Antistaphylococcal penicillins vs. cefazolin in the treatment of methicillin-susceptible Staphylococcus aureus infective endocarditis: a quasi-experimental monocentre study.

Whether cefazolin is as effective and safer than antistaphylococcal penicillins (ASPs) for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) is still debated in the absence of a randomized controlled trial. In this quasi-experimental study, we aimed to assess the effectiveness and safety of these two treatments in MSSA-IE, using the ASPs nationwide shortage in April 2016 as a unique opportunity to overcome the indication bias associated with observational studies. In this single-centre study, we compared patients with Duke-Li definite MSSA-IE treated with ASPs from January 2015 to March 2016 versus those treated with cefazolin from April 2016 to December 2018, when ASPs were not available. Effectiveness outcome was 90-day all-cause mortality. Safety outcomes included significant decrease in GFR and significant increase in serum liver enzymes. Logrank test was used to compare survival rates. Of 73 patients with MSSA-IE, 35 and 38 were treated with ASPs and cefazolin, respectively. Baseline patients' characteristics (demography, native or prosthetic valve IE, clinical characteristics, cardiac and septic complications) were similar between groups. Ninety-day all-cause mortality was 28.6% and 21.1%, in patients treated with ASPs and cefazolin, respectively (logrank p = 0.5727). There was no difference between groups for incident renal or liver toxicity events: acute kidney injury 45.7% vs. 44.7% (p = 0.933), increased ALT 5.7% vs. 13.2% (p = 0.432), bilirubin increase 5.7% vs. 10.5% (p = 0.676), in ASPs vs. cefazolin groups, respectively. In this quasi-experimental, effectiveness and safety did not statistically differ between ASPs and cefazolin for MSSA-IE treatment.

[AA-type amyloidosis secondary to multidrug resistant pulmonary tuberculosis: implications for therapy]. / Amylose AA secondaire à une tuberculose pulmonaire multi-résistante: implications thérapeutiques.

Multidrug resistant pulmonary tuberculosis was diagnosed to a 32-year-old man. An AA-amyloidosis was subsequently diagnosed on the renal biopsy performed for nephrotic syndrome and macroscopic hematuria. A 6-drug antibiotic treatment was delivered quickly after first results of genotypic antibiogram given the renal failure, and was secondarily adapted to the phenotypic antibiogram. Multidrug therapy was fairly well tolerated. Clinical and biological improving were slow. Although tuberculosis is a classic cause of amyloidosis, this is the first case reporting an association between a multidrug resistant case and an amyloidosis in adults. This case also raises the question of MDR probabilistic treatments in situations whether a vital organ prognosis is engaged.

Antifungal agents use in a French administrative region.

BACKGROUND: The increased use of new costly antifungal agents has led to a considerable increase in pharmaceutical expenditure. In December 2011, the Lorraine Regional Health Agency commissioned the Antibiolor network to evaluate costly antifungal agent stewardship using as reference regional, French, and international recommendations. METHODS: We performed a regional retrospective multicenter study. The criteria for evaluation were the appropriateness of the indication for treatment, the choice of the agent or of a combination, compliance with dose and treatment duration, and the absence of any alternative. RESULTS: One hundred and fourteen prescriptions were analyzed, in 7 intensive care units, 4 hematology units, and 1 infectious diseases unit. The indication for costly antifungal treatment was appropriate in 110 cases (96.5%), the choice of the antifungal agent in 102 cases (93%), the dose in 98 cases (89%), treatment duration in 102 cases (93%), and an alternative antifungal treatment was possible in 10 cases (9%). Eighty-two prescriptions (74.5%) complied with the marketing authorization, 19 (17%) were related to a protocol for temporary use, and 9 (8%) were considered as inappropriate. CONCLUSION: Our results show a high rate of appropriate prescriptions. The easily accessible and regularly updated local recommendations probably resulted in the standardization and optimization of costly antifungal agent prescriptions.

