V. Mondain

Direct-acting antiviral treatment in adults infected with hepatitis C virus: Reactivation of hepatitis B virus coinfection as a further challenge.

Use of direct-acting antiviral drugs (DAAs) greatly improves management of adults infected with hepatitis C virus (HCV) whether patients are treatment-naive or unsuccessfully pre-treated. Several inhibitors of viral nonstructural proteins (NS3/4A protease, NS5A and NS5B polymerase) allow a rapid HCV clearance and increase rates of sustained virological response. Both the EASL and AASLD guidelines have recently published up-to-date recommendations for their use, addressing each HCV genotype and particular situations. However, management of patients coinfected with hepatitis B virus (HBV) has been developed by these guidelines with reference to cases of HBV reactivation reported during previous anti-HCV regimens containing interferon known active against both HBV and HCV. In the setting of the interferon-free HCV therapies with DAAs only, the possibility of HBV reactivation during treatment of hepatitis C is raised due to viral interferences in HCV/HBV coinfected persons. Herein, we report a case of early HBV reactivation during DAAs-based anti-HCV treatment (ledipasvir/sofosbuvir) in a patient having a resolved HBV infection and chronically infected with HCV genotype 4 and HIV. Moreover, we review similar recent cases of HBV reactivation in patients infected with HBV and HCV genotype 1 during treatment of hepatitis C by regimen incorporating other combination of DAAs (sofosbuvir/simeprevir or daclatasvir/asunaprevir). Due to the potential risk of early HBV reactivation in HCV/HBV-coinfected patients during interferon-free DAAs-based HCV therapies, altogether these cases highlight the necessity to closely monitor HBV coinfection, regardless its stage (chronic, occult, resolved), whatever HCV genotype or class of DAAs used.

Concomitant Staphylococcus aureus bacteriuria is associated with complicated S. aureus bacteremia

OBJECTIVES To identify factors associated with complicated Staphylococcus aureus bacteremia (SAB) in adults. METHODS Prospective observational multicenter study during 2 years in Nice University Hospital and during 6 months in the Hôpital Européen Georges Pompidou, Paris, including all adult inpatients with SAB assessed by an Infectious Diseases (ID) specialist. RESULTS We included 104 SAB (79 in Nice and 25 in Paris), of which 45 were complicated, including 18 endocarditis and 23 bone and joint infections. A concomitant urine sample was performed in 65% of the cases, showing S. aureus bacteriuria 23/68 (34%) times. Blood cultures were drawn 48-96h after an appropriate antibiotic therapy had been started in 70 of the 104 cases (67%) and were positive in 28 cases (40%). CONCLUSIONS The 3 following factors were found to be associated with complicated SAB in univariate analysis: community acquisition (56% vs 26%, P=0.002), concomitant bacteriuria (47% vs 19%, P=0.016) and persistent bacteremia (55% vs 26%, P=0.016). This last factor was associated with endocarditis, but not with other complications such as bone and joint infections.

Fluoroquinolone prescriptions in a teaching hospital: a prospective audit.

The aim of this study was to identify prospectively the prevalence of unnecessary or inappropriate fluoroquinolone prescriptions in our teaching hospital and to identify the contributing factors. 55% of the 110 prescriptions evaluated were unnecessary or inappropriate. Ward and combination therapies were significantly associated with misuse.

An antibiotic stewardship program in a French teaching hospital

OBJECTIVES An antibiotic stewardship program was implemented in our teaching hospital in 1999, and strengthened in 2005. We report its organization and impact on antibiotic use. METHODS This observational study was conducted during a 10-year period (2002-2011). RESULTS Many interventions were implemented: Infectious Diseases Specialists (IDS) led systematic ward rounds in several departments (1999); nominative antibiotic order form (2005); documentation of IDS advice in the patients electronic medical record (2007); IDS advice triggered by the pharmacist (formulary restriction, 2007) or because of positive blood cultures (2009); automated weekly extraction of advice given into a database (2011). Seven thousand two hundred and five pieces of advice were recorded between 2007 and 2011: 63% following physician request, 26% triggered by the pharmacist and 9% because of positive blood cultures. Advice was provided by IDS in 95% of cases (63% by phone). The number of antibiotic prescriptions remained stable since 2005 at around 400 defined daily doses (DDD)/1000 patient-days. Documenting, sharing, and choice of action were improved due to the database. CONCLUSIONS Our antibiotic stewardship program is well accepted by physicians and allows controlling antibiotic use in our hospital.

Effect of subinhibitory concentrations of cefamandole and cefuroxime on adherence ofStaphylococcus aureus andStaphylococcus epidermidis to polystyrene culture plates

The ability of cefamandole and cefuroxime to inhibit adherence of staphylococci to polystyrene culture plates was tested in an in vitro assay using eight strains each ofStaphylococcus aureus andStaphylococcus epidermidis. The results indicated that subinhibitory concentrations of cefamandole and cefuroxime altered the adherence ability of both staphylococcal species, inhibition of adherence being more marked in the presence of cefamandole. It may be important to consider antiadherence properties in association with bactericidal activity when selecting agents for antibiotic prophylaxis.

Increased time exposure to tenofovir is associated with a greater decrease in estimated glomerular filtration rate in HIV patients with kidney function of less than 60 ml/min/1.73 m2.

