Prescribers' experience and opinions on antimicrobial stewardship programmes in hospitals: a French nationwide survey.

OBJECTIVES: To assess prescribers' experiences and opinions regarding antimicrobial stewardship programme (ASP) activities. METHODS: A cross-sectional paper-based survey was conducted among prescribers in 27 out of 35 randomly selected large hospitals in France. RESULTS: All 27 investigated hospitals (20 non-university public, 4 university-affiliated and 3 private hospitals) had an ASP and an appointed antibiotic advisor (AA), with a median of 0.9 full-time equivalents per 1000 acute-care beds (IQR 0-1.4). Of the 1963 distributed questionnaires, 920 were completed (46.9%). Respondents were mainly attending physicians (658/918, 71.7%) and medical specialists (532/868, 61.3%). Prescribers identified two main ASP objectives: to limit the spread of resistance (710/913, 77.8%) and to improve patient care and prognosis (695/913, 76.1%). The presence of an AA constituted a core element of ASP (96.2% agreement between answers of ASP leader and respondents). Respondents acknowledged an AA's usefulness especially on therapeutic issues, i.e. choosing appropriate antibiotic (agreement 84.7%) or adapting treatment (89.6%), but less so on diagnostic issues (31.4%). Very few respondents reported unsolicited counselling and post-prescription controls. Three-quarters of prescribers identified local guidelines (692/918, 75.4%). Prescribers did not approve of measures counteracting their autonomy, i.e. automatic stop orders (agreement 23.4%) or pre-approval by AAs (28.8%). They agreed more with educational interventions (73.0%) and clinical staff meetings (70.0%). CONCLUSIONS: Prescribers perceived ASP mainly through its 'on-demand' counselling activities. They preferred measures that did not challenge their clinical autonomy. High levels of antibiotic consumption in French hospitals bring into question the effectiveness of such an approach. However, limited ASP staffing and resources may preclude extended activities.

Clinical management of respiratory syndrome in patients hospitalized for suspected Middle East respiratory syndrome coronavirus infection in the Paris area from 2013 to 2016.

BACKGROUND: Patients with suspected Middle East respiratory syndrome coronavirus (MERS-CoV) infection should be hospitalized in isolation wards to avoid transmission. This suspicion can also lead to medical confusion and inappropriate management of acute respiratory syndrome due to causes other than MERS-CoV. METHODS: We studied the characteristics and outcome of patients hospitalized for suspected MERS-CoV infection in the isolation wards of two referral infectious disease departments in the Paris area between January 2013 and December 2016. RESULTS: Of 93 adult patients (49 male (52.6%), median age 63.4 years) hospitalized, 82 out of 93 adult patients had returned from Saudi Arabia, and 74 of them were pilgrims (Hajj). Chest X-ray findings were abnormal in 72 (77%) patients. The 93 patients were negative for MERS-CoV RT-PCR, and 70 (75.2%) patients had documented infection, 47 (50.5%) viral, 22 (23.6%) bacterial and one Plasmodium falciparum malaria. Microbiological analysis identified Rhinovirus (27.9%), Influenza virus (26.8%), Legionella pneumophila (7.5%), Streptococcus pneumoniae (7.5%), and non-MERS-coronavirus (6.4%). Antibiotics were initiated in 81 (87%) cases, with two antibiotics in 63 patients (67.7%). The median duration of hospitalization and isolation was 3 days (1-33) and 24 h (8-92), respectively. Time of isolation decreased over time (P < 0.01). Two patients (2%) died. CONCLUSION: The management of patients with possible MERS-CoV infection requires medical facilities with trained personnel, and rapid access to virological results. Empirical treatment with neuraminidase inhibitors and an association of antibiotics effective against S. pneumoniae and L. pneumophila are the cornerstones of the management of patients hospitalized for suspected MERS-CoV infection.

Pharmacokinetic interaction between rifampicin and clindamycin in staphylococcal osteoarticular infections.