Liver-related deaths in HIV-infected patients between 1995 and 2010 in France: the Mortavic 2010 study in collaboration with the Agence Nationale de Recherche sur le SIDA (ANRS) EN 20 Mortalité 2010 survey.

OBJECTIVES: The aim of this study was to describe the proportion of liver-related diseases (LRDs) as a cause of death in HIV-infected patients in France and to compare the results with data from our five previous surveys. METHODS: In 2010, 24 clinical wards prospectively recorded all deaths occurring in around 26 000 HIV-infected patients who were regularly followed up. Results were compared with those of previous cross-sectional surveys conducted since 1995 using the same design. RESULTS: Among 230 reported deaths, 46 (20%) were related to AIDS and 30 (13%) to chronic liver diseases. Eighty per cent of patients who died from LRDs had chronic hepatitis C, 16.7% of them being coinfected with hepatitis B virus (HBV). Among patients who died from an LRD, excessive alcohol consumption was reported in 41%. At death, 80% of patients had undetectable HIV viral load and the median CD4 cell count was 349 cells/µL. The proportion of deaths and the mortality rate attributable to LRDs significantly increased between 1995 and 2005 from 1.5% to 16.7% and from 1.2‰ to 2.0‰, respectively, whereas they tended to decrease in 2010 to 13% and 1.1‰, respectively. Among liver-related causes of death, the proportion represented by hepatocellular carcinoma (HCC) dramatically increased from 5% in 1995 to 40% in 2010 (p = 0.019). CONCLUSIONS: The proportion of LRDs among causes of death in HIV-infected patients seems recently to have reached a plateau after a rapid increase during the decade 1995-2005. LRDs remain a leading cause of death in this population, mainly as a result of hepatitis C virus (HCV) coinfection, HCC representing almost half of liver-related causes of death.

Comparison of hospital databases on antibiotic consumption in France, for a single management tool.

CONTEXT: The surveillance of antibiotic use in hospitals and of data on resistance is an essential measure for antibiotic stewardship. There are 3 national systems in France to collect data on antibiotic use: DREES, ICATB, and ATB RAISIN. We compared these databases and drafted recommendations for the creation of an optimized database of information on antibiotic use, available to all concerned personnel: healthcare authorities, healthcare facilities, and healthcare professionals. METHODOLOGY: We processed and analyzed the 3 databases (2008 data), and surveyed users. RESULTS: The qualitative analysis demonstrated major discrepancies in terms of objectives, healthcare facilities, participation rate, units of consumption, conditions for collection, consolidation, and control of data, and delay before availability of results. The quantitative analysis revealed that the consumption data for a given healthcare facility differed from one database to another, challenging the reliability of data collection. We specified user expectations: to compare consumption and resistance data, to carry out benchmarking, to obtain data on the prescribing habits in healthcare units, or to help understand results. CONCLUSIONS: The study results demonstrated the need for a reliable, single, and automated tool to manage data on antibiotic consumption compared with resistance data on several levels (national, regional, healthcare facility, healthcare units), providing rapid local feedback and educational benchmarking.

Real-life rilpivirine resistance and potential emergence of an E138A-positive HIV strain in north-eastern France.

OBJECTIVES: To assess the prevalence of resistance to rilpivirine and mutations at position 138 in reverse transcriptase and to identify associated epidemiological and biological characteristics. METHODS: This retrospective study included 238 patients with available HIV-1 nucleotide sequences analysed at the Laboratory of Virology at the University Hospital of Nancy between January 2011 and June 2013. Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was evaluated according to the ANRS algorithm (version 23) and correlated with clinico-epidemiological and therapeutic data. The virus strains were analysed by evaluating the distance and distribution of the phylogenetic tree (MEGAv5). RESULTS: Among previously treated patients (111/238, 46.6%), 68/111 (61.3%) had received NNRTIs; all were rilpivirine-naive. The prevalence of rilpivirine resistance in the whole cohort was 12.6% (30/238), and was 10.2% (13/127) and 15.3% (17/111) in naive and pre-treated patients, respectively. The E138A mutation was the most frequent mutation associated with resistance to rilpivirine (P < 0.0001). The prevalence of the E138A mutation tended to increase over time, from 3.6% (2/55) during the first half of 2011 to 9.3% (4/43) during the first half of 2013 (P = 0.0614). Seven viral strains from seven naive male patients positive for the E138A mutation appeared in the same cluster. CONCLUSIONS: In our cohort of patients, we observed significantly increased resistance to rilpivirine, mostly because of the E138A mutation, probably due to an E138A strain circulating in newly diagnosed men who have sex with men. Taken together, our results emphasize the need to investigate the prevalence of rilpivirine resistance-associated mutations in the coming years both in France and abroad.

