Treatment of infections caused by multi-drug-resistant Gram-negative bacilli: A practical approach by the Italian (SIMIT) and French (SPILF) Societies of Infectious Diseases.

INTRODUCTION: The emergence of multi-drug-resistant Gram-negative bacilli and the development of new antibiotics have complicated the selection of optimal regimens. International guidelines are valuable tools, but are limited by the scarcity of high-quality randomized trials in many situations. METHODS: A panel of experts from the French and Italian Societies of Infectious Diseases aimed to address unresolved issues in clinical practice based on their experience, an updated literature review and open discussions. RESULTS: The panel reached consensus for the following 'first choices': (i) cefepime for ventilator-acquired pneumonia due to AmpC ß-lactamase-producing Enterobacterales; (ii) the ß-lactam/ß-lactamase inhibitor combination most active in vitro, or cefiderocol combined with fosfomycin, and aerosolized colistin or aminoglycosides, for severe pneumonia due to Pseudomonas aeruginosa resistant to ceftolozane-tazobactam; (iii) high-dose piperacillin-tazobactam (including loading dose and continuous infusion) for complicated urinary tract infections (cUTIs) caused by extended-spectrum ß-lactamase-producing Enterobacterales with piperacillin-tazobactam minimum inhibitory concentration (MIC) ≤8 mg/L; (iv) high-dose cefepime for cUTIs due to AmpC ß-lactamase-producing Enterobacterales other than Enterobacter spp. if cefepime MIC ≤2 mg/L; (v) ceftolozane-tazobactam or ceftazidime-avibactam plus metronidazole for intra-abdominal infections (IAIs) due to third-generation cephalosporin-resistant Enterobacterales; (vi) ceftazidime-avibactam plus aztreonam plus metronidazole for IAIs due to metallo-ß-lactamase-producing Enterobacterales; (vii) ampicillin-sulbactam plus colistin for bloodstream infections (BSIs) caused by carbapenem-resistant Acinetobacter baumannii; (viii) meropenem-vaborbactam for BSIs caused by Klebsiella pneumoniae carbapenemase-producing Enterobacterales; and (ix) ceftazidime-avibactam plus fosfomycin for neurological infections caused by carbapenem-resistant P. aeruginosa. CONCLUSIONS: These expert choices were based on the necessary balance between antimicrobial stewardship principles and the need to provide optimal treatment for individual patients in each situation.

Comparative effectiveness of empirical antibiotic treatments in methicillin-susceptible Staphylococcus aureus infective endocarditis: A post hoc analysis of a prospective French cohort study.

OBJECTIVES: The empirical treatment of infective endocarditis is still debated. The aim of this study was to compare the impact of empirical treatment with antistaphylococcal penicillin (ASP) or cefazolin vs. other treatments in methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis. METHODS: A post hoc analysis of a prospective cohort study of patients hospitalized in a French reference centre with MSSA endocarditis was conducted between 2013 and 2022. The primary outcome was the duration of bacteraemia under treatment. RESULTS: Of the 208 patients included, 101 patients (48.6%) were classified in the reference group (ASP or cefazolin) and 107 (52.4%) in the non-reference group. Empirical treatment with ASP/cefazolin was associated with a shorter duration of bacteraemia compared to other treatments (3.6 d vs. 4.6 d, P = 0.01). This difference was not corrected by the addition of an aminoglycoside (3.6 d vs. 4.7 d, P < 0.01). In multivariate analysis, empirical treatment with ASP/cefazolin was associated with a duration of bacteraemia ≤72 h (P = 0.02), whereas endocarditis on native valves (P = 0.01), and intracardiac abscess were associated with longer duration of bacteraemia (P = 0.01). CONCLUSIONS: Empirical treatment of endocarditis with ASP or Cefazolin is more effective than other treatments in MSSA endocarditis, even when the other treatments are combined with aminoglycosides.

