Hospitalisations with infections related to antimicrobial-resistant bacteria from the French nationwide hospital discharge database, 2016.

Massive use of antibiotics has led to increased bacterial resistance to these drugs, making infections more difficult to treat. Few studies have assessed the overall antimicrobial resistance (AMR) burden, and there is a paucity of comprehensive data to inform health policies. This study aims to assess the overall annual incident number of hospitalised patients with AMR infection in France, using the National Hospital Discharge database. All incident hospitalisations with acute infections in 2016 were extracted. Infections which could be linked with an infecting microorganism were first analysed. Then, an extrapolation of bacterial species and resistance status was performed, according to age class, gender and infection site to estimate the total number of AMR cases. Resistant bacteria caused 139 105 (95% CI 127 920-150 289) infections, resulting in a 12.3% (95% CI 11.3-13.2) resistance rate. ESBL-producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus were the most common resistant bacteria (>50%), causing respectively 49 692 (95% CI 47 223-52 142) and 19 493 (95% CI 15 237-23 747) infections. Although assumptions are needed to provide national estimates, information from PMSI is comprehensive, covering all acute bacterial infections and a wide variety of microorganisms.

Autoimmune disorders and quadrivalent human papillomavirus vaccination of young female subjects.

OBJECTIVES: The aim of this study was to investigate whether the quadrivalent human papillomavirus (HPV) vaccine Gardasil is associated with a change in the risk of autoimmune disorders (ADs) in young female subjects. DESIGN: Systematic case-control study of incident ADs associated with quadrivalent HPV vaccination in young women across France. PARTICIPANTS AND SETTING: A total of 113 specialised centres recruited (from December 2007 to April 2011) females aged 14-26 years with incident cases of six types of ADs: idiopathic thrombocytopenic purpura (ITP), central demyelination/multiple sclerosis (MS), Guillain-Barré syndrome, connective tissue disorders (systemic lupus erythematosus, rheumatoid arthritis/juvenile arthritis), type 1 diabetes mellitus and autoimmune thyroiditis. Control subjects matched to cases were recruited from general practice. ANALYSIS: Multivariate conditional logistic regression analysis; factors included age, geographical origin, smoking, alcohol consumption, use of oral contraceptive(s) or vaccine(s) other than Gardasil received within 24 months before the index date and personal/family history of ADs. RESULTS: Overall, 211 definite cases of ADs were matched to 875 controls. The adjusted odds ratio (OR) for any quadrivalent HPV vaccine use was 0.9 [95% confidence interval (CI) 0.5-1.5]. The individual ORs were 1.0 (95% CI 0.4-2.6) for ITP, 0.3 (95% CI 0.1-0.9) for MS, 0.8 (95% CI 0.3-2.4) for connective disorders and 1.2 (95% CI 0.4-3.6) for type 1 diabetes. No exposure to HPV vaccine was observed in cases with either Guillain-Barré syndrome or thyroiditis. CONCLUSIONS: No evidence of an increase in the risk of the studied ADs was observable following vaccination with Gardasil within the time periods studied. There was insufficient statistical power to allow conclusions to be drawn regarding individual ADs.

The Bayesian microbial subtyping attribution model: robustness to prior information and a proposition.

Attributing foodborne illnesses to food sources is essential to conceive, prioritize, and assess the impact of public health policy measures. The Bayesian microbial subtyping attribution model by Hald et al. is one of the most advanced approaches to attribute sporadic cases; it namely allows taking into account the level of exposure to the sources and the differences between bacterial types and between sources. This step forward requires introducing type and source-dependent parameters, and generates overparameterization, which was addressed in Hald's paper by setting some parameters to constant values. We question the impact of the choices made for the parameterization (parameters set and values used) on model robustness and propose an alternative parameterization for the Hald model. We illustrate this analysis with the 2005 French data set of non-typhi Salmonella. Mullner's modified Hald model and a simple deterministic model were used to compare the results and assess the accuracy of the estimates. Setting the parameters for bacterial types specific to a unique source instead of the most frequent one and using data-based values instead of arbitrary values enhanced the convergence and adequacy of the estimates and led to attribution estimates consistent with the other models' results. The type and source parameters estimates were also coherent with Mullner's model estimates. The model appeared to be highly sensitive to parameterization. The proposed solution based on specific types and data-based values improved the robustness of estimates and enabled the use of this highly valuable tool successfully with the French data set.

Efficacy of a long-term antibiotic treatment in patients with a chronic Tick Associated Poly-organic Syndrome (TAPOS).

