Correlation between antifungal clinical practices and a new clinical decision support system ANTIFON-CLIC® for the treatment of invasive candidiasis: a retrospective multicentre study.

BACKGROUND: Invasive candidiasis is still recognized as a major cause of morbidity and mortality. To support clinicians in the optimal use of antifungals for the treatment of invasive candidiasis, a computerized decision support system (CDSS) was developed based on institutional guidelines. OBJECTIVES: To evaluate the correlation of this newly developed CDSS with clinical practices, we set-up a retrospective multicentre cohort study with the aim of providing the concordance rate between the CDSS recommendation and the medical prescription (NCT05656157). PATIENTS AND METHODS: Adult patients who received caspofungin or fluconazole for the treatment of an invasive candidiasis were included. The analysis of factors associated with concordance was performed using mixed logistic regression models with department as a random effect. RESULTS: From March to November 2022, 190 patients were included from three centres and eight departments: 70 patients from centre A, 84 from centre B and 36 from centre C. Overall, 100 patients received caspofungin and 90 received fluconazole, mostly (59%; 112/190) for empirical/pre-emptive treatment. The overall percentage of concordance between the CDSS and medical prescriptions was 91% (173/190) (confidence interval 95%: 82%-96%). No significant difference in concordance was observed considering the centres (P > 0.99), the department of inclusion (P = 0.968), the antifungal treatment (P = 0.656) or the indication of treatment (P = 0.997). In most cases of discordance (n = 13/17, 76%), the CDSS recommended fluconazole whereas caspofungin was prescribed. The clinical usability evaluated by five clinicians was satisfactory. CONCLUSIONS: Our results demonstrated the high correlation between current antifungal clinical practice and this user-friendly and institutional guidelines-based CDSS.

Early picc-line infections in non-neutropenic patients are mainly due to E. coli suggesting that third-generation cephalosporin may be used as a first-line antibiotic therapy.

PURPOSE: To describe the rate of peripherally inserted central catheter (PICC) -associated bloodstream infections, and the pathogens involved. METHODS: We prospectively analyzed data collected from all adult patients with a PICC insertion in a hematology unit in a tertiary care center between January 1, 2017 and June 30, 2020. RESULTS: A total of 370 PICCs were inserted in 275 patients with hematological malignancies: 54 (15 %) confirmed cases of central-line associated bloodstream infection (CLABSI) were identified. Enterobacteria were the most frequent bacteria identified, involved in 35 % of CLABSIs. Group 1 enterobacteria bacteremia occurred a much shorter time after insertion (median time to CLABSI 16 days) than group 2 or group 3 enterobacteria (median time to CLABSI 64 days, p-value = 0.049). CONCLUSION: Among Gram-negative bacilli CLABSI among non-neutropenic patients, E. coli identification was the most frequent and occurred earlier after insertion, suggesting that third-generation cephalosporin may be used as a first-line antibiotic therapy for enterobacteria bacteremia among non-neutropenic patients.

Comparing ethanol lock therapy versus vancomycin lock in a salvation strategy for totally implantable vascular access device infections due to coagulase-negative staphylococci (the ETHALOCK study): a prospective double-blind randomized clinical trial.

OBJECTIVES: Little is known about efficacy and safety of ethanol lock therapy (ELT) to treat totally implantable venous access device (TIVAD) infections. The objective of this trial was to evaluate the effectiveness and safety profile of a local treatment with ELT without removal for TIVAD infection due to coagulase-negative staphylococci. METHODS: We performed a prospective, multicenter, double-blind, randomized clinical trial comparing the efficacy of 40% ELT versus vancomycin lock therapy (VLT) in TIVAD infections due to coagulase-negative staphylococci, complicated or not by bloodstream infection. RESULTS: Thirty-one patients were assigned to the ELT group and 30 to the VLT arm. Concomitant bacteremia was present in 41 patients (67.2%). Treatment success was 58.1 % (18 of 31) for the ELT arm and 46.7% (14 of 30) for the VLT arm (p = 0.37). The overall treatment success was 52.5% (32). The risk of treatment failure due to uncontrolled infections, superinfections, and mechanical complications did not differ significantly between participants receiving ELT (13 out of 31 [42%]) and those receiving VLT (16 out of 30 [53%]) with a hazard ratio of 0.70 (p = 0.343; 95% CI [0.34-1.46], Cox model). Catheter malfunctions were significantly more frequent in the ELT arm (11 patients versus 2 in the VLT group, p = 0.01). CONCLUSIONS: We found an overall high rate of treatment failure that did not differ between the ELT arm and the VLT arm. TIVAD removal must be prioritized to prevent complications (uncontrolled infections, superinfections, and catheter malfunctions) except in exceptional situations.

