Treatment of enterococcal pyelonephritis with trovafloxacin and rifampin: in vitro-in vivo contrast.

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.

Ciprofloxacin-resistant Escherichia coli emerging in a rehabilitation medical center.

A retrospective review of laboratory records from 1988 to 1996 has shown an increased rate of ciprofloxacin-resistant (cip(r)) Escherichia coli in our rehabilitation center. Resistance increased from 0.6% in 1989 to 5.9% in 1996. Of 7870 E. coli strains isolated during this period, 257 cip(r)-E. coli were recovered from 257 patients. The majority (96%) of these resistant strains were isolated from the urine samples. One hundred and twenty strains of cip(r)-E. coli were also resistant to four other fluoroquinolones. MICs ranging from 64 to 512 micrograms/mL were observed in 75% of the strains and > or = 1028 micrograms/mL in 6.4% of the strains. Resistance to ciprofloxacin was due to possible mutations in topoisomerase gyrA.

Urethral cultures in female patients with a spinal cord injury.

Quantitative cultures of the urethral meatus were obtained from women with SCI undergoing intermittent catheterization. When compared with the urethral cultures of a group of female subjects, women with SCI had a greater number of isolates of Klebsiella pneumonia and Pseudomonas aeruginosa in the urethral flora. However there was not a significantly greater number of isolates or log numbers of E. coli or Enterococcus sp. in the urethral flora. The E. coli and Enterococcus sp. isolated from the urine were not isolated from the urethra of female patients with SCI in one third of the patients. This poor correlation between the simultaneous urethral and urine cultures of female subjects with SCI may reflect colonization of the urine with organisms that were unable to adhere to the mucosa and colonize the urethra. To what extent these organisms colonize or are temporary residents may be important in the pathogenicity of the infection.

Wound infections following spinal fusion with posterior segmental spinal instrumentation.

Twenty-three of 238 patients (9.7%) developed wound infections following segmental spinal instrumentation. When the infected group and a matched control group were compared, the infected group had a significantly higher number of patients with cerebral palsy and myelodysplasia (nonambulatory), patients with wound hematomas, patients with fusions that extended into the sacral region, and patients who were incontinent of urine. A high incidence of infections with gram-negative aerobic bacilli correlated with the extension of the surgery into the sacral region and bowel and/or bladder incontinence. Prophylactic antibiotics with broader coverage for gram-negative bacilli may be warranted for these procedures. Postoperative wound infections were managed by surgical drainage and debridement as well as antibiotics. Removal of the hardware was not necessary to control the infection in these patients who underwent segmental spinal instrumentation.

In vitro activity of the combination of trovafloxacin and other antibiotics against enterococci.

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.

The 28K protein in urinary bladder, squamous metaplasia and urine is triosephosphate isomerase.

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.

Treatment of urinary tract infections in persons with spinal cord injury: a review.

Despite improvements in the techniques to drain the urinary bladder in patients with spinal cord injury (SCI), urinary tract infection (UTI) remains one of the most common complications of SCI. Despite many studies of the management of UTIs, differences of opinion remain. This has resulted from the use of different definitions of UTI, including the definitions of "significant" bacteriuria, "asymptomatic" bacteriuria, the inclusion (or exclusion) of "soft" symptoms, evidence of few complications from the infection and other risks of infection. The need to treat patients with high fever who may have bacteremia and patients with symptoms is clear. Broad coverage may be necessary until the results of culture are available because of the frequent presence of resistant bacteria colonizing the perineum or bowel. Eradication of bacteriuria is not a reasonable goal in many patients with indwelling catheters. The treatment of patients with asymptomatic bacteriuria (those patients without symptoms or pyuria) remains controversial. Asymptomatic bacteriuria is often treated in recently injured inpatients and those that have their first infection and is not treated in persons in whom asymptomatic bacteriuria is detected more than one year following the injury. Selection of the antibiotics depends on the symptoms of UTI, but at the risk of developing colonization of the urinary tract, perineum, or bowel with resistant gram-negative bacilli.

Methicillin-resistant Staphylococcus aureus (MRSA) colonization in patients with spinal cord injury.

