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Clinical isolates of Escherichia coli were examined for the presence of hydroxamate siderophore (aerobactin). The incidence of aerobactin-positive strains of E. coli from the blood was greater than the incidence of these strains isolated from other sites. The presence of aerobactin and the virulence of strains of E. coli in urinary tract infection were also examined in mice. The presence of aerobactin in the strains of E. coli correlated with virulence as measured by proportion of deaths but not with renal infection. These results suggest that the presence of aerobactin may be a significant factor in the invasion of the blood stream.

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The course of experimental hematogenous pyelonephritis due to Streptococcus faecalis was compared in athymic (nu/nu) mice and euthymic (nu/+) littermates. Up to 7 weeks following infection, there were no significant differences in renal microbial populations. At 63 and 107-131 days there was significant escalation of infection in nu/nu mice, while the nu/+ mice were decreasing their infections. There was no increase in gross abscess formation in nu/nu mice, but in late stages significantly more gross scarring occurred in nu/nu as compared with nu/+ mice. Microscopically there was also greater scarring in nu/nu mice late in the disease, except for calyceal lesions. The data suggest that immunologic factors (T cells) are involved in the pathogenesis of chronic pyelonephritis.

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The therapeutic efficacy of N-formimidoyl thienamycin alone or coadministered with MK0791, an inhibitor of renal dehydropeptidase-I, compared to methicillin in experimental pyelonephritis in rats was investigated. Pyelonephritis was produced with a methicillin-sensitive strain (2776) and a methicillin-resistant strain (Berman) of Staphylococcus aureus. N-formimidoyl thienamycin alone or coadministered with the inhibitor was significantly better than methicillin when treating methicillin-sensitive or methicillin-resistant infection. There was a trend suggesting that N-formimidoyl thienamycin coadministered with MK0791 was overall the best agent. These studies show that N-formimidoyl thienamycin is efficacious in the treatment of S. aureus pyelonephritis in the rat regardless of methicillin sensitivity, and this agent plus the dehydropeptidase inhibitor should be considered in the treatment of such infections.

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This report describes the capacities of ampicillin, vancomycin, streptomycin, gentamicin, and combinations thereof to prevent endocarditis in rabbits challenged with either streptomycin-resistant (three strains) or streptomycin-susceptible (one strain) Streptococcus faecalis. Vancomycin (15 mg/kg) alone was effective in preventing infection with three of four strains, including two which were streptomycin resistant. Vancomycin (30 mg/kg) alone was effective against the other streptomycin-resistant strain. The vancomycin-gentamicin combination was the only therapeutic regimen to demonstrate complete prophylaxis for all strains regardless of streptomycin susceptibility. The ampicillin-gentamicin combination was variably effective despite in vitro synergism.

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The role of pili as a bacterial virulence factor has been studied. The model used was acute ascending Escherichia coli pyelonephritis in the mouse. Three strains of E. coli were injected in lightly or more heavily piliated phases into 15 mice each. At sacrifice of 13-15 animals 2 weeks later, no significant difference in severity of pyelonephritis was found as judged by numbers of bacteria in the kidney, nor intensity or frequency of gross abscesses. 27 strains of E. coli were order ranked for severity of pyelonephritis produced and compared with intensity of piliation in vitro under conditions designed to maximize pilus formation. No significant difference was found. 15 strains derived from patients in whom infections were confined to the bladder were compared for degree of piliation with 12 strains infecting the kidney. No significant difference was found. These studies do not support a significant role for the degree of piliation as a virulence factor in pyelonephritis.

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Administration of iron to rats exacerbated early inflammatory changes of pyelonephritis produced by intravenous inoculation of Escherichia coli. This effect was noted with four of eight strains of E. coli tested and was dependent on bacterial inoculum. Despite this increase in severity of acute pyelonephritis as judged by numbers of bacteria in the kidney and careful gross and microscopic evaluation, there was no enhancement of chronic changes seen 6 months later.

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Certain technical considerations which affected the status of methicillin tolerance in Staphylococcus aureus strains were studied. Methods which consistently demonstrated tolerance or intolerance of a given strain were avoidance of inoculum splashing, use of stationary-phase inoculum, 24-h tube incubation, and minimization of antibiotic carry-over. These studies suggested a need for the establishment of a standardized reference for the determination of tolerance.

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The effect of tolerance to methicillin on the response to treatment of hematogenous pyelonephritis due to Staphylococcus aureus was evaluated in rats. Tolerance was defined as a ratio of minimal bactericidal concentration to minimal inhibitory concentration of greater than or equal to 32. Rats that were infected with tolerant or nontolerant stains of S. aureus were treated with methicillin with equal success as judged by the number of bacteria in the kidneys and the proportion of rats with infected kidneys. In this animal model, tolerance does not play a role in the outcome of treatment.

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The activities of ampicillin, rifampin, streptomycin, and their combinations were evaluated in vitro against Streptococcus faecalis strain GK and in vivo in rats with an established pyelonephritis resulting from challenge with this same enterococcus. In vitro synergy was demonstrated between all combinations. Comparison of the log colony-forming units of S. faecalis recovered per gram of kidney tissue showed that all treated groups had significant lower numbers than controls (P less than 0.001). Ampicillin plus streptomycin or ampicillin alone was superior to rifampin alone or rifampin plus streptomycin at each interval (P less than 0.001). There was no significant difference between ampicillin and rifampin plus ampicillin. The disparity between in vitro and in vivo results again raises some doubts as to the relevance of in vitro observations to clinical outcome.

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Adherence of E. coli to bladder cells was studied by mixing E. coli with cells scraped from the surface of the normal mouse bladder. E. coli adherence to bladder epithelium did not correlate with renal infection, the ability of E. coli to resist phagocytosis, the growth of the strains, the presence of K-antigen or dulcitol fermentation. There was also no correlation with proportion of deaths, motility, or rough mutation. Pili were observed in three of the 22 strains of E. coli and their presence was not associated with increased virulence. In this model of renal infection neither adherence of E. coli to bladder epithelial cells nor the presence of pili were significant virulence factors.

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The effect of changes in certain physicochemical parameters, analogous to those occurring in the kidney, on stimulation of normal human lymphocytes by phytohemagglutinin was studied. Increase in osmolality by sucrose or urea, and increases in concentration of sodium, potassium and calcium all significantly inhibited stimulation while magnesium did not. Lowering pH to 6.8 and 6.5 inhibited stimulation. Raising the pH to 8.0 had no effect bu at pH 8.4 stimulation was decreased. The effect was largely but not entirely due to decrease in viability.

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L-forms of Streptococcus faecalis, Escherichia coli and Proteus mirabilis showed significantly less chemotactic activity for normal human leucocytes than did parent bacterial forms which were strongly chemotactic. Mycoplasma pneumoniae and Mycoplasma hominis did not demonstrate chemotactic activity.

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A study has been done of immunization against Streptococcus faecalis pyelonephritis in the rat. Intravenous, subcutaneous, and bladder immunizations were tested with intravenous and retrograde challenge. Logarithmic and stationary growth phase organisms were used separately for both immunization and challenge. The only instance of significant, but incomplete, protection was in animals immunized subcutaneously or intravenously and challenged intravenously with log phase organisms. No correlation was found between circulating antibody response and infection. Serum bactericidal activity was not increased by immunization or infection.

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