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Biomedical subjects

H Lode

Publications and source records attributed to H Lode.

At least 145 records · Page 8Linked to original sources
PubMed1990

Evaluation of safety and tolerance in clinical trials with antimicrobial agents.

In this review the general and specific difficulties encountered in the evaluation of safety and tolerance of antimicrobial agents in clinical trials are discussed. In addition to the usual pharmacological and toxicological effects (adverse drug reactions) occurring in individual patients, microbiologically induced side-effects also have to be considered. The different methods for registration of side-effects and their limitations are discussed. A system is proposed for evaluation of the cause/effect relationships of adverse drug reactions. A system is also discussed for the evaluation of the severity of adverse drug reactions, and different classifications are presented.

Anti-Bacterial Agents↗
PubMed1990

Quinolone pharmacokinetics and metabolism.

The pharmacokinetic properties of the new fluoroquinolones are characterized by a high volume of distribution, long biological half-life, low serum protein binding, elimination by renal and extrarenal mechanisms with high total and renal clearances, limited biotransformation and moderate to excellent bioavailability after oral administration. However, each quinolone derivative (ciprofloxacin, enoxacin, fleroxacin, norfloxacin, ofloxacin and pefloxacin) possesses individual pharmacokinetic parameters, which should be considered in the treatment of patients, especially when liver or renal dysfunction exists.

Administration, Oral↗
PubMed1990

Pharmacokinetics and serum bactericidal activities of quinolones in combination with clindamycin, metronidazole, and ornidazole.

To enhance the antimicrobial spectrum of the quinolones against anaerobic organisms and gram-positive bacteria, we investigated in two studies the parenteral combinations of ciprofloxacin (200 mg) and ofloxacin (200 mg) with metronidazole (500 mg) or clindamycin (600 mg) and the oral combinations of enoxacin (400 mg) and fleroxacin (400 mg) with metronidazole (400 mg), clindamycin (300 mg), or ornidazole (500 mg) (only with fleroxacin). The pharmacokinetics and serum bactericidal activities (SBAs) against 5 aerobic and 2 anaerobic species (total, 58 strains) were determined in two groups of 10 healthy volunteers by using a randomized crossover study design. The additions of metronidazole, clindamycin, and ornidazole did not affect the pharmacokinetics of the quinolones. The combination of clindamycin with ciprofloxacin, ofloxacin, and, to a lesser extent, fleroxacin resulted in an increase of the SBA against gram-positive strains (mean peak titers): Staphylococcus aureus, ciprofloxacin alone, 1:5.5; ciprofloxacin-clindamycin, 1:19.9; ofloxacin alone, 1:3.6; ofloxacin-clindamycin, 1:17.5; fleroxacin alone, 1:4.3; fleroxacin-clindamycin, 1:8.1; Streptococcus pneumoniae (fleroxacin and enoxacin were not tested), ciprofloxacin alone, 1:2.0; ciprofloxacin-clindamycin, 1:53; ofloxacin alone, 1:2.6; and ofloxacin-clindamycin, 1:49.2. The high SBA of quinolones against gram-negative bacteria was not affected by the combinations; however, relatively low activities against Pseudomonas aeruginosa were detected. In general, against anaerobic bacteria, low bactericidal activities were determined in both studies (mean peak titers ranged from 1:2.1 to 1:3.1; mean trough titers range from 1:2.0 to 1:2.9). In clinical settings with severe mixed infections, a parenteral therapy consisting of modern quinolones together with clindamycin or imidazole derivatives seems to be active and offers no obvious interactions.

4-Quinolones↗
PubMed1990

Pharmacokinetics of FCE 22891, a new oral penem.

FCE 22891 is the oral prodrug of FCE 22101, a new broad-spectrum penem. The pharmacokinetics of FCE 22891 after single-dose administration, its absolute bioavailability, and the effect of food intake on its absorption were investigated in three different randomized crossover studies in healthy volunteers. Drug levels in blood and urine were measured by high-pressure liquid chromatography and bioassay. For optimal comparison of the results of all studies, and since there was good agreement of both methods, only the high-pressure liquid chromatography results are included. The pharmacokinetics of the penem were linear, and its bioavailability after oral administration was 42 +/- 11%. Food intake increased the total area under the curve from 0 h to infinity from 11.9 +/- 3.5 to 14.1 +/- 2.4 mg.h/liter. A specific side effect, i.e., bladder complaints, was registered in some volunteers taking FCE 22891 at doses greater than or equal to 1.0 g.

Administration, Oral↗
PubMed1990

Comparative pharmacokinetics of glycopeptide antibiotics, and the influence of teicoplanin on granulocyte function.

The glycopeptide antibiotics teicoplanin and vancomycin differ in their pharmacokinetic properties. Teicoplanin is characterized by a high and prolonged serum concentration as a result of its long elimination half-life, which can be explained by high serum protein binding and renal tubular resorption. The apparent volume of distribution of teicoplanin is much larger than the extracellular space of the human body, indicating intracellular accumulation in different tissues. Elimination is primarily via the kidneys, though 15-20% is eliminated by non-renal mechanisms. Vancomycin has a shorter elimination half-life and lower protein binding than teicoplanin. At therapeutically relevant serum concentrations, teicoplanin has no influence on superoxide anion production and enzyme release by granulocytes.

Cells, Cultured↗
PubMed1990

[Randomized comparative study of secondary prevention of Pneumocystis carinii pneumonia in patients with acquired immunologic deficiency syndrome].

