Chlamydia trachomatis laboratory strains versus recent clinical isolates: implications for routine microbicide testing.

A topical microbicide that women can use to prevent sexually transmitted diseases (STDs) is essential, and many microbicide candidates are being tested for activity against human immunodeficiency virus and other STDs, including Chlamydia trachomatis. Screening assays for assessing the activity of microbicides against C. trachomatis are typically done with laboratory-adapted strains, but it is possible that recent clinical isolates may have different susceptibilities to microbicides, as has been seen with Neisseria gonorrhoeae and Lactobacillus spp. (B. J. Moncla and S. L. Hillier, Sex. Transm. Dis. 32:491-494, 2005). We utilized three types of microbicides to help define this aspect of our assay to test microbicides against C. trachomatis in vitro. To simulate conditions of transmission, we used an assay that we previously developed in which we exposed chlamydial elementary bodies to microbicides prior to contact with epithelial cells. We first determined the toxicity of microbicides to the cells used to culture Chlamydia trachomatis in the assay and, if necessary, modified the assay to eliminate toxicity at the concentrations tested. We compared the sensitivities of recent clinical isolates of Chlamydia trachomatis versus laboratory strains of the same serovar and found major differences in sensitivity to nonoxynol-9 (non-9), but only minor differences were seen with the other microbicides. We thus conclude that when assessing activity of potential topical microbicides versus the obligate intracellular bacteria C. trachomatis, the use of recent clinical isolates may not be necessary to draw a conclusion about a microbicide's effectiveness. However, it is important to keep in mind that differences (like those seen with non-9) are possible and that clinical isolates could be included in later stages of testing.

Horizontal transfer of tetracycline resistance among Chlamydia spp. in vitro.

There are no examples of stable tetracycline resistance in clinical strains of Chlamydia trachomatis. However, the swine pathogen Chlamydia suis is commonly tetracycline resistant, both in America and in Europe. In tested U.S. strains, this resistance is mediated by a genomic island carrying a tet(C) allele. In the present study, the ability of C. suis to mobilize tet(C) into other chlamydial species was examined. Differently antibiotic resistant strains of C. suis, C. trachomatis, and Chlamydia muridarum were used in coculture experiments to select for multiply antibiotic resistant progeny. Coinfection of mammalian cells with a naturally occurring tetracycline-resistant strain of C. suis and a C. muridarum or C. trachomatis strain containing selected mutations encoding rifampin (rifampicin) or ofloxacin resistance readily produced doubly resistant recombinant clones that demonstrated the acquisition of tetracycline resistance. The resistance phenotype in the progeny from a C. trachomatis L2/ofl(R)-C. suis R19/tet(R) cross resulted from integration of a 40-kb fragment into a single ribosomal operon of a recipient, leading to a merodiploid structure containing three rRNA operons. In contrast, a cross between C. suis R19/tet(R) and C. muridarum MoPn/ofl(R) led to a classical double-crossover event transferring 99 kb of DNA from C. suis R19/tet(R) into C. muridarum MoPn/ofl(R). Tetracycline resistance was also transferred to recent clinical strains of C. trachomatis. Successful crosses were not obtained when a rifampin-resistant Chlamydophila caviae strain was used as a recipient for crosses with C. suis or C. trachomatis. These findings provide a platform for further exploration of the biology of horizontal gene transfer in Chlamydia while bringing to light potential public health concerns generated by the possibility of acquisition of tetracycline resistance by human chlamydial pathogens.

Urinary tract infections in women with type 1 diabetes mellitus: survey of female participants in the epidemiology of diabetes interventions and complications study cohort.