Methicillin-resistant Staphylococcus aureus (MRSA) colonization has been a problem in the Rancho Los Amigos Medical Center (RLAMC) since 1978. This study reviews the latest 2 years' use of a protocol to prevent the spread of MRSA while allowing spinal cord injured patients to continue to participate in the rehabilitation program. The protocol included management in a private room, bathing with hexachlorophene, monitoring positive sites and clearing patients after 3 weeks of negative cultures. Clusters of cases were investigated by obtaining nasal cultures from the personnel. Sixty-seven of 584 (11%) SCI patients were colonized from July 1989 to July 1991. The prevalence of MRSA colonization was significantly greater in the pressure ulcer management service (PMS) 49/184 (27%) than in the rehabilitation spinal injury service (SIS) 18/400 (5%). The body sites colonized were wounds (58/67), nares (37/67), throat (30/67), urine (27/67) and perineum (17/67). Oral therapy with combinations of sulfamethoxazole trimethoprim (SXT) or Novobiocin with rifampin together with topical antibiotics (nares and wound sites), used in nine patients with healing wounds or recent flap surgery, resulted in clearing of the colonization in all cases. Identification and treatment of carriers in the personnel and use of preadmission screening cultures for MRSA in patients with pressure ulcers resulted in reduced inpatient admission.

Hematogenous endophthalmitis due to Candida tropicalis: report of two cases and review.

Candida tropicalis is a well-documented pathogen affecting humans. There is limited clinical and experimental evidence that C. tropicalis causes hematogenous endophthalmitis. We report two cases of C. tropicalis endophthalmitis and review 12 cases reported in the literature. Clinical presentation was similar to that described for Candida albicans endophthalmitis. Therapy with amphotericin B, with or without flucytosine, resulted in resolution of the lesions except in one patient, for whom enucleation of the eye was necessary to control the infection. None of the patients were leukopenic.

Randomized double-blinded trial of rifampin with either novobiocin or trimethoprim-sulfamethoxazole against methicillin-resistant Staphylococcus aureus colonization: prevention of antimicrobial resistance and effect of host factors on outcome.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen in hospitals. Current antimicrobial regimens for eradicating colonizing strains are not well defined and are often complicated by the emergence of resistance. The combination of novobiocin plus rifampin in vitro and in vivo was found to prevent the emergence of resistant populations of initially susceptible strains of MRSA, particularly resistance to rifampin. We therefore studied, in a randomized, double-blind, multicenter comparative trial, the combination of novobiocin plus rifampin versus trimethoprim-sulfamethoxazole (T/S) plus rifampin in order to determine the efficacy of each regimen in eradicating MRSA colonization and to further characterize the host factors involved in the response to this antimicrobial therapy. Among the 126 individuals enrolled in the study, 94 (80 patients; 14 hospital personnel) were evaluable. Among the 94 evaluable subjects, no significant demographic or medical differences existed between the two treatment groups. Successful clearance of the colonizing MRSA strains was achieved in 30 of 45 (67%) subjects receiving novobiocin plus rifampin, whereas successful clearance was achieved in 26 of 49 (53%) subjects treated with T/S plus rifampin (P = 0.18). The emergence of resistance to rifampin developed more frequently in 14% (7 of 49) of subjects treated with T/S plus rifampin than in 2% (1 of 45) of subjects treated with novobiocin plus rifampin (P = 0.04). Restriction endonuclease studies of large plasmid DNA demonstrated that the same strain was present at pretherapy and posttherapy in most refractory cases (24 of 29 [83%] subjects). Among the 56 successfully treated subjects, clearance of MRSA was age dependent: 29 of 36 (80%) subjects in the 18- to 49-year-old age group, 19 of 35 (54%) subjects in the 50- to 69-year-old age group, and 8 of 23 (35%) in the 70- to 94-year-old age group (P < 0.01). Clearance was also site dependent; culture-positive samples from wounds were related to a successful outcome in only 22 (48%) of 46 subjects, whereas culture-positive samples from sites other than wounds (e.g., nares, rectum, and sputum) were associated with a success rate of 34 of 48 (71%) subjects (P = 0.02). Foreign bodies in wounds did not prevent the eradication of MRSA by either regimen. T/S plus rifampin was less effective in clearing both pressure and other wounds, whereas novobiocin plus rifampin was equally effective in clearing both pressure and other wounds. There were no significant differences in toxicity between the two regimens. Thus, the combination of novobiocin plus rifampin, in comparison with T/S plus rifampin, was more effective in preventing the emergence of resistance to rifampin and demonstrated a trend toward greater activity in clearing the MRSA carrier state. The response to either combination depended on host factors, particularly age and the site of MRSA colonization.

28 K in squamous metaplasia of the bladder in patients with spinal cord injury.

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.

Increased frequency of large R-plasmids in Klebsiella pneumoniae colonizing patients with spinal cord injury.