Ceftolozane/Tazobactam for the Treatment of Complicated Infections in Hospital Settings-A French Real-world Study.

Background: This study describes the conditions of use of ceftolozane/tazobactam (C/T) and associated outcomes in French hospital settings. Methods: This was a prospective, multicenter, French observational study. Patients who received at least 1 dose of C/T were included and followed up as per routine clinical practice, until stop of C/T. Results: A total of 260 patients were enrolled between October 2018 and December 2019 in 30 centers across France. Of these, 177 (68.0%) received C/T as per indication of usage following the results of the antibiogram (documented cases). Among documented patients, the mean age was 61.8 years, 73.4% were males, and 93.8% presented with multidrug-resistant (MDR) bacteria at inclusion. C/T was most frequently prescribed for pneumonia (48.6%), bacteremia (14.7%), complicated intra-abdominal infections (13.0%), or complicated urinary tract infections (9.6%). Pseudomonas aeruginosa was the species most frequently isolated with 212 strains from 155 patients, and 96.2% of these strains were susceptible to C/T. The median duration of C/T treatment was 16.1 days (1-115, n = 176). Complete or partial cure was achieved in 71.7% of patients, C/T was discontinued upon adaptation to microbiology results in 11.3% of patients for the following reasons: treatment failure in 2.8%, death in 4.0%, adverse events in 1.7%, and other in 8.5%. Conclusions: This is the first prospective observational study of C/T utilization in a health care setting enrolling many patients in France. C/T demonstrated a high rate of clinical effectiveness in MDR infections, confirming it as an effective treatment option for complicated infections in a high-risk population.

Efficacy and safety of an early oral switch in low-risk Staphylococcus aureus bloodstream infection (SABATO): an international, open-label, parallel-group, randomised, controlled, non-inferiority trial.

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.

Characteristics and Prognosis Factors of Pneumocystis jirovecii Pneumonia According to Underlying Disease: A Retrospective Multicenter Study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical presentation, severity, and mortality of PcP has not been adequately evaluated. RESEARCH QUESTION: Does the underlying disease and immunosuppression causing PcP impact the outcome and clinical presentation of the disease? STUDY DESIGN AND METHODS: In this multicenter retrospective observational study, conducted from January 2011 to December 2021, all consecutive patients admitted with a proven or probable diagnosis of PcP according to the European Organisation for Research and Treatment of Cancer consensus definitions were included to assess the epidemiology and impact of underlying immunosuppressive diseases on overall and 90-day mortality. RESULTS: Overall, 481 patients were included in the study; 180 (37.4%) were defined as proven PcP and 301 (62.6%) were defined as probable PcP. Patients with immune-mediated inflammatory diseases (IMIDs) or solid tumors had a statistically poorer prognosis than other patients with PcP at day 90. In multivariate analysis, among the HIV-negative population, solid tumor underlying disease (OR, 5.47; 95% CI, 2.16-14.1; P < .001), IMIDs (OR, 2.19; 95% CI, 1.05-4.60; P = .037), long-term corticosteroid exposure (OR, 2.07; 95% CI, 1.03-4.31; P = .045), cysts in sputum/BAL smears (OR, 1.92; 95% CI, 1.02-3.62; P = .043), and SOFA score at admission (OR, 1.58; 95% CI, 1.39-1.82; P < .001) were independently associated with 90-day mortality. Prior corticotherapy was the only immunosuppressant associated with 90-day mortality (OR, 1.67; 95% CI, 1.03-2.71; P = .035), especially for a prednisone daily dose ≥ 10 mg (OR, 1.80; 95% CI, 1.14-2.85; P = .010). INTERPRETATION: Among patients who were HIV-negative, long-term corticosteroid prior to PcP diagnosis was independently associated with increased 90-day mortality, specifically in patients with IMIDs. These results highlight both the needs for PcP prophylaxis in patients with IMIDs and to early consider PcP curative treatment in severe pneumonia among patients with IMIDs.