Pneumocystis carinii pneumonia is one of the most frequent infectious complications in patients with the acquired immunodeficiency syndrome (AIDS). A prospective trial was initiated to compare azidothymidine alone with azidothymidine plus aerosolized pentamidine as a secondary prophylaxis for pneumocystis carinii pneumonia. 27 patients (24 male, three female, average age 39 years) were enrolled, 14 patients receiving azidothymidine and pentamidine aerosol and 13 azidothymidine alone. After 166 days of follow-up, this trial had to be terminated prematurely, since the efficacy of pentamidine aerosol in the prevention of pneumocystis carinii pneumonia was clearly demonstrated in two recently published studies. Two patients died during the study period, one in either group, but neither due to pneumocystis carinii pneumonia. Two patients developed histologically proven pneumocystis carinii pneumonia; both patients were allocated to the azidothymidine arm. Pneumocystis carinii pneumonia was suspected clinically but not proven in four patients, three were randomized in the azidothymidine arm. Pentamidine was well tolerated and produced no severe side effects. The sample size is too small to draw definitive conclusions concerning the efficacy of pentamidine aerosol in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Prospective randomized clinical trials of new quinolones versus beta-lactam antibiotics in lower respiratory tract infections.

In four prospective randomized clinical trials between November 1983 and March 1988, we studied 270 patients with severe bacterial infections, mainly lower respiratory tract ones. We compared ciprofloxacin and imipenem/cilastatin in the first study, ciprofloxacin and ofloxacin in the second study, ciprofloxacin and ticarcillin/clavulanic acid in the third study, and ofloxacin and cefpirome in the fourth study. A total of 90 pneumonias, 139 LRTIs, 22 septicaemias and 19 other bacterial infections were treated; the dominant pathogens were Pseudomonas aeruginosa and enterobacteria. Clinical success rates were high; cure or improvement was registered in 89% of the patients on ciprofloxacin, 89% on ofloxacin and 85% on beta-lactams. Treatment failures occurred mainly in ICU patients with terminal underlying diseases. Bacteriologically, eradication rates were high for enterobacteria and Staphylococcus aureus, but a relatively high persistence rate was seen for P. aeruginosa due to increased resistance and/or specific type and location of the infections. The incidence of side-effects was relatively high (23%-29%) which was related to careful monitoring. Adverse effects were group-specific (CNS reactions with quinolones, diarrhoea with beta-lactam antibiotics).

Cilastatin↗
PubMed1990

Development of clinically important resistance to quinolones and other antibiotic groups.

In a study conducted by the Paul Ehrlich Society in the Federal Republic of Germany (FRG), resistance patterns were registered over a period from 1975 to 1984. The results of this large multicentre study involving more than 35,000 strains demonstrated a relatively stable resistance pattern for most Gram-positive and Gram-negative bacteria against all antibiotic groups. Information on resistance to the new quinolones in FRG is still very limited. The only published results are from the University Hospital, Tübingen, FRG, which registered a slight decrease in the sensitivity of ofloxacin to Pseudomonas aeruginosa and the staphylococci. In clinical studies, resistance appeared in about 4-13% of antibiotic treatments but treatment failure was registered in only 30-80% of these cases.

4-Quinolones↗
PubMed1990

[Intensive care problems in AIDS patients].

The discussion regarding the need for intensive-care treatment of AIDS patients should be conducted in a highly differentiated manner and should depend on the prognosis of the underlying or basic disease, on the immunological situation, on the mental condition and on the consent of the individual patient. During the past two years the treatment results have improved markedly by the use of steroids, especially in pneumocystis carinii pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[Value of diagnostic procedures in fiberoptic bronchoscopy of pulmonary infections].

Fibreoptic bronchoscopy has become an important means of diagnosing infections of the lower respiratory tract, since it a method with few complications, whereas, on the other hand, the conventional non-invasive methods are hardly reliable in respect of diagnostic relevance. Frequent oropharyngeal contamination severely limits the significant assessment of the pathogenicity of cultured microorganisms. The protected specimen brush (PSB) or quantitative cultures of bronchoalveolar lavage (BAL) might be useful in solving this problem. These methods were studied in two prospective trials comprising 123 patients with suspected bronchopulmonary infection and 54 control patients. Both methods were found to be disappointing in respect of sensitivity; moreover, quantitative cultivation did not yield any differences with regard to specificity.

Bacterial Infections↗
PubMed1989

Ciprofloxacin intravenous dose variance.

Following different intravenous dosages of ciprofloxacin in volunteers, only limited variation in serum concentrations have been reported using volunteers in both single- and multiple-dose studies. In patients, a greater variability in serum concentrations was reported during intravenous ciprofloxacin treatment. This was also the case in patients with varying degrees of renal insufficiency. However, no report exists of nonmeasurable ciprofloxacin serum concentrations during intravenous treatment in patients.

Adult↗
PubMed1989

Combination effects of ciprofloxacin, clindamycin, and metronidazole intravenously in volunteers.

Despite the broad antibacterial spectrum of ciprofloxacin, most anaerobic organisms are resistant to the drug, whereas several gram-positive organisms are only moderately susceptible. Thus, in some clinical situations, combined treatment with ciprofloxacin and metronidazole or clindamycin could be useful. Therefore, the pharmacokinetics and serum bactericidal activities of ciprofloxacin in combination with clindamycin or metronidazole were investigated using a randomized crossover study design in 10 healthy volunteers. Ciprofloxacin (200 mg) was administered alone and in combination with clindamycin (600 mg) or metronidazole (500 mg); all drugs were given intravenously over 30 minutes. Serum and urine concentrations of the substances were measured using standard methods (high-performance liquid chromatography or gas chromatography). Blood samples for determination of serum bactericidal activity against five different aerobic and two anaerobic bacterial species (a total of 58 strains) were obtained one hour and six hours after drug infusion. All values were statistically analyzed by use of the Student t test.

Adult↗