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Biomedical subjects

M E Levison

Publications and source records attributed to M E Levison.

At least 55 records · Page 3Linked to original sources

Susceptibility to experimental Candida albicans urinary tract infection in the rat.

The urinary tract is resistant to ascending infection due to Candida albicans. Host and microbial factors that may alter such resistance were evaluated in the rat after inoculating C. albicans into the urinary tract. Diuresis, diabetes, candidal germ-tube formation, and vaginal Candida colonization (alone or in concert) failed to promote ascending urinary tract infection with two vaginal isolates of C. albicans capable of producing renal infection by the hematogenous route. Both germinated and ungerminated Candida adhered poorly to bladder mucosa. Unlike prior urinary tract infection due to an enterococcus that failed to agglutinate Candida in vitro, prior urinary tract infection with a mannose-binding strain of Escherichia coli that agglutinated C. albicans in vitro enhanced adherence of C. albicans to bladder mucosa and increased susceptibility to ascending C. albicans urinary tract infection. Thus, resistance to Candida ascending urinary tract infection is likely to be due to poor adherence of C. albicans to normal bladder mucosa.

Animals↗

beta-Lactamase production in experimental endocarditis due to aminoglycoside-resistant Streptococcus faecalis.

We used a beta-lactamase-producing (beta L+) strain of Streptococcus faecalis that also had high levels of resistance to all aminoglycosides to induce experimental endocarditis in rats. The rats were treated for five or 10 days with procaine penicillin, vancomycin, gentamicin, rifampin, or ciprofloxacin (alone or in various combinations), or with penicillin plus clavulanic acid. The levels of penicillin in serum and vegetations declined rapidly in the beta L+-infected rats treated with procaine penicillin alone, unlike the sustained levels of penicillin in either beta L- -infected rats treated with procaine penicillin or beta L+-infected rats treated with penicillin plus clavulanic acid. For the beta L+-infected rats, the enterococcal counts in vegetations were significantly reduced (greater than 3 log10 cfu/g) only by vancomycin and by penicillin plus clavulanic acid. The efficacy of the latter regimen probably resulted from the inhibition of penicillin inactivation by clavulanic acid in vegetations infected with the beta L+ strain. Our in vivo findings document the biologic significance of beta-lactamase production.

Aminoglycosides↗

Epidemiology of bacteriuria in an elderly ambulatory population.

This study of bacteriuria in elderly (mean age 85 years, range 68 to 103) Jewish subjects of mostly middle and upper class attempted to determine disease prevalence, define the turnover in infected subjects, and assess the relation between functional status and infection. The prevalence of bacteriuria (midstream clean-catch method) was assessed in 373 women and 150 men. It was higher in women (18.2 percent) than in men (6.0 percent) (p less than 0.001) and was more common in functionally impaired nursing home residents (23.5 percent) than in apartment house dwellers (12.1 percent) (p less than 0.01). In longitudinal studies, 260 subjects (184 women and 76 men) had three urine culture surveys at six-month intervals. The cumulative percent infected on at least one survey was high (women 30.4 percent, men 10.5 percent). However, persistence of the same organism on all three surveys was surprisingly infrequent (women 6.0 percent, men 1.3 percent), and the turnover of infected and noninfected subjects was considerable. Persistence of bacteriuria on all three surveys was significantly more common in nursing home residents (13.9 percent) than in apartment house dwellers (3.1 percent) (p less than 0.01). Thus, bacteriuria is common in the elderly and appears related to functional status. However, the turnover of infected and noninfected subjects was high, and surprisingly, persistence was not found in most. The transient nature of bacteriuria in most provides support against the treatment of asymptomatic bacteriuria in the elderly.

Activities of Daily Living↗

Lack of association between bacteriuria and symptoms in the elderly.

