Asymptomatic bacteriuria. Which patients should be treated?

Asymptomatic bacteriuria is common in both the community nursing home and hospital settings. Few data, however, are available about the potential complications arising from asymptomatic bacteriuria (eg, the development of symptomatic infection and renal damage) for various patient populations and for various medical conditions. On the basis of data in the literature, we believe that neonates and preschool children with asymptomatic bacteriuria should be treated. Pregnant women and "nonelderly" (less than 60 years old) men should be treated. We do not think that school-age children, nonpregnant, nonelderly women, or elderly men and women need antimicrobial treatment if their urinary tracks are normal. In addition, antimicrobial treatment is recommended for patients with asymptomatic bacteriuria and abnormal urinary tracts and those undergoing clean intermittent catheterization, genitourinary manipulation, or instrumentation. Patients with long-term indwelling catheters should not be treated. The treatment of asymptomatic bacteriuria in patients with short-term indwelling catheters and those with ileal conduits is controversial. These treatment recommendations should not necessarily be accepted as the standards of practice, since treatment is often controversial due to the lack of published data describing the natural course of asymptomatic bacteriuria in various patient populations.

Group C streptococcal meningitis in an adult. Probable acquistion from a horse.

Although group C streptococci are infrequent pathogens in man, they commonly cause disease in animals. Only recently have they been recognized as a causative agent in meningitis in man. To our knowledge, no previous report has documented a source for the infection. We treated a previously healthy young adult with group C streptococcal meningitis, who responded rapidly to antibiotic therapy. The same species (Streptococcus zooepidemicus) that was isolated from the CSF of the patient also grew from the pharynx of the patient's horse.

Trimethoprim alone in the treatment and prophylaxis of urinary tract infection.

Trimethoprim was used alone to treat urinary tract infections in 20 women who were unable to tolerate sulfonamides. Of ten acute symptomatic urinary tract infections, four were cured, three were not, and three cases could not be evaluated. Two other women received trimethoprim for suppression of infection complicating stag-horn calculi. The conditions of both patients improved clinically but the urine remained infected. Eight women treated prophylactically with low-dose trimethoprim for recurrent urinary tract infection accumulated a total of 16 patient-years of prophylaxis. During treatment, the incidence of infection was 0.56 per patient-year compared with 4.25 infections in the year preceding study. Adverse reactions occurred in eight of 20 patients and administration of the drug had to be stopped in five cases. Trimethoprim alone is effective for the treatment and prophylaxis of urinary tract infections, but may cause a high incidence of adverse reactions in patients known to be sensitive to sulfonamides.

Infectious complications of endoscopic injection sclerotherapy.

We prospectively assessed the infectious complications of esophageal injection sclerotherapy (EIS) in 38 patients who underwent 104 procedures. Blood cultures were taken prior to and five and ten minutes after injection of the sclerosing agent in all procedures in an attempt to determine the frequency of positive blood cultures. Surveillance cultures were obtained from each patient's pharynx and from the biopsy channel of the endoscope to identify potential sources of bacteremia. The rate of blood culture positivity before injection was not significantly different from that after injection (1.9% vs 4.3%). In only one procedure was the same organism isolated five and ten minutes after sclerotherapy. The isolate in both samples was a Corynebacterium species. Endoscope surveillance cultures were positive prior to 42 of 102 procedures, although none of those organisms subsequently were isolated in the blood cultures. Since the rate of positive blood cultures following EIS is no greater than that before the procedure, the use of prophylactic antibiotics is unnecessary.

Advances in the treatment of urinary tract infection.

Single dose treatment regimens are currently the treatment of choice in women with acute urethrocystitis. Women who have concomitant asymptomatic renal infections will have a recurrence and require further investigation and more conventional 14-day treatment regimens. Single dose treatment is a specific and moderately sensitive diagnostic aid for women with urinary infection. Further carefully planned studies are required to determine optimal treatment regimens for women with renal infection and men with infections originating in the kidneys or prostate.

Gross hematuria in residents of long-term-care facilities.

