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The in vitro bactericidal interaction of trovafloxacin and rifampin against Enterococcus spp. has indicated that antagonism occurs between these two antimicrobial agents. This drug combination was examined in vivo in rats with experimental pyelonephritis. The rats received trovafloxacin, rifampin, or both drugs. On the basis of the mean log10 CFU of Enterococcus faecalis from the kidneys, there was no evidence that trovafloxacin and rifampin were antagonistic in vivo.

The activities of trovafloxacin and ciprofloxacin against 38 strains of non-beta-lactamase-producing enterococci, resistant to ampicillin, 34 strains susceptible to ampicillin, and 3 vancomycin-resistant enterococci were studied. Trovafloxacin was more active than ciprofloxacin against all the enterococci studied. The ampicillin-resistant strains were more susceptible than the ampicillin-susceptible strains to both agents. The effect of combining trovafloxacin with gentamicin, ampicillin-sulbactam, novobiocin, rifampin, teicoplanin, and vancomycin was determined for 17 strains by the checkerboard method. An additive effect by inhibition was seen with all antibiotics studied. The results by killing varied with the different agents studied. Gentamicin, ampicillin-sulbactam, and novobiocin produced an additive killing effect with trovafloxacin. Reduced killing was seen when rifampin, vancomycin, or teicoplanin were added to trovafloxacin.

Objectives: The objective of this study was to establish the identity of a protein found in high concentrations in squamous metaplasia of the bladder., Design and Methods: The protein was isolated and subjected to a series of physical, chemical, and catalytic studies., Results: In the normal urothelium the protein was confined to a juxtanuclear pattern on the luminal side of the umbrella cells; in squamous metaplasia and squamous cell carcinoma the protein was increased and exhibited a more diffuse intracellular distribution. The protein was found to be identical to triosephosphate isomerase (EC 5.3.1.1; TPI) with respect to its immunological properties, native and subunit molecular weights, electrophoretic mobility, catalytic activity, and amino acid sequence., Conclusions: While the basis for the altered distribution of TPI remains to be established, the increased amounts of the protein in urine or bladder tissue may be indicative of squamous metaplasia, squamous cell carcinoma, or other bladder injuries.

Antibody to 28 K was used to examine sections of bladder biopsies obtained by cystoscopy from 14 patients with spinal cord injury (SCI). Most of the biopsies were obtained from patients with indwelling catheters during the investigation for possible malignancy. Sections of bladder were stained by the streptavidin procedure. The 28 K in the normal transitional epithelium of the bladder was in the superficial cells (umbrella cells). All the biopsies from patients with indwelling urethral catheters showed areas of squamous metaplasia usually associated with evidence of chronic inflammation. Cystitis cystica glandularis was also seen in one patient. Staining was most marked in the areas of squamous metaplasia with intracellular granular staining. The basal layers were not well stained. With marked squamous metaplasia, there was a superficial hyperkeratotic layer that stained variably and often did not stain at all. Staining was less marked in areas of hyperplasia, regenerating urothelium, and cystitis cystica glandularis. These findings raise the possibility that the presence of 28 K glycoprotein in the tissues or released into the urine may be used as an indicator of squamous metaplasia and chronic inflammation of the bladder.

Urinary tract infection of men with spinal cord injuries has been associated with a high incidence of colonization of the patients with gram-negative bacilli. We have examined the factors influencing colonization of 119 patients with Pseudomonas and Klebsiella and studied methods of reducing this colonization. The urethra, perineum, rectum, and drainage bag of all patients were cultured on selective media at two week intervals until discharge. The use of the external urinary collection system (EUCS) was discontinued in a group of patients at night, in an attempt to reduce colonization. Pseudomonas and Klebsiella were isolated from one or more body sites in 65 percent and 69 percent of total culture days. The urethra, perineum, rectum, and drainage bags were reservoirs of Pseudomonas and Klebsiella in men with spinal cord injuries, even in the absence of urinary tract infections. The EUCS proved to be an important factor influencing colonization. Pseudomonas and Klebsiella colonization was higher in patients using the EUCS. Removal of the EUCS at night reduced urethral colonization with Pseudomonas, but did not significantly reduce urethral colonization with Klebsiella. The prevalence of bacteriuria with Pseudomonas and Klebsiella was not significantly influenced by the use of the EUCS.

