Microbiological outcomes in women with diabetes and untreated asymptomatic bacteriuria.

BACKGROUND: Asymptomatic bacteriuria is common in diabetic women. Treatment of asymptomatic bacteriuria is not beneficial, but the natural history of the microbiology of asymptomatic bacteriuria has not been well described. OBJECTIVE: To describe the microbiological outcomes of bacteriuria in diabetic women with untreated asymptomatic bacteriuria. METHODS: Study subjects were initially identified through ambulatory endocrinology clinics. They were enrolled if they had two positive urine cultures > or = 10(8) cfu/l with the same organism within 2 weeks and no symptoms referable to urinary tract infection. Women initially received a 2-week course of placebo with follow-up cultures obtained at the end of treatment and 4 weeks post-treatment. Subsequently, the prevalence of bacteriuria was determined with urine cultures obtained every 3 months to a maximum of 36 months. Outcomes at yearly intervals were designated as one of: persistent bacteriuria; spontaneous resolution; resolution with antibiotics for symptomatic urinary infection; or resolution with antibiotics given for other indications. Women with and without persistent or frequent bacteriuria were compared to identify variables associated with bacteriuria. RESULTS: The prevalence of bacteriuria in the study cohort declined to about 50% by 9 months, and subsequently remained stable throughout 3 years follow-up. Almost 20% of subjects remained bacteriuric with the original infecting organism throughout the period of observation. With evaluation at 12-month intervals, approximately one-quarter of subjects had each of the four potential outcomes of: resolution following antibiotic therapy for symptomatic urinary infection, following antibiotic therapy for other indications, spontaneous resolution without antibiotics, and persistent bacteriuria with the same organism. Women infected with gram-negative organisms were more likely to have persistent bacteriuria. Many women with resolution of initial bacteriuria, with or without antibiotics, became bacteriuric again during follow-up. CONCLUSIONS: Women with asymptomatic bacteriuria and diabetes tend to have persistent or recurrent asymptomatic bacteriuria. Bacteriuria is benign, and seldom permanently eradicable.

Use of administrative healthcare claims to examine the effectiveness of trimethoprim-sulfamethoxazole versus fluoroquinolones in the treatment of community-acquired acute pyelonephritis in women.

OBJECTIVE: To evaluate the effectiveness of trimethoprim-sulfamethoxazole and fluoroquinolones in the treatment of community-acquired acute pyelonephritis. PATIENTS AND METHODS: We identified a population-based cohort of non-pregnant women aged 18-65 years, initially treated with trimethoprim-sulfamethoxazole or a fluoroquinolone for community-acquired pyelonephritis in an ambulatory care setting. Subjects were identified from a healthcare claims database in Manitoba, Canada for the period 15 February 1996 to 31 March 1999. Subsequent treatment failure, as evidenced by the provision of additional treatment up to 42 days post-diagnosis, was compared between the two treatments. RESULTS: A total of 1084 women met inclusion criteria: 653 (60.2%) treated with trimethoprim-sulfamethoxazole and 431 (39.8%) treated with a fluoroquinolone. Treatment outcomes were affected by subject age. At age 20, treatment with a fluoroquinolone resulted in a reduced probability of treatment failure compared with trimethoprim-sulfamethoxazole (odds ratio, 0.56; 95% CI, 0.33-0.97). At age 60, there was no difference in the probability of treatment failure (odds ratio, 1.61; 95% CI, 0.82-3.16). No other subject characteristics impacted comparative effectiveness; however, several characteristics increased the odds of treatment failure irrespective of the initial antibiotic. These included: recent urinary tract infection (odds ratio, 2.07; 95% CI, 1.14-3.57), recent antibiotic use (odds ratio, 1.40; 95% CI, 1.00-1.96;), and a treatment duration of less than 10 days (odds ratio, 2.18; 95% CI, 1.59-2.99). CONCLUSION: Younger subjects ( approximately 20 years) treated with fluoroquinolones were less likely to experience treatment failure than those treated with trimethoprim-sulfamethoxazole. Treatment durations of less than 10 days resulted in a higher probability of treatment failure regardless of the initial antibiotic.

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.

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.

