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Biomedical subjects

H Knothe

Publications and source records attributed to H Knothe.

At least 55 records · Page 3Linked to original sources

Kinetics of erythromycin uptake and release by human lymphocytes and polymorphonuclear leucocytes.

The uptake of 14C-labelled erythromycin by human lymphocytes and polymorphonuclear leucocytes was studied. Erythromycin was concentrated by the cells. The amount of accumulated erythromycin was correlated with the cell count and was found to increase with alkaline pH and with increasing temperature of the incubation medium. The uptake of erythromycin could be reduced by compounds which inhibit cell respiration, glycolysis and (Na+-K+)membrane ATPase. Furthermore, the uptake was saturable and followed Michaelis-Menten kinetics (Km = 0.7 and 1.6 mM for lymphocytes and polymorphonuclear leucocytes, respectively). The intracellular concentrations cannot be explained by the principle of non ionic diffusion. It is suggested that erythromycin is actively transported via the nucleoside transport system. The accumulated erythromycin was rapidly released when the cells were washed and re-incubated in antibiotic-free medium. Probably, no strong intracellular binding takes place.

Erythromycin↗

Changes in aerobic faecal bacterial flora of severely ill patients during antibiotic treatment.

The stool of patients both undergoing and not undergoing antibiotic treatment was examined for aerobic faecal bacterial flora (quality and quantity) in an intensive care unit. The bacterial flora in the stool of patients not undergoing antibiotic treatment was generally normal. In patients undergoing antibiotic treatment the faecal bacterial flora showed changes as a result of the use of the antibiotic. Under cephalosporin treatment alone (cefotaxime, cefazolin) E. coli was still to be found. In patients being treated with a combination of two or three antibiotics the frequency of occurrence of E. coli was markedly reduced. Pseudomonas aeruginosa were however substantially more often detected showing increased resistance. The wider the antibiotic spectrum, the more facultative pathogenic microorganisms in the faeces increase, especially Pseudomonas aeruginosa, which can then become an important source for nosocomial infections.

Adult↗

Impact of injectable cephalosporins on the gastrointestinal microflora: observations in healthy volunteers and hospitalized patients.

A disturbed microbiological ecosystem of the gut flora is frequently seen as a consequence of antibiotic therapy. Because this impact on the physiological balance is known to be causative for severe nosocomial infections and is mainly seen with antibiotics that are massively excreted via the bile (e.g. broadspectrum penicillins, ceftriaxone and cefoperazone), we investigated cefotaxime (CTX), cefotiam (CTM), cefmenoxime (CMX), ceftazidime (CAZ), ceftizoxime (CZX) and cefazolin + netilmicin (CEZ + NTL) in healthy volunteers. The respective daily i.v. doses, days of medication and numbers of volunteers were: CTX 3 g, 1 d, n = 8; CTM 6 g, 3 d, n = 15; CMX 4 g, 3 d, n = 15; CAZ 4 g, 1 d, n = 8; CZX 4 g, 1 d, n = 8; CEZ + NTL 2 X 3 g + 1 X 3 mg/kg/day, 4 d, n = 15. CTX was also investigated in 11 selected hospitalized patients. One or two stool specimens were taken before, during and several days after medication. The microorganisms were also tested for ampicillin and CEZ resistance on selective media. Ampicillin and CEZ resistance was much higher in hospitalized patients than in volunteers (mainly Proteus and Serratia sp.): 90% vs. 42% and 63.6% vs. 43%, respectively. CTX did not affect the anaerobes (Bacteroides sp. and lactobacilli) that are antagonistic to clostridia and Candida. No selection of strains resistant to ampicillin or CEZ occurred. In hospitalized patients, the level of resistance to these drugs was lower after treatment than before.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗

Cefamandole resistance transfer in bacterial strains from two newborn units.

Transfer of Cefamandole resistance was demonstrated from strains of Citrobacter freundii as well as from individual strains of Enterobacter cloacae, Acinetobacter anitratus and Klebsiella pneumoniae isolated from patients in two newborn units. In Citrobacter freundii, Cefamandole resistance was transferred always with Cephalotin resistance as well as with a TEM-like beta lactamase (conferring resistance to Ampicillin, Carbenicillin and Azlocillin). Citrobacter freundii strains from Hospital I were completely susceptible to gentamicin, while strains of other species, resistant to Cefamandole plus Cephalotin, were resistant to Gentamicin as well, and transferred this resistance, too. In one Enterobacter cloacae strain from Hospital I, Cefamandole resistance could be separated from resistance to Cephalotin, but only in clones selected with gentamicin and not with any of the cephalosporins. Acinetobacter anitratus strain was also resistant to Cefotaxime, but did not transfer this resistance. It might be concluded that special nosocomial bacteria may carry plasmids conferring a transferable type of resistance to Cefamandole together with resistance to classical cephalosporines. Second cycle of transfers, i.e. between two variants of E. coli K-12 strains confirmed the contransferability of Cefamandole and Cephalotin resistance.

Acinetobacter↗

[Hygienic problems of sanitation procedures in civil aviation].

Hygiene problems that arise in connection to sanitation procedures in civil aviation are described; the relevant international regulation and recommendation are explained. The particular problems that arise in connection to prophylaxis to infections, food hygiene, sanitation, refuse disposal and the maintenance lavoratory facilities are emphasized. Relevant rules and recommendations are quoted.

Aviation↗

The current state of cephalosporin antibiotics: microbiological aspects.