PURPOSE: To describe the epidemiology and characteristics of gross hematuria in elderly residents of nursing homes and to identify the associations of gross hematuria with urinary infection and the potential contribution of urinary infection to morbidity. PATIENTS AND METHODS: This was a prospective, descriptive study of episodes of gross hematuria identified by the nursing staffs at two long-term-care facilities over 2 years. Episodes were characterized with respect to patient variables, presence of bacteriuria, duration of hematuria, therapeutic interventions, and genitourinary investigations. Clinical and serologic criteria were used to identify invasive infection. RESULTS: The incidence of gross hematuria was 31/100,000 resident days. Bacteriuria was present in 58 (74%) of 78 episodes with evaluable cultures. Fifty-two (61%) episodes lasted more than 24 hours, 25 (29%) were temporally associated with fever, and antimicrobials were given for 53 (61%) episodes. Gross hematuria occurred more frequently in men than in women and was more frequently associated with fever in men. Twenty-four (28%) episodes occurred in subjects with indwelling catheters, 30 (34%) in subjects with known genitourinary abnormalities, 26 (30%) in subjects with no genitourinary investigations, and 4 (4.6%) in subjects with genitourinary investigations but no abnormalities identified. No adverse clinical outcomes were identified in patients in whom antimicrobial therapy was not initiated. The maximal estimated incidence of invasive urinary infection associated with hematuria was 5.8/100,000 resident days, and of bacterial hemorrhagic cystitis, 6.3/100,000 resident days. CONCLUSIONS: These data suggest that underlying genitourinary abnormalities are present in most elderly institutionalized subjects with gross hematuria when genitourinary investigations are performed. Although bacteriuria is usually present, urinary infection, by itself, is an infrequent cause of gross hematuria. Afebrile hematuria without irritative symptoms probably does not require antimicrobial therapy. A standard approach to this clinical problem in the institutionalized elderly should be developed to optimize patient management and appropriate use of antimicrobial therapy.

A prospective controlled investigation of prophylactic trimethoprim/sulfamethoxazole in hospitalized granulocytopenic patients.

Oral trimethoprim/sulfamethoxazole (TMP/SMZ) therapy was investigated in the prophylaxis of infections in granulocytopenia. Hospitalized granulocytopenic patients were allocated at random to receive TMP/SMZ (group 1) or to a control group (group 2). The percentage of febrile granulocytopenic days was significantly reduced in group 1, 19 per cent compared to 39 per cent in group 2 (P less than 0.01). In group 1, there were no bacteremias in 59 episodes of granulocytopenia (909 days). In group 2, there were nine bacteremias in 52 episodes of granulocytopenia (796 days)(P = 0.001). Disseminated candidiasis developed in two patients in each group. Candida occurred in similar numbers in surveillance cultures in both groups; Staphylococcus aureus and Pseudomonas aeruginosa were slightly decreased, and Enterobacteriaceae resistant to TMP slightly increased in group 1. This study suggest that oral prophylactic TMP/SMZ therapy is an effective, well tolerated, easily administered alternative to "gut sterilization" with nonabsorbable antibiotics.

Granulocytopenia in hospitalized patients: I. Prognostic factors and etiology of fever.

The clinical course of 126 hospitalized patients during 192 episodes of granulocytopenia and fever was studied. Fever was a regular accompaniment of granulocytopenia, occurring in 94 per cent of granulocytopenic episodes. The mean duration of granulocytopenia (less than 1,000/mm3) was 18 days, with fever (temperature greater than 38 degrees C) being present during 44 per cent of those days. Fever was present during 69 per cent of days with a granulocyte count less than 10/mm3. A presumed infection was present in 86 of 128 febrile granulocytopenic episodes in adults and in 19 of 64 febrile granulocytopenic episodes in children. A fungal infection was found in 11 patients; a viral infection in 23 patients. Bacteremia occurred during 44 granulocytopenic episodes with 16.8 bacteremias/1,000 days of granulocytopenia in adults and 12.7 bacteremias/1,000 days in children. The mortality was 33 per cent per granulocytopenic episode in adults and only 8 per cent per episode in children.