Characterization of a toxin A-negative, toxin B-positive strain of Clostridium difficile responsible for a nosocomial outbreak of Clostridium difficile-associated diarrhea.

Clostridium difficile-associated diarrhea (CAD) is a very common nosocomial infection that contributes significantly to patient morbidity and mortality as well as to the cost of hospitalization. Previously, strains of toxin A-negative, toxin B-positive C. difficile were not thought to be associated with clinically significant disease. This study reports the characterization of a toxin A-negative, toxin B-positive strain of C. difficile that was responsible for a recently described nosocomial outbreak of CAD. Analysis of the seven patient isolates from the outbreak by pulsed-field gel electrophoresis indicated that this outbreak was due to transmission of a single strain of C. difficile. Our characterization of this strain (HSC98) has demonstrated that the toxin A gene lacks 1.8 kb from the carboxy repetitive oligopeptide (CROP) region but apparently has no other major deletions from other regions of the toxin A or toxin B gene. The remaining 1.3-kb fragment of the toxin A CROP region from strain HSC98 showed 98% sequence homology with strain 1470, previously reported by M. Weidmann in 1997 (GenBank accession number Y12616), suggesting that HSC98 is toxinotype VIII. The HSC98 strain infecting patients involved in this outbreak produced the full spectrum of clinical illness usually associated with C. difficile-associated disease. This pathogenic spectrum was manifest despite the inability of this strain to alter tight junctions as determined by using in vitro tissue culture testing, which suggested that no functional toxin A was produced by this strain.

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.

A Canadian national surveillance study of urinary tract isolates from outpatients: comparison of the activities of trimethoprim-sulfamethoxazole, ampicillin, mecillinam, nitrofurantoin, and ciprofloxacin. The Canadian Urinary Isolate Study Group.

Ampicillin, trimethoprim-sulfamethoxazole, mecillinam, nitrofurantoin, and ciprofloxacin mean resistance rates for 2,000 urinary tract isolates collected from outpatients across Canada in 1998 were 41.1, 19.2, 14.7, 5.0, and 1.8%, respectively. For Escherichia coli isolates alone (n = 1,681) comparable rates were 41. 0, 18.9, 7.4, 0.1, and 1.2%, respectively. The majority of E. coli isolates resistant to ampicillin, trimethoprim-sulfamethoxazole, or ciprofloxacin were susceptible (MIC, <16 microg/ml) to mecillinam.

Low prevalence of VRE gastrointestinal colonization of hospitalized patients in Manitoba tertiary care and community hospitals.

OBJECTIVE: To determine the prevalence of vancomycin-resistant enterococci (VRE) bowel colonization in hospitalized patients in Manitoba who had stool specimens collected for Clostridium difficile toxin and/or culture testing. DESIGN: Two tertiary care and five community hospitals in Winnipeg and three rural Manitoba community hospitals participated in this study. From January 1 to December 31, 1997 stool specimens, one per patient, submitted to hospital microbiology laboratories for C difficile toxin and/or culture testing were screened for VRE on colistin-nalidixic acid-vancomycin (6 microg/mL) (CNAV) agar plates. The study was divided into six, eight-week intervals. Stool specimens received in the first two weeks of each eight week interval were screened for VRE. MAIN RESULTS: A total of 1408 stool specimens were submitted over the 48-week study period. Sixty-seven (4.8%) patients with VRE colonization of their lower gastrointestinal tract were identified. Three of the 67 (4.5%) VRE isolates were Enterococcus faecium, with the remaining 64 (95.5%) were Enterococcus gallinarum. The three vancomycin-resistant E faecium -VREF- (from two different Winnipeg hospitals) demonstrated the vanA genotype, and were resistant to vancomycin, teicoplanin and ampicillin. All three VREF isolates also demonstrated high level resistance to both gentamicin and streptomycin but were susceptible to quinuprisitin/dalfopristin and LY333328. CONCLUSION: VRE colonization in hospitalized patients in Manitoba is infrequent and most commonly due to E gallinarum. The prevalence of VREF colonization in the patients studied was 0.2% (three of 1408).

E test versus agar dilution for antimicrobial susceptibility testing of viridans group streptococci.