From 1978 to 1988 strains of gentamicin-susceptible (Gms) and gentamicin-resistant (Gmr) Klebsiella pneumoniae were saved from annual surveillance cultures of the perineal region of patients with spinal cord injury (SCI). Of 38 strains selected for further study (24 Gms and 14 Gmr), there were 23 different serotypes (two nontypable). Fourteen Gms as well as 14 Gmr strains displayed no common plasmid patterns, but all contained a large plasmid of 168-208 kb. Among the 14 Gmr strains, nine had large conjugative plasmids of approximately the same size (166-193 kb), which conferred to a susceptible Escherichia coli host an identical resistance pattern: ampicillin, chloramphenicol, gentamicin, piperacillin, trimethoprim-sulfamethoxazole, tetracycline, and tobramycin. Of the nine transconjugants, eight contained a single plasmid. One transconjugant contained a 168- and 80-kb plasmid. Restriction endonuclease digestion patterns of the R-plasmids revealed minimal similarity. We conclude that, during a 10-year period, different large R-plasmids have spread among multiple serotypes of K. pneumoniae in spinal cord injury (SCI) patients in one rehabilitation hospital. We hypothesize that other genes located on large, R-, and non-R-plasmids may confer an additional advantage for colonization by K. pneumoniae in SCI patients.

Nonmucinous nature of the surface material of the bladder mucosa.

The urinary bladder is lined by transitional epithelium, also known as urothelium. Some investigators have described a material known as mucin, which lines the luminal surface of the urothelium, but its nature is not well understood. The authors examined sections of bladder from rat, mouse, rabbit, and man and found that, although they reacted differently to common histochemical stains for complex carbohydrates, none showed any material that stained as mucin on the surface of the mucosa. Rather, intracellular granules that have varying staining characteristics in different animals were found on the luminal side of the urothelium. The authors speculate, based on their histochemical findings, that some form of mucin may be present in the urothelial granules in man and that studies on animals may not be applicable to man.

Postoperative wound infections following myocutaneous flap surgery in spinal injury patients.

Severe pressure ulcers in patients with spinal cord injury are frequently treated by using musculocutaneous (m-c) flap surgery. There have been few studies of the use of perioperative antibiotics to prevent postoperative infection in this setting. We reviewed 74 m-c flap surgeries in 53 patients (41 male and 12 female) from October 1989 for one year. The sites involved were ischial (31), sacral (24), trochanteric (18), deltoid (2), olecranon (1) and posterior thigh (1). An antibiotic was usually administered perioperatively for 5 days. Patients were followed for a median of 30 (8-96) weeks. Postoperative infections occurred at a median of 12 (4-25) days in 6 of 74 (8%) surgeries. The organisms cultured from the 6 infected wounds were: Bacteroides sp. (4), Proteus mirabilis (2), E. coli (2), MRSA (2), and others (6--each isolated once). These results indicate that antibiotics did not prevent postoperative infection in approximately 8% of patients undergoing m-c surgery. The frequency of isolation of Bacteroides sp. from these infections suggests that anaerobic bacteria may persist in healing pressure ulcers and perioperative antibiotics might include coverage for anaerobic bacteria.

Effect of external urinary collection system on colonization and urinary tract infections with Pseudomonas and Klebsiella in men with spinal cord injury.

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.

28K antigen in the urothelium.

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.

Septic ischial bursitis in patients with spinal cord injury.

Septic ischial bursitis is described in 4 patients with spinal cord injury. In these patients a pre-existing ischial bursitis probably became secondarily infected. Because these patients lack sensation, diagnosis may be difficult. The disease process in one patient with a prolonged fever was only recognized after a leucocyte scan detected an abscess extending to the thigh. At surgery it was found that the infection extended from the ischial bursa to the upper lateral thigh. Infection in these patients was due to beta hemolytic streptococcus, S. aureus, and S. epidermidis. The patients all responded well to local drainage and excision of the bursa.

Low mortality among patients with spinal cord injury and bacteremia.

We reviewed 103 episodes of bacteremia in 93 patients with spinal cord injury who had bacteremia during initial hospitalization (39 patients) or readmission (54 patients) during 1978-1988. Eighteen episodes (18%) were due to polymicrobial infections. Urinary tract infections (47%), infected pressure areas (19%), and pneumonia (9%) were the most frequent primary infections and sources of the bacteremia. The bacteria most frequently associated with urinary tract infections were enterococci (26%), Escherichia coli (26%), Pseudomonas species (20%), and Klebsiella pneumoniae (12%). Bacteria most frequently isolated from patients with infected pressure areas were anaerobes and Staphylococcus aureus. Bacteremia was the cause of death for 8 patients (9%). The urinary tract was identified only once as the source of gram-negative bacteremia in an immunocompetent patient who died. The reason for the low mortality in patients with spinal cord injury is unclear.