We have been investigating the nature of the mucosal lining of human urinary bladder. Surface material was obtained from bladders at autopsy and used for biochemical analysis. Western immunoblotting and tissue immunochemistry identified a molecule of Mr 28,000 (28K) which is present within surface cells of the urothelium (umbrella cells). Antiserum to 28K stained sections of the bladder of two patients with squamous cell carcinoma of the bladder and other patients with squamous metaplasia. We consider 28K to be a component of the normal human bladder surface that is increased in patients with squamous metaplasia and may also be present in squamous cell carcinoma of the bladder.

This study of Pseudomonas aeruginosa and Klebsiella pneumoniae colonization in humans with spinal cord injuries who were using the external urinary collection system showed that meticulous bathing with the bar soap issued by the hospital did not eliminated colonization and was frequently associated with the shifting of these bacteria to adjacent sites on the body. Bacterial counts of the skin showed that bathing did reduce the numbers of P. aeruginosa and K. pneumoniae found on the skin surface and temporarily eliminated these bacteria from some sites. The persistence of these organisms for long periods, even when patients were meticulously bathed, indicates that P. aeruginosa and K. pneumoniae may become part of the resident flora in these patients.

Pseudomonas aeruginosa colonization is found in a high percentage of males with spinal cord injury. The perineum is the body site most frequently colonized, and specific serotypes may persist for weeks. We examined patients for the presence of P. aeruginosa and Klebsiella pneumoniae on the perineum and adjacent body sites by using contact plates. P. aeruginosa, K. pneumoniae, or both were cultured from perineal swabs of 22 male patients. Wells (2.5 cm2) containing agar medium selective for these organisms were used to examine samples from 32 sites adjacent to the perineum in each patient. P. aeruginosa was most frequently cultured from samples taken from the perineum, the scrotum, and the penile shaft. K. pneumoniae isolation was more variable; this organism was most commonly found on the perineum and scrotum. Rectal swabs, obtained through a proctoscope, were positive for P. aeruginosa in four of eight patients with this organism on the perineum and positive for K. pneumoniae in eight of nine patients with this organism on the perineum. These studies more clearly define the extent of the colonization of the perineum and adjacent body sites which provides potential reservoirs of P. aeruginosa and K. pneumoniae.

The relationship of pH and moisture to Pseudomonas aeruginosa and Klebsiella pneumoniae colonization of the perineal skin was studied in male patients with spinal cord injury. The increased pH of the perineal skin was significantly associated with the presence of P. aeruginosa but not other bacterial species. No correlation between colonization and moisture or pH and moisture was found. An antiperspirant produced a significant reduction in the number of total aerobic bacteria, total gram-negative bacilli, P. aeruginosa and K. pneumoniae over a 24-h period. Long-term use of the antiperspirant for 10 days did not alter the persistence of P. aeruginosa of the same serotypes on the perineum.

Men with spinal cord injuries have a high incidence of Pseudomonas aeruginosa colonization of the perineum. Studies were carried out to determine whether colonization with Pseudomonas aeruginosa or Klebsiella pneumoniae is associated with changes in the pH or surface moisture of the perineal skin. Increased skin moisture correlated with a higher pH (P less than 0.01). In patients using the external urinary collection system, the pH was significantly higher on the perineum of patients colonized with P. aeruginosa or K. pneumoniae than on the perineum of patients not colonized with these bacteria. There was no correlation between moisture and colonization.

Serum antibodies to P. aeruginosa were measured in 28 patients with spinal cord injury before and after the development of bacteriuria during their hospital rehabilitation. Serum IgG, IgA and IgM were measured against the infecting strain of P. aeruginosa isolated from the urine of each patient. After bacteriuria was detected, a significant increase (fourfold or greater) in IgG and/or IgA antibodies was found in nine patients (33%). This increase was significantly associated with leucocytosis. These observations indicate that bacteriuria with P. aeruginosa in patients with spinal cord injury is associated with a serum antibody response in a significant number of patients, indicating tissue invasion by this microorganism.

