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Biomedical subjects

M E Levison

Publications and source records attributed to M E Levison.

At least 19 recordsLinked to original sources

Bactericidal activity of ramoplanin against antibiotic-resistant enterococci.

Ramoplanin, a new lipoglycodepsipeptide antibiotic, was uniformly active against 65 strains of enterococci, including strains highly resistant to vancomycin, penicillin G, and gentamicin. MBCs were usually within a fourfold dilution of the MICs. In time-kill studies, ramoplanin alone demonstrated dose-dependent bactericidal activity against enterococcal strains that resisted killing by vancomycin or penicillin in combination with gentamicin.

Anti-Bacterial Agents

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

Effect of aspirin on thrombogenesis and on production of experimental aortic valvular Streptococcus viridans endocarditis in rabbits.

Because thrombus formation at the site of endothelial injury has been thought to be a critical step in the pathogenesis of bacterial endocarditis, the effect of aspirin on experimental valvular thrombosis and bacterial endocarditis in rabbits was evaluated. Aortic valvular injury and thrombosis were induced in aspirin-treated and control rabbits with intracardiac catheters. A subsequent inoculation of Streptococcus viridans resulted in the development of infective endocarditis. Rabbits were sacrificed as early as 6 hr, and the effectiveness of aspirin was determined by the weight of the sterile vegetations and the quantitation of bacteria in the thrombotic vegetation. Aspirin, in levels in excess of 50 mg/dl did not attenuate the evolution of infective endocarditis, since the formation of sterile thrombotic vegetation and bacterial endocarditis in aspirin-treated rabbits was similar to those in controls.

Animals

In vitro activity of josamycin and rosamicin against Bacteroides fragilis compared with clindamycin, erythromycin, and metronidazole.

The inhibitory and bactericidal activities of josamycin and rosamicin against 29 clinical isolates of Bacteroides fragilis were compared with those of clindamycin, erythromycin, and metronidazole by a broth dilution technique. Josamycin and rosamicin had similar inhibitory activity to metronidazole and clindamycin. Rosamicin had similar bactericidal activity to clindamycin but was less bactericidal than metronidazole (the most bactericidal agent tested). Josamycin was slightly more bactericidal than erythromycin (the least bactericidal agent tested), but less so than rosamicin and clindamycin.

Aminoglycosides

A quantitative measurement of bacteremia and its relationship to plaque control.

Despite the improvement in the patients' oral hygiene, there was no significant decrease in the frequency of bacteremia. There was no significant difference in bacteremia between brushing, flossing, or deplaquing either before or after initial periodontal preparation and plaque control in 21 healthy subjects. Utilizing more sophisticated bacteriologic techniques for the cultivation of obligate anaerobes, a relatively high frequency of anaerobic bacteremia was found.

Bacteria

Effect of indomethacin and sodium meclofenamate on the renal concentrating defect in experimental enterococcal pyelonephritis in rats.

The present studies have confirmed a severe urinary concentrating defect early in the course of experimental enterococcal pyelonephritis. This defect in maximum concentrating ability was almost completely reversed immediately following indomethacin or sodium meclofenamate intravenously. This effect of indomethacin and sodium meclofenamate was transient and was not associated with a fall in numbers of enterococci per gram of kidney. Injection of indomethacin or sodium meclofenamate in noninfected rats had no effect on maximum renal concentrating ability. The potential mechanisms by which indomethacin and sodium meclofenamate, inhibitors of renal prostaglandin synthesis, could reverse a defect in maximum urinary concentration are discussed.

Animals

Sustained bacteremia and transvenous cardiac pacemakers.

Five patients with transvenous cardiac pacemakers had sustained staphylococcal bacteremia (defined as bacteremia for at least 12 hours) two weeks to ten months after pacemaker insertion. Three of the five patients had no evidence of an extravascular focus of infection at the time of stphylococcal bacteremia. An additional patient had a petechial rash, which is unusual in staphylococcal bacteremia, unless endocarditis is present. All patients were treated with antibiotics and drainage of the pacemaker packet when it was infected, removal of the pacemaker generator, or removal of the catheter electrode. One patient without evidence of pocket infection was treated successfully with antibiotic therapy alone.

Acute Disease