In a study of bacteriuria in elderly (mean age 85 years, range 69 to 101), mostly middle- and upper-class Jewish subjects, attempts were made to determine if bacteriuria without dysuria is otherwise asymptomatic. Seventy-two subjects (59 women and 13 men) without dysuria were questioned about other urinary symptoms (incontinence, frequency, urgency, suprapubic pain, flank pain, fever) and symptoms indicating a lack of well-being (anorexia, difficulty in falling asleep, difficulty in staying asleep, fatigue, malaise, weakness) when they were with and without bacteriuria. Twenty-two subjects had bacteriuria that resolved spontaneously; bacteriuria subsequently developed in 24 nonbacteriuric subjects; and 26 subjects had bacteriuria that resolved with antimicrobial therapy. Subjects occasionally reported urinary symptoms (especially incontinence) and commonly reported symptoms indicating a lack of well-being when they were with and/or without bacteriuria. However, no differences in symptoms were found when bacteriuric subjects were compared with themselves when they were nonbacteriuric. Thus, bacteriuria without dysuria in the elderly appears to be asymptomatic.

Aged↗

The importance of pharmacodynamics in determining the dosing interval in therapy for experimental pseudomonas endocarditis in the rat.

The efficacy of ciprofloxacin, BMY-28142, and ceftazidime was compared in vitro and in experimental left-sided endocarditis due to Pseudomonas aeruginosa in the rat. The dose, dosing interval, and duration of therapy were varied, and the resulting antibiotic levels in serum and vegetations were correlated with bacterial clearance from vegetations. These studies demonstrated that beta-lactams such as BMY exhibited a slow rate of bactericidal action and had no postantibiotic effect against P. aeruginosa in vitro or in vivo. As a consequence, BMY had to be given in multiple doses at relatively short intervals during which concentrations of antibiotics in vegetations were continuously in excess of the MBC for the pathogen. The earlier onset of rapid bactericidal action and the prolonged postantibiotic effect of ciprofloxacin (demonstrated in vivo and in vitro) were, in all likelihood, the factors that allowed the successful use of fewer doses of this antimicrobial agent at relatively longer dosing intervals.

Animals↗

Comparison of two beta-lactamase-producing strains of Streptococcus faecalis.

A second strain of enterococcus (PA) producing beta-lactamase (Bla+ phenotype) was compared with the previously reported Bla+ enterococcus, strain HH22. As with the original strain, there was a marked inoculum effect when PA was tested with penicillin, ampicillin, and piperacillin; no difference was noted with methicillin, cephalothin, imipenem, or vancomycin; the difference with ticarcillin was intermediate. High-level gentamicin resistance (Gmr) transferred from PA to an enterococcal recipient strain at a frequency approximately 100-fold lower than for HH22; all Gmr transconjugants from both strains were Bla+, but only PA showed linkage of Gmr and Bla+ with transfer of resistance to streptomycin, tetracycline, and chloramphenicol. EcoRI digestion of plasmid DNA from Gmr Bla+ transconjugants showed no similarities between the two strains. A 5.1-kilobase EcoRI Bla+-encoding fragment derived from HH22 was cloned into an Escherichia coli cloning vector and shown to hybridize to a 10.2-kilobase EcoRI fragment derived from PA; both fragments hybridized to an 840-base-pair staphylococcal Bla+ gene probe. These data indicate that the penicillinases are similar but encoded on different or differently arranged plasmids. The fact that both are transferable emphasizes the potential for this new streptococcal resistance determinant to disseminate.

Anti-Bacterial Agents↗

Effect of insulin treatment on the susceptibility of the diabetic rat to Escherichia coli-induced pyelonephritis.

