Amoxicillin-clavulanic acid prescriptions at the Greater Paris University Hospitals (AP-HP).

OBJECTIVE: We aimed to document amoxicillin-clavulanic acid prescription to improve the proper use of antibiotics in hospital settings. We used three criteria: quality of medical charts, adequacy of indications, and adequacy of treatment duration. METHOD: This study was designed as a one-day point prevalence survey carried out by antibiotic lead specialists. RESULTS: We included 387 prescriptions from 32 hospitals. Immunodeficiency was recorded as a risk factor in 30% of patients. Computerized prescriptions were observed in 79% of cases. The indication was mentioned in 73% of cases and a 48/78-hour re-assessment of the antibiotic therapy was performed in 54% of cases. The antibiotic indication was primarily for pneumonia and was deemed appropriate in 75% of patients. Adult mean treatment duration was 11.1 days. Use of dual combination therapy and/or treatment duration exceeding two weeks accounted for the main reasons for an inappropriate use of antibiotics. Prescriptions recorded as having been made by senior physicians were of the shortest treatment duration (P=0.0163). CONCLUSION: Medical charts should be better filled in. Reinforcing the role of senior physicians in supervising antibiotic prescriptions is likely to result in a better control of treatment duration and ultimately in a reduced antibiotic consumption. By reinforcing the collaboration between pharmacists and antibiotic lead specialists, the improvement of computerized prescriptions at hospital level should help better detect the "at risk" prescriptions, namely those exceeding seven days or those combining antibiotics.

Breakthrough invasive fungal disease in patients receiving posaconazole primary prophylaxis: a 4-year study.

Posaconazole (PSC) is currently recommended as primary prophylaxis in neutropenic patients with acute myeloid leukaemia (AML) and in allogenic haematopoietic stem cell transplantation (AHSCT) recipients with graft-versus-host disease (GVHD). Studies focusing on breakthrough invasive fungal disease (IFD) upon PSC prophylaxis show disparate results. In order to evaluate the incidence of IFD in patients on PSC prophylaxis and identify IFD risk factors, we carried out a retrospective study of all consecutive patients on PP from January 2007 to December 2010 in our hospital. Breakthrough IFDs were identified from the database of the central pharmacy and the French administrative database (PMSI), registering final medical diagnoses of hospitalized patients. Medical data were reviewed to study proven or probable IFD, according to EORTC/MSG definition. PSC plasma concentrations (PPC) were also retrieved. Poisson models were used for statistical analysis. Two hundred and seventy-nine patients received PSC prophylaxis for a median duration of 1.4 months (range 0.2-17.9). Proven (n=6) or probable (n=3) IFDs were diagnosed in nine cases (3.2%). IFD incidence rate per 100 person-month was 1.65 (95% CI, 0.79-2.97). IFDs were candidaemia (Candida glabrata, n=2), pulmonary invasive aspergillosis (n=3), disseminated fusariosis (n=2) and pulmonary mucormycosis (n=2). Seven deaths were reported, directly related to IFD in three patients (33.3%). First dosage of PPC under 0.3 mg/L was the single significant risk factor for IFD (RR, 7.77; 95% CI, 1.30-46.5; p 0.025). Breakthrough IFD in patients receiving PSC prophylaxis is rare but associated with a poor outcome. Low PSC plasma concentrations are associated with an increased risk of IFD.

[Treatment of scabies and Ascabiol(®) supply disruption: what about the pediatric population?]. / Traitement de la gale et rupture d'Ascabiol(®) : quid de la population pédiatrique ? Gale chez l'enfant et rupture d'Ascabiol(®)

Scabies is a disease in steady increase in Île-de-France region. Standard treatment, Ascabiol(®) (benzyl benzoate/sulfiram), is back-order for several months and its return remains uncertain. Facing this drug shortage, French Drug Agency (ANSM) has imported a drug from Germany, Antiscabiosum 10 % (benzyl benzoate), to treat patients having contraindications for other scabicides available in France (ivermectin, esdepallethrine). However, infants less than 1 year (<15 kg) and asthmatics infants have no alternative treatment. A multidisciplinary workgroup explored the various existing therapeutic alternatives in France and worldwide. From ANSM's recommendations and group's experience, a decision algorithm was proposed for treating patients. However, pediatric context implied the use of off-label drugs. Proposed treatments widely known by practitioners, prescriptions-types, dose, modalities of use and dispensation, and flyers to patients were realized to optimize treatment efficacy.

