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Biomedical subjects

M E Levison

Publications and source records attributed to M E Levison.

At least 73 records · Page 4Linked to original sources

In vitro activity, efficacy, and pharmacology of moxalactam, a new beta-lactam antibiotic.

Moxalactam, a potent new beta-lactam antibiotic with a relatively wide spectrum of activity against facultative and anaerobic gram-negative bacilli, was evaluated in vitro and in 28 patients with a variety of severe infections with moxalactam-susceptible organisms (minimum inhibitory concentration less than or equal to 31 microgram/ml). Although therapy was successful in most of these patients, caution is suggested because of the development of resistance on therapy in one patient, persistence of Bacteroides fragilis endocarditis in another, and for certain organisms, a significant inoculum effect on the minimum inhibitory concentration and minimum bactericidal concentration of moxalactam.

Adolescent↗

Adherence of bacteria to vaginal epithelial cells at various times in the menstrual cycle.

Adherence of vaginal isolates of Escherichia coli, Lactobacillus species, group B streptococci, Gardnerella vaginalis and Neisseria gonorrhoeae to exfoliated vaginal epithelial cells was studied in 10 healthy, sexually active medical students. Studies were done pre- and postmenstrually and at midcycle for two consecutive menstrual cycles. The mean number of adherent bacteria per vaginal epithelial cell (range) was 3.4 (0 to 14) for E. coli, 60.5 (12 to 152) for Lactobacillus species, 54.8 (21 to 76) for group B streptococci, 67.4 (15 to 161) for G. vaginalis, and 58.9 (15 to 186) diplococci for N. gonorrhoeae. Adherence of G. vaginalis increased with increasing acidity of the test medium (pH 4 to 8). There were no significant differences in adherence to vaginal epithelial cells obtained at the various times in the menstrual cycle for any of the organisms (p greater than 0.05). The pattern and extent of adherence among the women was similar for each organism. In this in vitro model, adherence characteristics did not vary with the menstrual cycle.

Adhesiveness↗

Experimental Candida albicans, Staphylococcus aureus, and Streptococcus faecalis pyelonephritis in diabetic rats.

Pyelonephritis was studied after an intravenous injection of Candida albicans, Staphylococcus aureus, or enterococcus in alloxan-diabetic rats and in water-diuresing or non-diuresing nondiabetic rats. The renal microbial populations of C. albicans or S. aureus were found to be greater than 10(5) colony-forming units per g for up to 42 days in diabetic rats, whereas the kidneys tended to become sterile in nondiabetic rats. No significant difference was found in the course of enterococcal pyelonephritis in diabetic versus control rats. The difference in the 50% infective dose for each microorganism between diabetic and control rats was less than or equal to log10. Neither duration of diabetes nor weight loss contributed to the greater and more sustained renal populations of C. albicans and S. aureus in diabetic rats. The inflammatory reaction in kidneys infected with S. aureus or C. albicans was greater in diabetic rats. Fungus balls associated with ureteral obstruction and gross multiple renal abscesses occurred in diabetic, but not in nondiabetic, rats infected with Candida. Growth of C. albicans and S. aureus in vitro in urine from diabetic rats was significantly greater than it was in urine from control rats. Addition of water or glucose to the urine of non-diuresing, nondiabetic rats significantly increased in vitro growth of S. aureus and C. albicans. These studies demonstrate greater severity of infection in the diabetic kidney due to S. aureus and C. albicans, which can be partially explained by decreased inhibitory activity of urine for these organisms in diabetic rats.

Animals↗

Comparison of mezlocillin, piperacillin, Bay k 4999 with carbenicillin and ticarcillin against enterobacteriaceae and Pseudomonas aeruginosa.

The minimal inhibitory concentration (MIC) of five penicillins (carbenicillin, ticarcillin, mezlocillin, piperacillin and Bay k 4999) against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, indole positive Proteus sp. and Enterobacter species was determined by an agar dilution method. Bay k 4999 and piperacillin were found to be the most active of the semi-synthetic penicillins tested against P. aeruginosa and Enterobacteriaceae. Bay k 4999 was slightly more active than piperacillin against E. coli, about as active as piperacillin against Pseudomonas, K. pneumoniae, P. mirabilis and indole positive Proteus, but more active than piperacillin against Enterobacter species.