SETTINGS: Despite a now codified antibiotic treatment for Lyme disease, a significant proportion of patients treated according to recommendations complain of persistent signs and symptoms. The pathophysiological mechanisms which underlie this syndrome of post-treatment chronic systemic illness remain unclear. For some physicians post-treatment symptoms indicate a persistent infection requiring prolonged antibiotic therapy. For others, there is no benefit from antimicrobial therapy. The difficulty of assessment encountered in studies is significant because many symptoms are subjective. We think that the term "chronic Lyme disease" is not appropriate and should be replaced by chronic "tick associated poly-organic syndrome" (TAPOS). OBJECTIVE: This open-label prospective study was made on a group of 100 patients having followed a medical treatment for a chronic TAPOS and to evaluate their evolution under prolonged antibiotic treatment. RESULTS: The medical management was found to be effective for symptoms, especially for patients with a high probability of chronic TAPOS (NEJM score). Patients with post tick-bite symptoms, which often worsens their quality of life, deserve particular attention. CONCLUSION: This study had methodological limitations but could help in terms of feasibility, choice of inclusion criteria, and design of follow-up for a future randomized, double blind study to test for an optimal management of TAPOS.

Impact of antimicrobial drug usage measures on the identification of heavy users, patterns of usage of the different antimicrobial classes and time-trends evolution.

Several measurement units are available to quantify antimicrobial usage in veterinary medicine, to obtain diverse measures such as the weight of active substance used, the live weight (LW) treated, the fraction of animals exposed, the number of treatments recorded or the cost represented. These measures can be applied to study practices variability between farms, to characterize patterns of usage of the different antimicrobial classes or to follow evolution of antimicrobial usage with time. An investigation was carried out to specifically explore the influence of measurement units on the conclusions obtained from such studies. Antimicrobial exposure was explored in a sample of turkey and chicken broiler flocks, using six different units [kg of active compound, treatments, days of administration, kg of LW treated, animal daily dose to treat 1 kg of LW (ADD(kg)) and euros] to compare flocks usage variability and patterns of use of the different antimicrobial classes. Time-trends evolutions of macrolides usage in turkey broilers, characterized by percentage of flocks exposed and LW treated, were also compared. In all analyses, the measure gave different results without equivalences, highlighting the necessity for care in choosing the measurement unit and caution in interpreting the figures obtained.

[Results of a prospective standardized study of 30 patients with chronic neurological and cognitive disorders after tick bites]. / Enquête étiologique standardisée sur une cohorte de 30 patients atteints de troubles neurologiques et cognitifs chroniques après piqûre de tiques results of a prospective standardized study of 30 patients with chronic neurological and cognitive disorders after tick bites.

OBJECTIVE: Patients with chronic neurological disorders and cognitive impairment after tick bites are difficult to manage despite standard antibiotic therapy for Lyme disease. We wanted to correctly assess the disorders. METHODS: Thirty patients were hospitalized for a standardized evaluation of their disorders: clinical examination, biological and serological studies, cerebral MRI, CSF study, neurophysiological exams, and neuropsychological evaluation of cognitive functions. RESULTS: Clinical and biological results were non informative. We observed significant CSF abnormalities (64%), MRI Flair pictures (41%), neurophysiological exams (47%), and cognitive evaluation (100%). CONCLUSIONS: A large and standardized evaluation should be made for each patient to improve the management and probably the treatment of these complex chronic symptoms observed after tick bites.

Relative-risk ratio was a useful measure of differential association in cohort and case-series studies.

OBJECTIVE: The framework consists of cohort or case-series studies with intermittent exposure and two types of events. The aim is to define and estimate an association measure between the exposure and the occurrence of one type of event rather than the other. STUDY DESIGN AND SETTING: The model and the estimation method are obtained by extending Farrington's approach for one type of recurrent event. The proposed association measure "RR(c)" is the ratio of the relative risks pertaining to each type of event. The estimated RR(c) and its confidence interval are derived under the independence assumption between the counts of the two types of events. The data that are analyzed are part of the data of a study on antimicrobial resistance in children. RESULTS: An interpretation of the RR(c) is proposed in terms of an odds ratio, which parallels a similar association measure defined in cross-sectional studies ("OR(c)"). The estimated value of the RR(c) agrees with the OR(c) reported in previous studies. CONCLUSION: The RR(c) appears as a useful tool for evaluating the risk of colonization (or infection) with resistant rather than susceptible bacteria following a previous intake of a given antibiotic conditional on colonization (or infection) with any bacteria.

