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.

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.

Adult patients hospitalized for measles in France, in the 21st century.

BACKGROUND: An epidemic of measles broke out in France in 2008. We designed a retrospective study focusing on adults hospitalized for measles in 2010/2011. METHODS: A case was any patient aged more than 15 years, hospitalized (September 2010 to September 2011) with a typical rash or a biological diagnosis. Data was collected with standardized questionnaires in participating hospitals. RESULTS: Four hundred and sixty cases were reported: sex-ratio (M/F) = 0.93, median age 26 years (σ = 8.8). Twenty-nine cases were severe (6.5%), 27 of which hospitalized in an ICU. Three hundred and twelve (68%) cases had elevated serum transaminases (EST), 155 (34%) cases had pneumonia, 34 (7%) cases had elevated serum creatinine (ESC), four (0.9%) cases had elevated serum amylase and lipase (ESAL), and three (0.7%) cases had neurological symptoms. One hundred and four (23%) patients presented simultaneously with EST and pneumonia. One patient presenting with severe pneumonia died (0.2%). One hundred and ten (24%) patients received antibiotics during a median seven days. CONCLUSION: Measles can present as various syndromes in adults and be responsible for a high burden during outbreaks. The immediate outcome is favorable in most patients. Long-term outcome needs further investigations to identify possible late complications.

Pharmacokinetic and dynamic study of levofloxacin and rifampicin in bone and joint infections.

OBJECTIVE: We studied the pharmacokinetic and pharmacodynamic parameters of levofloxacin and rifampicin in bone and joint infections. The optimal dose regimen of these two antibiotics has not been documented yet. PATIENTS AND METHOD: We performed plasma dosage for each antibiotic in patients with a bone and joint infection requiring treatment with a levofloxacin and rifampicin combination. We then computed the 6 hours post dose area under the concentration-time curve (AUC(0-6h)), the peak plasma concentration (Cmax), the area under the inhibitory concentration curve (AUIC), and the peak-to-minimum-inhibitory-concentration ratio (Cmax/MIC). The pharmacodynamic results were then compared to the published thresholds of effectiveness. The doses used were levofloxacin 500 mg bid and rifampicin 20mg/kg per day. RESULTS: The plasma of 17 patients was dosed. The average AUC(0-6h) for levofloxacin was 46.59 mg.h/l, the average Cmax 10.7 mg/l, the average AUIC 932, and the average Cmax/MIC 107.5. The averages for rifampicin were 42.2mg.h/l, 11.8 mg/l, 11,125 and 1514. Given that bone concentration of levofloxacin is 30% that of the plasma concentration, that concentration was divided by three to estimate bone concentration. CONCLUSION: The optimal thresholds of pharmacodynamic effectiveness were obtained for most patients with levofloxacin at 500 mg bid. Additional studies are still required to determine the optimal rifampicin dose.

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.

Role of intravenous cloxacillin for inpatient infections.

One of the issues of antibiotic treatment is to warrant its optimal effectiveness while minimizing the risk for emergence of resistance. The time above minimal inhibiting concentration (MIC) (T>MIC) is the best predictive pharmacological parameter of effectiveness for antibiotics with time-dependent activity, such as cloxacillin. Cloxacillin is the first line antibiotic in a great number of clinical situations generated by methicillin sensitive staphylococci, because of its intrinsic properties: bactericidal effect, tissue distribution and safety. The most recent anti-staphylococcal agents do not improve treatment of MSSA infections compared to penicillin M and especially cloxacillin. Cloxacillin has a narrow microbiological spectrum. This ecological feature is in line with the recommendation to use antibiotics with the narrowest spectrum to reduce the pressure of selection. The consensus is to have T>MIC for at least 40% of the dosing interval and is achieved by infusing 2g of cloxacillin per day (T>MIC=50%) or four infusions of 3g per day (T>MIC=42%) in adults.

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.

[Lyme uveitis: 2 case reports]. / Uvéites de Lyme: à propos de 2 observations.

Lyme borreliosis is a zoonosis characterized by great clinical polymorphism. We report 2 cases in patients who presented ocular manifestations: one anterior uveitis in an adult, which resolved under treatment, and one posterior uveitis in a child, whose initial ophthalmologic examination already showed retinal fibrous scars including the macular area. Lyme disease is on the long list of causes that must be discussed in cases of uveitis. The diagnosis is based on a series of epidemiological, clinical, and biological arguments with Western Blot serological profile analysis. Treatment is based especially on intravenous antibiotics.

[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.

Liens entre résistance et échec 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.

[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.