Sentinel monitoring of general community health during the 1998 World Football Cup.

BACKGROUND: Present knowledge of the consequences of mass gatherings for the health of the community is scant. Our objective was to determine the impact of the 1998 World Football Cup on general community health. METHODS: We set up an electronic sentinel disease surveillance, before, during and after the World Football Cup tournament held in France from June 10 to July 12, 1998. Medical activity, and the daily number of cases of communicable, environmental, and societal diseases relating to mass gatherings were surveyed. The incidence of the pathologies surveyed in real time during and after the World Cup versus the pre-Cup reference period was the main outcome measure. Five sentinel networks participated, comprising 553 general practitioners, 60 hospital adult emergency departments, 19 private emergency community services, 4 community health centres, and the medical centre of the Paris airports. RESULTS: Throughout the 66-day study period, physicians reported 558,829 medical encounters via 21,532 connections to the computer. Compared to the reference period, the level of medical activity reflected by the pathological items surveyed remained stable during the study period. CONCLUSION: The 1998 World Football Cup had no epidemiological impact on general community health, as observed by sentinel networks located downstream of the specific health services provided by the French authorities to ensure high standards of safety.

Accumulation of pefloxacin in the lower respiratory tract demonstrated by bronchoalveolar lavage.

The in-vivo pulmonary disposition of pefloxacin in alveolar macrophages alveolar macrophages and in the alveolar epithelial lining fluid recovered by bronchoalveolar lavage was studied in 10 healthy volunteers. Bronchoalveolar lavage was performed either 2 or 4 h after oral intake of 800 mg of the drug. The recovered fluid was immediately centrifuged and processed for the assays. Pefloxacin was assayed by High Pressure Liquid Chromatography (HPLC) and by a microbiological method. The mean concentrations of pefloxacin assayed by HPLC were 106 +/- 11.1 mg/L in alveolar macrophages and 88.2 +/- 10 mg/L in the epithelial lining fluid, whereas the mean serum concentration was 6.67 +/- 0.47 mg/L. Therefore, pefloxacin accumulated rapidly in human alveolar macrophages. The high epithelial lining fluid concentrations may be attributed to lipophilicity of the drug and to rapid diffusion from blood, pulmonary cells and interstitium during the bronchoalveolar lavage procedure. The substantial accumulation of pefloxacin in alveolar components (alveolar macrophages and epithelial lining fluid) endorses its use in the treatment of intracellular bacterial infections such as legionellosis; for these diseases, pefloxacin represents an alternative to the macrolide antibiotics.

Monitoring of pefloxacin serum concentrations in intensive care unit patients: comparison of a new immunoassay with high-performance liquid chromatography.

Serum quinolone concentrations are not routinely measured in clinical practice. However, in order to optimize quinolone treatment, monitoring of serum concentrations could sometimes be useful particularly in critically ill patients. A new enzyme-linked immunosorbent assay (ELISA) that permits direct determination of pefloxacin in serum is described. To validate this new assay, pefloxacin concentrations were measured in 314 serum samples from 74 intensive care unit patients treated with pefloxacin (400 mg i.v. twice daily). Reference concentrations were obtained by reverse phase high-performance liquid chromatography (HPLC) with spectrofluorometric detection. Results showed that concentrations measured by ELISA correlated very well with those by HPLC (r = 0.957; y = 1.03 and x -0.15). In this population, the concentrations found by ELISA varied between individuals (Cmin = 0.70-39 micrograms/ml; Cmax = 5.2-40 micrograms/ml). However, 86% of the measured Cmax and Cmin levels were adequate for optimal pefloxacin therapy. Only 11% of Cmin and 14% of Cmax were below the optimal values (i.e., 2 and 8 micrograms/ml, respectively). These results suggest that despite the large therapeutic index of pefloxacin, monitoring of its serum concentrations using a rapid ELISA technique may be useful for optimal antimicrobial treatment of certain intensive care unit patients.

Evaluation of Bayesian estimation in comparison to NONMEM for population pharmacokinetic data analysis: application to pefloxacin in intensive care unit patients.

