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Biomedical subjects

H Lode

Publications and source records attributed to H Lode.

At least 235 records · Page 13Linked to original sources
PubMed1985

Respiratory infection: the disease.

Infectious pneumonias are inflammations of the lung that can be localized in the alveoli or interstitial tissue or both. The pathogenic agent is usually airborne; more rarely it is hematogenous. Important distinctions are between bacterial and nonbacterial forms, between diseases acquired outside and inside hospitals, and between patients who are basically healthy and those with a previous illness. Pneumococci continue to be the dominant pathogens outside hospitals. In hospitals, gram-negative, anaerobic, and fungal pathogens are more often found. Usually, purulent chronic bronchitis or an acute exacerbation of chronic bronchitis is based on a prior viral infection or an impairment of bacterial clearance mechanisms of the respiratory tract. The dominant pathogens are Haemophilus influenzae and pneumococci. Worldwide, viral infections of the upper respiratory tract have great epidemiological significance. With 12 different groups of viruses and more than 150 serotypes, there can be many causes of symptoms of rhinitis, tonsillitis, pharyngitis, laryngitis, and tracheitis as well as bronchitis.

Acute Disease↗
PubMed1984

Comparative pharmacokinetics of apalcillin and piperacillin.

The pharmacokinetics of apalcillin and piperacillin, each administered intravenously as a single 2-g dose, were compared in 10 volunteers in a randomized study of crossover design using bioassay and high-pressure liquid chromatographic procedures. The concentrations of both penicillins in serum were determined over a period of 12 h and in urine over 24 h. Concentrations of apalcillin and piperacillin at the end of the 15-min infusion were similar; however, at 8 h, concentrations of piperacillin were below measurable levels, whereas concentrations of apalcillin were still measurable at 10 h. Pharmacokinetic parameters were calculated according to a two-compartment open model. The area under the curve and the half-life for apalcillin were larger than for piperacillin. On the other hand, renal clearance of piperacillin was substantially greater than that of apalcillin. Of the apalcillin excreted via the kidneys, approximately one-fifth was eliminated as two microbiologically inactive penicilloic acid derivatives. The nonrenal clearance of apalcillin was 79% of total clearance. Binding of apalcillin to serum protein was almost twice that of piperacillin.

Adult↗
PubMed1984

Pharmacokinetics of cefotaxime and desacetyl-cefotaxime in cirrhosis of the liver.

In 9 patients with advanced hepatic cirrhosis and a normal serum creatinine concentration, the pharmacokinetics of cefotaxime (CTX) and its desacetyl metabolite (DACM) were examined in serum and urine after intravenous administration of 2.0 g CTX. The peak serum levels were 130.3 +/- 33.9 and 8.5 +/- 4.6 mg/l for CTX and DACM, respectively. T50% beta was calculated to be 138.1 min (69.3-245.8 min) for CTX. The approximation of the terminal half-life of DACM revealed a prolongation which exceeded 10 h. Accordingly, the AUC amounted to 255.3 +/- 92.0 and 151.9 h X mg/l, respectively. Within 24 h, 62.9% was eliminated in urine as CTX and 19.4% as DACM. The total clearance of CTX was reduced to 164.3 ml/min (58.3-296.6 ml/min), but the renal clearance was only moderately decreased to 90.0 ml/min (24.1-169.3 ml/min). These altered kinetics can be explained by altered metabolic function of the liver as well as by cirrhosis-linked alterations of renal elimination mechanisms.

Adult↗
PubMed1983

[Diagnosis and antibiotic treatment of infectious diseases in general practice. Results of an inquiry].

In February 1982 a questionnaire was sent to 2138 doctors in general practice in West Berlin, to obtain data relating to the incidence and treatment of infectious diseases. Replies were received from 453 (21%). Regular bacteriological tests were undertaken only for urinary tract infections, by 60% of those replying. The 453 doctors reported a total of 9280 cases of infectious disease during a one-week period, 6094 respiratory and 1723 urinary ones. Antibiotic prescriptions numbered 6118 during this period, 56.7% for respiratory and 27% for urinary tract infections. Indications for antibiotic treatment were predominantly decided on clinical grounds.

Anti-Bacterial Agents↗
PubMed1983

[Septicemia. Etiology, epidemiology, clinical aspects and prognosis in 446 patients].

Between 1979 and 1982 446 patients with clinically and bacteriologically established septicaemia were ascertained in a prospective study in a university hospital complex with 1200 beds. This corresponded to an incidence of 8,4 cases of septicaemia in 1000 admissions. In 47.1% of patients the infection had been acquired as out-patient, 52.9% were hospital-acquired. 53.1% of patients were more than 60 years of age, 71.3% had predisposing underlying diseases or risk factors. Main signs of infection were increased temperatures of more than 38.5 degrees C (77.8%), anaemia and leukocytosis. The fairly equal distribution of gram-positive (207) and gram-negative (200) organisms was remarkable. The most frequently isolated bacterial species were E. coli (25.3%), Staph. aureus (21.8%), streptococci (11.1%), Staph. epidermidis (8.4%), enterococci (8.2%), and Klebsiellae (6.5%). 29.1% of patients succumbed. Nosocomial disease, liver cirrhosis, underlying malignant diseases, infections with Staph. aureus, enterococci, pneumococci, Pseudomonas aeruginosa and polymicrobial aetiology had an unfavourable prognostic influence. Thus, frequency and mortality of septicaemic diseases remain of unchanged considerable relevance in medical and surgical units. At present, aetiology and treatment will again have to consider gram-negative organisms to an increased extent.