PURPOSE: We determined the prevalence of and risk factors for urinary tract infection in women with type 1 diabetes, and compared the prevalence of cystitis to that in nondiabetic women. MATERIALS AND METHODS: Women enrolled in the Epidemiology of Diabetes Interventions and Complications study were surveyed at year 10 as part of the Uro-EDIC study to assess the prevalence of cystitis and pyelonephritis in the preceding 12 months. Multivariate logistic regression models including measures of glycemic control and vascular complications of type 1 diabetes were used for risk factor analyses. The prevalence of cystitis in Uro-EDIC women was compared to that in a nondiabetic subset of women participants in the National Health and Nutrition Examination Survey III (NHANES III). RESULTS: A total of 550 women participated in the Uro-EDIC survey. The prevalence of cystitis and pyelonephritis in the preceding 12 months was 15% and 3%, respectively. Duration of diabetes, hemoglobin A1C, retinopathy, neuropathy, nephropathy, composite vascular complication score and intensive glycemic therapy during the Diabetes Control and Complications Trial, and Diabetes Control and Complications Trial cohort were not associated with cystitis or pyelonephritis. Sexual activity was associated with increased cystitis risk (adjusted OR 8.28; 95% CI 1.45, 158.32; p = 0.01). The adjusted prevalence of cystitis was 19.1% in Uro-EDIC women and 23.1% in NHANES III participants (adjusted OR 0.78; 95% CI 0.51, 1.22; p = 0.28). CONCLUSIONS: In Uro-EDIC women sexual activity rather than measures of diabetes control and complications was the main risk factor for urinary tract infection. The prevalence of cystitis was similar to that in nondiabetic women participants in NHANES III.

Binding of uropathogenic Escherichia coli R45 to glycolipids extracted from vaginal epithelial cells is dependent on histo-blood group secretor status.

Women with a history of recurrent Escherichia coli urinary tract infections (UTIs) are two to three times more likely to be nonsecretors of histo-blood group antigens than are women without such a history. Further, uroepithelial cells from women who are nonsecretors show enhanced adherence of uropathogenic E. coli compared with cells from secretors. To investigate the hypothesis that nonsecretors express unique receptors for uropathogenic E. coli related to their genetic background, we extracted glycosphingolipids (GSLs) from vaginal epithelial cells collected from nonsecretors and secretors and used an assay in which radiolabeled uropathogenic E. coli were bound to these GSLs separated on TLC plates. An E. coli strain (R45) expressing both P and F adhesins, which was isolated from one of these patients' UTIs, was metabolically labeled with 35S for the TLC binding assay. The radiolabeled E. coli R45 bound to two extended globo-series GSLs, sialosyl gal-globoside (SGG) and disialosyl gal-globoside (DSGG), found in the GSL extracts from nonsecretors but not from secretors. The identity of SGG in the nonsecretor GSL extracts was confirmed in radioimmunoassays using an mAb to SGG and in immunofluorescence assays with this mAb and native vaginal epithelial cells. We show that SGG and DSGG are selectively expressed by epithelial cells of nonsecretors, presumably as a result of sialylation of the gal-globoside precursor glycolipid, which in secretors is fucosylated and processed to ABH antigens. The presence of SGG and DSGG may account for the increased binding of E. coli to uroepithelial cells from nonsecretors and for their increased susceptibility to recurrent UTI.

Partial deficiency of hepatic glucose-6-phosphatase in an adult patient.

Patients with hepatic glucose-6-phosphatase deficiency usually have a striking clinical syndrome during childhood and are readily diagnosed by the pediatrician. An adult patient had childhood manifestations of glucose-6-phosphatase deficiency that were mild and unrecognized; symptoms of tophaceous gout, urate nephropathy and characteristic blood chemical studies suggested the diagnosis at age 39. Subsequent epinephrine and galactose tolerance tests were characteristic of hepatic glucose-6-phosphatase deficiency and direct assay of hepatic glucose-6-phosphatase confirmed a partial deficiency of the enzyme. The case emphasized that patients with this deficiency may escape diagnosis during childhood and that internists should consider the diagnosis in adolescents or young adults with acute gouty arthritis or tophaceous gout.

Evaluation of chronic urethritis. Defining the role for endoscopic procedures.