OBJECTIVES: Oral combination of clindamycin and rifampicin is relevant for the treatment of staphylococcal osteoarticular infection (SOAIs). However, rifampicin induces CYP3A4, suggesting a pharmacokinetic interaction with clindamycin with unknown pharmacokinetic/pharmacodynamic (PK/PD) consequences. This study aimed to quantify clindamycin PK/PD markers before and during rifampicin co-administration in SOAI. METHODS: Patients with SOAI were included. After initial intravenous antistaphylococcal treatment, oral therapy was started with clindamycin (600 or 750 mg t.i.d.), followed by addition of rifampicin 36 h later. Population PK analysis was performed using the SAEM algorithm. PK/PD markers were compared with and without rifampicin co-administration, each patient being his own control. RESULTS: In 19 patients, clindamycin median (range) trough concentrations were 2.7 (0.3-8.9) mg/L and <0.05 (<0.05-0.3) mg/L before and during rifampicin administration, respectively. Rifampicin co-administration increased clindamycin clearance by a factor 16 and reduced the AUC0-8h/MIC by a factor 15 (P < 0.005). Clindamycin plasma concentrations were simulated for 1000 individuals, without and with rifampicin. Against a susceptible Staphylococcus aureus strain (clindamycin MIC 0.0625 mg/L), >80% of individuals would reach all proposed PK/PD targets without co-administration of rifampicin, even with low clindamycin dose. For the same strain, when rifampicin was co-administered, the probability to reach clindamycin PK/PD targets dropped to 1% for %fT>MIC = 100% and to 6% for AUC0-24h/MIC > 60, even with high clindamycin dose. CONCLUSION: Rifampicin co-administration with clindamycin has a high impact on clindamycin exposure and PK/PD targets in SOAI, which could result in clinical failure even for fully susceptible strains.

[Paraplegia associated with intramedullary spinal cord and epidural abcesses, meningitis and spondylodiscitis (Staphylococcus aureus)]. / Paraplégie flasque due à des abcès intramédullaires et épiduraux à staphylocoques dorés. Méningite et spondylodiscite associées.

INTRODUCTION: Intramedullary spinal cord abscesses are rare, frequently associated with meningitis, sometimes with epidural abscesses. They are frequently responsible for paraplegia. Staphylococcus aureus is the predominant organism. MRI shows an intramedullary collection giving a low-intensity signal on T1-weighted images with peripheral contrast uptake on enhanced TI-weighted studies and a high-intensity signal on T2-weighted images with generally extended adjacent medullary edema. They may be multiple. CASE REPORT: We report the case of a man who presented meningitis with intramedullary and epidural abscesses. The number of the lesions did not allow chirurgical drainage. The paraplegia did not resolve despite appropriate antibiotic therapy. CONCLUSION: Appropriate antibiotic therapy and early surgical drainage, if feasible, are key factors for better outcome and prognosis.

Pulmonary bacterial infections in adult patients hospitalized for COVID-19 in standard wards.

OBJECTIVES: During the COVID-19 pandemic, antibiotic use was very common. However, bacterial co-/secondary infections with coronaviruses remain largely unknown in standard wards. We aimed to investigate the characteristics of pulmonary bacterial infections associated with COVID-19 in hospitalized patients. METHODS: A retrospective monocentric observational study was conducted in Bichat hospital, France, between February 26 and April 22, 2020. All patients hospitalized in standard wards with COVID-19 (positive nasopharyngeal PCR and/or typical aspect on CT-scan) and diagnosed with pulmonary bacterial infection (positive bacteriological samples) were included. Bacteriological and clinical data were collected from the microbiology laboratories and patient's medical records. RESULTS: Twenty-three bacteriological samples from 22 patients were positive out of 2075 screened samples (1.1%) from 784 patients (2.8%). Bacterial infection occurred within a median of 10 days after COVID-19 onset. Diagnosis of pulmonary bacterial infection was suspected on increase of oxygen requirements (20/22), productive cough or modification of sputum aspect (17/22), or fever (10/22). Positive samples included 13 sputum cultures, one FilmArray® assay on sputum samples, one bronchoalveolar lavage, six blood cultures, and two pneumococcal urinary antigen tests. The most frequent bacteria were Pseudomonas aeruginosa (6/23), Staphylococcus aureus (5/23), Streptococcus pneumoniae (4/23), Enterococcus faecalis (3/23), and Klebsiella aerogenes (3/23). No Legionella urinary antigen test was positive. Four out of 496 nasopharyngeal PCR tests (0.8%) were positive for intracellular bacteria (two Bordetella pertussis and two Mycoplasma pneumonia). CONCLUSIONS: Pulmonary bacterial secondary infections and co-infections with SARS-CoV-2 are uncommon. Antibiotic use should remain limited in the management of COVID-19.

