Biomedical subjects
Publications and source records attributed to C Krasemann.
The composition of human fecal flora, the methods for its study, and the changes in the normal colonic flora caused by orally administered lincomycins, tetracyclins and aminoglycosides are reviewed. Recent studies concerning the effect of the benzo-diazaborine derivative CG 3401 on human fecal flora, especially Bacteroides species, are reported.
Anaerobic bacteria in the lochia are frequently isolated healthy post-partum patients and from those with post-partum infections. The true pathogenic significance of these anaerobic bacteria is uncertain. Investigations appeared to show that the incidence of anaerobic bacteria is by and large the same as in the vaginal and intestinal flora. In this investigation we showed: 1) anaerobic bacteria are rare in the vaginal flora of pregnant patients in the third trimester, 2) a definite difference exists in the number of anaerobic bacteria in normal lochia versus infected lochia, 3) in post-partum infections qualitative differences exist between the anaerobic isolates. The strains of the bacteroides oralis group become the predominant anaerobic bacteria. It is concluded that members of the bacteroides oralis group which are normally not present in the human intestinal flora play a specific role in post-partum infections. The anti-microbial treatment of post-partum infections has to take this into account. The eminent therapeutic importance of the 5-Nitro-Imidazoles is discussed.
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The susceptibility of 115 Bacteroidaceae strains to LY 127935 was determined by broth dilution, agar dilution and agar diffusion tests. Simultaneously, the strains were tested for degradation of the oxa-beta-lactam. Only five strains (3 Bacteroides fragilis and 3 Bacteroides oralis/Bacteroides bivius) partially degraded LY 127935. No major discrepancies between the results of the agar dilution and broth dilution tests were observed. According to the results obtained by the agar dilution method, 50 strains of B. fragilus were inhibited by concentrations of less than or equal to 8 microgram oxa-beta-lactam per ml. Members of the Bacteroides melaninogenicus group of organisms had agar dilution MICs of less than or equal to 0.5 microgram LY 127935 per ml and Fusobacterium/Sphaerophorus species were inhibited by less than or equal to 64 microgram/ml. Strains of Bacteroides thetaiotaomicron, B. oralis/B. bivius and Bacteroides spp. were less susceptible. Due to the narrow range of MICs observed with B. fragilis strains, no regression line could be computed for the relationship between MIC and zone size.
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Azlocillin concentrations in the rabbit eye were studied after intravenous and subconjunctival injections. The following results were found: therapeutic levels of Azlocillin were achieved in the aqueous humor, using either way of administration. Concentrations of the antibiotic were much higher after s. c. injection than after i. v. administration. The pharmacocinetics of Azlocillin proved to be comparable to those of other penicillins. No antibiotic could be detected in the vitreous body, irrespectively of the administration. With regard to the better antibacterial activity of Azlocillin in comparison with other known penicillins it should be preferred in eye infections caused by gramnegative rods, especially by Pseudomonas aeruginosa.
The in vitro activity of doxycycline against 147 strains of gram-positive and gram-negative anaerobes was determined by broth dilution, agar dilution and agar diffusion tests. The strains were isolated from clinical specimens in 1977. Saccharolytic Bacteroides strains (39 B. fragilis, 6 B. thetaiotaomicron, 4 B. vulgatus) showed broth dilution MICs of less than or equal to 0.0625-4.0 microgram/ml after 5 h incubation and MICs of less than or equal to 16 microgram/ml after 15 h incubation at 37 degrees C. With strains of B. oralis, B. melaninogenicus ss. intermedius, B. corrodens, Veillonella sp. and Megasphaera elsdenii the broth dilution MICs were less than or equal to 0.0625-32 microgram/ml after 15 h incubation. Peptostreptococcus spp., Propionibacterium acnes, Eubacterium sp., Bifidobacterium sp. and Clostridium sp. had broth dilution MICs of less than or equal to 2 microgram/ml, whereas Peptococcus spp. were inhibited by less than or equal to 0.0625 to greater than 32 microgram/ml. With the great majority of strains tested, MICs were 2 to 256 times higher in agar than in broth dilution tests. Clinical and experimental studies seem to be needed to determine which of the in vitro data are correlated to the outcome of doxycycline therapy. Several groups and species were separately considered for statistical analysis of the relationship between zone size and MIC. With gram-positive anaerobes, correlation was poor between broth dilution MIC and zone size (correlation coefficients r = - 0.168 for Peptococcaceae, and r = - 0.108 for P. acnes). When calculating the regression lines for agar dilution MICs and zone diameters, a higher correlation was found (r = - 0.9 for Peptococcaceae; r = - 0.397 for P. acnes). With B. fragilis and other Bacteroides species correlation coefficients were r = - 0.807 to r = - 0.891 for broth and agar dilution MICs and zone size but stochastic linearity was lacking.
Following intravenous injection of 50 mg/kg Mezlocillin into rabbit eyes the concentrations measured in the aqueous humor were of low-grade therapeutic efficacy. In the vitreous, this dose and form of application had no therapeutic effect. The transfer concentration in the aqueous humor after subconjunctival application of 20 mg Mezlocillin was comparably low. High therapeutic levels in the aqueous humor and even, in isolated cases, traces of Mezlocillin in the vitreous were found after subconjunctival injection of 100 mg.