Relevance of fluoroquinolone use in a French teaching hospital.

OBJECTIVE: The objective of our study was to assess the good use of fluoroquinolone (FQ) in a French teaching hospital by a two round relevance review before and after proposal for better use of FQ prescriptions. PATIENTS AND METHODS: The relevance of FQ prescription according to regional guidelines was assessed using a standard card filled out retrospectively by physicians in the 3 previous months, in volunteer hospital wards. Then, two experts checked the relevance of prescriptions according to the regional antibiotherapy guidelines, a book called "Antibioguide", and determined a therapeutic index of adequacy for each card. The first survey (R1) took place in January 2008. The second survey (R2) took place in June 2009 to evaluate the impact of corrective measures, adopted at a meeting of the regional antibiotics commission in January 2009. RESULTS: Physicians in 18 wards completed 475 cards in R1 and physicians in 16 wards completed 263 in R2. The inappropriateness of FQ indication was significantly improved by 57% (P<0.001) between the two rounds and the rate of adequate cards was 33% in R1 and 55% in R2, giving an improvement of 66% (P<0.001). CONCLUSIONS: The improvement of FQ prescriptions and observance of guidelines demonstrate the importance of assessing the state of things before introducing corrective actions. "Antibioguide" was updated at the end of this study.

[Impact of corrective measures on fluoroquinolones prescriptions for urinary tract infections during a 2-round relevance study]. / Amélioration de la prescription des fluoroquinolones dans les infections urinaires. Revue de pertinence à deux tours.

OBJECTIVES: Evaluating the impact of corrective measures on fluoroquinolones (FQ) prescriptions for urinary tract infections (UTI) during a 2-round relevance study on a regional scale. METHODS: FQ prescriptions of voluntary hospitals were checked by an infectious diseases physician and a pharmacist according to regional guidelines. A first round (R1) took place in January 2008, with feedback and proposal for personalized corrective measures in January 2009. A second round (R2) was organized in June 2009. UTI data were extracted and the results of the two rounds were compared. RESULTS: Four hundred and thirty-five and 302 FQ prescriptions for UTI, coming from 28 and 24 different hospitals, were analyzed at R1 and R2, respectively. Thirty-six percent and 55% of these prescriptions were entirely in accordance with regional guidelines, at respectively R1 and R2 (P<0.001). All the analyzed criteria (choice of the molecule, dosage, duration of the treatment) significantly improved between R1 and R2. The route of administration non-significantly deteriorated. The rate of FQ prescriptions for non conform indications decreased from 24% to 12% between R1 and R2 (P<0.05). CONCLUSION: Most hospitals of Lorraine took part in this study, confirming its feasibility on a regional scale. The regional guidelines were reviewed at the end of R2, taking into account the last national guidelines. There was a significant improvement of FQ prescriptions for UTI through better adhesion to the regional guidelines between the two rounds. This is probably due to first turn results feedback, and corrective measures suggestion.

[Antimicrobial consumption reported through standardized reports on infection control activities, relationship with the ICATB public reporting indicator]. / Consommation des antibiotiques rapportée via les bilans standardisés de lutte contre les infections nosocomiales et relation avec l'ICATB.