Adult↗
PubMed1983

Pharmacokinetics of multiple doses of ceftizoxime and their influence on fecal flora.

The pharmacokinetics of ceftizoxime, a new beta-lactam antibiotic, were studied in eight normal volunteers after single and multiple i.v. doses of 2 X 2 g daily for eight days. The mean maximum serum concentration after the first 20 min of infusion on the first day was 176.9 +/- 32.9 micrograms/ml decreasing to 11.0 +/- 4.1 micrograms/ml after 4 h and to 0.67 +/- 0.2 micrograms/ml after 12 h. Mean 12 h urine recovery was 78.8 +/- 9.0%. The half-life of ceftizoxime was 136 +/- 36 min. Volume of distribution was 22.9 +/- 8.1 1/100 kg body weight, AUCtot 208 +/- 33 micrograms/ml x h, total body clearance 151 +/- 33 ml/min, and renal clearance 110 +/- 23 ml/min. No ceftizoxime accumulation was registered during the administration period. Computed multiple-dose values were in good agreement with the measured values, and the pharmacokinetic parameters on the first, fourth and eighth days showed no significant differences. During the study period, the fecal flora displayed a reduction of sensitive gram-negative aerobic bacteria, a slight increase in the amount of enterococci (10(6) to 10(8)/g feces), and no change in the number of Bacteroides fragilis. Some resistant gram-negative strains increased during the administration period, but most of them could no longer be detected two weeks after administration. Tolerance of ceftizoxime was good in four volunteers. Four other volunteers had gastro-intestinal symptoms and mild fever reactions. One female volunteer was assumed to have an allergic drug reaction. Biochemical, hematological, virological and serological data showed no abnormalities in seven volunteers.

Adult↗
PubMed1983

Determination of cefmenoxime in human body fluids by high-performance liquid chromatography.

A rapid and reliable method for the quantitative determination of cefmenoxime in serum and urine by reversed phase high-performance liquid chromatography is described. Serum was deproteinized with acetonitrile. Urine was diluted with dilute acetic acid (17.5 mmol/l). Separations were performed in isocratic mode using a C18 type column and a precolumn packed with Perisorb RP/8. The eluant consisted of a mixture of acetonitrile and 25.0 mmol/l acetic acid in a ratio of 32/69 (vol/vol). In normal subjects cefmenoxime was well separated from endogenous compounds and various added drugs. Its complete separation was confirmed by selective degradation with beta-lactamase from Bacillus cereus and UV spectrophotometry. The detection limit was 0.3 mg/l at a detection wave-length of 254 nm. Peak areas gave linear results up to concentrations of 500 mg/l. Within-batch precision (coefficient of variation) ranged from 1.1 to 6.2%. Recovery rates varied from 99.0 to 103.3%. Results of a standard microbiological assay correlated well with those obtained by the present HPLC method. Eight healthy volunteers who were given a single intravenous dose of 1 g cefmenoxime excreted 86.3 +/- 5.8% of the unchanged drug within 24 h in urine.

Biological Assay↗
PubMed1983

Serum bactericidal activity and kinetics of azlocillin and moxalactam after single and combined administration.

Ten healthy volunteers received 5 g azlocillin and 2 g moxalactam iv in single and combined administration. Serum and urine concentrations were measured with bioassay and HPLC (high pressure liquid chromatography), and serum bactericidal activity (SBA) was determined at 1 h and 6 h against 6 different clinical isolates. The combined applications of both antibiotics resulted in minor differences in serum kinetics and urine recovery in comparison to single administration. SBAs of both antibiotics against Enterobacteriaceae were between 1:4 and 1:8.4 for azlocillin and between 1:3 and 1:8 for moxalactam after 1 h. The combination of both beta-lactam antibiotics did not result in a decrease in SBA against any strain; rather all Enterobacteriaceae showed a slight increase of SBA at 1 h. It can be concluded from these results that combination therapy with azlocillin and moxalactam has no adverse influence on the pharmacokinetics or the bactericidal activity of either substance.

Adult↗
PubMed1983

Biliary excretion and pharmacokinetics of cefoperazone in humans.