Dalbavancin plasma concentrations in 133 patients: a PK/PD observational study.

OBJECTIVES: Limited pharmacokinetics data support dalbavancin long-term use in off-label indications and the optimal dosing regimen is debated. We aimed to describe dalbavancin concentrations in an observational retrospective multicentre study. METHODS: Patients from 13 French hospitals, treated with 1500 mg doses of dalbavancin and for whom therapeutic drug monitoring was performed from June 2018 to March 2021 were included. Dalbavancin plasma concentrations were described at peak and 1, 2, 3, 4, 6 and 8 weeks after the last 1500 mg dose. Concentrations in patients weighing more or less than 75 kg and with a GFR greater or less than 60 mL/min were compared. Microbiological data were collected and dalbavancin MIC was measured when possible. RESULTS: One hundred and thirty-three patients were included (69% treated for bone and joint infections, 16% for endocarditis). Thirty-five patients received a single dose of dalbavancin and 98 received several administrations. Two, 3 and 4 weeks after the last dose, median plasma concentrations were respectively 25.00, 14.80 and 9.24 mg/L for the first doses and 34.55, 22.60 and 19.20 mg/L for the second or subsequent doses. Weight and renal function had an impact on pharmacokinetics. Infection was documented in 105 patients (Staphylococcus spp. in 68% of cases). Staphylococcus aureus was isolated in 32.5% of cases (median MIC: 0.047 mg/L) and Staphylococcus epidermidis in 27% of cases (median MIC of 0.047 mg/L). CONCLUSIONS: Plasma concentrations of dalbavancin were consistent with those described in clinical trials and those sought during the industrial development of the molecule.

Effectiveness and safety of dalbavancin in France: a prospective, multicentre cohort study.

OBJECTIVES: Dalbavancin is a lipoglycopeptide antibiotic approved for the treatment of acute bacterial skin and skin structure infections. However, several studies have suggested that it is used mostly for off-label indications. We aimed to describe the use of dalbavancin in patients who received at least one dose of the antibiotic in France. METHODS: Prospective, observational, multicentre study conducted in France from September 2018 to April 2020. The primary outcome was the clinical response at 30 days after the last dalbavancin dose. RESULTS: A total of 151 patients in 16 centres were included in this study. The main infection sites were bone and joint infections (55.0%), multisite infections (15.9%), and vascular infections (14.6%), and the primary pathogens were coagulase-negative staphylococci (N = 82), Staphylococcus aureus (N = 51), and enterococci (N = 27). Most patients (71.5%) received three previous antibiotic treatments. The number of dalbavancin injections per patient was 1 in 26 patients (17.2%), 2 in 95 patients (62.9%), 3 in 17 patients (11.3%), and more than 3 in 13 patients (8.6%), with a mean cumulative dose of 3089 ± 1461 mg per patient. Among the 129 patients with a complete follow-up, clinical success was achieved in 119 patients (92.2%). At least 1 adverse event was reported in 67 patients (44.4%), including 12 (7.9%) patients with dalbavancin-related adverse events. CONCLUSIONS: The results of the study showed that dalbavancin is used mostly for off-label indications and in heavily pretreated patients in France. The clinical response at 30 days after the last dose was favourable in most patients, with a good safety profile.

Improving Diagnosis of Pulmonary Mucormycosis: Leads From a Contemporary National Study of 114 Cases.