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.

Diagnostic performances and therapeutic impact of the Unyvero Implant and Tissue Infection multiplex PCR in periprosthetic joint infections.

Aim: We evaluated the diagnostic performances of Unyvero Implant and Tissue Infection multiplex PCR (mPCR) (Curetis) and the clinical impact of this PCR on therapeutic decisions. Materials & methods: A mPCR was performed on 33 joint fluids in addition to standard culture. A group of experts analyzed a posteriori the impact of the mPCR in the patient management. Results: The rate of concordance with culture was 74% (20/27). The sensitivity of the PCR was 59% and the specificity 90%. Clinicians would have started an appropriate treatment sooner for six patients (from 2 to 22 days earlier). Conclusion: The PCR would improve the management of 22% of the patients. For other patients, mPCR results have to be completed with the culture.

Infectious disease hotlines to provide advice to general practitioners: a prospective study.

BACKGROUND: Telephone hotlines in infectious diseases (ID) are part of antimicrobial stewardship programs designed to provide support and expertise in ID and to control antibiotic resistance. The aim of the study was to characterize the activity of the ID hotlines and estimate their usefulness for general practitioners (GPs). METHODS: This was a multicenter prospective observational study in different French regions. ID teams involved in antimicrobial stewardship with a hotline for GPs were asked to record their advice from April 2019 to June 2022. In these regions, all GPs were informed of the ID hotline's operating procedures. The main outcome was usage rate of the hotlines by GPs. RESULTS: Ten volunteer ID teams collected 4138 requests for advice from 2171 GPs. The proportion of GPs using the hotline varied pronouncedly by region, from 54% in the Isere department, to less than 1% in departments with the lowest usage. These differences were associated with the number of physicians in ID teams and with the age of the hotline. These results highlighted the value of working time as a means of ensuring the permanence of expertise. The main reasons for calling were: a diagnostic question (44%); choice of antibiotic (31%). The ID specialist provided advice on antibiotic therapy (43%) or a proposal for specialized consultation or hospitalization (11%). CONCLUSIONS: ID hotlines could help to strengthen cooperation between primary care and hospital medicine. However, the deployment and perpetuation of this activity require reflection concerning its institutional and financial support.

Fatal HSV-2 primary infection most likely acquired by kidney transplantation: A case report.

Herpes simplex virus 2 (HSV-2) rarely causes severe disease, even in solid organ transplant recipients. This paper describes a fatal case of HSV-2 infection, probably transmitted from a donor to a kidney transplant recipient. The donor was seropositive for HSV-2 but not for HSV-1, whereas the recipient was seronegative for both viruses before transplantation, suggesting that the graft was the source of infection. The recipient received valganciclovir prophylaxis due to cytomegalovirus seropositivity. Three months after transplantation, the recipient presented with rapidly disseminated cutaneous HSV-2 infection with meningoencephalitis. The HSV-2 strain was resistant to acyclovir, probably acquired under valganciclovir prophylaxis. Despite early initiation of acyclovir therapy, the patient died. This fatal case of HSV-2 infection, probably transmitted by the kidney graft with acyclovir-resistant HSV-2 from the onset, is uncommon.

Practical checklist for implementation of antifungal stewardship programmes.

Introduction. Antifungal stewardship programmes are needed in healthcare facilities to limit the overuse or misuse of antifungals, which are responsible for an increase in antifungal resistance.Hypothesis/Gap Statement. Core recommendations for antifungal stewardship were published by the Mycoses Study Group Education and Research Consortium, while the Centers for Disease Control and Prevention (CDC) provided a Core Elements of Hospital Antibiotic Stewardship Programs checklist. The recommendations offer global core elements for best practices in antifungal stewardship, but do not provide a framework for the implementation of antifungal stewardship programmes in healthcare facilities.Aim. In line with the recommendations, it is of the utmost importance to establish a practical checklist that may be used to implement antifungal stewardship programmes.Methodology. The practical checklist was established by a national consensus panel of experts involved in antifungal stewardship activities. A preliminary checklist was sent to all experts. The final document was approved by the panel after discussion and the resolution of any disagreements by consensus.Results. The final checklist includes the following items: leadership support; actions to support optimal antifungal use; actions to monitor antifungal prescribing, use and resistance; and an education programme.Conclusion. This antifungal stewardship checklist offers opportunities for antifungal resistance containment, given that antifungal stewardship activities promote the optimal use of antifungals.