Granulocytopenia in hospitalized patients. II. A prospective comparison of two antibiotic regimens in the empiric therapy of febrile patients.

The results of empiric antibiotic therapy in 126 hospitalized patients with fever during 192 episodes of granulocytopenia were studied. Febrile granulocytopenic patients were randomly allocated to receive either carbenicillin, methicillin and gentamicin, or carbenicillin and cephalothin. The response rate for the two antibiotic regimens was similar, 49 (60 per cent) of 81 responded to the former and 42 (54 per cent) of 78 to the latter. The response rate in patients receiving other antibiotics because of specific indications or counterindications was 19 (58 per cent) of 33. Thirty-nine (35 per cent) of 110 patients who responded to initial antibiotic therapy had an increase in circulating granulocytes of one log10 or more compared to only 10 (12 per cent) of 79 nonresponders with such an increase. The mortality rate in adult patients receiving carbenicillin, methicillin and gentamicin was eight (16 per cent) of 51, compared to 18 (37 per cent) of 49 in those receiving cephalothin and carbenicillin (P less than 0.05). The significance of this difference in the initial response rate or mortality rate between patients treated with the two antibiotic regimens when only patients with documented bacterial infection were considered. Patients who responded to their initial antibiotic regimen, and patients for whose fever no explanation was found, had the best prognosis.

Febrile urinary infection in the institutionalized elderly.

PURPOSE: Bacteriuria is common among institutionalized elderly populations, but the contribution of urinary infection to febrile morbidity is unknown because of difficulties in clinical ascertainment. This study was undertaken to febrile morbidity using both clinical and serologic criteria. METHODS: Episodes of fever in residents of two long-term care institutions were identified prospectively for 2 years. Serum and urine specimens were obtained initially and at 4 weeks. The proportion of episodes attributable to urinary infection was determined by both standard clinical criteria proposed for use in these populations and serum antibody response to uropathogens. RESULTS: For 372 fewer episodes, 211 met clinical criteria for infection: 147 (40%) of the respiratory tract; 26 (7%) of the genitourinary tract; 25 (6%) of the gastrointestinal tract; and 13 (3%) of skin and soft tissue. Of the remaining 161 fever episodes, 2 (1%) were noninfectious and 159 (43%) were of unknown origin. The prevalence of bacteriuria for residents with nongenitourinary sources of fever varied from 32% to 75%. An antibody response meeting serologic criteria for urinary infection occurred in 26 (8.3%) of 314 episodes with paired sera obtained; 10 (43%) of 23 identified clinically as genitourinary infection, 14 (11%) of 132 unknown, 1 (4%) of 25 gastrointestinal, and 1 (0.8%) of 122 respiratory. The positive predictive value of bacteriuria for febrile urinary infection identified by clinical criteria was was 11% (95% confidence interval [CI] 4%, 18%) and identified by serologic criteria was 12% (95% CI 7%, 17%). CONCLUSIONS: Urinary infection contributes to less than 10% of episodes of clinically significant fever in this high-prevalence bacteriuric population. A restrictive clinical definition for genitourinary infection has poor sensitivity and specificity compared with serologic criteria for identification of fever of urinary source, and bacteriuria has a low predictive value for identifying febrile urinary infection.

Randomized controlled trial comparing trimethoprim/sulfamethoxazole and trimethoprim for infection prophylaxis in hospitalized granulocytopenic patients.

The clinical and microbiologic efficacy of trimethoprim alone and trimethoprim/sulfamethoxazole for infection prevention was evaluated in 75 patients during 92 episodes of granulocytopenia. Ultimately, 60 patients were evaluable during 77 episodes of granulocytopenia, 36 episodes in the trimethoprim group and 41 episodes in the trimethoprim/sulfamethoxazole group. The incidence of infection was higher in the trimethoprim group (50 percent) than in the trimethoprim/sulfamethoxazole group (39 percent), but this did not reach statistical significance. Trimethoprim did not appear to be as protective as trimethoprim/sulfamethoxazole when the granulocyte count was less than 100/mm3. In patients receiving trimethoprim/sulfamethoxazole, aerobic gram-negative bacilli cleared from fecal surveillance cultures more often and new aerobic gram-negative bacilli were acquired less often than in those receiving trimethoprim alone (p less than 0.05). More myelosuppression was observed among patients receiving trimethoprim/sulfamethoxazole (p less than 0.001). These observations suggest that trimethoprim alone may not be optimal for preventing colonization and infection in granulocytopenic patients and that combination with other agents may be necessary to increase the spectrum of activity. Trimethoprim/sulfamethoxazole itself may predispose toward an increased risk of infection by prolonging myelosuppression.