BACKGROUND: Pulmonary mucormycosis (PM) is a life-threatening invasive mold infection. Diagnosis of mucormycosis is challenging and often delayed, resulting in higher mortality. RESEARCH QUESTION: Are the disease presentation of PM and contribution of diagnosis tools influenced by the patient's underlying condition? STUDY DESIGN AND METHODS: All PM cases from six French teaching hospitals between 2008 and 2019 were retrospectively reviewed. Cases were defined according to updated European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria with the addition of diabetes and trauma as host factors and positive serum or tissue PCR as mycologic evidence. Thoracic CT scans were reviewed centrally. RESULTS: A total of 114 cases of PM were recorded, including 40% with disseminated forms. Main underlying conditions were hematologic malignancy (49%), allogeneic hematopoietic stem cell transplantation (21%), and solid organ transplantation (17%). When disseminated, main dissemination sites were the liver (48%), spleen (48%), brain (44%), and kidneys (37%). Radiologic presentation included consolidation (58%), pleural effusion (52%), reversed halo sign (26%), halo sign (24%), vascular abnormalities (26%), and cavity (23%). Serum quantitative polymerase chain reaction (qPCR) was positive in 42 (79%) of 53 patients and BAL in 46 (50%) of 96 patients. Results of transthoracic lung biopsy were diagnostic in 8 (73%) of 11 patients with noncontributive BAL. Overall 90-day mortality was 59%. Patients with neutropenia more frequently displayed an angioinvasive presentation, including reversed halo sign and disseminated disease (P < .05). Serum qPCR was more contributive in patients with neutropenia (91% vs 62%; P = .02), and BAL was more contributive in patients without neutropenia (69% vs 41%; P = .02). Serum qPCR was more frequently positive in patients with a > 3 cm main lesion (91% vs 62%; P = .02). Overall, positive qPCR was associated with an early diagnosis (P = .03) and treatment onset (P = .01). INTERPRETATION: Neutropenia and radiologic findings influence disease presentation and contribution of diagnostic tools during PM. Serum qPCR is more contributive in patients with neutropenia and BAL examination in patients without neutropenia. Results of lung biopsies are highly contributive in cases of noncontributive BAL.

Non-HACEK gram-negative bacilli endocarditis: a multicentre retrospective case-control study.

BACKGROUND: Infective endocarditis (IE) caused by non-HACEK gram-negative bacilli (GNB) is poorly characterised and may be emerging as a consequence of medical progress. METHODS: We performed an observational retrospective case-control study. Cases were non-HACEK GNB IE, definite or possible (modified Duke criteria), diagnosed in adults between 2007 and 2020 in six French referral hospitals. Two controls were included for each case (IE due to other bacteria, matched by sites and diagnosis date). RESULTS: Non-HACEK GNB were identified in 2.4% (77/3230) of all IE during the study period, with a mean age of 69.2 ± 14.6 years, and a large male predominance (53/77, 69%). Primary pathogens were Escherichia coli (n = 33), Klebsiella sp. (n = 12) and Serratia marcescens (n = 9), including eight (10%) multidrug-resistant GNB. Compared to controls (n = 154: 43% Streptococcus sp., 41% Staphylococcus sp. and 12% Enterococcus sp.), non-HACEK GNB IE were independently associated with intravenous drug use (IVDU, 8% vs. 2%, p = .003), active neoplasia (15% vs. 6%, p = .009), haemodialysis (9% vs. 3%, p = .007) and healthcare-associated IE (36% vs. 18%, p = .002). Urinary tract was the main source of infection (n = 25, 33%) and recent invasive procedures were reported in 29% of cases. Non-HACEK GNB IE were at lower risk of embolism (31% vs. 47%, p = .002). One-year mortality was high (n = 28, 36%). Comorbidities, particularly malignant hemopathy and cirrhosis, were associated with increased risk of death. CONCLUSIONS: Non-HACEK GNB are rarely responsible for IE, mostly as healthcare-associated IE in patients with complex comorbidities (end-stage renal disease, neoplasia), or in IVDUs.

Social representations of mask wearing in the general population during the COVID-19 pandemic.