Incidence of Avoidable 30-Day Readmissions Following Hospitalization for Community-Acquired Pneumonia in France.

Importance: Rates of 30-day readmissions following hospitalization for pneumonia are used to publicly report on hospital performance and to set financial penalties for the worst-performing hospitals. However, the rate of avoidable readmission following hospitalization for pneumonia is undefined. Objective: To assess how often 30-day readmissions following hospitalization for community-acquired pneumonia (CAP) are avoidable. Design, Setting, and Participants: This cohort study analyzed the results of an independent review of readmissions following hospitalization for CAP within 30 days among patients discharged from 2 large hospitals in France in 2014. Structured clinical records including clinical information (ie, baseline characteristics, physical examination, laboratory findings, x-ray or computed tomography scan findings, discharge plan, and treatments) for both index and readmission stays were independently reviewed by 4 certified board physicians. All consecutive adult patients hospitalized in 2014 with a diagnosis of CAP in our 2 eligible hospitals were eligible. All analyses presented were performed in March 2021. Main Outcomes and Measures: Avoidable readmission within 30 days of discharge from index hospitalization. The likelihood that a readmission was avoidable was quantified using latent class analysis based on the independent reviews. A readmission was considered avoidable if Bayes posterior probability exceeded 50%. Results: The total analytical sample consisted of 1150 index hospital stays with a diagnosis of CAP, which included 651 (56.6%) male patients. The median (IQR) age for all patients was 77.8 (IQR, 62.7-86.4) years. Out of the 1150 index hospital stays, 98 patients (8.5%) died in hospital, and 108 (9.4%) unplanned readmissions were found. Overall, 15 readmissions had a posterior probability of avoidability exceeding 0.50 (13.9% of the 108 unplanned readmissions; 95% CI, 8.0%-21.9%). The median (IQR) delay between the hospital discharge index and readmission was considerably shorter when readmission was deemed avoidable (4 [6-21] days vs 12 [2-18] days; P = .02). Conclusions and Relevance: Only a small number of readmissions following hospitalization for CAP were deemed avoidable, comprising less than 10% of all readmissions. Shorter time interval between hospitalization discharge and readmission was associated with avoidability.

Dalbavancin in clinical practice: a particular place for the elderly?

We investigate dalbavancin efficiency and tolerance among elderly in Grenoble-Alpes 32 university hospital. Among the 65 patients who received dalbavancin, 51% (33) were considered as old. Patients presented mainly bones and joint infections (52%), surgical site infection 34 (31%), and infective endocarditis (IE) (8%). Clinical cure was confirmed for 79% of old 35 patients at 1, 3, and 6 months. Six adverse events (9%) were reported after 36 dalbavancin's administration, but each time in combination with other antibiotics. 37 Dalbavancin had a significant effectiveness and safety profile and represents a real 38 therapeutic option in the management of deep and complex infections of elderly patients.

Epidemiology and outcome of occult bacteremia in patients discharged from emergency departments or ambulatory units: one-year study.

Microbiological diagnosis of bloodstream infection (BSI) is made several hours after blood culture sampling. This delay could be critical in ambulatory clinics, emergency departments, and hospital day care units, as the patient may be discharged prior to blood culture positivity. Our aim was to evaluate the clinical outcome (including the number of readmissions) of patients diagnosed with BSI after discharge. We prospectively included all adult patients with positive blood culture for BSI that was confirmed after discharge from our center (Grenoble-Alpes University Hospital) in 2016. Patients were contacted about their blood culture results, and their clinical status was controlled via an external consultation or their family physician, with hospital readmission if necessary. Clinical outcome, accuracy of initial diagnosis, microbiological epidemiology, and antibiotic prescription were assessed. In 2016, 1433 episodes of positive blood culture were detected in our hospital, with 50 (3.5%) occurring after patient discharge. Clinically relevant bacteria were determined in 32/50 cases (64%), while other positive blood culture results were considered to be contaminants. Clinical reevaluation was performed in 45 patients (90%). The diagnosis was changed during the clinical reassessment of 24/49 patients (49%). Antibiotics were prescribed prior to discharge for 24/50 patients (48%), modified during follow-up for 15/45 (33%), and initiated for 13/45 (29%) at the reevaluation. Overall, 24/45 (53%) patients were readmitted to hospital units after reevaluation. The clinical follow-up of patients with positive blood culture after discharge led to diagnostic changes and hospital readmission in around half of patients.

Dalbavancin treatment for prosthetic joint infections in real-life: a national cohort study and literature review.