Clinical trial protocols of repurposed prophylaxis for COVID-19: A review.

Efficient therapeutic strategies are needed to counter the COVID-19 pandemic, caused by the SARS-CoV-2 virus. In a context where specific vaccines are not yet available, the containment of the pandemic would be facilitated with efficient prophylaxis. We screened several clinical trials repositories and platforms in search of the prophylactic strategies being investigated against COVID-19 in July 2020. Up to July 5, 2020, only one clinical trial result was published, although we found 112 clinical trial protocols targeting medical workers (n=70, 63%), patients relatives (n=20, 18%) or individuals at risk of severe COVID-19 (n=14, 13%). (Hydroxy)chloroquine was the most frequently evaluated treatment (n=69, 62%), before BCG vaccine (n=12, 11%), this followed by numerous antivirals and immune enhancers. Ninety-eight (88%) clinical trials were randomized with a median of planned inclusions of 530 (IQR 258-1299). Both pre- and post-exposure prophylaxes are investigated.

[Emergence of Chagas' disease in Europe: description of the first cases observed in Latin American immigrants in mainland France]. / Emergence de la maladie de Chagas en Europe: à propos des premiers cas observés chez des migrants latino-américains en France métropolitaine.

This article describes the first cases of imported Chagas' disease detected in Paris, France. A total of 18 cases were recorded in two teaching hospitals between 2004 and 2007. There were 12 women and six men with a mean age of 38 years. All patients were Latin American immigrants who had recently arrived in France from Bolivia (Cochabamba and Santa-Cruz departments) 17 cases and from Salvador in 1. Eleven patients presented an asymptomatic indeterminate form of the chronic disease. Seven presented chronic Chagas cardiomyopathy including two with severe symptoms requiring placement of a pacemaker. Obtaining serological tests to confirm the diagnosis was difficult. All except one patient who was older than 50 years were treated with benznidazole. Based on these findings, the main priorities for management imported Chagas' disease in France are improvement of serological diagnosis and prevention of vertical transmission.

Machine learning in the clinical microbiology laboratory: has the time come for routine practice?

BACKGROUND: Machine learning (ML) allows the analysis of complex and large data sets and has the potential to improve health care. The clinical microbiology laboratory, at the interface of clinical practice and diagnostics, is of special interest for the development of ML systems. AIMS: This narrative review aims to explore the current use of ML In clinical microbiology. SOURCES: References for this review were identified through searches of MEDLINE/PubMed, EMBASE, Google Scholar, biorXiv, arXiV, ACM Digital Library and IEEE Xplore Digital Library up to November 2019. CONTENT: We found 97 ML systems aiming to assist clinical microbiologists. Overall, 82 ML systems (85%) targeted bacterial infections, 11 (11%) parasitic infections, nine (9%) viral infections and three (3%) fungal infections. Forty ML systems (41%) focused on microorganism detection, identification and quantification, 36 (37%) evaluated antimicrobial susceptibility, and 21 (22%) targeted the diagnosis, disease classification and prediction of clinical outcomes. The ML systems used very diverse data sources: 21 (22%) used genomic data of microorganisms, 19 (20%) microbiota data obtained by metagenomic sequencing, 19 (20%) analysed microscopic images, 17 (18%) spectroscopy data, eight (8%) targeted gene sequencing, six (6%) volatile organic compounds, four (4%) photographs of bacterial colonies, four (4%) transcriptome data, three (3%) protein structure, and three (3%) clinical data. Most systems used data from high-income countries (n = 71, 73%) but a significant number used data from low- and middle-income countries (n = 36, 37%). Performance measures were reported for the 97 ML systems, but no article described their use in clinical practice or reported impact on processes or clinical outcomes. IMPLICATIONS: In clinical microbiology, ML has been used with various data sources and diverse practical applications. The evaluation and implementation processes represent the main gap in existing ML systems, requiring a focus on their interpretability and potential integration into real-world settings.