Antifungal therapy for patients with proven or suspected Candida peritonitis: Amarcand2, a prospective cohort study in French intensive care units.

OBJECTIVE: The clinical characteristics and prognosis of patients treated for Candida peritonitis (CP) were compared according to the type of systemic antifungal therapy (SAT), empiric (EAF) or targeted (TAF) therapies, and the final diagnosis of infection. METHODS: Patients in intensive care units (ICU) treated for CP were selected among the AmarCAND2 cohort, to compare patients receiving EAF for unconfirmed suspicion of CP (EAF/nonCP), to those with suspected secondarily confirmed CP (EAF/CP), or with primarily proven CP receiving TAF. RESULTS: In all, 279 patients were evaluated (43.4% EAF/nonCP, 29.7% EAF/CP and 25.8% TAF patients). At SAT initiation, the severity of illness was similar among EAF/nonCP and EAF/CP patients, lower among TAF patients (median Simplified Acute Physiology Score II (SAPS II) 49 and 51 versus 35, respectively; p 0.001). Candida albicans was involved in 67%, Candida glabrata in 15.6%. All strains were susceptible to echinocandin; 84% to fluconazole. Echinocandin was administered to 51.2% EAF/nonCP, 49% EAF/CP and 40% TAF patients. At day 28, 72%, 76% and 75% of EAF/nonCP, EAF/CP and TAF patients, respectively, were alive. An increased mortality was observed in patients with a Sequential Organ Failure Assessment (SOFA) score <7 if SAT was delayed by ≥6 days (p 0.04). Healthcare-associated CP (OR 3.82, 95% CI 1.52-9.64, p 0.004), SOFA ≥8 at ICU admission (OR 2.61, 95% CI 1.08-6.34; p 0.03), and SAPS II ≥45 at SAT initiation (OR 5.08, 95% CI 1.04-12.67; p 0.001) impacted the 28-day mortality. CONCLUSIONS: In summary, only 56.6% of ICU patients receiving SAT had CP. Most strains were susceptible to SAT. A similar 28-day mortality rate was observed among groups; the late administration of SAT significantly worsened the prognosis of patients with less severe CP.

Control of an ACC-1-producing Klebsiella pneumoniae outbreak in a physical medicine and rehabilitation unit.

This article describes an outbreak of ACC-1-producing Klebsiella pneumoniae involving 40 patients. These were mainly men under 40 years old with a spinal cord injury, in a physical medicine and rehabilitation unit. The main risk factors were prolonged hospital stay, multiple-bed rooms, tracheostomy care and assisted defaecation. The outbreak was only controlled after the introduction of rigorous patient placement (i.e. single rooms or cohorting in the same room), while allowing the patients to have free access to the various technical services (e.g. physiotherapy and occupational therapy) and living spaces necessary for re-education.

Antibiotic use in humans and bacterial resistance.

As with any public health problem, the evolution of antibacterial resistance must be viewed from a perspective of risk, and analysed in terms of probabilities within the populations. It is necessary to be able to predict the risk of antibacterial resistance, in the future, and two main strategies have recently been developed in mathematical models that may help to evaluate these risks. It is also important to understand how antibiotics are used and how their use affects the evolution of antibacterial resistance. Understanding the epidemiology of antibacterial resistance will enable us to develop preventive strategies to limit existing resistance and to avoid the emergence of new strains of resistant bacteria.

Thirty-day mortality of nosocomial systemic bacterial infections according to antibiotic susceptibility in an 800-bed teaching hospital in France.

Overall 30-day mortality among patients with nosocomial bacterial infections was analysed according to antibiotic susceptibility in an 800-bed hospital. Survival analysis identified three factors associated with an increased mortality rate: (1) a longer interval between admission and onset of infection; (2) bacterial resistance; and (3) the severity of the initial illness in the intensive care unit. The increased mortality rate associated with antibiotic resistance was observed for all bacterial species with the exception of Gram-positive cocci, and remained significant or near-significant regardless of the hospital ward.

Invoices and farmer interviews for vaccine-exposure measurement in turkey-broiler production.

