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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 mannosebinding 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.

We used a β-lactamase-producing (βL+) 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 βL+-infected rats treated with procaine penicillin alone, unlike the sustained levels of penicillin in either βL−-infected rats treated with procaine penicillin or βL+-infected rats treated with penicillin plus clavulanic acid. For the βL+-infected rats, the enterococcal counts in vegetations were significantly reduced (>3 log10 cfu/g) only by vancomycin and by pencillin 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 βL+ strain. Our in vivo findings document the biologic significance of β-lactamase production.

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 (α-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.

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.