[Relay drugs in the treatment of chronic pulmonary tuberculosis patients].
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Biomedical subjects
Publications and source records attributed to E Bernard.
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Pharmacokinetic parameters and killing rates in serum of volunteers receiving amoxicillin, cefadroxil or cefixime alone or associated with niflumic acid or paracetamol were studied. Niflumic acid (250 mg) or analgesic and antipyretic drugs such as paracetamol (500 mg) are often combined with antibiotics to avoid inflammation and pain in acute ear, nose and throat diseases. Pharmacokinetic interactions between these two classes of drugs have been described in experimental models, and exceptionally in humans. The aim of the present investigation was to study the interactions of these two drugs with three antibiotics (amoxicillin 500 mg x 2, cefadroxil 500 mg x 2, cefixime 200 mg and one placebo capsule) on pharmacodynamic parameters and on rate of killing in the serum of six healthy volunteers receiving the antibiotic associated or not with the product in a randomized cross-over double-blind trial. The bacteria most often involved in sinusitis, bronchitis and otitis media (Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus) three target diseases for oral cephalosporins and amoxicillin, were chosen for bacteriological study. Blood samples were obtained at 0.25, 0.50, 1, 1.5, 2, 4, 6 and 12 h after oral administration of antibiotics alone or associated with the drugs. There was a wash-out period of at least 1 week between the eleven sequences. Antibiotics were measured by two methods: bioassay and high performance liquid chromatography (HPLC). All serum samples obtained at peak level, 4 and 6 h were tested for killing rate. Area under the time kill curve was calculated by the trapezoidal rule method and relative bioactivity in percent was defined as follows: (AUC control - AUC test)/AUC control x 100. No pharmacokinetic interaction was found in the AUC and T1/2 of the plasma concentrations of the antibiotics or associated with the drugs, regardless of dose, as determined by HPLC or microbiological assay. For these beta-lactam antibiotics killing rate was found to be time-dependent. Bactericidal activity was improved on H. influenzae when cefixime was associated with niflumic acid and became concentration-dependent. A significant concentration relation was also found with niflumic acid or paracetamol associated with cefixime on Strep. pneumoniae.
BACKGROUND: Since 2000, syphilis has reappeared in the form of an epidemic in France and more particularly, in the Paris region. However, there is little available data concerning other regions of France. The purpose of this study was to identify the chief characteristics of this epidemic in the Côte d'Azur region. PATIENTS AND METHODS: Between January 2001 and July 2003, cases of syphilis were collated by the Department of Dermatology and Infectious Diseases of Nice University Teaching Hospital and by the Department of Dermatology and Infectious Diseases of Fréjus hospital and based on spontaneous reports submitted by general practitioners in private practice. RESULTS: We collected 54 reports of cases of syphilis: 37 in the Alpes-Maritimes region and 17 in the eastern Var region. The epidemic chiefly affected men since 44 of the 54 cases reported (81%) concerned males. 70% of these men were contaminated during homosexual contact (31 patients). In the majority of cases, contamination concerned local subjects. 50% of the patients in the study were infected with human immunodeficiency virus (HIV). The clinical forms observed were distributed as follows: 12 primary syphilis, 28 secondary syphilis, 13 latent syphilis, 1 case not specified. There was no difference in terms of clinical form between patients with and without HIV. DISCUSSION: Syphilis, which had become rare in France as a whole and in our region in particular, reappeared in the form of an epidemic in the Côte d'Azur region after first resurfacing in the Paris region. This outbreak principally affected homosexual and bisexual male patients, half of whom were HIV-positive. Screening for syphilis, potentially latent, should thus be carried out routinely during initial assessment and at subsequent monitoring of HIV patients.
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Pefloxacin (Peflacine) can give rise to thrombocytopenia, although the responsibility of the drug can be difficult to demonstrate in infectious patients and those receiving other drugs simultaneously. We have collated 18 cases in which the responsibility of pefloxacin was suspected. In 13 cases, the patients were also taking other drugs which may have been contributory (heparin, Bactrim, Augmentin, ranitidine,...). The remaining five cases were of particular interest as pefloxacin was the only drug administered. The mean age of the patients was 75 years, and the mean bodyweight 56 kg (range, 47-65 kg). The pefloxacin dosage was 800 to 1,600 mg/day i.v. or p.o., i.e. 13-18 mg/kg/day. Thrombocytopenia occurred from five to 19 days after beginning treatment and resolved between 7 and 12 days after drug withdrawal. A number of factors argue in favor of dose dependency: 1 patient had high plasma concentrations (peak and residual); thrombocytopenia occurred in one patient when the previous, well-tolerated dosage of 800 mg/day (for 15 days) was increased to 1,600 mg/day; thrombocytopenia resolved in one patient when the dosage was reduced to 400 mg/day (1 tablet) and continued for a further 10 days. This toxic reaction may be avoided by reducing the drug dosage to 400 mg/day in elderly patients with a low bodyweight. Differential blood counts appear to be warranted for patients at risk.
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Amplification of DNA by the polymerase chain reaction (PCR) offers a highly sensitive and specific method for detecting DNA sequences in biological samples. We applied this technology to develop an assay for the P. carinii dihydrofolate reductase (DHFR) gene. This assay was found to be sensitive enough to detect as little as 1 organism-'equivalent' of DHFR DNA. In rats with experimentally-induced P. carinii pneumonia, DHFR DNA amplification demonstrated the presence of pulmonary P. carinii 2 wk prior to the onset of histopathological changes. When rat serum was analyzed by PCR, serum P. carinii DNA was found in 5 of 14 experimental rats. Finally, P. carinii DNA was detected in the serum of 7 of 18 patients (39%) with AIDS and active P. carinii pneumonia. These results suggest that circulating serum P. carinii DNA can be detected frequently in the course of pulmonary infection and may represent a blood-borne phase of infection. The PCR detection of P. carinii DNA provides a useful tool to study the natural history of P. carinii infection and may offer a non-invasive diagnostic procedure in some patients with P. carinii pneumonia.
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