Application of guidelines for aminoglycosides use in French hospitals in 2013-2014.

In 2011, the French Agency for Safety of Health Products issued guidelines underlining the principles of proper aminoglycosides' use. The aim of the survey was to evaluate adherence to these guidelines two years after their issue. Characteristics of patients receiving aminoglycosides were recorded by voluntary facilities during a 3-month survey in 2013-2014. The modalities of aminoglycosides treatment were analysed by comparison with the French guidelines. A total of 3,323 patients were included by 176 facilities. Patients were mainly hospitalized in medical wards (33.0%), and treated for urinary-tract infections (24.7%). Compliance regarding the clinical indication and the daily aminoglycosides dose was observed in 65.2% and 62.9% of the cases, respectively. A 30-min once-daily IV administration was recorded in 62.5% of the cases. Aminoglycosides treatment duration was appropriate (≤5 days) for 93.6% of the patients. When considering the four criteria together, 23.2% of the patients had a treatment regimen aligned with the guidelines. Requests for measurements of peak and trough AG serum concentrations matched the guidelines in 24.9% and 67.4% of the cases, respectively. Two years after guidelines issue, aminoglycosides use remains unsatisfactory in French health-care facilities. Efforts should be made for guidelines promotion, especially regarding the issue of underdosing.

Point prevalence survey of antibiotic use in French hospitals in 2009.

OBJECTIVES: To evaluate the feasibility of a point prevalence survey for monitoring antibiotic use in a voluntary sample of French hospitals. METHODS: Demographic and medical data were collected for all inpatients. Additional characteristics regarding antimicrobial treatment, type of infection and microbiological results were collected only for patients receiving antimicrobials. RESULTS: Among 3964 patients in 38 hospitals, 343 (8.7%) received antimicrobial prophylaxis and 1276 (32.2%) antimicrobial therapy. The duration of surgical antimicrobial prophylaxis was >1 day in 41 out of 200 (21%) of the cases. Among patients with antimicrobial therapy, 959 (75.2%) received ß-lactams (including 34.8% penicillins with ß-lactam inhibitors, 22.1% third-generation cephalosporins and 7.8% carbapenems) and 301 (23.6%) received fluoroquinolones (50% orally). A total of 518 (40.6%) patients were treated with more than one drug and 345 (27.2%) were treated for >7 days. Patients treated for hospital-acquired infections (39.2%) were more likely to receive combinations (47.6% versus 34.4%, P < 0.01), carbapenems (14.4% versus 2.6%, P < 0.01), glycopeptides (14.4% versus 3.7%, P < 0.01) and antifungals (17% versus 5.3%, P < 0.01) for a longer duration (7.8 versus 6 days, P < 0.01). Fifty-six patients (4.4%) were treated for >7 days and did not have any microbiological sample drawn. The time allocated for the survey represented 18.3-25.0 h for 100 patients. CONCLUSIONS: The data provide directions for further interventions, such as better use of diagnostic tools, decreasing the treatment duration and the use of combinations. In addition, the survey shows that, although cumbersome, it is feasible to improve the representativeness of national data in European surveys.

Re-emergence of brucellosis in cattle in France and risk for human health.

A case of human brucellosis was diagnosed in France in January 2012. The investigation demonstrated that the case had been contaminated by raw milk cheese from a neighbouring dairy farm. As France has been officially free of bovine brucellosis since 2005, veterinary investigations are being conducted to determine the origin of the infection and avoid its spread among other herds. Hypotheses about the source of this infection are discussed.

[Forgotten hepatitis: the hepatitis E]. / Hépatite oubliée: l'hépatite E.

Hepatitis E is caused by the Hepatitis E Virus (HEV), entericaly transmitted. In areas with poor sanitation, HEV is responsible for high endemicity and major outbreaks. In countries with high sanitary conditions, HEV is a zoonosis responsible for sporadic cases, and is encountered in travellers returning from endemic areas. The clinical manifestations are not distinguishable from that caused by other causes of acute viral hepatitis. Fulminant hepatitis are encountered in 1 to 4% of acute hepatitis E. Remarquably, mortality among pregnant women is very high. Diagnosis can be made by serological testing and eventually viral detection by PCR. HEV can cause chronic infection in immunocompromised patients. There is no specific therapy. There is no vaccine currently available.

[Fosfomycin prescription during production shortage]. / Prescription de la fosfomycine en situation critique.

The supply of fosfomycin had to be carefully controlled over metropolitan France during 10 weeks because of a unique crisis in production. Three hundred and forty prescriptions were collected and re-examined by an expert committee. The main indications were osteoarthritis (27%), lung infections (21%), severe sepsis (12.5%), and urinary tract infections (11%). The main bacteria involved, often multidrug resistant, were Pseudomonas aeruginosa (40%) and methicillin-resistant Staphylococcus. A careful analysis of the antibiogram proved fosfomycin to be irreplaceable in 36% of the cases. This study confirms and specifies the interest of fosfomycin. To our knowledge, this study was a unique opportunity to collect such specific data from the whole of France over a two-month shortage period.