Escherichia coli-induced pyelonephritis was studied in untreated alloxan-diabetic rats, insulin-treated diabetic rats, glucose water-drinking (diuresing) nondiabetic rats, and tap water-drinking (nondiuresing) nondiabetic rats following injection of E. coli either into the emptied urinary bladder, into the left kidney, or intravenously. For prevention of an ascending infection in the right kidney, the right ureter was ligated and transected immediately prior to bladder or intrarenal inoculation. These experiments established that in normal rats ascending renal infection alone occurred following introduction of small inocula into the bladder--and then only when facilitated by diuresis. In diabetic rats both ascending and hematogenous renal infection occurred following introduction of small inocula into the bladder. Insulin treatment that reduced hyperglycemia also reduced glycosuria and restored urinary antibacterial activity against small inocula of E. coli but only partially reduced polyuria and prevented hematogenous but not ascending infection. Thus, hyperglycemia was probably the major factor promoting hematogenous renal infection, whereas polyuria--and therefore vesicoureteral reflux--was the major factor promoting ascending infection.

Animals↗

Mezlocillin and ticarcillin alone and combined with gentamicin in the treatment of experimental Enterobacter aerogenes endocarditis.

The efficacies of mezlocillin and ticarcillin, each alone and in combination with gentamicin, in the therapy of experimental left-sided Enterobacter aerogenes endocarditis in rabbits were compared. Each beta-lactam was administered intramuscularly at a dose of 180 mg/kg every 6 h either alone or with gentamicin (1.7 mg/kg intramuscularly every 8 h). Bacterial populations at the start of therapy (7 days after initiation of infection) were 9 to 10 log10 CFU/g of vegetation. Ticarcillin produced concentrations in serum that were twice those produced by mezlocillin, but the therapeutic ratios of mezlocillin and ticarcillin (ratio of peak level in serum to MBC) were the same. All of the therapeutic regimens given for either 5 or 10 days were effective in reducing vegetation counts when compared with the untreated controls (P less than 0.01 for all comparisons), except mezlocillin alone and ticarcillin alone, which caused insignificant reductions in counts after 5 days of therapy (P greater than 0.05). After 10 days of therapy, the only regimen that was significantly different from another was that of mezlocillin plus gentamicin, which was significantly better than that of ticarcillin alone (P less than 0.01). These studies document that mezlocillin and ticarcillin were both effective in reducing the numbers of E. aerogenes CFU in vegetations in rabbits with experimental endocarditis when the drugs were given over a prolonged course. More rapid and extensive reduction in vegetation counts was achieved with combinations of an aminoglycoside plus mezlocillin or ticarcillin. Mortality was significantly less among rabbits treated with mezlocillin plus gentamicin.

Animals↗

Pharmacokinetics of cefoperazone in normal subjects and patients with hepatosplenic schistosomiasis.

The pharmacokinetics of cefoperazone were studied and compared in four normal subjects and six patients with hepatosplenic schistosomiasis (HSS) with mild liver disease but marked portal hypertension. All subjects received a 2 g intravenous infusion of cefoperazone over 15 min. Although most pharmacokinetic parameters did not differ significantly between normal subjects and patients with HSS, the serum beta half-life of cefoperazone was longer in patients with HSS compared to normal subjects (3.0 h vs. 1.7 h). This demonstrates only mild impairment of excretion of cefoperazone in patients with HSS.

Adult↗

Cefoperazone pharmacokinetics in normal subjects and patients with cirrhosis.

The pharmacokinetics of cefoperazone were studied and compared in six normal subjects and six patients with severe liver disease. All subjects received a 2-g intravenous infusion of cefoperazone over 15 min. Significantly different results were noted between normal subjects and patients with cirrhosis (range [mean]) for the following: peak serum concentrations (203 to 345 [239] versus 82 to 206 [141] micrograms/ml; P less than 0.01); serum beta half-lives (1.0 to 1.8 [1.5] versus 2.3 to 9.9 [4.5] h; P less than 0.05); renal excretion (17 to 27 [21] versus 32 to 60 [50]%; P less than 0.01); and apparent volumes of distribution at steady state (4.1 to 7.8 [6.3] versus 12.7 to 23.8 [15.9] liters/1.73 m2; P less than 0.01). Lower peak serum levels in the patients with cirrhosis were probably related to an increased apparent volume of distribution secondary to ascites and to decreased serum protein binding of cefoperazone. Longer beta half-lives in the patients with cirrhosis were probably secondary to both decreased hepatic excretion caused by severe liver disease and to increased apparent volume of distribution. However, the longest beta half-life among the patients with cirrhosis was in a subject with a serum creatinine level of 2.1 mg/dl. We conclude that, although mild to moderate impairment of cefoperazone excretion occurs in patients with hepatic disease, adjustment of dosage may be necessary only with concomitant renal insufficiency.