Klebsiella pneumoniae colonization of 53 patients with spinal cord injury was studied. Cultures of multiple body sites from patients, the environment, food, and hospital personnel were obtained. K. pneumonaie was cultured from one or more body sites in 46% of male patients. Significant bacteriuria was found in 10% of male patients. Positive cultures of the urethra and perineum for K. pneumoniae were significantly associated with the use of the external condom catheter (p less than 0.05, Fisher's exact test). K. pneumoniae colonization increased with length of stay in the hospital. Serotype 64, the predominant serotype found, was isolated only from patients who had been in the hospital for at least 4 wk and primarily in those patients using the external condom catheter. Urinary drainage bags were frequently colonized with K. pneumoniae at a time when the patients did not have significant bacteriuria. Colonized male patients were found to be the primary reservoir of K. pneumoniae and may serve as the major source for cross-contamination.

Selective media for Klebsiella pneumoniae have been important in studies of hospital-acquired infections. On an agar medium which included ornithine, raffinose, and Koser citrate, K. pneumoniae strains grew as yellow mucoid colonies at 24 h and there was some increase in colony size at 48 h. Other members of Enterobacteriaceae were inhibited or produced small pink colonies on this same medium. Pseudomonas, Providencia, Acinetobacter, and Proteus species did not grow or showed very poor growth. The growth and appearance of these bacteria were not influenced by pH changes over a pH range of 5.2 to 6.4. Of 368 swabs of body sites cultured on MacConkey agar and on the test medium, 121 K. pneumoniae isolates on MacConkey agar and the same number on the test medium resulted. There were no discrepancies between the two media. Upon direct plating of stool, however, more K. pneumoniae colonies were isolated on the test medium than on MacConkey agar. Colonies on the test medium were more readily selected and identified than the colonies on MacConkey agar. There was also no inhibition of K. pneumoniae growth on the test medium compared with blood agar medium. This medium may be useful for the selective isolation of K. pneumoniae.

Male patients with spinal cord injury are frequently colonized with P. aeruginosa and K. pneumoniae on the perineum. Regular bathing with bar soap has not influenced this colonization. We have attempted to remove these bacteria using antiseptic agents. The number of P. aeruginosa, K. pneumoniae and total aerobic bacteria on the perineum and the penile shaft was determined before and after cleaning with bar soap, chlorhexidine, povidone-iodine and pHresh. Povidone-iodine and chlorhexidine had no advantage over bar soap or pHresh in the removal of P. aeruginosa or K. pneumoniae from the perineum of patients with spinal cord injury.

The duration of colonization of the human perineum, bowel, and urethra with Klebsiella pneumoniae was studied in 10 male patients with spinal cord injury while they were undergoing rehabilitation in the hospital. Colonization defined as persistence of klebsiellae of the same serotype occurred on 13 occasions in five of the patients for up to 55 days. Colonization was less marked with Klebsiella than with Pseudomonas spp. The presence of quadriplegia correlated with Klebsiella colonization and also with the presence of positive Klebsiella cultures from the urethra and perineum. Seven episodes of significant bacteriuria occurred with or after the finding of positive cultures from body sites.

The prevalence of Pseudomonas aeruginosa colonization of patients with spinal cord injury was studied annually from 1976 to 1980. The urethra, perineum, rectum, drainage bag, and urine of patients on the spinal cord injury service were cultured. A total of 224 men and 32 women were studied. Most patients were managed with an external urinary collection system or padding, with or without intermittent catheterization. P. aeruginosa was cultured from one or more body sites (urethra, perineum, or rectum) in 65% of men and 18% of women. Drainage bags on the beds were frequently colonized with P. aeruginosa (73%). Significant bacteriuria with P. aeruginosa was present in 19% of the men and 13% of the women. P. aeruginosa colonization of body sites in men was closely associated with the use of an external urinary collection system. Significantly greater urethral and perineal colonization was found in men using an external urinary collection system. P. aeruginosa serotype 11 was the predominant serotype for the first 3 years, and the number of patients colonized with serotype 11 increased with length of hospital stay. The prevalence of serotype 11 significantly decreased in the last 2 years. The antibiotic susceptibility of the strains of P. aeruginosa isolated from these patients did not change in the 5 years, except that there was increasing susceptibility to carbenicillin in later years. This increasing susceptibility to carbenicillin was a reflection of a decreased prevalence of serotype 11 in these patients, since serotype 11 was more resistant than other serotypes to carbenicillin.