[Link between resistance and failure in community-acquired respiratory infections]. / Liens entre résistance et echec dans les infections respiratoires communautaires.

Resistance is one of failure's reasons. We tried, through clinical experience, to approach the magnitude and nature of the links, between phenotypically defined acquired resistance and clinical failure, in community acquired respiratory infections. An efficient resistance mecanism, able to suppress antibiotic action, is clearely associated to a risk of clinical failure (e.g. betalactamase secretion, target modification using methilation for macrolides, target mutation for fluoroquinoles). Resistance mecanism due to reduction of target affinity (pneumococcus and betalactams) progressively decreasing beta lactam activity depending on its expression, is at present time, not clearely associeted with clinical failure. Critical concentration, defining phenotypical resistance, is predictive of failure if it identifies a bacterial population owning an efficient resistance mecanism. It will not be predictive of failure if that concentration do not detect the resistance mecanism (e.g. parC mutation and levofloxacin) or if the link between antibiotic and resistant bacteria is not binary but depends also on pharmacokinetic parameters (pneumococcus and betalactam). Using resistance as a parametre for antibiotic choice, must integrate several elements: presence or not of a resistance mecanism, type and efficiency of the mecanism, links with clinical failure and antibiotic concentration, type and site of infection. Critical concentration is not allways the magic number that predict failure or success.

Antibiotic use and good practice in 314 French hospitals: The 2010 SPA2 prevalence study.

OBJECTIVES: We aimed to assess antibiotic prescriptions to identify potential targets for improvement. METHODS: We conducted a point prevalence survey (November 2010) of antibiotic use in 314 voluntary hospitals recruited by the French Infectious Diseases Society (SPILF) and the National Observatory for Epidemiology of Bacterial Resistance to Antimicrobials (ONERBA). Data were entered online, immediately analyzed and exported. RESULTS: The prevalence of antibiotic use was 19.5% (9059/46,446patients). A higher prevalence was observed in the infectious disease (58.4%), hematology (58%), and intensive care (48.7%) units. The three most frequently used antibiotic classes were aminopenicillins (23.8%), fluoroquinolones (17.9%), and 3rd-generation cephalosporins (16.7%). A monotherapy was prescribed to 64% of patients. The reasons for the antibiotic prescription were written in the medical records of 74% of patients and 62% were consistent with the local guidelines. CONCLUSION: Our results are similar to that of other studies. Various local targets for improvement have been identified to help hospitals define a better antibiotic stewardship.

Acute HIV infection: impact on the spread of HIV and transmission of drug resistance.

OBJECTIVE: To assess the impact of primary HIV infection (PHI) on the spread of HIV and the temporal trends in transmission of HIV drug resistance between 1996 and 1999 in Switzerland. METHODS: Sequencing of the genes for reverse transcriptase (RT) and protease was performed for 197 individuals with documented PHI. Phylogenetic analyses were confronted with epidemiological data. RESULTS: Significant clustering was demonstrated for 29% of the RT sequences. All these cases occurred closely together in place and time; contact tracing demonstrated transmission at the time of PHI in 30% of them. Genotypic drug resistance was detected in 8.6% of PHI individuals in 1996, 14.6% in 1997, 8.8% in 1998 and 5.0% in 1999. Drug-resistant variants were identified in 11.3% of individuals infected by homosexual contacts, 6.1% by heterosexual contacts, 13% of intravenous drug users and more frequently in men (10.4%) than women (2.6%). Potential factors involved in the recent decrease of transmission of drug-resistant variants include increase of HIV non-B subtypes from 23% in 1996 to 35% in 1999 (only one non-B subtype had resistance mutations) and a steady increase of patients with undetectable viraemia as documented in Swiss HIV Cohort Study (10% in 1996 vs 53% in 1999). CONCLUSIONS: Phylogenetic and epidemiological analyses underline the impact of PHI in the spread of HIV. Moreover, this study indicates that drug resistance transmission may have decreased recently in Switzerland through the increased frequency of infection with HIV non-B subtypes and the steady increase of patients with undetectable viraemia.

Is there a rationale for the continuous infusion of cefepime? A multidisciplinary approach.

This review is the fruit of multidisciplinary discussions concerning the continuous administration of beta-lactams, with a special focus on cefepime. Pooling of the analyses and viewpoints of all members of the group, based on a review of the literature on this subject, has made it possible to test the hypothesis concerning the applicability of this method of administering cefepime. Cefepime is a cephalosporin for injection which exhibits a broader spectrum of activity than that of older, third-generation cephalosporins for injection (cefotaxime, ceftriaxone, ceftazidime). The specific activity of cefepime is based on its more rapid penetration (probably due to its zwitterionic structure, this molecule being both positively and negatively charged) through the outer membrane of Gram-negative bacteria, its greater affinity for penicillin-binding proteins, its weak affinity for beta-lactamases, and its stability versus certain beta-lactamases, particularly derepressed cephalosporinases. The stability of cefepime in various solutions intended for parenteral administration has been studied, and the results obtained demonstrated the good compatibility of cefepime with these different solutions. These results thus permit the administration of cefepime in a continuous infusion over a 24-h period, using two consecutive syringes.