Viridans group streptococci (VGS) are commonly isolated from the blood of hospitalized patients. The E test represents a convenient method for determining the MICs for VGS, but for this purpose it has not been well validated against reference methods. In this study, 180 unselected VGS isolates were identified to a species level, and the MICs of penicillin, cefuroxime, cefotaxime, and vancomycin were determined by both agar dilution and the E test. Available data regarding demographic and laboratory variables for each VGS bacteremic episode were collected, the significance of each VGS isolate was assessed, and the associations between and among laboratory and clinical variables were investigated. Among all VGS isolates, 68.3% (median of three runs) were found to be fully susceptible to penicillin by agar dilution. The E test and agar dilution showed average agreements (within +/-1 dilution) of 92.2% for penicillin, 95.7% for cefuroxime 91.3% for cefotaxime, and 86.7% for vancomycin. Agreements over serial E tests and serial agar dilutions were excellent for beta-lactam agents (intraclass correlation coefficients, >0.9) but less impressive for vancomycin. Very major error rates for the E test were

Screening pregnant women for group B streptococcal colonization.

The recovery rates of group B streptococcus (GBS) from anorectal swabs (RS) and vaginal swabs (VS) that were enriched were compared to the routine method to determine the optimal procedure. Separate RS and VS were collected from women attending antenatal clinics. RS and VS were placed in 2 ml enrichment and selective broth. Swabs were inoculated onto colistin/nalidixic acid agar (CNA) upon arrival in the laboratory and onto 5% sheep blood agar (SBA) and CNA after 24 h enrichment. The routine method consisted of a VS sent in transport medium and inoculated in the laboratory onto SBA (no enrichment). The overall GBS colonization rate was 24% (64/264). Of the 64 GBS carriers, 77% were colonized in the vagina and 89% were colonized in the anorectum. The anorectum was the only site of colonization in 24% of the women, whereas the vagina was the only site of colonization in 11% of cases. Enrichment increased the detection of GBS from both RS (55 versus 42; P < 0.025) and from VS (49 versus 27; P < 0.001). Of the 64 cases, enriched RS detected 86%, enriched VS detected 77% and the standard VS detected only 41%. Enriched RS and enriched VS collectively detected 99% of cases. SBA was better than CNA for subculture of the enrichment broth because of a higher recovery rate (98-100% versus 80-82%; P < 0.01) and the fact that the hemolysis on SBA made it easier to differentiate GBS from enterococci. The data confirm that optimal screening of pregnant women for GBS should include a combined RS/VS swab placed in enrichment broth that is then subcultured onto SBA after 24 h incubation.

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.

Improved detection of bacterial growth in continuous ambulatory peritoneal dialysis effluent by use of BacT/Alert FAN bottles.

Culture-negative peritonitis is a major complication for patients on continuous ambulatory peritoneal dialysis (CAPD) and precludes organism-specific therapy. The aim of the present study was to compare inoculation of 10 ml of CAPD effluent into BacT/Alert blood culture bottles (FAN [fastidious antimicrobic neutralizing], BacTAlert aerobic [BTA], and BacT/Alert anaerobic [BTAn] bottles) to our conventional method of using 50 ml of concentrated CAPD effluent to inoculate peptone broth bottles (BD bottles) and MacConkey agar and blood agar medium (BA-MAC). The FAN, BTA, and BTAn bottles were monitored automatically in the BacT/Alert blood culture instrument. A total of 207 CAPD effluents were studied, and in 97 bacteria were detected by at least one method. Compared to BTA bottles (79 of 97; 81.4%), BTAn bottles (78 of 97; 80.4%), and BD bottles (88 of 97; 90.7%), the single best broth medium for detecting bacterial growth in CAPD effluents was the FAN bottle (90 of 97 effluents; 92.8%). A total of 125 bacterial species were detected by any method, and the majority (91.8%) of CAPD effluents were infected with a single species. A combination of FAN and BTAn bottles detected 111 of 125 (88.8%) of all organisms, whereas a combination of BD bottles and BA-MAC detected 107 of 125 (85.6%) of all organisms. One or more organisms that would have been completely missed by the conventional method with BD bottles and BA-MAC were detected in 18 CAPD effluents. Of these 18 CAPD effluents, 6 showed no growth by the conventional method with BD bottles and BA-MAC. On the basis of our data, the most sensitive and least labor intensive method was direct inoculation of 10 ml of CAPD effluent into a FAN bottle and a BTAn bottle, which could be automatically monitored by the BacT/Alert blood culture instrument. On the basis of case definitions for peritonitis, the sensitivities and specificities of the methods with FAN and BTAn bottles and with BD bottles and BA-MAC were 81.1 and 98.8% and 74.5 and 96.5%, respectively.