Netilmicin, a half-synthetic aminoglycoside, was given to 22 patients with urinary-tract infections at a dose of 2 mg/kg body weight twice daily intramuscularly for 7--9 days. Pharmacokinetics (in ten patients), efficacy and tolerance to the drug were analysed. Mean serum peak concentrations on the first and last days of treatment, was 8.7 microgram/ml at 45 min after injection, 9.5 microgram/ml after 60 min. After 12 hours the level had fallen to 0.8 microgram/ml and 1.2 microgram/ml, respectively. Mean half-life was 3.08 hours for the first and 3.57 hours for the last day. The corresponding mean values for plasma clearance were 53.6 ml/min and 42.4 ml/min, respectively. Within 12 hours an average of 77.6% and 78.0%, respectively, of the netilmicin dose were eliminated in the urine. The causative organism was eliminated in 12 of 16 patients with chronic or reccurent and in all six with acute urinary infections. There were two re-infections and two failures. Superinfection did not occur. Local and general tolerance was good and there were no signs of renal or inner-ear toxicity.
The susceptibility of more than 40 strains of Gram-negative and Gram-positive anaerobes to tiamulin (Sandoz 81.723 hfu), a new pleuromulin (pleuromutilin) derivative, was determined by broth dilution and agar dilution tests. The influences of density of the inoculum upon MICs was studied by a specially designed pour plate-technique. Bacteroides fragilis, B. vulgatus, B. splanchnicus, B. oralis, B. asaccharolyticus, B. melaninogenicus, Fusobacterium fusiforme (F. nucleatum), Sphaerophorus necrophorus, Clostridium perfringens, C. fallax, Propionibacterium acnes and several species of Peptococcaceae showed broth dilution MICs of 0.03 similar to 1 microgram/ml. Members of B. thetaiotaomicron, B. distasonis and S. freundii (F. mortiferum) were inhibited by 8 similar to 32 microgram/ml and 2 strains of S. varius had a broth dilution MIC of 256 microgram/ml. With most strains, the agar dilution MICs were 2 similar to 4 similar to 8 times the broth dilution MICs. In pour plate-tests, the MICs were not considerably influenced influenced by varying initial concentrations of viable cells. With most anaerobes, the MBCs of tiamulin were more than 100-fold higher than the MICs. The results obtained indicated that, apart from S. varius, B. thetaiotaomicron, B. distasonis and S. freundii (F. mortiferum), members of 16 other anaerobic species including B. fragilis were without exception sensitive to tiamulin.
The one antibiotic-one disk agar diffusion test for susceptibility testing of clinical isolates, though technically similar to that used for determining antibiotic concentrations in body fluids, lacks the exactness of the latter. In correlating zone diameters to MICs, stochastic linearity should be evaluated besides the regression lines and the correlation coefficient.
For antibacterial prophylaxis in intraocular surgery minocycline was administered in oral dosage in 22 cataract-patients. The concentration levels reached in the aqueous humor were determined. The detected levels ranged in some cases from 0.08 to 0.2 mcg/ml, the majority was below 0.06 mcg/ml.
The compatibility of amikacin as well as its penetration into the different tissues of the eye were studied experimentally in rabbits. Amikacin is well tolerated, both when applying drops and subonjunctival injections. When 1% solution of amikacin is dropped into the eye, antibacterially effective concentrations are achieved in the cornea and in the aqueous humour. There was only minimum penetration in the cornea found after subconjunctival injection. No amikacin was found in the vitreous body, neither when applying drops nor subconjuctival injections.
Sisomicin is a new aminoglycoside, which sometimes is active against bacterial isolates resistant to other antibiotics of this group. The compatibility of sisomicin and its penetration into the different tissues of the eye were studied in rabbits. The substance was well tolerated, when applied as drops or injected subconjunctivally. Concentrations of sisomicin which are effective against most bacteria were found in the cornea and in the aqueous humour, but it did not penetrate into the vitreous body.
Investigation of the resistance of 290 strains of the Klebsiella-Enterobacter group (252 Klebsiella and 38 Enterobacter strains) against cefazolin showed that 63% of the Enterobacter strains were resistant and 50% of the Klebsiella strains were sensitive both in the serial dilution test and in the agar diffusion test. A total of 78% were inhibited by 32 mug cefazolin per millilitre. Isolates from the genitourinary tract were significantly more resistant than those from the respiratory tract.
The activity of the new cephamycin C derivatives cefoxitin against 102 clinical isolates of Bacteroidaceae (95 Bacteroides strains and 7 Fusobacterium-Sphaerophorus cultures) was determined by tube dilution and standardized agar diffusion tests and compared to that of cephalothin. Cefoxitin was more active than cephalothin against 56 Bacteroides fragilis strains, 19 Bacteroides thetaiota-omicron strains and two Bacteroides splanchnicus strains. The difference seemed less pronounced with five Bacteroides vulgatus and four Bacteroides variabilis cultures. Three Bacteroides melaninogenicus and six Bacteroides oralis strains displayed similar sensitivity to both cephalosporins. At concentrations of 32 microng/ml or less, cefoxitin inhibited 91% and cephalothin 33% of the Bacteroides strains. Two strains of Sphaerophorus varius were likewise much more sensitive to cefoxitin than to cephalothin (MIC values 8 micron8/ml of cefoxitin and 256 microng/ml of cephalothin). Three other Sphaerophorus strains (the species necrophorus and freundii/mortiferum) and two of Fusobacterium fusiforme (Fusobacterium nucleatum) strains were very similar in their susceptibility to both cephalosporins. Statistical analysis of the relationship between MIC and zone size diameter showed relatively high correlation coefficients for cefoxitin and cephalothin (r=-0.741 and r=-0.703 respectively).