Introduction: Although one of the most prominent interventions against COVID-19, face masks seem poorly adopted by the general population. A growing body of literature has found that using face masks has social meaning. This qualitative study assessed the perceptions, representations and practices of mask wearing in the general population. Methods: A qualitative survey by short semi-structured walking interviews was carried out from April to December 2021 in 11 cities in France's Pays de la Loire region. Study locations were selected for their varied geographical, social, and economic characteristics, with urbanized and rural areas. Four domains linked to perceptions of masks and wearing them were explored: (i) evolution in mask wearing, (ii) decision-making methods for wearing and not wearing; (iii) incorporating the mask into way of life; (iv) projecting into the future. Results: A total of 116 people were interviewed. Masks marked a shift from the ordinary world to the pandemic. Overall, interviewees considered masks an obstacle to breathing, communication, and social interactions, leading to establishing strategies circumventing the mask mandate. Poor attention was paid to their medical usefulness as an obligatory clothing accessory. Mask-wearing decisions were driven by social relations, common sense, and vulnerability. The greater the feeling of security (i.e., being with close relatives), the less it was worn or worn properly, with decreased attention to others and their health. Most participants did not remember learning to wear a mask. Some were convinced that mask-wearing could not be learned (experiential knowledge). Institutions (school and work) played a central role by facilitating incorporation of masks into daily life. Conclusions: This study emphasizes the need to reinforce the individual medical values of face masks to prevent COVID-19. Ambitious education and training programmes should be planned to learn how and when to wear masks. Institutions (work and school) may be critical for this purpose.

18F-FDG-Based Radiomics and Machine Learning: Useful Help for Aortic Prosthetic Valve Infective Endocarditis Diagnosis?

BACKGROUND: Fluorine-18 fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET)/computed tomography (CT) results in better sensitivity for prosthetic valve endocarditis (PVE) diagnosis, but visual image analysis results in relatively weak specificity and significant interobserver variability. OBJECTIVES: The primary objective of this study was to evaluate the performance of a radiomics and machine learning-based analysis of 18F-FDG PET/CT (PET-ML) as a major criterion for the European Society of Cardiology score using machine learning as a major imaging criterion (ESC-ML) in PVE diagnosis. The secondary objective was to assess performance of PET-ML as a standalone examination. METHODS: All 18F-FDG-PET/CT scans performed for suspected aortic PVE at a single center from 2015 to 2021 were retrospectively included. The gold standard was expert consensus after at least 3 months' follow-up. The machine learning (ML) method consisted of manually segmenting each prosthetic valve, extracting 31 radiomics features from the segmented region, and training a ridge logistic regressor to predict PVE. Training and hyperparameter tuning were done with a cross-validation approach, followed by an evaluation on an independent test database. RESULTS: A total of 108 patients were included, regardless of myocardial uptake, and were divided into training (n = 68) and test (n = 40) cohorts. Considering the latter, PET-ML findings were positive for 13 of 22 definite PVE cases and 3 of 18 rejected PVE cases (59% sensitivity, 83% specificity), thus leading to an ESC-ML sensitivity of 72% and a specificity of 83%. CONCLUSIONS: The use of ML for analyzing 18F-FDG-PET/CT images in PVE diagnosis was feasible and beneficial, particularly when ML was included in the ESC 2015 criteria. Despite some limitations and the need for future developments, this approach seems promising to optimize the role of 18F-FDG PET/CT in PVE diagnosis.

Expert consensus on monitoring antimicrobial stewardship in French nursing homes using assessed reimbursement database indicators.