[Clinical trial of an antipneumococcal vaccine in elderly subjects living in institutions]. / Essai clinique du vaccin antipneumococcique chez des personnes âgées vivant en institution.

Pneumococcal vaccine effectiveness was assessed in a randomized trial among 1,686 old people (mean age: 74, standard deviation: 4 years) living in 24 geriatric hospitals and 26 homes for the aged in our district; 937 were vaccinated with Merck-Sharp and Dohme pneumococcal vaccine (14 serotypes). The 749 others composed the reference group. This study was performed during 2 years, since December 1980. Both groups were randomized after a two-criteria stratification: by clinical risk assessed before the study, and by type of homes for the aged. Forty pneumonias were diagnosed, with 13 proved pneumococcal etiology. The incidence of pneumonia was significantly reduced in the vaccinated group (p less than 10(-4) but the mortality rate was not modified. We concluded in favor of the effectiveness of pneumococcal vaccine: etiological fraction 77.1% (51.2%-89.3% confidence limits, 95% risk) in the population we studied. The incidence of pneumococcal-proved pneumonia was not significantly reduced.

[Deep candidiasis in agranulocytic patients: mycological and serological surveillance in 91 febrile episodes and management of an antifungal and antibacterial protocol]. / Candidoses profondes chez l'agranulocytaire: surveillance mycologique et sérologique au cours de 91 épisodes fébriles et gestion d'un protocole antibactérien et antifongique.

This study took place between February 1984 and February 1985 in 76 febrile neutropenic patients. We evaluated the whole mycological and serological results, in 91 febrile episodes. We separated two groups: group I (acute leukemia, chronic myeloïd leukemia, medullar aplasia, lymphomas) and group II (chronic lymphoïd leukemia, Hodgkin disease, myelomas, solid tumors). Patients were included in this study if they developed a temperature of 38.5 degrees C or greater and if they had less than five hundred neutrophils per mm3. They were treated with mono or bi-antibiotherapy. If the patient remained febrile more than 72 hours, an antifungal therapy was added (Amphotericin B IV). Through these weekly results, we conclude: the high frequency of digestive tract candidiasis in such patients; disseminated candidiasis occurs only in the first group patients with fungal digestive colonization; the overall response rate in this study was 77 per cent. This underlines the interest of empiric treatment with amphotericin B IV.

[Adenocarcinoma of unknown primary site with thoracic localization and HIV: four case reports]. / Adénocarcinomes d'origine inconnue à manifestation thoracique et VIH: à propos de quatre cas.

INTRODUCTION: Non AIDS-defining cancer would have increased in HIV-patients as suggested by numerous studies. Four cases of adenocarcinoma of unknown primary site with thoracic localization that occurred in HIV-infected patients are described. EXEGESIS: To date, there have been no published data about carcinomas of unknown primary site relating to HIV-infected patients; however, immunodepression could promote them. Carcinomas of unknown primary site account for 0.5 to 10% of all cancer in general population. Primary carcinoma is identified in approximately one third of the cases and often corresponds to lung cancer in case of sus-diaphragmatic metastasis, particularly in case of pleural metastasis. Lung cancer in HIV-infected patients affects mostly young men who smoke and are often intravenous drug addicts. Adenocarcinoma is the most common histological type of cancer. CONCLUSION: Further studies of lung cancer in HIV-infected patients will help evaluate their frequency. In case of increasing frequency, lung cancer should then be included in AIDS-defining cancers.

[Treatment of Listeria monocytogenes meningoencephalitis with cotrimoxazole in monotherapy]. / Traitement des méningo-encéphalites à Listeria monocytogenes de l'adulte par le cotrimoxazole en monothérapie.

L. monocytogenes meningo-encephalitis are still a therapeutic problem, with most of the time a poor prognosis. In vitro, cotrimoxazole has about the same bactericidal activity as the ampicillin-aminoglycoside combination. So we treated 8 patients with L. M. meningoencephalitis with cotrimoxazole alone, with a mean duration of treatment of 13 days. All patients recovered without sequellae from their infectious episode.

[First intention treatment with josamycin in primary acute pneumopathies of infectious origin in adults]. / Traitement de première intention par josamycine au cours des pneumopathies aiguës primitives d'origine infectieuse chez l'adulte.

In a prospective study 128 community acquired pneumoniae were treated with a macrolide (josamycin) by oral route. Patients improved in 94 p. 100 (113). Complications were as following: 2 deaths, 2 sequels, 3 failures. Authors discuss macrolides effectiveness in acute pneumoniae, particularly pneumococcal ones. They conclude macrolides are a good choice in first intention in acute pneumoniae of adults.