Asymptomatic bacteriuria, urinary antibody, and survival in the institutionalized elderly.

OBJECTIVE: To compare clinical status of elderly institutionalized subjects with asymptomatic bacteriuria and normal urinary antibody to those with elevated urinary antibody to the major outer membrane of Escherichia coli. DESIGN: Retrospective review. SETTING: Long term facility for the elderly. PARTICIPANTS: Convenience sample of 63 elderly subjects, 26% of those resident in the institution, aged 78.8 +/- 8.4 years with urine specimens collected and stored in 1987. MAIN OUTCOME MEASURES: Differences in clinical or functional status, demographic features, and outcome during 3-years follow-up between bacteriuric subjects with normal and elevated urine antibody. RESULTS: Thirteen subjects had no bacteriuria, and 12 had infrequent, intermittent bacteriuria; 38 (60%) had persistent bacteriuria, including four with frequent, intermittent infections. In the persistently bacteriuric group, 18 (47%) had persistently elevated urine antibody. There was no significant differences between bacteriuric residents with normal vs elevated urine antibody in clinical or functional status, age, duration of residence, or infecting organisms. However, 11 of 20 in the cohort with normal urine antibody were alive at 3 years compared to 3 of 18 with elevated urine antibody (P = 0.014). CONCLUSIONS: Elderly institutionalized subjects with persistent bacteriuria and elevated urine antibody have decreased survival compared to those with normal urine antibody. No differences in underlying illness or clinical course to explain this survival difference were identified.

Urinary antibody level and survival in bacteriuric institutionalized older subjects.

OBJECTIVE: In a previous study, elevated urine antibody levels in institutionalized subjects with asymptomatic bacteriuria were associated with decreased survival. This study was undertaken to confirm the previous observation in a prospective study in a larger cohort and to explore selected other variables that may be associated with survival. DESIGN: A prospective, 24-month, observational cohort study. SETTING: Three large nursing homes in Winnipeg, Manitoba. PARTICIPANTS: Permanent residents were identified by initial screening urine cultures and subjects with bacteriuria were enrolled. The median age of subjects was 76 years, 51% were women, and the median duration of residence before enrollment was 26 months. Subjects were highly functionally impaired. MEASUREMENTS: Monthly urine specimens were collected for culture, leukocyte count, and urine antibody. Serum specimens for antibody to uropathogens and IL6 were obtained at enrollment and every 6 months. Anthroporphometric tests of nutritional status and functional and mental status were also measured every 6 months. Residents were stratified as having elevated or not elevated urine antibody, based on the initial urine specimen. The mean urine antibody for all of each subject's specimens was also calculated, and subjects were stratified as low, intermediate, or elevated urine antibody. Outcomes measured included mortality, infection and antibiotic use, and functional, mental, and nutritional decline. RESULTS: Ninety-eight bacteriuric subjects were enrolled in the study; 34 (35%) had elevated urine antibody and 64 (65%) had not elevated urine antibody. The two groups did not differ in demographic features, co-morbidities, functional status, medication use, or infecting organisms. Survival was significantly (P < .001) poorer in the group with elevated urine antibody. At 24 months, 35% of subjects with an elevated urine antibody were alive compared with 75% with a low urine antibody level. This survival difference was consistent when the two groups were stratified by sex, institution, and presence of a chronic indwelling catheter. Subjects with elevated urine antibody had no evidence for accelerated functional or nutritional decline during the study period compared with the group with low urine antibody. These subjects did, however, have an increased incidence of episodes of symptomatic urinary infection and infections at non-urinary sites. CONCLUSIONS: Older, bacteriuric, institutionalized subjects with elevated urine antibody had decreased survival rates compared with subjects with lower urine antibody levels. There is no clinical evidence to support accelerated decline caused by chronic infection to explain this observation. Urine antibody may be a marker for immune dysregulation, which precedes death in older impaired subjects.

