The pharmacokinetics of ciprofloxacin were studied in cystic fibrosis patients and healthy volunteers following oral administration of 500 mg and 1000 mg. Serum kinetics as well as urinary recovery were monitored. As the body weights of cystic fibrosis patients and the healthy volunteers differed significantly, kinetic parameters were calculated on the basis of a constant relative dose in mg/kg body weight. Neither serum kinetics nor urinary recovery differed significantly between the two groups, as indicated by the serum concentration versus time curves ranging from 1.1 to 1.4 mg X h/l, the elimination half-life of 4.4 to 5.1 h and the 24 h urinary recovery which amounted to 35% to 41% of the dose administered. Serum concentrations were linearly proportional to the doses administered. Sputum concentrations were monitored in cystic fibrosis patients. Again, ciprofloxacin sputum levels were linearly proportional to the doses and were within the same range as serum concentrations. Thus, ciprofloxacin kinetics are not altered in cystic fibrosis patients as compared to healthy volunteers.
In investigations into the dosis-activity relationships of bactericidal antibiotics used against E. coli, K. pneumoniae and Staph. aureus four types of activity could be demonstrated. The penicillin type shows almost no improvement in bactericidal activity despite increasing the dosage above a certain level. An increase in concentration of aminoglycoside antibiotics led to a more rapid killing of the bacteria. In cefalotin there was a linear dosis-activity relationship: rising concentrations of antibiotics led to an ever increasing bactericidal effect. The paradoxical bactericidal effect ("Eagle effect'') described for penicillin G with enterococci could not be demonstrated.
Studies on the chemical constituents of the aerial parts of Skimmia laureola have led to the isolation of four new alkaloids, ptelefoliarine (1), acetoxyptelefoliarine (2), acetoxyedulinine (3), and orixiarine (4). Their structures were established by spectroscopic studies.
The objective of the presented, randomized study was to compare the efficacy of antimicrobial monotherapy with imipenem (3 x 0.5g/d) to a combination therapy with cefotaxime (3 x 2g/d) plus piperacillin (3 x 4g/d) for empirical treatment of infections in neutropenic patients. In 165 patients, 237 infectious episodes were evaluable. The overall response rate of patients treated with cefotaxime plus piperacillin was 67/115 (58%), of those treated with imipenem 66/122 (54%). In patients not responding to the initial therapy regimen within 2 or 3 days, the antimicrobial therapy was modified. After therapy modification 85/100 patients were cured. Fever of unknown origin (FUO) showed the most favourable course compared to other infection types, with a response in 46/59 (78%) and in 35/50 (70%) cases, respectively. In comparison, pneumonias were successfully treated in only 3/21 (14%) and 7/37 (19%) cases. Even including patients with modified therapy, only 66% (21/32) of pneumonia episodes responded. The unfavourable results in pneumonias is mainly due to the high rate of 13 systemic mycoses in this group (22%). Overall, a similar response was observed in patients treated with cefotaxime plus piperacillin in comparison with imipenem. In primary bacteremias however, an advantage was observed in patients treated with imipenem (20/27; 74%) compared with cefotaxime plus piperacillin (11/23; 48%).
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