Objectives: Monitoring the appropriateness of antibiotic prescriptions with indicators based on reimbursement data is required to guide antibiotic stewardship (AMS) interventions in nursing homes (NHs). Quantity metrics (QMs) monitor the volume of prescriptions while proxy indicators (PIs) reflect the appropriateness of antibiotic use. Our objectives were: (i) to provide a relevant consensual set of indicators to be used in French NHs; and (ii) to assess the feasibility of their implementation at the national and local scale. Methods: Nine French professional organizations implicated in AMS in NHs were asked to nominate at least one member to create a national expert panel of 20 physicians. Twenty-one recently published QMs and 11 PIs were assessed by the expert panel. Indicators were evaluated using a RAND-modified Delphi procedure comprising two online surveys and a videoconference meeting. Indicators were kept in the final list if >70% of stakeholders validated their relevance for estimating the volume (QMs) and appropriateness (PIs) of prescriptions. Results: Of the 21 QM indicators submitted to the panel, 14 were selected, describing the consumption of antibiotics overall (n = 3), broad-spectrum (n = 6) and second-line antibiotics (n = 2). The three remaining QMs evaluated the route of administration (n = 1) and urine culture prescriptions (n = 2). Ten PIs (six modified, two rejected, one new) were selected to assess the appropriateness of prescriptions for urinary tract infections (n = 2), seasonal variations in prescriptions (n = 2), repeated prescriptions of fluoroquinolones (n = 1), cephalosporins' route of administration (n = 1), duration of treatment (n = 1), rate of second-line antibiotics (n = 1), co-prescriptions with non-steroidal anti-inflammatory drugs (n = 1), and flu vaccine coverage (n = 1). The panel was in favour of using these indicators for regional and facility level AMS programmes (91%), feedback to NH prescribers (82%), benchmarking by health authorities (55%) and public reporting at the facility level (9%). Conclusions: This consensual list of indicators, covering a wide range of frequent clinical situations, may be used as part of the French national AMS strategy for monitoring antibiotic prescriptions in NHs at the national and local levels. Regional AMS networks might manage this selected list to guide personalized action plans with concrete objectives of reducing the quantity and improving the quality of antibiotic prescriptions.

Qualitative assessment of the national initiative to implement antimicrobial stewardship centres in French administrative regions.

BACKGROUND: In May 2020, the French Ministry of Health funded the creation of regional antimicrobial stewardship (AMS) coordination centres (CRAtb) in preparation for the new national framework for the prevention of antimicrobial resistance. This study aimed to assess through qualitative methods the implementation process, the activities carried out, and the interactions with other regional stakeholders of the newly created CRAtb. METHODS: We conducted a mixed-method study based on a cross-sectional survey and semi-structured interviews by French regions among implemented CRAtb. Of the eight eligible French regions with an existing CRAtb, seven participated to the online survey. Regional partners involved in AMS from the eight regions were interviewed between September 2021 and April 2022. The survey questionnaire addressed, through closed questions, the organization of the CRAtb, articulation with other regional actors involved in AMS and infection prevention and control (IPC), and AMS activities. The semi-structured interviews approached the implementation and the role of CRAtb, and the collaboration of other AMS and IPC stakeholders. Interview transcripts were analysed using thematic content analysis methodology. RESULTS: AMS activities carried out by CRAtb were mainly focusing on hospitals (n = 3), primary care (n = 2) and nursing homes (n = 1). Education mostly relied on training days and AMS help lines, communication on websites and newsletters. CRAtb members reported still being more engaged in providing advice to professionals for individual antibiotic treatments rather than collective-level AMS activities. Interactions were frequent between CRAtb, IPC regional centres and health authorities, but rarely involved other stakeholders. Interviews were performed with 28 professionals involved in AMS from eight regions. Pre-existing networks and working relationships in AMS and more broadly facilitated the implementation of CRAtb. Streamlining and decompartmentalizing IPC and AMS regional activities were considered a way to optimise the prevention of antimicrobial resistance across sectors. The engagement with liberal health professionals was identified as a significant obstacle for CRAtb. CONCLUSIONS: Two years after the launch of a new national framework, the implementation of CRAtb appeared complex in most regions. An integrative model joining IPC and AMS efforts, relying on existing networks, with engagement from liberal health profession organisations may be the next pivotal step.

Invasive bone and joint infections from the French Scedosporiosis/lomentosporiosis Observational Study (SOS) cohort: no mortality with long-term antifungal treatment and surgery.