We determined the prevalence of structural and functional abnormalities of the lower urinary tract in a carefully defined population of 36 men with chronic urethritis who were attending a sexually transmitted disease clinic. They had experienced symptoms for an average of 12.1 months and had been treated with an average of 5.1 courses of antimicrobial drugs. All had objective evidence of urethral inflammation and negative cultures for both Neisseria gonorrhoeae and Chlamydia trachomatis. Structural abnormalities were documented in nine (25%) of 36 patients but were considered clinically significant in only four. Physical examination and uroflow testing led to clinical suspicion of anatomic abnormalities in all four patients with significant lesions, which included urethral strictures in three patients and benign prostatic hypertrophy in one patient. Additional abnormal findings included wide-bore strictures in three patients and developmental abnormalities of doubtful significance in two patients. Increased numbers of inflammatory cells in expressed prostatic secretions were associated with the presence of structural abnormalities. We conclude that among men with chronic urethritis, careful physical examination and uroflow studies can be used to screen for evidence of structural abnormalities that merit endoscopic evaluation.

Association between bacterial vaginosis and acute cystitis in women using diaphragms.

We hypothesized that the increased vaginal fluid pH and altered vaginal microflora characteristic of bacterial vaginosis might predispose young women to introital colonization with Escherichia coli and to acute cystitis. To evaluate this hypothesis, we studied 291 women who presented with acute urinary symptoms for association of clinically defined bacterial vaginosis and vaginal conditions associated with this syndrome (increased vaginal fluid pH, absence of lactobacilli, and abnormal vaginal fluid gas-liquid chromatographic patterns) with E coli introital colonization and urinary tract infection. Escherichia coli introital colonization and urinary tract infection were both significantly more frequent among women with a high vaginal fluid pH, an absence of vaginal lactobacilli, or an abnormal vaginal fluid gas-liquid chromatographic pattern characteristic of bacterial vaginosis. Escherichia coli introital colonization was also more frequent in women with bacterial vaginosis. These associations and an association of bacterial vaginosis and E coli urinary tract infection were strong only among the 144 women who were diaphragm users. We conclude that bacterial vaginosis, or an altered vaginal microflora as reflected by an abnormal gas-liquid chromatographic pattern characteristic of bacterial vaginosis, is associated with E coli introital colonization and acute symptomatic urinary tract infection in women who use diaphragms.

Incidence of HIV and sexually transmitted diseases (STD) in a cohort of HIV-negative men who have sex with men (MSM).

OBJECTIVE: To determine the prevalence of sexually transmitted diseases (STD) and incidence of and risk factors for STD, including HIV-1, among a cohort of HIV-negative men who have sex with men (MSM). SETTING: Seattle, Washington, United States. PARTICIPANTS: Prospective cohort of 578 HIV-negative MSM in which risk factors for acquiring a STD over 12 months follow-up were evaluated using a cumulative incidence analysis. MAIN OUTCOME MEASURES: Baseline tests obtained were: herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) Western blots, hepatitis B, and syphilis serologies; anorectal and pharyngeal Neisseria gonorrhoeae (GC) cultures; first-catch urine for leukocyte esterase (LE) and Chlamydia trachomatis (CT) ligase chain reaction (LCR). Men with a positive urine LE had urethral GC cultures obtained. The following outcomes were measured over 12 months follow-up: incident symptomatic bacterial STD (urethritis, proctitis, epididymitis), HSV-1 and HSV-2 seroconversion, and HIV-1 seroconversion. The 31 incident cases of STD (men with bacterial STD) were compared with those 489 men without symptomatic bacterial STD or seroconversion to HSV-1, HSV-2 or HIV-1 infection. RESULTS: Bacterial STD were found in nine participants at enrollment; there were two cases of nonchlamydial urethritis, two cases of nonchlamydial epididymitis, and five cases of asymptomatic GC infection. At enrollment, HSV-2 antibodies were detected in 149 (26.0%) of 572 men and prior hepatitis B infection in 145 (34.8%) of 417 unvaccinated men. During the 1-year of follow-up, 31 men (5.7/100 person-years) had 34 episodes of a symptomatic bacterial STD syndrome (urethritis, epididymitis or proctitis). Urethritis was the most common STD syndrome, detected in 29 men, of whom 10 had GC and 19 had nongonococcal urethritis. In the 1-year of follow-up, five participants seroconverted to HIV-1 (1.3/100 person-years), four to HSV-2 (1.0/100 person-years), and seven to HSV-1 (4.3/100 person-years). Unprotected insertive anal sex [odds ratio (OR) 2.6; 95% confidence interval (CI) 1.2-5.6]; and nitrite inhalant ('poppers') use (OR, 2.3; 95% CI, 1.0-5.0) were independently associated with incident STD. CONCLUSIONS: STD and HIV infection continue to be acquired even in a city with an overall low bacterial STD prevalence and among educated MSM receiving regular HIV screening and risk-reduction. Urethritis was the most common STD detected, and public health messages aimed at MSM need to emphasize safe insertive as well as receptive sexual practices.