Tenofovir (TDF), atazanovir (ATAZ) and indinavir (IND) have been reported as possible risk factors for incident chronic kidney disease (CKD) in HIV-infected patients. We investigated the relationship between the duration of antiretroviral exposure and estimated glomerular filtration rate (eGFR) evolution in CKD patients. In a cohort of 1,750 HIV-infected patients, we identified 121 CKD patients with a mean follow-up of 44 ± 35 months. The relationship between mean eGFR at baseline, eGFR slope and time exposure to antiretroviral treatment as well as confounding factors were investigated using a joint modeling procedure. Seventy (58%), 30 (25%) and 33 patients (27%), with a mean age of 50.3 ± 11.7 years, mean eGFR at baseline of 53.0 ± 0.8 (ml/min/1.73 m2) and eGFR slope of 0.46 ± 0.07 ml/min/1.73 m2/year, were exposed to TDF, ATAZ and IND, respectively. In univariate analysis, hepatitis C virus infection, decreased nadir of log CD4 count, high blood pressure at baseline, angiotensin-converting enzyme inhibitor treatment and greater time exposure to TDF during follow-up were associated with a higher slope, whereas greater time exposure to IND was associated with a lower slope. In multivariate analysis, higher TDF time exposure was still significantly associated with eGFR decline, with a dose-effect relationship (slope ± standard error of the mean: 1.1 ± 0.1, 0.5 ± 0.1, –0.07 ± 0.08 and –0.87 ± 0.06 ml/min/1.73 m2/year for no time exposure, <34, 34–67 and ≥67%, respectively; trend test: p < 0.001), whereas the IND time exposure association was abolished. In HIV patients with CKD, a greater TDF time exposure was independently associated, in a graded manner, with a greater eGFR decline.

High negative predictive value diagnostic strategies for the reevaluation of early antifungal treatment: A multicenter prospective trial in patients at risk for invasive fungal infections

Early antifungal therapeutic strategies are proposed during invasive fungal infection (IFI), but antifungal stewardship programs should institute a systematic reevaluation of prescriptions, particularly in the context of empirical treatment. Here, we aimed to evaluate the performances and particularly the negative predictive value (NPV) of diagnostic strategies, including a whole blood panfungal quantitative PCR assay (PF-qPCR) in a high risk population for IFI. The first step was to standardize and optimize a new PF-qPCR targeting ITS2 region. Then, this method was evaluated in a multicenter prospective study including 313 patients with suspected IFI for whom an early antifungal treatment was prescribed. All patients enrolled at day 0 of their treatment benefited from serum Aspergillus galactomannan (GM) antigen detection twice a week, weekly PF-qPCR assay, and when indicated and feasible, CT-scan and mycological sampling. In total, 125 of 313 patients were diagnosed with IFI: 68 invasive aspergillosis (eight proven, 48 probable and 12 possible), one fusariosis, 47 candidemia, three disseminated candidiasis and six cryptococcosis. Globally, the sensitivity of the PF-qPCR assay was only 40%, but the specificity, PPV and NPV were 96%, 88% and 69%, respectively. In the population of patients at high risk for invasive aspergillosis who also benefited from Aspergillus GM detection, the sensitivity and the NPV of the combined detection reached to 78% and 84%, respectively. Even higher NPV were obtained when combining negative PF-qPCR and CT scan (95%) as well as negative GM and CT scan (93%), thus allowing to rationalize and re-evaluate the prescription of empirical treatment in such highly selected population.

Possible prevention of in vitro selection of resistantStreptococcus pneumoniae by beta-lactamase inhibitors

The development of resistance in vitro in five strains ofStreptococcus pneumoniae (3 with full susceptibility and 2 with intermediate susceptibility to penicillin) was investigated by serial passages in the presence of subinhibitory concentrations of amoxicillin and ampicillin. At the end of passaging, MICs of antibiotics for all the strains increased by a factor of four or more, reaching at least intermediate levels. MICs of cephalosporins, ampicillin and amoxicillin increased for almost all variants obtained. Similar results were obtained with amoxicillin plus clavulanic acid at a ratio of 2:1 and at a constant concentration of 2 µg/ml, and with ampicillin plus sulbactam at a ratio 2:1. In contrast, no significant modification of MIC was seen with ampicillin plus sulbactam at a constant concentration of 4 µg/ml sulbactam. These results suggest interaction of sulbactam with penicillin binding proteins as described previously for other bacterial species, and merit further investigation.

Safety of antibiotics combinations against Staphylococcal bone and joint infections

Joint Bone Spine - In Press.Proof corrected by the author Available online since dimanche 22 juin 2014

Improved quality of care for patients infected or colonised with ESBL-producing Enterobacteriaceae in a French teaching hospital: impact of an interventional prospective study and development of specific tools

The increasing incidence of ESBL-producing Enterobacteriaceae (ESBL-E) in France prompted the publication of national recommendations in 2010. Based on these, we developed a toolkit and a warning system to optimise management of ESBL-E infected or colonised patients in both community and hospital settings. The impact of this initiative on quality of care was assessed in a teaching hospital. The ESBL toolkit was developed in 2011 during multidisciplinary meetings involving a regional network of hospital, private clinic and laboratory staff in Southeastern France. It includes antibiotic treatment protocols, a check list, mail templates and a patient information sheet focusing on infection control. Upon identification of ESBL-E, the warning system involves alerting the attending physician and the infectious disease (ID) advisor, with immediate, advice-based implementation of the toolkit. The procedure and toolkit were tested in our teaching hospital. Patient management was compared before and after implementation of the toolkit over two 3-month periods (July–October 2010 and 2012). Implementation of the ESBL-E warning system and ESBL-E toolkit was tested for 87 patients in 2010 and 92 patients in 2012, resulting in improved patient management: expert advice sought and followed (16 vs 97%), information provided to the patient’s general practitioner (18 vs 63%) and coding of the condition in the patient’s medical file (17 vs 59%), respectively. Our multidisciplinary strategy improved quality of care for in-patients infected or colonised with ESBL-E, increasing compliance with national recommendations.