Little is known about localized osteoarticular Scedosporiosis (LOS). Most data come from case reports and small case series. Here we present an ancillary study of the nationwide French Scedosporiosis Observational Study (SOS), describing 15 consecutive cases of LOS diagnosed between January 2005 and March 2017. Adult patients diagnosed with LOS defined by osteoarticular involvement without distant foci reported in SOS were included. Fifteen LOS were analyzed. Seven patients had underlying disease. Fourteen patients had prior trauma as potential inoculation. Clinical presentation was arthritis (n = 8), osteitis (n = 5), and thoracic wall infection (n = 2). The most common clinical manifestation was pain (n = 9), followed by localized swelling (n = 7), cutaneous fistulization (n = 7), and fever (n = 5). The species involved were Scedosporium apiospermum (n = 8), S. boydii (n = 3), S. dehoogii (n = 1), and Lomentospora prolificans (n = 3). The species distribution was unremarkable except for S. boydii, which was associated with healthcare-related inoculations. Management was based on medical and surgical treatment for 13 patients. Fourteen patients received antifungal treatment for a median duration of 7 months. No patients died during follow-up. LOS exclusively occurred in the context of inoculation or systemic predisposing factors. It has a non-specific clinical presentation and is associated with an overall good clinical outcome, provided there is a prolonged course of antifungal therapy and adequate surgical management.

Localized osteoarticular scedosporiosis mostly occurs following direct inoculation. Management was most often based on voriconazole therapy and concomitant surgery. Unlike other invasive scedosporiosis, no patient died during follow-up.

Development and validation of a dosing nomogram for continuous infusion cloxacillin in infective endocarditis.

BACKGROUND: Cloxacillin is the first-line treatment for methicillin-susceptible staphylococcal infective endocarditis (IE). The recommended dose is 12 g per day regardless of the patient characteristics, despite the importance of renal function on its pharmacokinetics. OBJECTIVES: We sought to build a population pharmacokinetics model of continuous infusion cloxacillin in IE patients to evaluate the influence of multiple covariates and then develop a nomogram based on significant covariates for individual adaptation. PATIENTS AND METHODS: We included patients of a local IE cohort who were treated with cloxacillin administered by continuous infusion, excluding those who received intermittent or continuous dialysis, extracorporeal membrane oxygenation or extracorporeal circulation. The population pharmacokinetic analysis was performed using Pmetrics. The influence of weight, ideal weight, height, body mass index, body surface area, glomerular filtration rate (GFR) calculated with the Chronic Kidney Disease Epidemiology Collaboration formula (both expressed in mL/min/1.73 m² and in mL/min) and serum protein level on cloxacillin pharmacokinetics was assessed. Accounting for relevant covariates, a dosing nomogram was developed to determine the optimal daily dose required to achieve a steady-state plasma concentration range of 20-50 mg/L with a probability ≥0.9. RESULTS: A total of 114 patients (331 plasma concentrations) were included. A one-compartment model including GFR expressed in mL/min as a covariate was chosen. Using the nomogram, achieving the cloxacillin concentration target requires a daily dose ranging from 3.5 to 13.1 g for a GFR ranging from 20 to 125 mL/min. CONCLUSIONS: This work provided a practical tool for cloxacillin dose adjustment in IE according to renal function.

Impact of Enterococcus faecalis Endocarditis Treatment on Risk of Relapse.