Exposure measurement in pharmaco-epidemiological studies can be based on various sources that do not always concur. However, reliability is an important criterion when selecting the method used to assess exposure and interpreting the results obtained. An analysis based on invoices might be more informative and more accurate to assess vaccines exposure (yes/no) in turkey broiler production than a questionnaire administered to farmers, which is nevertheless more feasible and less time-consuming. We compared the two methods to assess vaccination exposure in 239 turkey broiler flocks reared in 129 farms in 2000-2001. The agreement (crude agreement and kappa) was calculated, and association between discrepancy and farm and flock characteristics was investigated. Marek's-disease vaccine, Newcastle-disease vaccine, turkey haemorrhagic-enteritis vaccine and turkey-rhinotracheitis vaccine exposures were reported on the questionnaire for 2.1, 27.6, 93.0, and 98.3% of flocks, respectively, and for 2.1, 29.3, 89.4, and 86.6%, of invoices for the flocks studied, respectively. A discrepancy was observed in 24.9% of flocks. A discrepancy was observed more frequently in specialised farms without any other animal production (OR = 3.6; CI = 1.5, 8.9) and when the farmer did not know whether vaccination had been performed in the hatchery (OR = 7.1; CI = 2.6, 19.7).

Use of avilamycin for growth promotion and avilamycin-resistance among Enterococcus faecium from broilers in a matched case-control study in France.

We assessed the putative link between avilamycin-resistant Enterococcus faecium carriage and avilamycin consumption in broilers. As part of the French programme of monitoring for antimicrobial resistance, broilers sampled at slaughterhouse in 1999 and 2000 and carrying avilamycin-resistant E. faecium were matched by slaughterhouse, slaughter month and production type (free-range, standard, light) with control broilers carrying avilamycin-susceptible strains. History of antibiotics consumption (either for growth promotion or therapeutic purpose) in the broiler flocks sampled was collected from the monitoring programme and consumption of each antibiotic class was screened as a potential risk factor. Avilamycin was a risk factor for avilamycin-resistant E. faecium carriage: OR=2.3.

[Impact of population exposure on the risk of bacterial resistance]. / Impact de l'exposition des populations sur le risque de résistance bactérienne.

Exposure of populations to antibiotics is a condition for the emergence and the diffusion of bacteria resistant to antibiotics. Analysis of epidemiological causality between antibiotic exposure and expansion of antibiotic resistance in human pathogens requires the study of the basis for the emergence and the subsequent epidemic spread of the strains. Emergence of antibiotic resistance under the selective pressure of antibiotics is unavoidable. However, the rapidity of the emergence depends on several parameters including the biochemical mechanism and the genetic support of the resistance and on the couple bacteria/antibiotic considered. Several of these parameters may be studied and measured in vitro. In vivo, relationship between antibiotic exposure and risk for infection or colonisation by pneumococci resistant to beta-lactams or macrolides and methicillin-resistant staphylococci are among the best studied models. In particular for pneumococci, quantitative relationship between antibiotic consumption and resistance, including geographical correlations have been shown but do not allow to establish any causality relationship. Overall, there is no doubt on the question of the impact of antibiotic exposure and the risk of antibiotic resistance. However, the quantification of the risks remains to be accurately studied.

Occupational determinants of methicillin-resistant Staphylococcus aureus colonization among healthcare workers: a longitudinal study in a rehabilitation center.

BACKGROUND Staphylococcus aureus carriage among healthcare workers (HCWs) is a concern in hospital settings, where it may provide a reservoir for later infections in both patients and staff. Earlier studies have shown that the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) carriage in HCWs is highly variable, depending notably on location, hospital department type, MRSA prevalence among patients, and type of contacts with patients. However, MRSA incidence in HCWs and its occupational determinants have seldom been studied. METHODS A prospective, observational cohort study was conducted between May and October 2009 in a French rehabilitation center hospital. HCWs and patients were screened weekly for S. aureus nasal carriage. Methicillin-susceptible S. aureus and MRSA prevalence and incidence were estimated and factors associated with MRSA acquisition were identified using generalized estimating equation regression methods. RESULTS Among 343 HCWs included in the analysis, the average prevalence was 27% (95% CI, 24%-29%) for methicillin-susceptible S. aureus and 10% (8%-11%) for MRSA. We observed 129 MRSA colonization events. According to the multivariable analysis, high MRSA prevalence level among patients and HCW occupation were significantly associated with MRSA acquisition in HCWs, with assistant nurses being more at risk than nurses (odds ratio, 2.2; 95% CI, 1.4-3.6). CONCLUSIONS Our findings may help further our understanding of the transmission dynamics of MRSA carriage acquisition in HCWs, suggesting that it is notably driven by carriage among patients and by the type of contact with patients.

Inappropriateness and variability of antibiotic prescription among French office-based physicians.

