Nonsteroidal Anti-Inflammatory Drug without Antibiotics for Acute Viral Infection Increases the Empyema Risk in Children: A Matched Case-Control Study.

OBJECTIVE: To investigate the risk factors of empyema after acute viral infection and to clarify the hypothesized association(s) between empyema and some viruses and/or the use of nonsteroidal anti-inflammatory drugs (NSAIDs). STUDY DESIGN: A case-control study was conducted in 15 centers. Cases and controls were enrolled for a source population of children 3-15 years of age with acute viral infections between 2006 and 2009. RESULTS: Among 215 empyemas, 83 cases (children with empyema and acute viral infection within the 15 preceding days) were included, and 83 controls (children with acute viral infection) were matched to cases. Considering the intake of any drug within 72 hours after acute viral infection onset and at least 6 consecutive days of antibiotic use and at least 1 day of NSAIDs exposure, the multivariable analysis retained an increased risk of empyema associated with NSAIDs exposure (aOR 2.79, 95% CI 1.4-5.58, P = .004), and a decreased risk associated with antibiotic use (aOR 0.32, 95% CI 0.11-0.97, P = .04). The risk of empyema associated with NSAIDs exposure was greater for children not prescribed an antibiotic and antibiotic intake diminished that risk for children given NSAIDs. CONCLUSIONS: NSAIDs use during acute viral infection is associated with an increased risk of empyema in children, and antibiotics are associated with a decreased risk. The presence of antibiotic-NSAIDs interaction with this risk is suggested. These findings suggest that NSAIDs should not be recommended as a first-line antipyretic treatment during acute viral infections in children.

Interaction of Vaccination and Reduction of Antibiotic Use Drives Unexpected Increase of Pneumococcal Meningitis.

Antibiotic-use policies may affect pneumococcal conjugate-vaccine effectiveness. The reported increase of pneumococcal meningitis from 2001 to 2009 in France, where a national campaign to reduce antibiotic use was implemented in parallel to the introduction of the 7-valent conjugate vaccine, provides unique data to assess these effects. We constructed a mechanistic pneumococcal transmission model and used likelihood to assess the ability of competing hypotheses to explain that increase. We find that a model integrating a fitness cost of penicillin resistance successfully explains the overall and age-stratified pattern of serotype replacement. By simulating counterfactual scenarios of public health interventions in France, we propose that this fitness cost caused a gradual and pernicious interaction between the two interventions by increasing the spread of nonvaccine, penicillin-susceptible strains. More generally, our results indicate that reductions of antibiotic use may counteract the benefits of conjugate vaccines introduced into countries with low vaccine-serotype coverages and high-resistance frequencies. Our findings highlight the key role of antibiotic use in vaccine-induced serotype replacement and suggest the need for more integrated approaches to control pneumococcal infections.

Fluoroquinolone use is a risk factor for methicillin-resistant Staphylococcus aureus acquisition in long-term care facilities: a nested case-case-control study.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization is a well-established risk factor for subsequent infection and a key event in interindividual transmission. Some studies have showed an association between fluoroquinolones and MRSA colonization or infection. The present study was performed to identify specific risk factors for MRSA acquisition in long-term care facilities (LTCFs). METHODS: A prospective cohort of patients naive for S. aureus colonization was established and followed (January 2008 through October 2010) in 4 French LTCFs. Nasal colonization status and potential risk factors were assessed weekly for 13 weeks after inclusion. Variables associated with S. aureus acquisition were identified in a nested-matched case-case-control study using conditional logistic regression models. Cases were patients who acquired MRSA (or methicillin-sensitive S. aureus [MSSA]). Patients whose nasal swab samples were always negative served as controls. Matching criteria were center, date of first nasal swab sample, and exposure time. RESULTS: Among 451 included patients, 76 MRSA cases were matched to 207 controls and 112 MSSA cases to 208 controls. Multivariable analysis retained fluoroquinolones (odds ratio, 2.17; 95% confidence interval, 1.01-4.67), male sex (2.09; 1.10-3.98), and more intensive care at admission (3.24; 1.74-6.04) as significantly associated with MRSA acquisition, and body-washing assistance (2.85; 1.27-6.42) and use of a urination device (1.79; 1.01-3.18) as significantly associated with MSSA acquisition. CONCLUSIONS: Our results suggest that fluoroquinolones are a risk factor for MRSA acquisition. Control measures to limit MRSA spread in LTCFs should also be based on optimization of fluoroquinolone use.

Outpatient antibiotic use in France between 2000 and 2010: after the nationwide campaign, it is time to focus on the elderly.

Antibiotic overconsumption is the main force driving the emergence of multidrug-resistant bacterial strains. To promote better antibiotic use in France, a nationwide campaign has been run every year from October to March since 2002. In 2007, it was shown that winter outpatient antibiotic consumption had decreased by 26.5% compared to the 2000-2002 baseline period. Here, we quantified outpatient antibiotic use between 2000 and 2010 as a follow-up analysis of the nationwide campaign. Reimbursed outpatient antibiotic prescriptions were extracted from computerized French National Health Insurance databases. Entire series and age group and antibiotic class analyses were computed. Time series analyses used autoregressive moving-average models with exogenous variables and intervention functions. Two periods were considered: October to March "campaign" periods and April to September "warm" periods. Compared to the precampaign (2000-2002) baseline period, the numbers of weekly antibiotic prescriptions per 1,000 inhabitants during campaign periods decreased until winter 2006 to 2007 (-30% [95% confidence interval {CI}, -36.3 to -23.8%]; P < 0.001) and then stabilized except for individuals >60 years of age, for whom prescriptions reached the precampaign level. During the warm periods from April to September, no significant differences were estimated compared to the baseline level for the entire series, but seniors had an increasing trend that became significant as of 2005, reaching +21% (95% CI, +12.9 to +29.6%) in 2009 (P < 0.0001). These results highlight the need for a better understanding of antibiotic use by the elderly, requiring research with targeted and tailored public health actions for this population.