Machine learning for clinical decision support in infectious diseases: a narrative review of current applications.

BACKGROUND: Machine learning (ML) is a growing field in medicine. This narrative review describes the current body of literature on ML for clinical decision support in infectious diseases (ID). OBJECTIVES: We aim to inform clinicians about the use of ML for diagnosis, classification, outcome prediction and antimicrobial management in ID. SOURCES: References for this review were identified through searches of MEDLINE/PubMed, EMBASE, Google Scholar, biorXiv, ACM Digital Library, arXiV and IEEE Xplore Digital Library up to July 2019. CONTENT: We found 60 unique ML-clinical decision support systems (ML-CDSS) aiming to assist ID clinicians. Overall, 37 (62%) focused on bacterial infections, 10 (17%) on viral infections, nine (15%) on tuberculosis and four (7%) on any kind of infection. Among them, 20 (33%) addressed the diagnosis of infection, 18 (30%) the prediction, early detection or stratification of sepsis, 13 (22%) the prediction of treatment response, four (7%) the prediction of antibiotic resistance, three (5%) the choice of antibiotic regimen and two (3%) the choice of a combination antiretroviral therapy. The ML-CDSS were developed for intensive care units (n = 24, 40%), ID consultation (n = 15, 25%), medical or surgical wards (n = 13, 20%), emergency department (n = 4, 7%), primary care (n = 3, 5%) and antimicrobial stewardship (n = 1, 2%). Fifty-three ML-CDSS (88%) were developed using data from high-income countries and seven (12%) with data from low- and middle-income countries (LMIC). The evaluation of ML-CDSS was limited to measures of performance (e.g. sensitivity, specificity) for 57 ML-CDSS (95%) and included data in clinical practice for three (5%). IMPLICATIONS: Considering comprehensive patient data from socioeconomically diverse healthcare settings, including primary care and LMICs, may improve the ability of ML-CDSS to suggest decisions adapted to various clinical contexts. Currents gaps identified in the evaluation of ML-CDSS must also be addressed in order to know the potential impact of such tools for clinicians and patients.

[Infection with SARS-CoV-2 in pregnancy. Update of Information and proposed care. CNGOF]. / Infection par le SARS-CoV-2 chez les femmes enceintes. Actualisation de l'état des connaissances et de la proposition de prise en charge. CNGOF.

OBJECTIVES: The coronavirus SARS-CoV-2 identified late 2019 in China had spread across all continents. In the majority of cases, patients have mild symptoms (fever, cough, myalgia, headache, some digestive disorders) or are asymptomatic, however it can cause serious lung diseases and lead to death. On September 2020, over 28 million people have been infected with over 920,000 deaths. METHODS: In view of the evolution of the epidemic the French National College of Obstetricians and Gynecologists has decided to update the recommendations previously issued. To do this, the same group of experts was called upon to carry out a review of the literature and take into account the opinions of the General Directorate of Health (DGS), the "Haute Autorité de Santé" (HAS) and the "Haut Conseil de santé Publique" (HCSP). RESULTS: The data on consequences during pregnancy have accumulated. The symptoms in pregnant women appear to be similar to those of the general population, but an increased risk of respiratory distress exists in pregnant women especially in the third trimester. A case of intrauterine maternal-fetal transmission has been clearly identified. Induced prematurity and cases of respiratory distress in newborns of infected mothers have been described. CONCLUSION: In light of the new data, we propose updated recommendations. These proposals may continue to evolve in view of the pandemic and of advances in studies in pregnant women.