OBJECTIVE: To describe oral antibiotic prescription in the community. DESIGN: Audit of anti-infective prescribing in office-based medical practice. SETTING: Center of France, in the Loiret, a 600,000 inhabitant administrative division. MAIN OUTCOME MEASURES: Clinical hypothesis and antimicrobial drugs used as well as daily doses and durations of treatment. RESULTS: Respiratory tract infections with a presumed viral etiology accounted for 36% of prescriptions. In children, a high percentage of antibiotic prescriptions were underdosed as compared to clinical recommendations, particularly in acute otitis media. The variability of the daily dose was high, with coefficients of variation over 40% in acute otitis media or acute tracheobronchitis. Whatever the clinical hypothesis, the duration of treatment was close to 8 days. In acute otitis media, the coefficient of variation was 14%, the lowest for all diagnoses. CONCLUSION: Our investigation identified two main areas for improving antimicrobial drug prescribing: (1) reduction of useless prescriptions in respiratory tract infections with a presumed viral etiology, and (2) increasing the prescribed daily dose of antimicrobials to the recommended levels.

Clinical and microbiological epidemiology of Streptococcus pneumoniae bacteremia in eight French counties.

OBJECTIVE: To describe the incidence of pneumococcal bacteremia not associated with infection of the central nervous system, investigate the susceptibility of bacterial isolates to beta-lactams, evaluate risk factors for antibiotic resistance, and determine factors predicting patient outcome. METHODS: Over a period of 1 year, 919 Streptococcus pneumoniae isolates were collected from 919 patients with bacteremia in eight French counties. Their clinical and microbiological features were recorded. Univariate and multivariate analyses were used to determine risk factors for penicillin-non-susceptible pneumococcal bacteremia and predictors of fatal outcome. RESULTS: Of the 919 patients in the study, 27% were infected with penicillin-non-susceptible pneumococci (PNSP): 17.8% of the isolates were intermediate to penicillin, 7.2% were resistant to penicillin, 16% were intermediate to amoxicillin, and 11% were intermediate to cefotaxime; no PNSP were resistant to either of the last two antibiotics. The most common PNSP serotypes isolated were 14 (41%) and 23 (24%). A statistically significant relationship between PNSP infection and age below 5 years or above 60 years in the different counties was observed by univariate and multivariate analysis. Gender, origin of bacteremia, co-morbidity, immunodeficiency, previous hospitalization and nosocomial infection were not predisposing factors associated with PNSP. The mortality rate was 20.6%: there was no increase in mortality among patients with PNSP bacteremia. Age was the strongest risk factor for mortality, but immunodeficiency also seemed to have had an impact on mortality. Clinical outcome was more closely related to clinical conditions than to the susceptibility status of S. pneumoniae. CONCLUSION: Among cases of bacteremia, 27% were caused by PNSP, but this level varies according to the counties and the age of the patients. Infection-related mortality was high, but there was no increase related to penicillin G non-susceptibility of the infecting strain.

Bacterial resistance to antibiotics in France : a public health priority.

For a few years, France has been faced to a rapid spread of anti-microbial resistance in hospitals and in general practice despite the many recommendations issued to solve this problem. In 1999, the Institut de Veille Sanitaire conducted a collective expe

[Medical interns and AIDS: perceptions and attitudes in 3 French regions]. / Les internes en médecine face au Sida: perceptions et attitudes dans 3 régions françaises.

This study has been conducted to clarify certain issues regarding residency training with regard to acquired immunodeficiency syndrome (AIDS). The objective was to evaluate resident physicians' experiences in, and attitudes toward, the care of persons with AIDS in France. The design was a cross sectional study, using a self administered mailed questionnaire to 627 residents in 3 French areas: Ile-de-France, Nord-Pas de Calais and Province-Côte d'Azur, with a follow up of non responders. The subjects of this study were a random sample of residents in the second year of specialty medicine or family medicine residencies (biological residents, surgeons, public health residents and research residents were excluded). The response rate was 56%. More than half of residents indicated that their training was deficient in AIDS ambulatory care and less of 40% felt competent to provide usual and primary care for AIDS patients. The social and psychosocial aspect of care seems to be the greatest difficulties for them. About the half of residents reported at least one needle stock contaminated by a patient's blood. Needle stick injuries from patients known to have HIV infection were reported by 8% of them. About 25% expressed great concern about the professional risk of HIV contamination and 24% indicated it is dangerous to provide care for AIDS patients. It appears that an important component of future education in medical residency programs should emphasize strategies to address social and psychosocial issues in the medical care of AIDS patients and to decrease the risk of needle stick injuries.