Catheter-associated urinary tract infections: epidemiology, pathogenesis, and prevention.

Catheter-associated urinary tract infections (UTIc) remain the most common nosocomial infection. Although usually benign, UTIc cause bacteremia in 2-4% of patients and have been associated with a case fatality rate three times as high as nonbacteriuric patients. Risk factors for UTIc identified in multivariate analyses include increasing duration of use, female sex, absence of systemic antibiotics, and disconnection of the catheter-collecting tube junction. Recent studies suggest that most episodes of low colony count bacteriuria (10(2)-10(4) cfu/ml) rapidly progress to high (greater than or equal to 10(5)/ml) colony counts within 24-48 hours. In persons with long-term catheterization, bacteriuria inevitably develops and the infecting strains change frequently. In this setting, Proteus and Morganella species produce catheter encrustations and persistent bacteriuria. Routes of bacterial entry have been well defined and differ by gender, with the periurethral route predominating in women and the intraluminal route in men. Growth of bacteria in biofilms on the inner surface of catheters promotes encrustation and may protect bacteria from antimicrobial agents. Bacterial virulence factors have not been well characterized in UTIc, but fimbrial adhesins have been associated with bacterial persistence in the catheterized urinary tract, and urease production has been associated with stone formation and catheter encrustation. Recent efforts to prevent UTIc have focused mainly on preventing bacterial entry to the urinary tract or eradicating bacteriuria after its onset and have been largely unsuccessful. Systemic antimicrobials, sealed tubing and catheter junctions, silver ion-coated catheters, and antiseptics in the collecting bag have all been efficacious in one or more controlled trials. Failure to stratify patients by major risk factors, especially gender, antimicrobial exposure, and catheter duration, makes interpretation of many trials difficult. Further research in the areas of innovative catheter system design, bacterial-host epithelial cell interaction, and targeted antimicrobial prophylaxis seem the most likely approaches to controlling UTIc in the future.

Problems in the treatment of bacterial sexually transmitted diseases.

Although most bacterial sexually transmitted diseases (STDs) can be effectively treated, currently available regimens are far from ideal. Increasingly widespread plasmid-mediated resistance to the penicillins limits the use of these agents in the treatment of Neisseria gonorrhoeae and Hemophilus ducreyi infections. Chromosomally mediated antimicrobial resistance to the tetracyclines, penicillins, erythromycins, and sulfonamides further limits therapeutic options in the treatment of gonorrhea, and plasmid-mediated resistance to sulfonamides and tetracyclines is frequent in H. ducreyi infections. In patients with Chlamydia trachomatis infections, effective regimens that can more easily be complied with (shorter duration, less frequent dosing) are needed, as are effective alternative regimens for use in pregnancy and in infants. In selected STDs that are polymicrobial (pelvic inflammatory disease and bacterial vaginosis, for example) or that often present simultaneously (gonorrhea-chlamydia, gonorrhea-syphilis, chancroid-syphilis), single-drug regimens that are effective against several genital pathogens would be ideal. Only limited therapeutic alternatives are available for some STDs, especially in pregnant women or in patients with penicillin allergy. Thus, antimicrobial resistance, drug toxicity, poor compliance, limited alternatives in pregnancy or allergy, and the lack of single agents possessing a broad spectrum of activity against multiple genital pathogens limit currently available therapy.