Review of trials currently testing treatment and prevention of COVID-19.

BACKGROUND: As COVID-19 cases continue to rise globally, evidence from large randomized controlled trials is still lacking. Currently, numerous trials testing potential treatment and preventative options are being undertaken all over the world. OBJECTIVES: We summarized all registered clinical trials examining treatment and prevention options for COVID-19. Additionally, we evaluated the quality of the retrieved studies. DATA SOURCES: Clinicaltrials.gov, the Chinese Clinical Trial Registry and the European Union Clinical Trials Register were systematically searched. STUDY ELIGIBILITY CRITERIA: Registered clinical trials examining treatment and/or prevention options for COVID-19 were included. No language, country or study design restrictions were applied. We excluded withdrawn or cancelled studies and trials not reporting therapeutic or preventative strategies for COVID-19. PARTICIPANTS AND INTERVENTIONS: No restrictions in terms of participants' age and medical background or type of intervention were enforced. METHODS: The registries were searched using the term 'coronavirus' or 'COVID-19' from their inception until 26 March 2020. Additional manual search of the registries was also performed. Eligible studies were summarized and tabulated. Interventional trials were methodologically analysed, excluding expanded access studies and trials testing traditional Chinese medicine. RESULTS: In total, 309 trials evaluating therapeutic management options, 23 studies assessing preventive strategies and three studies examining both were retrieved. Finally, 214 studies were methodologically reviewed. Interventional treatment studies were mostly randomized (n = 150/198, 76%) and open label (n = 73/198, 37%) with a median number of planned inclusions of 90 (interquartile range 40-200). Major categories of interventions that are currently being investigated are discussed. CONCLUSIONS: Numerous clinical trials have been registered since the onset of the COVID-19 pandemic. Summarized data on these trials will assist physicians and researchers to promote patient care and guide future research efforts for COVID-19 pandemic containment.

Mycobacterium xenopi pulmonary infections: a multicentric retrospective study of 136 cases in north-east France.

BACKGROUND: Owing to its low incidence, the management of Mycobacterium xenopi pulmonary infections is not clearly defined. A multicentre retrospective study was performed to describe the features of the disease and to evaluate its prognosis. METHODS: All patients with M xenopi satisfying the 1997 ATS/IDSA criteria from 13 hospitals in north-east France (1983-2003) were included in the study. Clinical, radiological and bacteriological characteristics and data on the management and outcome were collected. RESULTS: 136 patients were included in the analysis, only 12 of whom presented with no co-morbidity. Three types of the disease were identified: (1) a classical cavitary form in patients with pre-existing pulmonary disease (n = 39, 31%); (2) a solitary nodular form in immunocompetent patients (n = 41, 33%) and (3) an acute infiltrate form in immunosuppressed patients (n = 45, 36%). 56 patients did not receive any treatment; the other 80 patients received first-line treatment containing rifamycin (87.5%), ethambutol (75%), isoniazid (66.2%), clarithromycin (30%) or fluoroquinolones (21%). After a follow-up of 36 months, 80 patients (69.1%) had died; the median survival was 16 months (range 10-22). Two independent prognostic factors were found: the acute infiltrate form was associated with a bad prognosis (hazard ratio 2.6, p = 0.001) and rifamycin-containing regimens provided protection (hazard ratio 0.325, p = 0.006). Clarithromycin-containing regimens did not improve the prognosis. CONCLUSIONS: In contrast to recent guidelines, this study showed three different types of the disease (cavitary, nodular or diffuse infiltrate forms) with a different prognosis. In order to improve survival, all patients with M xenopi infection should be treated with a rifamycin-containing regimen. The usefulness of clarithromycin remains to be evaluated.