Did media attention of the 2009 A(H1N1) influenza epidemic increase outpatient antibiotic use in France?: A time-series analysis.

BACKGROUND: In France, the 2009 A(H1N1) influenza epidemic occurred between September 2009 and January 2010. Sparking widespread controversy, it was intensely reported in the media. Despite therapeutic inefficacy, antibiotic consumption and viral respiratory infections are positively correlated, particularly in France, where antibiotic overconsumption is well-known. We first determined the period when media coverage was high, and then compared, during this period, observed outpatient antibiotic consumption to estimated outpatient antibiotic consumption "without media attention". MATERIALS AND METHODS: TO EVALUATE MEDIA COVERAGE, TWO ONLINE DATABASES WERE CONSULTED: Factiva and Europresse. To quantify outpatient antibiotic consumption, we used data on reimbursements of outpatient systemic antibiotics from the computerized databases of the two main National Health Insurance agencies. Influenza-like syndromes data came from the French GPs Sentinelles Network. Weekly time-series of antibiotic consumption were modeled by autoregressive moving-average models with exogenous inputs and interventions. Analyses were computed for the entire series and by age group (0-5, 6-15, 16-60, and >60 years). RESULTS: Media coverage was intense between April 2009 and January 2010. No effect on total outpatient antibiotic consumption was observed during the whole mediatic period. However, during the epidemic in France (September 2009-January 2010), we found an antibiotic underconsumption for the entire series, 0-5 and >60 years. Additionally, at the beginning of the pandemic, when cases were still outside France (June 2009-August 2009), we found an antibiotic overconsumption for patients >16 years. CONCLUSION: The early period of A(H1N1) virus circulation compared with seasonal influenza or an overdeclaration of ILS cases might explain the antibiotic underconsumption observed during the period of active A(H1N1) virus transmission in France. At the pandemic onset, when uncertainty was high, the overconsumption observed for individuals >16 years might have been caused by alarmist media reporting. Additional analyses are needed to understand the determinants of antibiotic consumption during this period.

The 2009 A(H1N1) influenza pandemic in the French Armed Forces: evaluation of three surveillance systems.

BACKGROUND: The French military forces had to modify their epidemiological surveillance systems at the time of the 2009 A(H1N1) influenza pandemic. The aim of this article was to present an evaluation of the different systems used. METHODS: Two influenza surveillance systems are usually used in the French forces: one permanent (Surveillance épidémiologique des armées or SEA) and one seasonal (Système militaire d'observation de la grippe or SMOG). The pandemic required the implementation of a daily surveillance system (Surveillance quotidienne--SQ), which aimed to monitor disrupted activity owing to 2009 A(H1N1) influenza. The qualitative evaluation of these three systems during the period from September 2009 to February 2010 was performed using 11 criteria based on the list defined by Centers for Disease Control and Prevention of Atlanta. RESULTS: Although it included only 30 sentinel units vs. 320 for the other systems, the SMOG system was the best-performing system in terms of relevance, feasibility, efficacy, quality of data, usefulness, acceptability, efficiency and cost/benefits/costs ratio. The SQ proved very expensive in terms of logistics. CONCLUSION: The SQ did not bring any significant advantage compared with the weekly surveillance schemes. In the eventuality of another similar episode, influenza surveillance could be significantly improved by using the SMOG system extended to more units for better geographical coverage.

Adverse events following pandemic influenza vaccine Pandemrix® reported in the French military forces--2009-2010.

BACKGROUND: In the face of the A(H1N1) 2009 influenza pandemic, in October 2009 the French military health service (SSA) initiated a large vaccination campaign with Pandemrix(®) vaccine in the military forces. The aim of this study was to describe vaccine adverse events (VAE) reported during this campaign. METHODS: VAE and the number of people vaccinated were surveyed by the SSA Epidemiological network across all military forces during the campaign, from October 2009 to April 2010. For each case, a notification form was completed, providing patient and clinical information. Three types of VAE were considered: non-serious, serious and unexpected. RESULTS: There were 315.4 reported VAE per 100,000 vaccinations. Vaccination and VAE incidence rate peaks coincided with influenza epidemic peak in early December. The number of injected doses was 49,138, corresponding to a 14.5% vaccination coverage among military personnel, and 155 VAE were reported, including 5 serious VAE (1 Guillain-Barre syndrome, 2 malaises and 1 convulsive episode). Most VAE were non-serious (97.1%). Among these, 6 cases of local, rapidly regressive paresthesia were observed. DISCUSSION: The military VAE surveillance system constitutes the only observatory on benign VAE in France. The reporting rate was much higher after the pandemic vaccine than after the seasonal vaccine, which may be a reflection of stimulated reporting. This report provides a useful description of VAE among military personnel during a mass emergency vaccination program, showing that the tolerance of the pandemic vaccine appeared acceptable.