factors associated with echocardiography suggestive of IE were 2 or more positive blood cultures (OR 11.55 (CI95% 3.24-74.20)), cardiac conditions with a high risk of IE (OR 7.34 (CI95% 2.95-18.61)), unknown heart murmur (OR 4.59 (CI95% 1.79-11.74)), multifocal infection (OR 2.26 (CI95% 1.21-4.23)) and an infection due to S. bovis (OR 3.52 (CI95% 1.26-9.79)). The factor associated with the absence of an echocardiography evocative of IE was infection due to unconventional bacteria for IE (OR 0.13 (CI95% 0.01-0.76)). According to the factors associated with echocardiography evocative of IE, we propose the Normandy score based on three kinds of data: cardiac condition, bacterial strain and NJBI mechanism. Echocardiography should be realized when this score, whose negative predictive value is 100% CI95% (98-100%) for prescription of echocardiography, is more than zero. CONCLUSIONS: A score based on valvular condition, bacterial strain and NJBI mechanism could guide clinicians in prescribing echocardiography during NJBI with an excellent negative predictive value.

Tolerance of BNT162b2 mRNA COVI-19 vaccine in patients with a medical history of COVID-19 disease: A case control study.

INTRODUCTION: Studies evaluating BNT162b2 mRNA Covid-19 vaccine safety excluded subjects with a previous history of COVID-19 infection. The aim of our study was to focus on the tolerance of this vaccine this population. METHODS: An anonymous self-reporting survey related to safety and tolerance of vaccine was completed by subjects 21 to 28 days after the first vaccine dose in two vaccination centers. RESULTS: Subjects with prior COVID-19 disease history (n = 61) had higher systemic reactions than subjects without any previous history (n = 1987) (45.9% vs 29.7%, p = 0.01). Asthenia, headache and fever were significantly more frequent in COVID-19 + group than negative group (25.6% vs 15.2% p = 0.045, 19.7% vs 9.3% p = 0.01, 6.5% vs 0.9% p = 0.003 respectively). Grade of severity was higher in COVID-19 + than in COVID-19 - group (p = 0.03). CONCLUSION: Our study confirms a higher risk of side effects in patients with preexisting SARS-CoV-2 disease but with a good overall tolerance.

Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection.

BACKGROUND: The management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear. METHODS: We performed an open-label, randomized, controlled, noninferiority trial to compare 6 weeks with 12 weeks of antibiotic therapy in patients with microbiologically confirmed prosthetic joint infection that had been managed with an appropriate surgical procedure. The primary outcome was persistent infection (defined as the persistence or recurrence of infection with the initial causative bacteria, with an antibiotic susceptibility pattern that was phenotypically indistinguishable from that at enrollment) within 2 years after the completion of antibiotic therapy. Noninferiority of 6 weeks of therapy to 12 weeks of therapy would be shown if the upper boundary of the 95% confidence interval for the absolute between-group difference (the value in the 6-week group minus the value in the 12-week group) in the percentage of patients with persistent infection within 2 years was not greater than 10 percentage points. RESULTS: A total of 410 patients from 28 French centers were randomly assigned to receive antibiotic therapy for 6 weeks (205 patients) or for 12 weeks (205 patients). Six patients who withdrew consent were not included in the analysis. In the main analysis, 20 patients who died during follow-up were excluded, and missing outcomes for 6 patients who were lost to follow-up were considered to be persistent infection. Persistent infection occurred in 35 of 193 patients (18.1%) in the 6-week group and in 18 of 191 patients (9.4%) in the 12-week group (risk difference, 8.7 percentage points; 95% confidence interval, 1.8 to 15.6); thus, noninferiority was not shown. Noninferiority was also not shown in the per-protocol and sensitivity analyses. We found no evidence of between-group differences in the percentage of patients with treatment failure due to a new infection, probable treatment failure, or serious adverse events. CONCLUSIONS: Among patients with microbiologically confirmed prosthetic joint infections that were managed with standard surgical procedures, antibiotic therapy for 6 weeks was not shown to be noninferior to antibiotic therapy for 12 weeks and resulted in a higher percentage of patients with unfavorable outcomes. (Funded by Programme Hospitalier de Recherche Clinique, French Ministry of Health; DATIPO ClinicalTrials.gov number, NCT01816009.).

Value of the synovial C-reactive protein test in the diagnosis of total hip and knee periprosthetic joint infections: A case-control study.