OBJECTIVES: Dalbavancin is a long-lasting lipoglycopeptide active against Gram-positive bacteria, especially methicillin-resistant staphylococci. Few data are available on dalbavancin use for treatment of prosthetic joint infections (PJIs). We describe a cohort of patients treated for PJI with dalbavancin and review the literature regarding this condition. METHODS: All adult patients with PJI from the French dalbavancin national cohort from 1 June 2017 to 1 January 2019 were included. We collected clinical and microbiological characteristics and outcome through a standardised questionnaire. Clinical cure was defined as absence of clinical signs of infection at last visit. Failure was a composite criterion defined by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. The literature review was performed using PubMed. RESULTS: Seventeen patients were included. Bacteria were identified in 16 cases: Staphylococcus aureus (n = 10), including methicillin-resistant S. aureus (n = 1); and coagulase-negative staphylococci (n = 10), including methicillin-resistant Staphylococcus epidermidis (n = 4). Sixteen patients (94.1%) had received antibiotic therapy prior to dalbavancin use (mean of 2.2 ± 1.3 lines). Clinical cure was achieved in 8/17 patients after a median follow-up of 299.0 (IQR 97.0-476.0) days. We reviewed all cases of PJI treated with dalbavancin available in the literature and the overall clinical cure was estimated at 73.1%. CONCLUSION: Our study and literature data suggest that use of dalbavancin in PJI could be considered, even as salvage therapy. Dalbavancin appears to be a safe and easy treatment for patients with staphylococcal PJIs.

Description of an influenza outbreak in a French university hospital and risk factors of nosocomial influenza.

Our objective was to evaluate risk factors of nosocomial influenza (NI) in an university hospital during the 2015/2016 influenza season. All hospitalized patients with influenza-like illness associated with laboratory confirmation by polymerase chain reaction were included in a prospective observational study. We identified 44 cases (19%) of NI among the 233 cases of influenza: 38/178 (21%) in adults and 6/55 (11%) in children. Among adults, hospitalization in a double or multi-occupancy room was independently associated with NI (adjusted Odds Ratio, 3.42; 95% CI, 1.29-9.08; p = 0.013). The results of the study underline the importance of single room to prevent NI.

Evaluation of Microbiological Performance and the Potential Clinical Impact of the ePlex® Blood Culture Identification Panels for the Rapid Diagnosis of Bacteremia and Fungemia.

Molecular rapid diagnostic assays associated with antimicrobial stewardship have proven effective for the early adaptation of empiric therapy in bloodstream infections. The ePlex® BCID (GenMark Diagnostics) Panels allow identification of 56 bacteria and fungi and 10 resistance genes in 90 min directly from positive blood cultures. We prospectively evaluated 187 sepsis episodes at Grenoble University Hospital and retrospectively analyzed the cases to measure the potential clinical impact of the ePlex BCID results. Identification of all pathogens was obtained for 164/187 (88%) bloodstream infections with 100% detection of antimicrobial resistance genes (17 blaCTX-M , 1 vanA, and 17 mecA genes). Only 15/209 (7%) strains were not covered by the panels. Sensitivity for detection of micro-organisms targeted by the RUO BCID-GP, BCID-GN, and BCID-FP Panels was respectively 84/84 (100%), 103/107 (96%), and 14/14 (100%). Interestingly, accurate identification of all pathogens was achieved in 15/17 (88%) polymicrobial samples. Retrospective analysis of medical records showed that a modification of antimicrobial treatment would have been done in 45% of the patients. Treatment modifications would have been an optimization of empiric therapy, a de-escalation or an escalation in respectively 16, 17, and 11% of the patients. Moreover, 11% of the samples were classified as contaminants or not clinically relevant and would have led to early de-escalation or withdrawal of any antibiotic. Detection of resistance genes in addition to identification alone increased escalation rate from 4 to 11% of the patients. Absence of the ePlex result was considered a lost opportunity for therapy modification in 28% of patients.

Evaluation of Rapid Sepsityper® protocol and specific MBT-Sepsityper module (Bruker Daltonics) for the rapid diagnosis of bacteremia and fungemia by MALDI-TOF-MS.