[Experience of targeted screening of Chagas disease in Ile-de-France]. / Expérience de dépistage ciblé de la maladie de Chagas en Ile-de-France.

2009 is marked by the centenary of the discovery by Carlos Chagas of Human American Trypanosomiasis. As a result of international cooperation its incidence has been falling in endemic areas, whereas North America and Europe are witnessing an increase in the number of imported cases. In metropolitan France, 18 such cases were reported between 2004 and 2007. Recently, estimates based on immigration figures have been made and suggest that about 1,500 imported cases can be expected in France. The object of this article is to assess the value of targeted screening of an at-risk population, originally from Latin America and now living in the Ile-de-France (area centred on Paris). The serological techniques employed were indirect immunofluorescence (IIF) and, depending on the case, 2 or 3 Elisa tests (Biomérieux, Biokit and Wiener). Trypanosoma cruzi serology was considered positive when the IIF was superior or equal to 200, or when two Elisa's were > 1, or when the IIF was superior or equal to 100 with at least one Elisa > 1. PCR was performed in 48 cases, which were considered to be positive. The tests were carried out on a voluntary basis after a publicity campaign within the Latin American community in the Ile-de-France. In this article, we present the findings of the first year of screening. Two hundred and fifty-four individuals were screened for Chagas' disease between June 2008 and June 2009. The median age was 33 years [11-63], the male/female ratio 102/152. Overall prevalence of positive serology was 23.6% (60/254). For six patients, the results were classified as "uncertain" (discordant serological tests). Of the seropositive group, 87.4% were Bolivian and 100% presented as a chronic form. Of these, 23.6% presented with functional cardiac manifestations and 22% with gastro-intestinal problems. The PCR was positive in 61% of the seropositive individuals. Clinical evaluation together with other investigations and therapeutic intervention is being carried out at present. These results confirm that metropolitan France is subject to the emergence of Chagas' disease in a non-endemic zone. This confirms the value of screening in at-risk populations, in particular because of the recent broadening of indications for antiparasitic treatment. In addition it is relevant to the prevention of vertical transmission or infection via organ donation, which could arise in France. These results also demonstrate continuing difficulties in the interpretation of serological results and the usefulness of PCR, which might increase sensitivity substantially.

[Chagas disease]. / Maladie de Chagas.

Chagas disease (human American trypanosomiasis) is a zoonose caused by the protozoan Trypanosoma cruzi. Vectors are Triatoma spp. insects. T. cruzi can also be transmitted by blood transfusion, organ transplantation, and transplacentally. Infection is generally acquired during infancy. The acute infection is rarely symptomatic and is followed by a chronic phase. Chronic infected people are asymptomatic (indeterminate stage) and may remain at this stage for the rest of their lives. About a third of infected people will develop a chronic Chagas disease which affects the heart and the digestive tract. Morbidity and mortality of chronic Chagas cardiomyopathy (CCC) are high. Specific treatment of asymptomatic infected individual could reduce the risk of progression to CCC. With control initiatives case incidence declined in most endemic countries. American trypanosomiasis has become an emerging imported disease in North America and Europe because of the migration of population originating from endemic zones. They are only two available drugs for specific treatment of Chagas disease: benznidazole and nifurtimox. Both have frequent side effects and variable efficacy according the phase of the disease. There is an urgent need for new treatments and better serological tests. Policies must be developed to avoid the risk of transmission trough blood transfusion and transplantation in developed countries.

[Treatment of osteoarticular infections with clindamycin in adults]. / Traitement des infections ostéoarticulaires par clindamycine chez l'adulte.

