Studies were undertaken to investigate the relationship of the sensitivity of Escherichia coli to the bactericidal properties of serum and the ability of different strains to induce and sustain endocardial infection in rats. Strains of E. coli demonstrated different degrees of serum sensitivity, as determined by a method which employed concentrations of serum from 10 to 95% and periods of incubation as long as 24 h. The greater the serum sensitivity of the E. coli strain, the less able it was to initiate infection and the more rapidly it was spontaneously eliminated from established infections. Endocardial infection with E. coli was established by intravenous challenge in rats with polyethylene catheters passing through the aortic valve into the left ventricle. An E. coli strain of low serum sensitivity was used; the initiation of infection depended upon the length of time the catheter had been in place and, in addition, whether the catheter was in place at the time of bacterial challenge. Removal of the catheter permitted spontaneous sterilization of the endocardial vegetations. The time necessary for sterilization was in direct proportion to the length of time the catheter remained in place following bacterial challenge. If the catheter was not removed, sterilization of the endocardial vegetations did not take place. These studies suggest that serum bactericidal activity is an important host defense mechanism, acting to prevent the initiation of endocarditis in the case of highly serum-sensitive E. coli and to sterilize experimentally induced endocarditis in the case of less-serum-sensitive bacteria. The catheter used to induce nonbacterial endocardial vegetations favored the colonization of vegetations by E. coli, and it delayed the spontaneous sterilization of infected vegetations which occurred in relation to the susceptibility of the strain to the bactericidal properties of the serum. This effect of the catheter was not attributable to bacteria remaining viable in its lumen, nor was it attributable to inhibition of the bactericidal capacity of the serum as measured in vitro. Whatever the mechanism responsible for the catheter effect, experimental studies of the evolution of infections established with this technique must take into consideration the duration of catheter placement and whether and for how long it was present before or after inoculation with test bacteria.

Journal Article Strain-Dependent Difference in Susceptibility of Mice to Experimental Ascending Pyelonephritis Get access Phyllis A. Guze, Phyllis A. Guze Please address requests for reprints to Dr. Phyllis A. Guze, West Los Angeles Veterans Administration Medical Center, Department of Medicine (WIII), Wilshire & Sawtelle Boulevards, Los Angeles, California 90073. Search for other works by this author on: Oxford Academic PubMed Google Scholar George M. Kalmanson, George M. Kalmanson Search for other works by this author on: Oxford Academic PubMed Google Scholar Kenji Ishida, Kenji Ishida Search for other works by this author on: Oxford Academic PubMed Google Scholar Lucien B. Guze Lucien B. Guze Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 156, Issue 3, September 1987, Pages 523–525, https://doi.org/10.1093/infdis/156.3.523 Published: 01 September 1987 Article history Received: 15 December 1986 Revision received: 14 April 1987 Published: 01 September 1987

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.

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.

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.

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.

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.

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.

In a previous study, 88% of rabbits with disseminated infection caused by Candida albicans developed ophthalmoscopically visible, hematogenous endophthalmitis (chorioretinitis) over a 2 week period. To determine the incidence of this ocular complication in disseminated infection caused by Cryptococcus neoformans, Candida glabrata, and Aspergillus fumigatus compared with that caused by C. albicans, the first three species of fungi were injected intravenously (between 10(5) and 10(9) organisms per animal) into 36 New Zealand white rabbits. No chorioretinal lesions were seen by indirect ophthalmoscopy over a 2 week period. C. glabrata and A. fumigatus were not cultured from chorioretinas despite positive cultures from brains and kidneys at 1 and 2 weeks. In contrast, C. neoformans was cultured from 12 of 18 chorioretinas. (mean Log10 3.45 colony forming units/gm of tissue) as well as from the brains and kidneys. The less intense inflammatory cell response to C. neoformans compared with that 10 C. albicans seen on histopathologic examination most likely explains the nondetectability of the cryptococcal chorioretinitis by indirect ophthalmoscopy. These data suggest that C. glabrata. A. fumigatus, and possibly C. neoformans have less ocular pathogenicity than C. albicans in rabbits and correlate with the small number of documented human cases of ophthalmoscopically visible hematogenous endophthalmitis caused by fungi other than C. albicans.

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.

Several neurologic syndromes (including Guillain-Barré) complicated Mycoplasma pneumoniae pneumonitis in a young man. At onset of neurologic disease, buffy coat and cerebrospinal fluid cultures on inert media were negative for M. pneumoniae. However, metabolically active mycoplasma were identified in both body fluids by enhanced uptake of 14C-uracil versus 3H-uridine, with marked reduction in normal uridine-to-uracil uptake ratios (> 1000:1) in tissue culture. Uridine-to-uracil ratios were 8.5:1 and 15:1 for buffy coat and cerebrospinal fluid, respectively. Indirect fluorescent antibody (FA) studies confirmed the species as M. pneumoniae. In convalescence, uridine-to-uracil ratios and FA studies of buffy coat normalized, indicating clearance of M. pneumoniae from blood. Cell lines inoculated with "convalescent" cerebrospinal fluid showed slightly increased uracil uptake, slightly decreased uptake ratios, and persistent FA staining of approximately 5% of cells, indicating incomplete clearance of M. pneumoniae. Immune complexes were undetectable in either buffy coat or spinal fluid. This indicates that certain M. pneumoniae-associated neurologic disorders may be related to direct neural infection and not immunologically mediated as has been suggested.

By using a recently developed rabbit model, we examined the efficacy of relatively low-total-dose intravenous amphotericin B (Am-B; 7 to 14 mg/kg) in the treatment of intraabdominal candidiasis due to Candida albicans. Forty-eight percent of the rabbits developed evidence of hematogenously disseminated infection (Candida endophthalmitis) before therapy. By day 7 of therapy, there was a significant decrease in the mean log10 colony-forming units per gram of peritoneal abscess in comparison with both pretherapy cultures and concomitantly sacrificed controls (no Am-B treatment; P less than 0.25). By day 11 of therapy, peritoneal abscesses were sterilized by Am-B, whereas control rabbit cultures remained positive. In contrast, low-dose Am-B therapy produced no significant decrease in colony-forming units per gram of renal or chorioretinal abscess in rabbits which developed hematogenously disseminated candidiasis. Serum Am-B levels approached or exceeded the minimal fungistatic concentrations for this C. albicans strain in most animals tested. Low-dose Am-B was effective in eradicating intraabdominal candidiasis, but was not curative when extraperitoneal dissemination occurred.

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.