INTRODUCTION: The diagnosis of periprosthetic joint infection (PJI) can be challenging and rests on several principles. The use of diagnostic biomarkers, such as the synovial C-Reactive Protein (CRP), seems promising. The purpose of this study was to determine whether synovial CRP was a more discriminating test than serum CRP for the diagnosis of hip and knee PJI. MATERIALS AND METHODS: In total, 194 patients were included in this single center prospective study: 42 primary arthroplasties (control group [CG]), 111 revisions for aseptic prosthesis (aseptic revision group [ARG]), and 41 revisions for septic prosthesis (septic revision group [SRG]) based on the Musculoskeletal Infection Society (MSIS) criteria. RESULTS: The serum and synovial CRP levels were significantly higher in the SRG than the other two groups (SRG serum CRP=75.6mg/L vs. ARG serum CRP=6mg/L and CG serum CRP=2.7mg/L, p<0.001; SRG synovial CRP=31.5mg/L vs. CG synovial CRP=2.6mg/L and ARG synovial CRP=1.7mg/L, p<0.001). The positive likelihood ratios (LR+) were very similar for both the synovial CRP cut-off value of 4.4mg/L (LR+=7.04; sensitivity [Se] 82.5%, specificity [Sp] 88.3%) and the serum CRP cut-off value of 9mg/L (LR+=6.3; Se 87.5%, Sp 86.1%). CONCLUSION: This study showed that synovial CRP testing was not more discriminating than serum CRP in the diagnosis of hip and knee PJI. A serum CRP level greater than 9mg/L was a sign of PJI. LEVEL OF EVIDENCE: III; case-control study.

Vaccination perception and coverage among healthcare students in France in 2019.

BACKGROUND: Vaccine hesitancy in healthcare workers has been increasing especially in France while they are the cornerstone of vaccination programs. Greater understanding of healthcare students (HCS) vaccine knowledge, attitudes and beliefs is necessary to provide an adequate vaccination education to better equip them to promote vaccination in their future careers. The aim of this study was to assess vaccination perception (VP) (perception of benefits and risks of vaccines) and its impact on vaccination coverage (VC) for mandatory and recommended vaccines among HCS. METHODS: A standardized, anonymous self-reporting electronic questionnaire was prospectively sent to HCS (medicine, nursing, pharmacy, midwifery, physiotherapy students and 1st year of health sciences students) of Normandy University in France between 18/03/2019 and 8/04/2019. VP was evaluated with questions regarding vaccination hesitancy, safety of vaccine and the benefit/risk balance of vaccination. Global VC (GVC) was defined as being vaccinated according to the mandatory and/or recommended vaccination schedule by national French law in 2018. RESULTS: 542 HCS took part in this survey. VC was high for mandatory (diphtheriae, poliomyelitis, tetanus 93.5%, hepatitis B virus 88.6%) and even most of recommended vaccinations (measles 95%, pertussis 88.2%). Global VC (40.4%) was not statistically different between HCS except for 1st year health sciences students who were less vaccinated (25.6%). Regarding VP, 97.8% of HCS thought that vaccine are effective. When vaccine safety and level of vaccine hesitancy were assessed (on a 0-10 scale, 0: not safe or not hesitant and 10: completely safe and strongly hesitant for vaccine), 91% of respondents stated that vaccine safety is ≥7 and in 80% the vaccine hesitancy was < 3. There was no difference among student categories. 80.6% of HCS recommended all vaccines but only 52% agreed that flu vaccination should be mandatory for HCS. In the multivariate analysis, being a 1st year health care sciences student was associated with a lower GVC (OR 95% CI = 2 [1.2-3.3], p = 0.004) than being a medical student. CONCLUSION: HCS perceived vaccine as effective and secure. Despite the good perception of vaccines, less than half HCS are well vaccinated.

Corrigendum to "Successful Pelvic Resection for Acetabular Hydatidosis".

[This corrects the article DOI: 10.1155/2017/9495783.].

In vitro activity of novel anti-MRSA cephalosporins and comparator antimicrobial agents against staphylococci involved in prosthetic joint infections.