Serological study of responses to selected pathogens causing respiratory tract infection in the institutionalized elderly.

In a prospective 2-year study, serological responses to selected pathogens were analyzed in 224 episodes of fever attributable to respiratory tract infection (51.8%) or of unknown source (48.2%) in 131 residents of two long-term-care facilities. A serological response was identified in 45 episodes (20.1%): Chlamydia pneumoniae (14 episodes), Haemophilus influenzae type b (1), influenza virus type A (14), respiratory syncytial virus (RSV;2), parainfluenza virus type 3 (7), C. pneumoniae and H. influenzae (3), C. pneumoniae and influenza virus type A (2), C. pneumoniae and RSV (1), and C. pneumoniae and parainfluenza virus type 3 (1). No serological responses to Chlamydia psittaci, Chlamydia trachomatis, parainfluenza virus types 1 and 2, influenza virus type B, or Mycoplasma pneumoniae were seen. Vaccination did not affect the duration of fever in those residents with serologically confirmed influenza A. Serologically confirmed C. pneumoniae infection was detected in 9.4% of all febrile episodes. Serological responses to a second agent were detected in 33% of the patients with C. pneumoniae infections, and these dual infections were associated with an underlying malignancy (P = .02). C. pneumoniae should be recognized as a potential pathogen when choosing empirical antimicrobial therapy for respiratory tract infection in residents of long-term-care facilities.

Hospitalization for acute pyelonephritis in Manitoba, Canada, during the period from 1989 to 1992; impact of diabetes, pregnancy, and aboriginal origin.

Population-based rates of hospitalization for acute pyelonephritis were estimated over 3 years with use of provincial administrative data on health care. Retrospective review of records of ICD9-CM discharge codes of pyelonephritis and urinary infection was performed in two acute care institutions to validate the discharge diagnosis; 80% of patients with a discharge diagnosis of pyelonephritis and 7% to 20% of patients with a discharge diagnosis of urinary infection met clinical criteria for admission for acute pyelonephritis. Mean rates of hospitalization +/- SD for acute pyelonephritis were 10.86 +/- 0.51 per 10,000 population among women and 3.32 +/- 0.27 per 10,000 population among men. From 18% to 31% of hospitalized women aged 20-39 years pregnant; 36% of 797 hospitalized women and 21% of 402 hospitalized men 40 years of age or older were diabetic. The hospitalization rates among Native American women with treaty status were five to 20 times greater than those among other women, which was partially attributable to a significantly greater frequency of pregnancy and diabetes in the former women. Hospitalization for acute pyelonephritis is common, and pregnancy and diabetes contribute substantially to hospitalization rates. The increased hospitalization rate among Native American women with treaty status is not fully explained by pregnancy or diabetes.

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.

Mycobacterium abscessus infection of a Norplant contraceptive implant site.

The authors report a case of Mycobacterium abscessus infection of a subdermal levonogestrel implant (Norplant) site. The infection lasted 12 weeks and was indolent, skin manifestations were low grade and difficult to detect. Culture of exudate samples showed that M. abscessus was the only causative agent. After the implant was removed the patient's arm healed uneventfully without antimycobacterial therapy. The authors recommend that if Gram staining of apparently infected material from an implant site does not reveal a causative organism, then cultures should be done for mycobacteria and fungi. Kinyoun staining for acid-fast bacteria and calcoflour-white staining for fungi should also be performed. The implant should be removed and the patient given antimicrobial therapy as indicated. The authors emphasize the need to be aware of the potential for M. abscessus infection of implant sites and stress that appropriate microbiologic culture procedures are essential for accurate diagnosis.