Adult↗

Single-dose cefonicid therapy for urinary tract infections.

The efficacy of single-dose therapy with cefonicid (1 g intramuscularly) and multidose therapy with amoxicillin (500 mg orally three times a day for 7 days) was compared for the treatment of uncomplicated lower urinary tract infection in women. Of 50 patients with symptoms of lower urinary tract infection randomized to receive either cefonicid or amoxicillin, 39 were infected with greater than or equal to 10(5) bacteria per ml. At early posttherapy follow-up (5 to 18 days), 19 of 21 (90%) cefonicid-treated patients and 16 of 18 (89%) amoxicillin-treated patients were cured. At late posttherapy follow-up (6 to 7 weeks), 16 of 18 (89%) cefonicid-treated patients and 14 of 15 (93%) amoxicillin-treated patients were cured. One patient was lost to follow-up in each late follow-up group. There were fewer side effects in the cefonicid-treated group. There were significantly more organisms resistant to amoxicillin than to cefonicid in the study population. Considering the small size of the series, single-dose therapy with cefonicid for lower urinary tract infection in women appears to be as safe and effective as conventional multidose therapy with amoxicillin.

Adult↗

Clindamycin compared with penicillin for the treatment of anaerobic lung abscess.

The clinical efficacy of clindamycin was compared with that of penicillin in a randomized study of the treatment of community-acquired putrid lung abscess. After starting therapy, patients treated with clindamycin had a shorter febrile period and fewer days of fetid sputum than patients treated with penicillin (mean 4.4 versus 7.6 days and 4.2 versus 8.0 days, respectively, p less than 0.05). Four of 20 patients treated with penicillin had clinically significant pulmonary or pleural extension of their infection within 10 days after starting therapy; this was not found in any of 19 patients treated with clindamycin (p less than 0.05). Penicillin treatment failed in two additional patients after 20 days of therapy. Within 1 month after treatment, 1 of 4 patients given penicillin for 3 weeks had relapse, but none of the 13 patients given clindamycin for 3 or 6 weeks, and none of the 5 patients given penicillin for 6 weeks had relapse. Overall, only 8 of 15 patients treated with penicillin who could be followed to the end of the study were cured, whereas all 13 patients treated with clindamycin who could be followed were cured (p less than 0.01). These results suggest that penicillin may not be optimal therapy for anaerobic lung abscess.

Adult↗

Comparison of bacterial and fungal adherence to vaginal exfoliated epithelial cells and human vaginal epithelial tissue culture cells.

The adherence of four bacterial species and Candida albicans to a new in vitro tissue culture model of human vaginal stratified squamous epithelium was investigated and compared with in vitro adherence to vaginal exfoliated cells. Gardnerella vaginalis, group B streptococci, Lactobacillus sp., and C. albicans adhered well to both exfoliated and tissue culture cells. Similarly, a piliated fecal isolate of Escherichia coli, but not a nonpiliated vaginal isolate of E. coli, adhered well to both cell types. Adherence of the piliated E. coli was markedly inhibited by preincubation of bacteria with D-mannose. No inhibition of adherence by D-mannose of G. vaginalis, nonpiliated E. coli, and C. albicans was demonstrated. Scanning electron microscopy of tissue cultures showed nonuniform distribution of adherent microorganisms with diminished adherence in areas of active mitosis and proliferation and increased adherence to mature flat cells, often in the process of desquamation.