UNLABELLED: The main characteristics of clindamycin are adequate for treatment of osteoarticular infections (OAI): good bone diffusion, broad spectrum of antibacterial activity and oral use. METHOD: A number of 61 patients was included in an observational retrospective study of efficacy and tolerance. RESULTS: Prosthetic infections accounted for 50.8% of the cases and chronic osteitis for 36.1%. The causative micro-organisms were Staphylococci (72.2%) and Streptococci (15.3%); 86.5% of these strains were susceptible to erythromycin, 9.6% were erythromycin resistant and susceptible to lincomycin. Clindamycin was associated with either ofloxacine, rifampicin, or teicoplanin in 88.5% and the average course duration was 101 days. A surgical procedure was performed in 84% of cases. Complete cure was obtained in 91.1% at 18 months of follow up. Only one cutaneous rash and one Clostridium difficile-associated diarrhea occurred. The other adverse effects were gastrointestinal in 36%, cutaneous in 6.6%, and hematological in 1.6%, but did not lead to discontinuation of therapy. CONCLUSION: Clindamycin can be used in OAI in association with or as an alternative to rifampicin, fluoroquinolones, or glycopeptides according to microbiological data.

Evaluation of broad-spectrum beta-lactam prescriptions (except carbapenems) in a French teaching hospital.

OBJECTIVES: We aimed to assess broad-spectrum beta-lactam prescriptions (except carbapenems) in a French teaching hospital and the impact of controlled dispensing, antimicrobial management team, and antibiotic treatment reassessment on Day 2-3. PATIENTS AND METHODS: We performed a point-prevalence study in all hospital units and analyzed curative antibiotic broad-spectrum beta-lactam prescriptions. The assessment focused on indication, dosing, combinations, revaluation on Day 2-3, and treatment duration. RESULTS: Sixty-seven broad-spectrum beta-lactam prescriptions were identified. The main prescriptions were amoxicillin-clavulanic acid (37%, n=25), ceftriaxone (36%, n=24), and piperacillin-tazobactam (16%, n=11). Indications, doses, combinations, and reassessment on Day 2-3 were appropriate, respectively 90% (n=60), 96% (n=64), 94% (33/35 combinations), and 88% (n=59). However, appropriate treatment durations amounted to only 63% (n=42). The benefit of controlled dispensing was observed in terms of overall antibiotic treatment duration: 86% versus 51% adequacy for uncontrolled dispensing of beta-lactams (P=0.02). The antimicrobial management team improved the antibiotic treatment duration: 73% of appropriate durations versus 44% for beta-lactams not monitored by the team, but this difference was not significant. CONCLUSION: Broad-spectrum beta-lactams were usually well prescribed but the adequacy of treatment duration could be improved, especially by reinforcing the monitoring of prescriptions.

Cefazolin versus anti-staphylococcal penicillins for treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a narrative review.

BACKGROUND: Anti-staphylococcal penicillins (ASPs) are recommended as first-line agents in methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. Concerns about their safety profile have contributed to the increased use of cefazolin. The comparative clinical effectiveness and safety profile of cefazolin versus ASPs for such infections remain unclear. Furthermore, uncertainty persists concerning the use of cefazolin due to controversies over its efficacy in deep MSSA infections and its possible negative ecological impact. AIMS: The aim of this narrative review was to gather and balance available data on the efficacy and safety of cefazolin versus ASPs in the treatment of MSSA bacteraemia and to discuss the potential negative ecological impact of cefazolin. SOURCES: PubMed and EMBASE electronic databases were searched up to May 2017 to retrieve available studies on the topic. CONTENTS: Although described in vitro and in experimental studies, the clinical relevance of the inoculum effect during cefazolin treatment of deep MSSA infections remains unclear. It appears that there is no significant difference in rate of relapse or mortality between ASPs and cefazolin for the treatment of MSSA bacteraemia but these results should be cautiously interpreted because of the several limitations of the available studies. Compared with cefazolin, there is more frequent discontinuation for adverse effects with ASP use, especially because of cutaneous and renal events. No study has evidenced any change in the gut microbiota after the use of cefazolin. IMPLICATIONS: Based on currently available studies, there are no data that enable a choice to be made of one antibiotic over the other except in patients with allergy or renal impairment. This review points out the need for future prospective studies and randomized controlled trials to better address these questions.