OBJECTIVE: The study's objective was to describe the evolution of antibiotic consumption between 2006 and 2008 in French health care facilities (HCF) its relations with the national policy of good antibiotics use using the ICATB score. METHOD: Data from standardized reports on infection control activities collected from 2006 to 2008 by the Ministry of Health (antibiotic consumptions and elements of antibiotic stewardship of every HCF) were analyzed with linear regression models to multilevel random intercept adjusted on HCF characteristics (public or private) and activity. RESULTS: The analysis was performed on 4062 (48,2%) observations after exclusion of HCF not concerned by the ICATB public reporting indicator (7.2% of observations), invalid or missing data (21,2% of observations) and irrelevant values (23.4%). The global antibiotic consumption was 343 defined daily doses (DDD) per 1000 patient-days (PD) and varied little between 2006 and 2008. However, the linear regression model showed an increase of 5.7 DDD per 1000 PDs per year (P<0.001). There was a positive association between antibiotic consumption and ICATB score, mainly concerning sub-scores ICATB-action and ICATB-organization. CONCLUSION: The recent lack of decrease in antibiotic consumption in French HCF between 2006 and 2008 is coherent with other available national data, but exclusion of more than 50% of observations limits the impact of this analysis. The relationship between policy of good use and consumption of antibiotics remain difficult to specify, because of the short (three years) study length and because of the nature of ICATB, a composite indicator assessing only partly antibiotic policies.

[Study of new HIV infection between 2000 and 2007 in the north and east of France]. / Étude des infections à VIH nouvellement découvertes entre 2000 et 2007 dans le Nord et l'Est de la France.

UNLABELLED: In France, since 2003, all new HIV infection must be reported. Data collected with the declaration system is not exhaustive and only concerns epidemiological data. OBJECTIVE: The authors' aim was to study the epidemiologic evolution of new HIV cases between January 1, 2000 and December 31, 2007 in North and East of France, to compare them with national and local data, to complete them, and to identify local specificities. METHOD: A retrospective observational study was made, with a standardized questionnaire completed by any volunteer HIV care center in the North and the East of France. RESULTS: Three thousand and thirty questionnaires were analyzed. The main trends over these eight years were similar to those observed in the rest of France: a decreasing number of women and patients of foreign origin, a decreasing number of patients with a late diagnosis, an increasing number of primary infections, and a higher CD4 count on initiation of antiretroviral treatment. However, local specificities appeared, such as: increasing proportion of men having sex with men and a less important proportion of co-infected patients with hepatitis B and/or C than on the national level. The therapeutic regimen is adequate according to expert recommendations, with, however, a marked "center effect" concerning prescription habits. DISCUSSION: Such a local epidemiological study, even if it confirms observed trends in the rest of France, allows detailing them and suggesting prevention measures more specifically adapted to local settings.

[Interventions implemented to control an outbreak of vancomycin-resistant enterococci in a university hospital]. / Conduite adoptée face à une épidémie à ERG (ERV) dans un établissement de santé

At the end of 2004, a Vancomycin-resistant enterococci (VRE) outbreak occurred in the university hospital of Nancy. Interventions were simultaneous implemented in this hospital (promotion of hand washing, gathering of VRE carriers in the same part of units) and the outbreak seemed to be controlled before the end of 2005. But one year later, the number of discovered new colonisations increased again. Then, promotion of exclusive hand disinfection with alcohol-based hand-rub solutions and cohorting of VRE carriers in a dedicate ward were the only two effective interventions to control the outbreak. At the beginning of the year 2007, before being controlled, this outbreak expanded to several other healthcare centres in Lorraine. A specific regional team was set up in July 2007. A programme to eradicate VRE was elaborated based on national guidelines modified and adapted regarding particularities of each situation. These new guidelines were published on an internet site. A list of all healthcare centres accommodating patients colonized with VRE is established weekly and diffused to all hospitals in Lorraine which then could optimise readmission conditions of potential VRE carriers or contact patients. Between 2004 and 2008, more than 900 patients were found colonized with VRE in Lorraine. Finally, the application of all the measures previously described, seemed to be efficient to control the ERV outbreak in Lorraine.