Azlocillin↗

Pharmacology of a new 1-oxa-beta-lactam (LY127935) in normal volunteers.

The pharmacokinetics of 1-oxa-beta-lactam (LY127935), a new semisynthetic beta-lactam antibiotic, was studied in four healthy adult volunteers (mean age of 27 years, mean body surface area +/- standard error [SE] of 1.87 +/- 0.08 m(2), and mean creatinine clearance +/- SE of 116 +/- 12 ml/min per 1.73 m(2)). Immediately after completion of a 1-g, 20-min intravenous (i.v.) infusion, the mean serum level +/- SE was 70.7 +/- 8.5 mug/ml. After a 1-g intramuscular (i.m.) injection, peak serum levels occurred from 30 min to 1 h, and the mean peak serum level +/- SE was 52.3 +/- 1.6 mug/ml. Beginning at 1 h, the serum concentrations after i.m. administration were higher than those after i.v. administration. At 8 h, the mean serum level +/- SE was 3.8 +/- 0.6 mug/ml after completion of the i.v. infusion and 4.8 +/- 0.7 mug/ml after the i.m. injection. The mean serum half-lives for the beta phase i.v. and i.m. administration were similar (2.3 +/- 0.7 h and 2.4 +/- 0.2 h, respectively). The mean apparent volume of distribution +/- SE was 16.6 +/- 1.9 liters per 1.73 m(2). The mean serum clearance +/- SE of LY127935 was 85.4 +/- 12.7 ml/min per 1.73 m(2), and the mean renal clearance +/- SE was 54.5 +/- 4.4 ml/min per 1.73 m.(2) Urine concentrations of LY127935 were at least 140 mug/ml in each volunteer during the first 12 h after i.m. or i.v. administration. The mean percentages of the dose recovered in the urine +/- SE within 2 h after i.v. or i.m. administration were similar (30 +/- 4 and 34 +/- 11, respectively). Only 67 +/- 3% and 75 +/- 13% were recovered in the urine within 24 h after i.v. and i.m. administration, respectively.

Adult↗

Quantitative bacteriology of the vaginal flora in vaginitis.

Vaginal flora was studied quantitatively in 29 sexually active women, 16 to 33 years of age, to define the role of C. vaginale in vaginitis. Seventeen were asymptomatic and 12 complained of symptoms of vaginitis. Seven asymptomatic women had scant secretions: four of these seven had C. vaginale at log10 6 to 9 CFU per milliliter, none of whom had "clue" cells; none had trichomonas or candida; six had lactobacilli at log10 7 to 9.7 per milliliter; only one had Bacteroidaceae at greater than log10 5 per milliliter. Ten asymptomatic women had easily collectable secretions; eight of 10 had C. vaginale at log10 6.5 to 9.6 per milliliter, three of whom had "clue" cells; four had trichomonas and none candida; nine had Lactobacilli at log10 7 to 9.3 per milliliter; four had Bacteroidaceae at greater than log10 5 per milliliter. Twelve had vaginitis: five of 12 had C. vaginale at log10 7.9 to 11 per milliliter, one of whom had "clue" cells; nine had either trichomonas or candida or both and three had no pathogen, including C. vaginale; 10 had Lactobacilli at log10 7 to 10 per milliliter; six had Bacteriodaceae at greater than log10 5 per milliliter. Three had "clue" cells in absence of C. vaginale.

Adolescent↗

Human vaginal epithelial multilayer tissue culture.

Fragments of normal human adult vagina, when explanted onto glass slides gave rise to outgrowing sheets of pure epithelium, which had microscopic morphological features in common with normal vaginal epithelium. Infrequent fibroblast contamination was observed. Proliferating epithelial cells formed multilayers of stratified squamous epithelium and demonstrated a progressive decrease in proliferative activity after 14 days. Continuous lines of epithelial cells were not obtained. Even in the absence of estrogens, transmission electron microscopy revealed evidence of keratinization of the superficial cells of the multilayer. Scanning electron microscopy of the surface of mature epithelial cells in culture revealed ultrastructural features that closely resembled those present on the surface of exfoliated cells obtained by scraping the vagina in vivo. This in vitro tissue culture model of human vaginal epithelium may provide a simple method of studying factors that influence vaginal epithelium growth, maturation and function.