Surgical site infection with extended-spectrum ß-lactamase-producing Enterobacteriaceae after cardiac surgery: incidence and risk factors.

OBJECTIVE: To determine the incidence, microbiology and risk factors for sternal wound infection (SWI) with extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) following cardiac surgery. METHODS: We performed a retrospective analysis between January 2006 and December 2015 of prospective surveillance of a cohort of patients with cardiac surgery at a single centre (Paris, France). SWI was defined as the need for reoperation due to sternal infection. All patients with an initial surgery under extracorporeal circulation and diagnosed with an SWI caused by Enterobacteriaceae isolates were included. We compared patients infected with at least one ESBL-PE with those with SWI due to other Enterobacteriaceae by logistic regression analysis. RESULTS: Of the 11 167 patients who underwent cardiac surgery, 412 (3.7%) developed SWI, among which Enterobacteriaceae were isolated in 150 patients (36.5%), including 29 ESBL-PE. The main Enterobacteriaceae (n = 171) were Escherichia coli in 49 patients (29%) and Enterobacter cloacae in 26 (15%). Risk factors for SWI with ESBL-PE in the multivariate logistic regression were previous intensive care unit admission during the preceding 6 months (adjusted odds ratio (aOR) 12.2; 95% CI 3.3-44.8), postoperative intensive care unit stay before surgery for SWI longer than 5 days (aOR 4.6; 95% CI 1.7-11.9) and being born outside France (aOR 3.2; 95% CI 1.2-8.3). CONCLUSIONS: Our results suggest that SWI due to ESBL-PE was associated with preoperative and postoperative unstable state, requiring an intensive care unit stay longer than the usual 24 or 48 postoperative hours, whereas being born outside France may indicate ESBL-PE carriage before hospital admission.

Incidence of and risk factors for severe liver toxicity in HIV-infected patients on anti-tuberculosis treatment.

OBJECTIVE: To assess the incidence and risk factors for severe liver toxicity in human immunodeficiency virus (HIV) infected patients on anti-tuberculosis treatment and the impact of patients' characteristics and concomitant medications instituted during the first week of antituberculosis treatment. METHODS: HIV-infected patients referred to six French hospitals between 1 January 1992 and 31 December 2004, with confirmed or 'presumptive' tuberculosis (TB). Liver toxicity was studied during the first 2 months of TB treatment. RESULTS: During the 12 years of the study period, 144 patients were enrolled. Severe liver toxicity developed in 15 (10.7%). The median time to development of liver toxicity was 14 days. In the univariate analysis, high baseline bilirubin levels (P = 0.004), CD4 cell counts between 50 and 100 cells/mm3 (P = 0.022) and the use of fluconazole (P = 0.0005) were associated with liver toxicity. In the multivariate analysis, independent risk factors were abnormal baseline alanine aminotransferase (ALT) (P = 0.028) and bilirubin levels (P = 0.033) and the use of fluconazole (P = 0.008). CONCLUSION: Severe liver toxicity is frequent, and occurs early in the course of anti-tuberculosis treatment. ALT and bilirubin levels should be closely monitored during the first month of treatment, especially in patients with high baseline ALT or bilirubin levels. We suggest caution when prescribing fluconazole and anti-tuberculosis drugs concomitantly, although this needs to be confirmed and further investigated.

[Treatment in primary Streptococcus pneumoniae peritonitis in adult: a case report and review of the literature]. / Prise en charge thérapeutique de la péritonite primitive à Streptococcus pneumoniae de l'adulte: étude d'un cas et revue de la littérature.

INTRODUCTION: Streptococcus pneumoniae primary peritonitis is rare. The diagnosis is uneasy and the treatment is not standardised. CASE REPORT: We report a single case of S. pneumoniae primary peritonitis needing surgical treatment. DISCUSSION: S. pneumoniae primary peritonitis can be medically treated. Surgery is needed in case of sepsis, associated digestive injuries or failure of medical treatment.