Biomedical subjects
Publications and source records attributed to M Wundschock.
Although four types of meningitis/encephalitis must be reported by the Federal Communicable Disease Act since 1980, the incidence of etiologically not identified cases is constant over the years. We report on the first results in 1097 patients with meningitis who were examined by microbiological methods. These examinations were free of charge for the clinics in Berlin.
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The antibiotic concentrations were determined in 28 serum samples, 24 samples of lung parenchyma and 21 samples of the skeletal muscle from 28 patients who had undergone pneumonectomy. 5 g mezlocillin had been given i. v. as a bolus injection 30 to 150 minutes before sampling. The concentrations in the lung tissue were higher than the MICs for most bacteria for two hours. If a strain is less sensitive, a dose of more than 5 g is recommended. The concentrations in muscle tissue were also effective antibacterially.
Using photometry in measuring the growth of mycobacteria in liquid medium 7 H 9 Middlebrook slightly modified, we could achieve a 5 to 8 fold increase of extinction values within 8 days. The reproducibility of these results were investigated by tenfold assay of the laboratory mycobacterial strain H37Rv and about 10 strains recently isolated from patients. As antituberculous chemotherapeutic agents require different pH for their optimal activity, the experiments were performed at pH 5.5, pH 6.8 and pH 7.3. By daily measuring the extinction values of all strains showed less growth at pH 5.5 compared to their behaviour at pH 6.8 and 7.3. Yet growth at pH 5.5 was sufficient to estimate the inhibitory effect of Pyrazinamide as later experiments could show. The variation coefficient at pH 5.5 revealed to be significantly lower than at pH 6.8 and pH 7.3. Isoniazid, Prothionamid and Rifampicin were tested at pH 6.8, Streptomycin, Ethambutol and Tetracyclin at pH 7.3 and Pyrazinamide at pH 5.5. The results of our calculations were expressed as growth percentages in relation to growth in the control tubes. Usüally the measurements of the last day of incubation were chosen for this evaluation. Inhibition of growth in 50% or more of the extinction values of the control tubes was the criterion for regarding a strain as sensitive to a given drug. All drugs were tested in two concentrations. In case of only one concentration effecting inhibition of growth in 50% ore more, the strain was reported to give a borderline result. Sensitivity testing with photometry was compared to conventionally performed tests on Loewenstein-Jensen-Medium which were in good agreement between 80 and 100%. Results being available within 8 days in an advantage of the photometric method of sensitivity testing. Furthermore Pyrazinamide and Tetracyclin can be tested without difficulties while these drugs give unsatisfactory results when tested on Loewenstein-Jensen-medium.
Ethambutol is said to be capable of elevating serum urate concentration. This statement was reconsidered in three investigations using strictly supervised administration of ethambutol in a single daily dose of 25 mg. per kg. of body weight: (1) In short term administration 10 healthy subjects received ethambutol for eight days. (2) In a pilot study 13 patients suffering from pulmonary tuberculosis were treated with a triple combination including thambutol for six months. (3) In a controlled trial 23 patients were randomly allocated to one of the following regiments: In the first group patients received ethambutol plus isoniazid plus rifampicin for six months. In the second group patients received streptomycin plus isoniazid plus PAS for three months and thereafter streptomycin plus isoniazid plus ethambutol for another three months. Serum urate concentrations and clearances of uric acid and of creatinine were determined periodically in all subjects. A slight increase in serum urate concentration occurring in long term therapy showed no relation to ethambutol administration, but was obviously dependant on parameters related to the course of the disease in form of increase in body weight and physical activity, or related to the well known syntropy of chronic alcoholism and tuberculosis.
In 27 patients it was experimentally demonstrated that after an i. m. injection of 80 mg tobramycin concentrations are obtained in human lung tissue which for about two hours are higher than the minimal inhibition concentration of most gramnegative organisms. In 14 samples of the latissimus dorsi muscle no detectable tobramycin concentrations were found up two hours after injection of the same dose. The ratio of whole blood concentration and lung tissue concentration is 2 : 1. The measurement of tobramycin concentration in whole blood thus enables the concentration in lung tissue to be estimated. The results show--like all serum and tissue level assays--a high individual variation, which might be dependent on the non-defined factors of binding or metabolism, especially as during the examination period of two hours no concentration balance is accomplished between the two compartments. Administration of 80 mg tobramycin i. m. every six hours is recommended in patients with pulmonary infections due to gramnegative organisms.
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