Cell Differentiation↗

Activity of semisynthetic penicillins and synergism with mecillinam against Bacteroides species.

The minimal inhibitory concentrations (MIC) of six penicillins (ampicillin, carbenicillin, ticarcillin, piperacillin, mezlocillin, and Bay k 4999) against 29 clinical isolates of Bacteriodes spp. (including Bacteroides fragilis, Bacteroides thetaiotaomicron, and Bacteroides vulgatus) were determined by an agar dilution method. Bay k 4999 was most active, followed in descending order by ampicillin, piperacillin, mezlocillin, ticarcillin, and carbenicillin. Mecillinam, a 6 beta-amidino-penicillanic acid, inhibited no strains at 50 micrograms/ml, but when compared with ampicillin, a fourfold or greater increase in MIC for ampicillin (antagonism) was noted in 3 of 29 strains, with no effect on MIC for 26 strains, whereas when combined with carbenicillin, a fourfold or greater decrease in MIC for both antibiotics (synergism) was noted in 12 strains, 4 of which had an MIC of greater than or equal to 250 micrograms/ml for carbenicillin alone. These studies demonstrate the increased activity of some newer semisynthetic penicillins and the potential synergy obtained with mecillinam and carbenicillin against Bacteroides sp.

Amdinocillin↗

In vitro activity and pharmacokinetics of cefaclor in normal volunteers and patients with renal failure.

In both Mueller-Hinton agar (MHA) and antibiotic medium no. 1 (AB1) cefaclor was more active than cephalothin or cephalexin against Enterobacteriaceae. Its activity was equivalent to cephalexin against S. aureus in MHA. Cefaclor was particularly active against P. mirabilis. The activity of this antibiotic was greated in AB1 than in MHA. The inoculum effect was pronounced for cefaclor when compared with cephalothin, but cefaclor retained greater activity even against the higher inoculum. In volunteers with normal renal function, cefaclor produced slightly lower blood levels than those reported for cephalexin. Absorption after eating was decreased and delayed. Despite severe renal failure, substantial urine levels of antibiotic were still achieved. In contrast to cephalexin, plasma half-life for cefaclor was only moderately prolonged by renal failure (two-to-threefold) and only minimally shortened by haemodialysis. Adequate concentrations of cefaclor in sputum, active against common respiratory pathogens, could not be consistently demonstrated after the oral administration of a 1 gram dose of cefaclor.

Adult↗

Pharmacology of cefaclor in normal volunteers and patients with renal failure.

After a 500-mg dose of cefaclor, the mean peak plasma level was 12.4 mug/ml and after a 250-mg dose it was 5 mug/ml in normal volunteers. Food intake significantly reduced absorption. Probenecid prolonged plasma levels. Mean plasma half-life in normal volunteers was 0.8 h. Only about 50% of the dose was excreted in the urine within 4 h in normal volunteers. Plasma half-life in patients with renal insufficiency was only about 3 h, which suggests that cefaclor may be eliminated by nonrenal mechanisms in humans. Urinary levels of cefaclor were adequate to inhibit susceptible pathogens even in patients with moderately severe renal failure. Plasma half-life during hemodialysis was 2.1 h and rose to 2.8 h after dialysis.

Adult↗

Rat model of experimental endocarditis.

A simple model of infective endocarditis was produced in rats. With the aid of a guide wire, polyethylene catheters were passed into the left ventricle through the right carotid artery of Sprague-Dawley rats weighing 300 to 350 g. A volume of 1 ml of an overnight culture of Streptococcus mitis, Staphylococcus aureus, or Streptococcus faecalis was intravenously injected 1 to 2 days after catheterization. Bacterial titers of Streptococcus mitis in vegetations were about 10(4)-fold greater than in other tissues. Blood cultures were always positive after 6 h. Mortality was 19% at 1 week and 82% at 2 weeks. Catheters were pulled 24 h after infection, and vegetation titers of greater than 7.0 log10 colony-forming units per g were sustained at 5 days. In intravenously infected rats without catheters, blood and tissues were sterile after 3 to 5 days. With Staphylococcus aureus, vegetations had greater than 9.0 log10 colony-forming units and with Streptococcus faecalis 8.8 +/- 0.3 log10 colony-forming units per g at 2 days. The rat model of infective endocarditis should prove to be suitable for further pathological and therapeutic studies.