The pharmacokinetics of pefloxacin (PF) were investigated in a population of 74 intensive care unit patients receiving 400 mg bid as 1-hr infusion using (i) Bayesian estimation (BE) of individual patient parameters followed by multiple linear regression (MLR) analysis and (ii) NONMEM analysis. The data consisted of 3 to 9 PF plasma levels per patient measured over 1 to 3 dosage intervals (total 113) according to four different limited (suboptimal) sampling 3-point protocols. Twenty-nine covariates (including 15 comedications) were considered to explain the interpatient variability. Predicted PF CL for a patient with median covariates values was similar in both BE/MLR and NONMEM analysis (4.02 and 3.92 L/hr, respectively). Bilirubin level and age were identified as the major determinants of PF CL by both approaches with similar predicted magnitude of effects (about 40 and 30% decrease of median CL, respectively). Confounding effects were observed between creatinine clearance (26% decrease of PF CL in the BE/MLR model), simplified acute physiology score (a global score based on 14 biological and clinical variables) (18% decrease of median CL in the NONMEM model) and age (entered in both models) which were highly correlated in our data base. However, both models predicted similar PF CL for actual subpopulations by using actual covariate values. Finally, the NONMEM analysis allowed identification of an effect of weight on CL (decrease of CL for weight < 65 kg) whereas the BE/MLR analysis predicted an increase of CL in patients treated with phenobarbital. In conclusion, both approaches allowed identification of the major risk factors of PF pharmacokinetics in ICU patients. Their potential use at different stages of drug development is discussed.

[Determination of elimination of pefloxacin and of its derivatives in continuous hemodiafiltration]. / Détermination de l'élimination de la péfloxacine et de ses dérivés en hémodiafiltration continue.

Continuous venovenous hemofiltration with dialysis (CVVHD) is being increasingly used to treat acute renal failure. However, because of the-lack of data on the clearance of therapeutic agents during this treatment, there is a risk of using inappropriate dosages. This in vitro study was undertaken to determine the clearance of pefloxacin (P) and its two main metabolites (active N-desmethyl P and inactive N-oxide P) during CVVHD. Acitrate-dextrose (ACD) anticoagulated fresh human blood containing P and its two metabolites in the usual therapeutic levels was circulated at a rate of 100 ml min.-1 through a closed-circuit continuous venovenous hemofiltration with dialysis unit (BSM 22-Hospal hemofilter). Temperature and ionic composition of the blood were controlled. Dialysate (L2D, Hospal) was circulated on the other side of the continuous venovenous hemofiltration with dialysis membrane at three different flow rates (Qdi) (0, 500 and 1,000 ml.h-1. The dialysate/ultrafiltrate outflow was adjusted using a withdrawal pump to obtain nul ultrafiltration. Arterial blood, venous blood and ultrafiltrate were sampled simultaneously at different time points for High Performance Liquid Chromatography (HPLC) assays and determination of the clearances (Cl) and sieving coefficients (s) of each compound. Pefloxacin had a sieving coefficient of 0.42 and a clearance of 6.8 ml min-1 when Qdi was nul. With the blood flow used, clearances were found to be correlated with the dialysate flow rate; when this rate was 500 ml h-1, a pefloxacin clearance similar to that seen in healthy subjects was obtained (15.2 ml min-1). The two bacteriologically active forms of the drug (pefloxacin and N-desmethyl P) had similar elimination parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

[Respiratory pathology in occupational medicine: evaluation of 3 methods of data collection and research on risk factors]. / Pathologie respiratoire en médecine du travail: évaluation de trois modes de recueil des données et recherche des facteurs de risque.

Three methods of gathering data of respiratory symptoms (using a self questionnaire, a detailed interview and a shortened interview) were compared in 4.206 construction workers in different branches of their profession. There was non significant difference between the replies given, in either sex, to the self questionnaire and those given in the detailed interview by employees of the research bureau. The comparison between the long and the short interview, carried out on the painters, plumbers, carpenters and brick-layers did not show any difference for those questions asked in the same manner in the two documents. On the other hand the question relating to intrathoracic wheezing, which was more condensed in the shortened interview, did not have the same degree of affirmative replies. The replies concerning cough and expectoration obtained by the two methods enabled a comparison to be made between prevalance of chronic bronchitis in the different occupations. This pathology was most frequently seen amongst bricklayers and painters. Other factors (nationality, age, smoking habits) were also linked to chronic bronchitis. Taking all these factors into account has not weakened the link between chronic bronchitis and occupation.