An increasing number of new cephalosporins continue to become available in the clinic so that the clinician requires something akin to Ariadne's thread to work through the labyrinth of confusing names and product claims. The parenteral cephalosporins may be grouped on the basis of structure, antimicrobial activity and metabolic stability as follows: 1. cephacetrile, cephalothin, cefapirin; 2. cefotaxime; 3. cephaloridine, cefazedone, cefazolin, cefotiam; 4. cefamandole, cefoperazone, cefsulodin, cefuroxime, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, lamoxactam. Groups 2 and 4 contain the most interesting compounds in terms of their biological activity and therapeutic significance. Even carbenicillin-resistant strains of Pseudomonas aeruginosa are inhibited by one of the recent broad-spectrum cephalosporins. In the clinic, minor differences between the highly active cephalosporins are not likely to be of therapeutic significance.

Bacteria↗

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↗

Comparative study of fosfomycin activity in Mueller-Hinton media and in tissues.

Fosfomycin utilizes two uptake systems as ways of entry into microorganisms: the L-a-glycerophosphate and the hexose phosphate transport system. The latter is inducible by glucose-6-phosphate. The relationship between glucose-6-phosphate (concentration range 0-100 mg/l) and the susceptibility of Staphylococcus aureus was studied in Mueller-Hinton broth. An almost maximal enhancement of fosfomycin activity was found at 25 mg/l glucose-6-phosphate. Fosfomycin activity against Staph. aureus, Escherichia coli, Proteus mirabilis, Enterobacter cloacae, Klebsiella spp., Serratia spp., and Pseudomonas aeruginosa was studied by use of the broth and the agar dilution method, in the presence and absence of glucose-6-phosphate (25 mg/l). The minimum inhibitory concentrations (MICs) of fosfomycin against Staph. aureus Streptococcus faecalis, E. coli, Ent. cloacae, Pr. mirabilis, and Ps. aeruginosa were estimated in particle free supernatants of 25% tissue homogenates (liver, kidney, lung, heart) and in parallel in Mueller-Hinton broth. With few exceptions the MICs in Mueller-Hinton broth (with glucose-6-phosphate) were similar to those found in tissues (no glucose-6-phosphate added).

Animals↗

Cefotetan: antimicrobial activity in-vitro compared with that of cefotaxime.

The antimicrobial activity of cefotetan and cefotaxime were compared in vitro against 547 strains of aerobes and 24 strains of Bacteroides fragilis. The strains were recent clinical isolates from 20 hospitals. Cefotetan was found to exhibit an activity two- to fourfold lower than that of cefotaxime against most of the enterobacteriaceae. About half the number of Enterobacter aerogenes and Enterobacter cloacae strains resistant to cefotetan were resistant also to cefotaxime. Cefotetan was more active than cefotaxime against most of the strains of Proteus vulgaris. In contrast to cefotaxime which was moderately active, cefotetan was inactive against Pseudomonas aeruginosa. Cefotetan had limited activity against Staphylococcus aureus and Streptococcus faecalis was resistant to both cefotetan and cefotaxime. Bact. fragilis was inhibited more effectively by cefotetan than by cefotaxime. Depending on the species tested, the activity of cefotetan was influenced significantly by the inoculum size in some cases. Different test media did not affect the results.

Anti-Bacterial Agents↗

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↗

[Cefotaxime and desacetylcefotaxime in cerebrospinal fluid of newborn and premature infants].

On the occasion of clinically indicated lumbar of cisternal punctures in 19 newborn and premature babies treated with Cefotaxime 33 CSF-levels of Cefotaxime (CTX) and it's metabolite Desacetyl-Cefotaxime (D-CTX) were measured by means of HPLC. 6 of the 19 infants suffered from meningitis. The highest CTX-levels were found 2 to 4 hours after the last infusion of CTX (50 or 100 mg/kg within 20 min, each 12 hours). Patients with meningitis showed CTX-levels between 20 mg/l and less than 0.5 mg/l (limit of detection), those without meningitis between 11 mg/l and less than 0.5 mg/l. Because of the widely scattered CTX-levels any dependence from CTX-dosage or from degree of meningeal inflammation is not to be shown. With two exceptions D-CTX-levels ranged from 2 to 20 mg/l. Up to 9 1/2 hours after the last CTX-dose no clear decrease of the D-CTX-concentration in CSF may be seen. On the other hand, D-CTX-levels are also widely scattered. Nevertheless D-CTX apparently stays significantly longer in the CSF than CTX does. An influence of meningeal inflammation on the D-CTX-levels can not be observed. In E. coli- and in Klebsiella-spp. The geometrical means of MIC are found to range below 0.5 mg/l for CTX and below 2 mg/l for D-CTX. Therefore CTX might be recommended for treatment of meningitis caused by these germs. This recommendation may be supported by some reports about good clinical results, from our unit and from the literature as well.

Bacterial Infections↗

[In-vitro activity of cefotaxime].

From 1979 to 1982, a large number of freshly isolated strains of bacteria were investigated at our institute with regard to their sensitivity to cefotaxime in comparison to other antibiotics. The isolates came from 42 clinics in the Rhine-Main region. The results of the investigations demonstrate that cefotaxime, due to its high stability against beta-lactamases, has advantages over to older cephalosporins, and even cefoperazon and cefoxitin. Despite increased use of cefotaxime, there was no change in the sensitivity of the organisms from 1979 to 1982.

Cefotaxime↗