Six patients, 40 to 81 years of age, requiring T-tube drainage of their common bile duct, were studied to assess the biliary tract excretion and pharmacokinetics of cefoperazone. Each patient received 2.0 g of cefoperazone iv over 15 min. Cefoperazone concentrations were determined in serum, urine and bile by means of bioassay and HPLC. The results were compared with a pharmacokinetic study in healthy volunteers. The mean total recovery rate of cefoperazone in urine and bile was with bioassay: 64.5 +/- 15.3% (HPLC: 62.4 +/- 15.5%) in 24 h. 18.6 +/- 14.0% (11.5 +/- 7.1%) were found in the bile and 45.9 +/- 16.2% (50.9 +/- 19.7%) in urine. Peak bile concentrations were 3642 +/- 2975 mg/l (2259 +/- 1337 mg/l) after 2-3 h. The serum levels of cefoperazone showed a slow decrease in patients with a long terminal half life (T1/2 gamma) of 380 min from 295 +/- 90 mg/l initially to 15.9 +/- 11.3 mg/l after 12 h. In normal subjects, serum concentrations decreased much faster (T1/2 gamma = 143.5 +/- 20.0 min) from 232.8 +/- 28.6 mg/l to 1.16 +/- 0.73 mg/l after 12 h. Recovery in urine was 21.4 +/- 5.6%. Using HPLC analysis, we found cefoperazone A in small concentrations in the serum and in higher concentrations in the bile and urine of the operated patients. It is debatable whether cefoperazone A is a true metabolite in vivo or a physical degradation product.

Adult↗
PubMed1983

Comparative pharmacokinetics of cefoperazone, cefotaxime, and moxalactam.

The pharmacokinetics of cefoperazone, cefotaxime, and moxalactam were compared in a cross-over randomized study in 10 healthy volunteers. Each subject received 1.0 g of the three drugs by bolus intravenous injection over 3 min. Serum and urine concentrations were assayed by a microbiological method and in addition by high-pressure liquid chromatography (HPLC) for cefotaxime in five subjects. Maximal concentrations in serum 5 min after the injection were 163 +/- 40.3 mg/liter for cefoperazone, 86.1 +/- 19.0 mg/liter for cefotaxime, and 95.5 +/- 21.1 mg/liter for moxalactam. After 12 h, 1.2 +/- 1.4 mg of cefoperazone per liter and 1.8 +/- 0.9 mg of moxalactam per liter could still be measured. Eight hours after the administration of cefotaxime, serum concentrations were below the detection limit of 0.3 mg/liter in most subjects. By HPLC analysis, the mean maximal concentration of desacetyl cefotaxime was 16.6 +/- 10.5 mg/liter 5 min after application; the metabolite exceeded the serum concentration of the parent compound after 1 to 2 h. Relevant pharmacokinetic parameters were calculated, using two- and three-compartment models. The terminal half-life was 144.1 +/- 37.3 min for cefoperazone, 76.1 +/- 32.0 min for cefotaxime, and 272.4 +/- 114.1 min for moxalactam. The apparent volume of distribution corresponded to the extracellular volume. Only 25.1 +/- 8% of cefoperazone could be detected in urine compared with 53.3 +/- 8.1% of cefotaxime and 61.0 +/- 9.2% of moxalactam in 24 h. A total of 89.6 +/- 11.4% of the cefotaxime dose could be recovered by HPLC in urine, 60.6 +/- 7.7% as cefotaxime and 29.1 +/- 7.0% as desacetyl cefotaxime.

Adult↗
PubMed1983

Multiple-dose pharmacokinetics of ceftazidime and its influence on fecal flora.

Eight healthy volunteers each received 2.0 g of ceftazidime by constant intravenous infusion over 20 min twice daily every 12 h for 8 days. Concentrations of ceftazidime in serum and urine were measured by a microbiological assay and by high-pressure liquid chromatography. Qualitative and quantitative studies on aerobic and anaerobic fecal flora were carried out before, during, and 2 weeks after the end of treatment. The mean (+/- standard deviation) maximum drug concentration in serum at the end of the 20-min infusion (day 1) was 185.5 +/- 28.5 micrograms/ml, decreasing to 0.8 +/- 0.4 microgram/ml after 12 h. The mean recovery of drug in urine at 12 h was 71.5 +/- 12.2%. Pharmacokinetic parameters calculated on the basis of a two-compartment model were as follows: elimination half-life, 110.5 +/- 15.2 min; volume of distribution at steady state, 21.2 +/- 2.6 liters/100 kg; volume of distribution by the area method, 26.2 +/- 4.0 liters/100 kg; area under the serum concentration-time curve, 293.3 +/- 47.8 micrograms X h/ml; total body clearance, 116.4 +/- 20.3 ml/min per 70 kg; renal clearance, 82.2 +/- 15.1 ml/min per 70 kg. The agar diffusion test and high-pressure liquid chromatographic analysis showed a good correlation of results. Metabolites of ceftazidime could not be detected by high-pressure liquid chromatography in serum or urine. No accumulation of ceftazidime could be observed during the 8-day study period. Mean maximum drug levels in serum were 185.5 to 214.5 micrograms/ml, and mean trough levels were 0.8 to 1.1 micrograms/ml (days 1 to 8). No severe side effects were noted. During ceftazidime treatment, anaerobes were left intact, whereas members of the family Enterobacteriaceae could be isolated from stool in only three of eight subjects. Two weeks after discontinuation of the drug, all stool specimens contained ampicillin- and cefazolin-resistant gram-negative rods.

Adult↗