OBJECTIVES: Ceftaroline and ceftobiprole are new parenteral cephalosporins with potent activity against methicillin-resistant (MR) staphylococci, which are the leading cause of prosthetic joint infections (PJIs). The aim of this study was to determine and compare the in vitro activities of both molecules against staphylococcal isolates recovered from clinically documented PJIs. METHODS: A collection of 200 non-duplicate clinical isolates [100 Staphylococcus aureus and 100 coagulase-negative staphylococci (CoNS), including 19 and 27 MR isolates, respectively] was studied. Minimum inhibitory concentrations (MICs) of oxacillin, ceftaroline, ceftobiprole, vancomycin, teicoplanin, clindamycin, levofloxacin, linezolid and daptomycin were determined by the broth microdilution method. Bactericidal activity (at 4× MIC) of ceftaroline, ceftobiprole, vancomycin, teicoplanin, linezolid and daptomycin was assessed by time-kill assay. RESULTS: Among the S. aureus isolates, 100% were susceptible to ceftaroline (MIC50/90, 0.25/0.5µg/mL) and 98% were susceptible to ceftobiprole (MIC50/90, 0.5/1µg/mL), regardless of their methicillin resistance. The two ceftobiprole-non-susceptible strains (including one MRSA) showed MICs at 4mg/L. Against CoNS isolates, ceftaroline and ceftobiprole exhibited in vitro potency with MIC50/90 values at 0.06/0.25µg/mL and 0.25/1µg/mL, respectively. At 4× MIC, ceftaroline and ceftobiprole showed rapid and marked bactericidal activity against both S. aureus and CoNS (after 24/12h and 12/6h of incubation, respectively), whilst none of the other molecules tested had a bactericidal effect by 24h. CONCLUSIONS: This study showed that ceftaroline and ceftobiprole have excellent in vitro activity against clinical isolates of staphylococci involved in PJIs. These molecules may therefore represent promising alternatives for the treatment of such infections.

In vitro activity of tedizolid and comparator agents against Gram-positive pathogens responsible for bone and joint infections.

Tedizolid, a second-generation oxazolidinone that displays a potent activity against Gram-positive pathogens, could be an interesting option for the treatment of bone and joint infections (BJIs). The aim of the study was to determine minimal inhibitory concentration (MIC) of tedizolid against a collection of 359 clinical isolates involved in clinically-documented BJIs and to compare them to those of comparator agents used in Gram-positive infections. Of the 104 Staphylococcusaureus and 102 coagulase-negative staphylococci (CoNS) isolates, 99 and 92 % were categorized as susceptible to tedizolid, respectively (MIC25=0.12/0.25 µg ml-1 and MIC90=0.25/0.5 µg ml-1), regardless of their methicillin resistance. MIC50 and MIC90 for the 51 enterococci, the 50 Corynebacterium spp. and the 52 Propionibacterium spp. were either equal or inferior to 0.5 µg ml-1. Altogether, tedizolid possessed a potent in vitro activity against most of the BJI Gram-positive pathogens with 95 % of them exhibiting a MIC ≤0.5 µg ml-1.

Study on daptomycin use and implementation of an antimicrobial stewardship program.

BACKGROUND: Treatment of Gram-positive pathogens remains a major health issue due to the presence of methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus spp. Daptomycin offers an alternative after therapeutic failure using glycopeptides. Yet its use requires strict control given its financial impact and environmental risks. Since 2014, the use of daptomycin within our hospital has intensified, occasionally outside the scope of its approved indications. OBJECTIVES: The aim of this study is to analyze the appropriateness of daptomycin prescriptions. SETTING: This work was conducted in a 1500-bed University Hospital. METHOD: A descriptive retrospective study was conducted from November 2013 to July 2014. All patients having received at least 2 days of treatment were included. Analysis of the appropriateness of daptomycin prescriptions was conducted by a multidisciplinary team comprised of infectious diseases specialists, pharmacists and a microbiologist. The appropriateness of daptomycin prescriptions was established based on Infectious Diseases Society of America recommendations published in 2011. MAIN OUTCOME MEASURES: The indicators chosen to determine appropriateness of prescription were: treatment indication, prescribed dose and other antibiotics associated with the daptomycin prescription. RESULTS: 19 patients (14 men/5 women) were included. Observed indications were: bone and joint infection (n = 6; 32 %), infectious endocarditis (n = 5; 26 %), bacteremia (n = 5; 26 %) and complicated skin and soft tissue infection (n = 3; 16 %). Identified pathogens were: MRSA (n = 14; 74 %), methicillin-resistant coagulase-negative Staphylococcus (n = 4; 21 %) and Streptococcus mitis (n = 1; 5 %). Daptomycin was prescribed as first-line treatment in 32 % of cases (n = 6). The mean dosage was 9 mg/kg/day (5-11 mg/kg/day) for a mean duration of 11 days (2; 55 days). Clinical success was observed in 42 % of cases (n = 8). Appropriateness for daptomycin use was only established for 15 % of prescriptions (n = 3). CONCLUSION: Faced with a lack of recent recommendations on the subject, our multidisciplinary team issued a local consensus, defining the indications and dosage modalities for this reserve antibiotic. This multidisciplinary approach enables improved use of recent anti-MRSA drugs.