BACKGROUND: Enterococcus faecalis infective endocarditis (EFIE) is characterized by a higher frequency of relapses than other infective endocarditis. The role of the treatment on its occurrence remains poorly understood. The aim of this study was to investigate whether the antibiotic regimen could impact the risk of relapse in EFIE. MATERIALS: This was a multicenter retrospective study of patients diagnosed with definite EFIE between 2015 and 2019 in 14 French hospitals. The primary endpoint was the occurrence of relapses within the year following endocarditis diagnosis. As death was a competing risk for relapse, Fine and Gray models were used for studying risk factors and impact of treatment. RESULTS: Of the 279 patients included, 83 (29.7%) received the amoxicillin-gentamicin (A-G) combination, 114 (40.9%) amoxicillin-ceftriaxone (A-C), 63 (22.6%) A-G and A-C (A-G/A-C) sequentially, 9 (3.2%) amoxicillin (A), and 10 received other treatments. One-year-relapse rate was 9.3% (26 patients). Relapse occurred after a median delay of 107 days from EFIE diagnosis; 6 occurred after 6 months, and 6 were diagnosed by blood cultures in asymptomatic patients. In multivariate analysis, surgery during treatment was a protective factor against one-year relapse and death.The cumulative incidence of relapse 1 year after endocarditis was 46.2% for patients treated with amoxicillin, 13.4% with A-G, 14.7% with A-C, and 4.3% with A-G/A-C (P≥.05 in multivariate analysis). CONCLUSIONS: Relapses after treatment of EFIE are frequent, frequently asymptomatic, and may occur more than 6 months after the initial episode.

Assessment of Factors Associated With Community-Acquired Extended-Spectrum ß-Lactamase-Producing Escherichia coli Urinary Tract Infections in France.

Importance: Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli is considered a leading pathogen contributing to the global burden of antimicrobial resistance. Objective: To better understand factors associated with the heterogeneity of community-acquired ESBL-producing E coli urinary tract infections (UTIs) in France. Design, Setting, and Participants: This cross-sectional study performed from January 1 to December 31, 2021, was based on data collected via PRIMO (Surveillance and Prevention of Antimicrobial Resistance in Primary Care and Nursing Homes), a nationwide clinical laboratory surveillance system in France. Strains of E coli isolated from community urine samples from January 1 to December 31, 2019, from 59 administrative departments of metropolitan France were included. Main Outcomes and Measures: Quasi-Poisson regression models were used to assess the associations between several ecological factors available on government and administration websites between 2010 and 2020 (demographic population structure, living conditions, baseline health care services, antibiotic consumptions, economic indicators, animal farming density, and environmental characteristics) and the number of ESBL-producing E coli strains isolated from urine samples of individuals with community-acquired UTI in 2019. Results: Among 444 281 E coli isolates from urine samples tested in 1013 laboratories, the mean prevalence of ESBL-producing E coli was 3.0% (range, 1.4%-8.8%). In an adjusted model, the number of community-acquired ESBL-producing E coli UTIs in each department was positively associated with the percentage of children younger than 5 years (adjusted ß1 coefficient, 0.112 [95% CI, 0.040-0.185]; P = .004), overcrowded households (adjusted ß1 coefficient, 0.049 [95% CI, 0.034 to 0.062]; P < .001), consumption of fluoroquinolones (adjusted ß1 coefficient, 0.002 [95% CI, 0.001-0.002]; P < .001), and tetracyclines (adjusted ß1 coefficient, 0.0002 [0.00004 to 0.00039]; P = .02), and poultry density (adjusted ß1 coefficient, 0.0001 [95% CI, 0.0001-0.0002]; P < .001). The social deprivation index (adjusted ß1 coefficient, -0.115 [95% CI, -0.165 to -0.064]; P < .001) and the proportion of water surface area (adjusted ß1 coefficient, -0.052 [-0.081 to -0.024]; P = .001) were negatively associated with a higher number of community-acquired ESBL-producing E coli UTIs. Conclusions and Relevance: The findings of this cross-sectional study suggest that multiple human health, animal health, and environmental factors are associated with the occurence of community-acquired ESBL E coli UTI. Strategies to mitigate ESBL in the community should follow the One Health approach and address the role played by fluoroquinolones, tetracycline use, poultry density, overcrowded households, and preschool-aged children.