False positive galactomannan Platelia due to piperacillin-tazobactam.

INTRODUCTION: Invasive aspergillosis is a serious disease, the lethality of which is important among hematology patients. Early diagnosis is crucial for treatment options and the prognosis. Detection of the antigen galactomannan is the most frequently used microbiological tools. But galactomannan detection may be falsely positive, and this false positivity has been associated with piperacillin-tazobactam treatment, the main antibiotic combination used in clinical hematology. OBJECTIVE: The purpose of our study, carried out from January 2009 to December 2010 at the Versailles hospital on in-patients with hematological disorders, was to evaluate the association between false galactomannan positivity and administration of piperacillin-tazobactam, and to study a possible variability of products issued by three manufacturers. PATIENTS AND METHOD: We noted that 207 patients were included (n=207), accounting for 69 false positive and 138 true negative results. The intrinsic galactomannan values in the study were sensitivity 100%, specificity 68%, positive and negative predictive values respectively 16%, 100%, and a likelihood positive and negative test at respectively 3.12, and 0. RESULTS: The statistical analysis did not determine any association between false positivity in galactomannan and piperacillin-tazobactam issued by two manufacturers (P=0.87 and P=0.94). But, there was a significant association between false galactomannan positivity and piperacillin-tazobactam issued by the third manufacturer (P=0.02). Four of the 25 batches issued by this manufacturer were tested and negative "in vitro" for galactomannan. DISCUSSION: This study results suggest that the association between false galactomannan positivity and piperacillin-tazobactam is not longer systematic, but can still prevail depending on the manufacturers. It also confirmed the positive contribution of testing piperacillin-tazobactam batches "in vitro" before using the antibiotic.

High rate of breakthrough invasive aspergillosis among patients receiving caspofungin for persistent fever and neutropenia.

A number of agents are now available for empirical antifungal treatment (EAFT) of patients with persistent fever and neutropenia. We carried out a study of efficacy of antifungal drugs to prevent breakthrough invasive aspergillosis by reviewing the medical records of all consecutive patients who received EAFT from November 2005 to February 2006. Patients' characteristics and the type, dose and duration of antifungal therapy were recorded. Breakthrough invasive fungal infections were documented according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definition. Fifty-six episodes of persistent fever with neutropenia requiring EAFT were recorded among 49 patients. All patients received high-dose chemotherapy for acute myeloid leukaemia (51%), acute lymphoid leukaemia (12%), lymphoma (14%) or other haematologic conditions (22%). Fourteen (29%) and five (10%) patients were allogeneic and autologous haematopoietic stem cell transplant recipients, respectively. Caspofungin was prescribed initially in 40 episodes (71%), amphotericin B (AmB) desoxycholate and liposomal AmB being prescribed in six (10%) and ten (18%) episodes, respectively. Six patients were switched from liposomal AmB to caspofungin because of adverse events. The median duration of antifungal therapy was 9 days. During follow-up, six patients (12%) were diagnosed with invasive aspergillosis after a median of 8 days (range 3-16 days) of EAFT. Invasive aspergillosis breakthrough occurred in 6/46 (13%) caspofungin recipients and in 0/16 (0%) AmB recipients (OR 3.1, p 0.32). The observed high rate of invasive aspergillosis among caspofungin recipients requires further evaluation.

[Fluoroquinolones use at the Saint-Louis Hospital: investigations before and after diffusion of recommendations and interventions of the anti-infectious referent]. / Prescription des fluoroquinolones à l'hôpital Saint-Louis: enquête avant et après diffusion de recommandations et interventions du référent anti-infectieux.