Complicated urinary tract infections.

Urinary infections complicated by structural anomalies, metabolic alterations, abnormalities of host response, or unusual or difficult-to-treat pathogens commonly occur in our practices. Therapeutic regimens for most of these patient populations are empiric and unproven. Our understanding of specific microbial virulence factors is inadequate. Until well-designed interventions are proven, management strategies will depend on clinical biases and "trial and error" therapeutic attempts. Presumably, over the course of the next decade, better answers will emerge that will improve our ability to prevent and more adequately manage our patients with complicated UTIs.

Cefoxitin plus tobramycin and clindamycin plus tobramycin. A prospective randomized comparison in the therapy of mixed aerobic/anaerobic infections.

The efficacy of therapy with cefoxitin sodium plus tobramycin sulfate, with the tobramycin therapy discontinued if no cefoxitin-resistant pathogens grew from appropriate cultures, was compared with clindamycin phosphate plus tobramycin therapy in mixed aerobic/anaerobic intra-abdominal and female pelvic infections. Of 96 evaluable patients, 39 (76%) of 51 randomized to cefoxitin and 38 (84%) of 45 randomized to clindamycin were cured and an additional seven (14%) of 51 and three (6.7%) of 45, respectively, were improved. Bacteroides fragilis "group" was isolated from 44 (54%) of 82 patients with appropriate specimens. Duration of aminoglycoside therapy was significantly shorter in patients randomized to cefoxitin and tobramycin (mean, 4.1 +/- 1.8 days vs 7.0 +/- 3.2 days). There was a tendency to greater nephrotoxic reactions in patients randomized to clindamycin and tobramycin. We conclude that cefoxitin plus tobramycin with selective early discontinuation of aminoglycoside therapy is an acceptable regimen for the therapy of mixed aerobic/anaerobic infections.

Assessment of the FAN anaerobic bottle for culture of continuous ambulatory peritoneal dialysis fluid using the BacT/Alert system.

The purpose of this study was to determine if the newly available FAN anaerobic bottle (FANAN) alone would be comparable to the combination of the FAN aerobic (FANAE) plus the standard BacT/Alert anaerobic (REGAN) bottles for culture of continuous ambulatory peritoneal dialysis (CAPD) fluid from patients with CAPD peritonitis. CAPD fluid (10 mL) was injected into each bottle, which was then monitored by the BacT/Alert instrument by using a 7-day protocol. Aerobic and anaerobic terminal subculture were performed on all bottles before they were classified as being culture negative. There were 181 effluents received that were suitable for analysis. Growth was detected in 76 (42%) effluents by at least one method. FANAE was the single best medium detecting 84/96 (88%) of all organisms whereas the FANAN and REGAN each detected 69/96 (72%). The combination of FANAE and REGAN bottles detected 92/96 (96%) isolates, which was significantly better than the FANAN or FANAE alone for isolate recovery (p < 0.001). The isolates that were missed by the FANAN but that were recovered by either FANAE or REGAN were all facultative anaerobes commonly detected in CAPD fluids. Terminal subculture revealed otherwise undetected pathogens in 3.9% of positive effluents, usually Pseudomonas aeruginosa. Based on our data, FANAE was the single best bottle for detection of CAPD peritonitis and, in combination with an anaerobic bottle, detected growth from the most effluents. FANAN alone could not substitute for the FANAE/REGAN combination. Although terminal subculture remains controversial, we recommend routine aerobic subculture to ensure that no P. aeruginosa isolates are missed.

The diagnosis of Clostridium difficile-associated diarrhea: comparison of Triage C. difficile panel, EIA for Tox A/B and cytotoxin assays.