During bloodstream infections, rapid adaptation of empirical treatment according to the microorganism identified is essential to decrease mortality. The aim of the present study was to assess the microbiological performances of a new rapid version of the Sepsityper® kit (Bruker Daltonics) allowing identification of bacteria and yeast by MALDI-TOF mass spectrometry directly from positive blood cultures in 10 min and of the specific MBT-Sepsityper module for spectra analysis, designed to increase identification performance. Identification rates were determined prospectively on 350 bacterial and 29 fungal positive blood cultures, and compared to conventional diagnostic method. Our rapid diagnosis strategy (Rapid Sepsityper® protocol: one spot with and one without formic acid extraction step) combined to MBT-Sepsityper module provided 65.4%, 78.9% and 62% reliable identification to the species level of monomicrobial positive blood cultures growing respectively Gram-positive, Gram-negative bacteria or yeast. Importantly, identification rates of Gram-positive bacteria were higher in anaerobic than in aerobic bottles (77.8% vs 22.2%; p = 0.004), if formic acid extraction step was performed (60.8% vs 39.2%; p = 1.8e-6) and if specific MBT-Sepsityper module was used (76.2% vs 61.9%, p = 0.041) while no significant differences were observed for Gram-negative bacteria. For yeasts identification, formic acid extraction step improved rapid identification rate by 37.9% while the specific MBT-Sepsityper module increased overall performances by 38%, providing up to 89.7% reliable identification if associated with the standard Sepsityper® protocol. These performances, associated with a reduce turnaround time, may help to implement a rapid identification strategy of bloodstream infections in the routine workflow of microbiology laboratories.

Development of a risk prediction model of potentially avoidable readmission for patients hospitalised with community-acquired pneumonia: study protocol and population.

INTRODUCTION: 30-day readmission rate is considered an adverse outcome reflecting suboptimal quality of care during index hospitalisation for community-acquired pneumonia (CAP). However, potentially avoidable readmission would be a more relevant metric than all-cause readmission for tracking quality of hospital care for CAP. The objectives of this study are (1) to estimate potentially avoidable 30-day readmission rate and (2) to develop a risk prediction model intended to identify potentially avoidable readmissions for CAP. METHODS AND ANALYSIS: The study population consists of consecutive patients admitted in two hospitals from the community or nursing home setting with pneumonia. To qualify for inclusion, patients must have a primary or secondary discharge diagnosis code of pneumonia. Data sources include routinely collected administrative claims data as part of diagnosis-related group prospective payment system and structured chart reviews. The main outcome measure is potentially avoidable readmission within 30 days of discharge from index hospitalisation. The likelihood that a readmission is potentially avoidable will be quantified using latent class analysis based on independent structured reviews performed by four panellists. We will use a two-stage approach to develop a claims data-based model intended to identify potentially avoidable readmissions. The first stage implies deriving a clinical model based on data collected through retrospective chart review only. In the second stage, the predictors comprising the medical record model will be translated into International Classification of Diseases, 10th revision discharge diagnosis codes in order to obtain a claim data-based risk model.The study sample consists of 1150 hospital stays with a diagnosis of CAP. 30-day index hospital readmission rate is 17.5%. ETHICS AND DISSEMINATION: The protocol was reviewed by the Comité de Protection des Personnes Sud Est V (IRB#6705). Efforts will be made to release the primary study results within 6 months of data collection completion. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02833259).

Risk factors for Staphylococcus aureus surgical site infections after orthopaedic and trauma surgery in a French university hospital.

BACKGROUND: Surgical site infections (SSI) after orthopaedic surgery are responsible for reduced quality of life, increased length of hospital stay and costs. The most commonly identified organism is Staphylococcus aureus but risk factors for S. aureus SSI are not well-known. The aim of this study was to evaluate the incidence rate trend of S. aureus SSI over the years and risk factors of these infections in a French University Hospital. METHODS: SSI rates were expressed as cumulative incidence rates per year. A case-control study nested within a prospective cohort of patients undergoing orthopaedic or trauma surgery from January 1st, 2012 to April 30th, 2015 was performed. Cases were patients with S. aureus SSI; controls were patients without SSI. Risk factors of S. aureus SSI were identified by univariate and multivariable analysis. RESULTS: Of 7438 interventions, 50 (0.7%) S. aureus SSI were identified, without significant increase by years. A total of 46 S. aureus SSI was matched to 91 controls. Risk factors for S. aureus SSI were smoking (odds-ratio (OR) = 8.4, 95%CI 1.2-59.6) and National Nosocomial Infections Surveillance System score (NNISS) ≥1 (OR = 5.8, 95%CI 1.8-19.1). Having 1 or 2 preoperative antiseptic showers (OR = 0.3, 95%CI 0.1-0.7) was a protective factor. CONCLUSION: The rate of S. aureus SSI is not negligible after orthopaedic and trauma surgery. It seems imperative to strengthen smoking cessation recommendations, and to recall the importance of preoperative antiseptic showers. Systematic screening and decolonization for S. aureus carriage before orthopaedic and trauma surgery could be a means to prevent these infections.