OBJECTIVE: The increase of bacterial resistance and of fluoroquinolones consumption led to set up an action plan in order to improve the use of fluoroquinolones. METHODS: Two audits "on a given day" in February 2005 (before action) and January 2007 (after action) allowed evaluating the effects of several interventions: restitution of the results from the first audit and antibiotics counselling by an infectious diseases expert, conception and diffusion of local recommendations and follow-up of antibiotic consumption. RESULTS: The prevalence of the fluoroquinolones' prescriptions was 49/503 hospitalized patients in 2005 (1st audit) and 30/482 in 2007 (2nd audit). Global conformity to the recommendations was 47% in 2005 and 40% in 2007. The number of inappropriate indications remained stable between 2005 (12, 25%) and 2007 (10, 33%) with a reduction in the use of fluoroquinolones for empirical treatments: 74% in 2005 and 50% in 2007. The use of the intravenous route decreased from 45% in 2005 to 27% in 2007. Consumption of antibiotics and fluoroquinolones decreased by 7% and 30% between 2005 and 2007 respectively. CONCLUSION: The interventions allowed to decrease the use of fluoroquinolones in empirical treatments and to limit the use of the intravenous route. The impact on the fluoroquinolones and antibiotics consumption has been demonstrated. However, the proportion of inappropriate indications remained unchanged. The impact of the fluoroquinolones consumption decrease on the bacterial resistance will be the next step of our action.

Evaluation of current practices in surgical antimicrobial prophylaxis before and after implementation of local guidelines.

The aim of antibiotic prophylaxis (ABP) is to prevent or at least decrease the incidence of postoperative surgical wound infections. In 1992 and 1995, ABP was the subject of two French consensus conferences. Following these conferences, the local Antibiotics Committee of Hopital Saint-Louis has undertaken a study to evaluate and eventually improve the current practices of ABP. This study was carried out in three steps: a first survey of ABP, the writing of local ABP guidelines and a second survey of ABP after the implementation of these recommendations. Concerning all surgical wards, the first survey found 69% (N = 100/145) of ABP practice is to be inappropriate vs. 18% (N = 25/139) in the second survey. Indications, choice of drugs, selection of dosage, administration timing and treatment duration were significantly improved in the second survey. Writing and implementing local recommendations promoted a more rational use of ABP. In addition, this study allowed Saint-Louis Hospital to set up recommendations for plastic surgery; such recommendations are poorly described in the literature.

[Regulatory aspects of disinfection of endoscopes]. / Aspects réglementaires de la désinfection des endoscopes.

The circular on the sterilization and the law of july 1, 1998 enact clearly that the medical devices that support steam sterilization must be sterilized with an organization of sterilization that ensure quality. Endoscope that enter normally sterile tissues should be subjected to a sterilization procedure before each use; if this is not feasible, they should receive high-level disinfection to destroy bacterial spores. The endoscope must be immersed for at least one hour in aqueous solution of 2% glutaraldehyde. This lengthened duration of processing must be integrate in the organization of medical department. The endoscopes not penetrating in a sterile cavity are disinfected with manual processing according to the protocol of the circular of april 1996, or with automated endoscope reprocessing machine. The different types of automated machine used to wash and disinfect endoscope must now answer to criterion concerning their design described in the circular of july 15, 1998. A significant work has to be made in hospitals to conform automated machine and procedure, to control the risk dependent with their use.

Chemical stability of lignocaine (lidocaine) and adrenalin (epinephrine) in pH-adjusted parenteral solutions.

Recent clinical studies have shown that alkalinizing lignocaine (lidocaine) solutions is an effective way of shortening the time of onset and increasing the duration of anaesthesia. However, alkalinizing lignocaine solutions raises the problem of the stability of these preparations. Moreover, the adrenalin usually associated with it is unstable in alkalinized solutions designed for peridural injection. This study was performed to define the range of pH over which lignocaine and adrenalin in commercial solution is stable. The results indicate that it is possible to alkalinize lignocaine solutions and that the solutions prepared are stable for at least 6 h.