This study prospectively compared; Triage(R) C. difficile test (TCT), TechLab C. difficile toxin A-B enzyme immuno-assay (EIA), and cell-culture cytotoxin test (CT). Of the 400 stools tested, 99 were positive by any test with 92, 41 and 58 detected by TCT, EIA and CT, respectively. Culture of discordant samples indicated that 52 contained C. difficile (42 toxigenic, 10 non-toxigenic), 10 contained Clostridium species and 2 had no detectable clostridium isolates. There were 21/42 toxigenic C. difficile isolates from 17 patients whose stools were negative when originally tested by CT. Review of available patient charts indicated that 12/14 did not previously or currently have C. difficile associated diarrhea, whereas 2 patients developed disease within a few days. Compared to CT as the gold standard, the sensitivity and specificity were; 93%, 89% and 66%, 99% for TCT and EIA respectively. The 8 stool samples with Toxin A(-) Toxin B(+) isolates were detected in 8, 4, and 6 samples by TCT, EIA and CT, respectively. In summary, TCT as a screening test allowed reliable reporting for 85% of stools on the day of receipt. For the 15% of stools requiring further testing we recommend the use of CT.

The management of urinary infections: what have we learned in the past decade?

User-friendly, cost-effective practices to manage urinary infection should become routine. The vast majority of inflections are relatively easy to treat and many of these can be prevented with appropriate interventions. Additional research is urgently needed to compare various clinical strategies and determine which is most acceptable to patients at a reasonable cost with satisfactory health outcomes.

A prospective, randomized, double-blind studyof single high dose versus multiple standard dose gentamicin both in combination withmetronidazole for colorectal surgicalprophylaxis.

Single, high dose regimens of gentamicin plus metronidazole for colorectal surgical prophylaxis have not been adequately studied. Patients received single high dose gentamicin (4.5 mg/kg) plus metroni-dazole (500 mg) preoperatively or multiple standard dose gentamicin (1.5 mg/kg) plus metronidazole (500 mg) preoperatively and every 8h for 24h postoperatively. The deep surgical site infection (SSI) rates were 8.1% (6/74) and 6.9% (5/72) in the single high dose and multiple standard dose groups, respectively (P= 0.94). There was a trend towards fewer superficial SSIs in the single high dose group with infection rates of 18.9% (14/74) vs. 30.6% (22/72) (P= 0.05). Diabetes mellitus (odds ratio = 7.04) and surgery duration of longer than 3h (odds ratio = 5.46) were independent risk factors for the development of SSIs. A subset analysis of prolonged operations found significantly fewer superficial SSIs in the single high dose group than in the multiple standard dose group with rates of 22.2% (6/27) vs. 55% (11/20), respectively (P= 0.021). Single high dose gentamicin plus metronidazole preoperatively was at least as effective as the multiple standard dose regimen and may be more effective for prolonged operations.

Comparative activity of daptomycin and teicoplanin against enterococci isolated from blood and urine.

The authors compared the activity of daptomycin with that of ampicillin, penicillin, teicoplanin and vancomycin against 304 strains of Enterococcus species isolated from blood and urine. Daptomycin was as active as penicillin against Enterococcus faecalis: 90% of strains were inhibited by 2 mg/L. Daptomycin was more active than vancomycin (90% minimal inhibitory concentration [MIC(90)] 2 mg/L; 90% minimal bactericidal concentration [MBC(90)] 8 mg/L) but was less active than teicoplanin (MIC(50) 0.25; MBC(90) 8 mg/L) or ampicillin (MIC(90) 1 mg/L; MBC(90) 2 mg/L) against E faecalis. In time-kill studies daptomycin was not more rapidly bactericidal than ampicillin or penicillin but was significantly more rapidly bactericidal than either teicoplanin or vancomycin. In combination with gentamicin, daptomycin has activity similar to that of penicillin, vancomycin and teicoplanin. Daptomycin may be a suitable alternative to penicillin in patients allergic to penicillins or for the treatment of enterococcal infections caused by beta-lactamase-producing enterococci.