Adhesiveness↗

Free water reabsorption during saline diuresis in experimental enterococcal pyelonephritis in rats.

Inability to attain Umax after overnight dehydration is the earliest functional abnormality in human and experimental pyelonephritis caused by diverse microorganisms. In order to characterize the defect in Umax in experimental enterococcal pyelonephritis, another index of renal concentrating ability. TcH2O, was determined during saline loading. Normal TcH2O depends on adequate sodium chloride delivery and reabsorption in the ascending limb of Henle's loop and water reabsorption from the collecting duct. Rats with early pyelonephritis, 3 days after intravenous injection of enterococci, were compared with normal rats in studies of Umax during hydropenia and TcH2O during 1.2% saline infusion. Mean Umax in infected rats was significantly lower than in uninfected rats (1120 vs. 2767 mOsm/kg H2O) (p less than 0.01), but CIn in infected rats was not significantly different from that in uninfected rats (0.96 vs. 0.89 ml/min per 100 gm) (p less than 0.05). During saline diuresis, maximal Cosm/CIn was more than 35% in both the normal and infected rats. The relationship between TcH2O/CIn and Cosm/CIn was linear in both groups, and the r, slope, any y intercept of the regression equation of TcH2O/CIn vs. Cosm/CIn in infected rats were not significantly different from those in normal rats. During saline diuresis the regression of sodium excretion UNaV/CIn) vs. Cosm in infected rats was not significantly different from that in control rats. The finding of normal TcH2O during saline loading suggests that reabsorption of increasing amounts of sodium chloride from the ascending limb of Henle's loop and reabsorption of water in the collecting duct are normal in early pyelonephritis.

Animals↗

Adherence of Candida albicans to human vaginal and buccal epithelial cells.

Factors that may influence adherence of Candida albicans to exfoliated human vaginal and buccal epithelial cells were studied in vitro. Factors that enhanced germination enhanced adherence. Heat-killed, germinated Candida organisms demonstrated poorer adherence than viable Candida organisms and no better adherence than nonviable, ungerminated Candida organisms. The difference between adherence of C. albicans to buccal epithelial cells and that to vaginal epithelial cells was significant, as were differences among volunteers. Preincubation in fucose but not mannose, glucose or galactose solutions, preincubation of germinated yeast or of epithelial cells in chymotrypsin or trypsin, a culture supernatant of germinated yeast killed by ultraviolet light, or precoating of epithelial cells with lactobacilli each inhibited adherence. These studies indicate that adherence of C. albicans is enhanced by a surface component of germinated yeast, probably a surface protein that binds to the epithelial receptor, possibly a glycoprotein.

Adult↗

Minimal concentrations of aminoglycoside that can synergize with penicillin in enterococcal endocarditis.

Minimal concentrations of aminoglycoside that could produce a synergistic effect with penicillin were investigated in broth cultures containing 10(8) enterococci per ml, in vitro in vegetations infected with ca. 10(8) enterococci per g, and in vivo in an experimental model of enterococcal endocarditis. Penicillin G plus gentamicin (1.5 or 0.75 microgram/ml) sterilized a broth culture of a streptomycin-resistant strain (E1) at 48 h. In contrast, penicillin G plus gentamicin (1.5 or 0.75 microgram/ml) sterilized only 2 of 15 in vitro vegetations at 5 days. Similarly, doses of gentamicin that resulted in peak serum levels of 1.5 microgram/ml failed after 10 days of therapy with penicillin G plus gentamicin to sterilize in vivo vegetations infected with E1, and doses of gentamicin that resulted in peak serum levels of about 8 micrograms/ml sterilized four of six vegetations. Similar results were obtained with a streptomycin-susceptible strain. These studies indicated that the rate of bactericidal activity in broth cultures is greater than the bacteriological response in infected vegetations and that aminoglycoside concentrations that appear efficacious on the basis of synergy studies in broth cultures may not be satisfactory clinically.

Aminoglycosides↗