Animals↗

Quantitative microflora of the vagina.

This study enumerated the predominant vaginal flora in 25 healthy patients: 18 prenatal (six with and 12 without gonorrhea) and seven nonpregnant without gonorrhea. All 25 patients had aerobes and 19 of the 25 had anerobes isolated in titers of greater than or equal to 10(5) colony-forming units (CFU per milliliter). The most frequently isolated microorganism was the lactobacillus (aerobic and anaerobic species) followed by C. vaginale, viridans streptococci, anaerobic gram-positive cocci, and Bifidobacterium sp. Bacteroides fragilis was not isolated. There were no significant differences in the frequency of isolation of any specific microorganism or bacterial counts between pregnant and nonpregnant women or between pregnant women with and without gonorrhea (p greater than 0.05), except pregnant patients had significantly higher total facultative counts associated with significantly lower anaerobic lactobacilli counts and higher C. vaginale counts (p less than 0.01) than in nonpregnant patients.

Actinomycetaceae↗

In vitro activity and clinical efficacy of clindamycin in the treatment of infections due to anaerobic bacteria.

Clindamycin, rosamicin, josamycin, and metronidazole had similar inhibitory activity against 29 clinical isolates of Bacteroides fragilis, i.e., 100% of strains were inhibited by 0.8 microng of metronidazole or josamycin/ml and 100% by 1.6 microng of clindamycin or rosamicin/ml. Metronidazole was bactericidal against 97% of the isolates, and clindamycin or rosamicin (in concentrations of 1.6 microng/ml) was bactericidal against 80%. Erythromycin and josamicin were the least bactericidal agents in vitro. Thirty-two patients with pleuropulmonary and intraabdominal or pelvic infections caused by anaerobic bacteria were treated with clindamycin. Cure was achieved in 27 patients. In another group of 37 patients treated with parenteral clindamycin, diarrhea developed in 30% and was significantly more common in those patients with abdominal or pelvic infection. Only one patient developed pseudomembranous colitis. These observations suggest that clindamycin is an excellent and relatively safe antibiotic for treatment of infections caused by anaerobes when combined with surgery or with other antibiotics selected for activity against aerobic gram-negative bacilli.

Aminoglycosides↗

In vitro activity of cefaclor, a new orally administered cephalosporin antibiotic.

The in vitro antibacterial activity of cefaclor, cephalothin, and cephalexin against 261 clinical isolates of Staphylococcus aureus and Enterobacteriaceae was compared. Cefaclor and cephalexin were about equally active against S. aureus. Cefaclor was the most active cephalosporin against Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. The effect on the antimicrobial activity using a relatively high and low inoculum was pronounced for cefaclor when compared with that of cephalothin.

Bacteria↗

Experimental Bacteroides fragilis endocarditis in rabbits.

A serum-resistant strain of Bacterioides fragilis that did not produce heparinase was used to study the characteristics of B. fragilis endocarditis in the rabbit experimental model. The infective dose required to produce endocarditis in 50% of rabbits was significantly lower for rabbits with left-sided intracardiac catheters (log10 6.3 colony-forming units +/- 0.6/ml) as compared with right-sided intracardiac catheters (log10 7.7 colony-forming units +/- 0.8/ml). After 3 days of infection, bacterial titers of the tricuspid vegetations were significantly lower than titers of aortic vegetations (P less than 0.01), although at 5 days the titers were similar (P greater than 0.05). The weights of tricuspid vegetations, although similar at 3 days (P less than 0.05). There were no spontaneous deaths during 12 days of infection. In rabbits with the catheter removed before infection, bacterial titers were similar to those titers in rabbits with the catheter continuously in place. This model will permit study of various drug regimens for treatment of this disease.

Anaerobiosis↗