Measurement of pyuria and its relation to bacteriuria.

Excluding specimen contamination, bacteriuria indicates either urinary colonization (replication of bacteria in urine without evidence of tissue invasion) or urinary tract infection (bacteriuria associated with clinical, histologic, or immunologic evidence of host injury). Practically speaking, measuring pyuria is the most readily available means of establishing the presence of host injury, thus differentiating colonization from infection. Careful studies have established the nonpathologic limits for pyuria (less than 10 leukocytes/mm3 in uncentrifuged urine) and have compared methods for its measurement. The most commonly used method, determination of cells per high power field in centrifuged urine, is not reproducible and does not correlate with either the actual leukocyte excretion rate or the cells per cubic millimeter as enumerated in a counting chamber. When clinical studies using the latter method of determining pyuria were reviewed, the following conclusions emerged: (1) 10 leukocytes/mm3 or greater occur in less than 1 percent of asymptomatic, nonbacteriuric patients but in greater than 96 percent of symptomatic men and women with significant bacteriuria; (2) most symptomatic women with pyuria but without significant bacteriuria have urinary infection either with bacterial uropathogens present in colony counts less than 10(5)/ml or with Chlamydia trachomatis; (3) women with asymptomatic bacteriuria probably should be divided into two subgroups: those with true asymptomatic infection (associated with pyuria) and those with transient, self-limited bladder colonization; and (4) most patients with catheter-associated bacteriuria also have pyuria and hence infection. In view of its potential value to both clinicians and microbiologists, pyuria should be accurately determined and expressed as cells per cubic millimeter in uncentrifuged urine.

Prevention of urinary tract infections.

Potential candidates for measures designed to prevent urinary tract infections include (1) women (or girls) with frequent exogenous reinfections; (2) pregnant women; (3) hospitalized patients with short-term indwelling catheters; (4) men with chronic bacterial prostatitis; (5) patients with neurogenic bladders being managed with either intermittent catheterization or chronic indwelling catheters; and (6) men undergoing urologic surgery. Patients in the first three categories represent the vast majority of men and women with preventable urinary tract infections. On the basis of our current understanding of the pathogenesis of urinary infections in women, potential preventive measures can be envisioned. To date, the most successful methods in susceptible women include continuous low-dose antimicrobial prophylaxis or postintercourse antibiotic prophylaxis. In controlled clinical trials, the efficacy of low-dose trimethoprim-sulfamethoxazole, trimethoprim, or nitrofurantoin has repeatedly been demonstrated, and the cost effectiveness of this approach has also been established. An alternative strategy, intermittent, self-administered, single-dose antimicrobial therapy, may be useful in selected circumstances. Screening of high-risk patients for asymptomatic infections has largely been abandoned except in pregnant women in whom this practice remains an important preventive measure. Exciting newer approaches to prevention based on studies clarifying the fimbrial structures mediating bacterial adherence to receptors on uroepithelial cells include the use of receptor analogs and immunoprophylaxis, but these approaches are not yet of demonstrated clinical efficacy.

Azithromycin in the treatment of uncomplicated genital chlamydial infections.

Chlamydia trachomatis is among the most prevalent of sexually transmitted diseases and causes serious sequelae, especially in women. A major difficulty facing the clinician has been the effective treatment of patients with chlamydial infections, since existing drugs require 7 or more days of multidose therapy, and hence considerable commitment from the patient. Many patients, especially those who are minimally symptomatic or asymptomatic, are likely to be noncompliant when given such multiple day regimens and thus may fail therapy. Azithromycin is an azalide antibiotic that has a minimum inhibitory concentration against C. trachomatis of between 0.03 and 0.25 mg/L, as well as good in vitro activity against other sexually transmitted pathogens that are often present concurrently. Azithromycin also achieves high intracellular concentrations, which may be beneficial in eradicating Chlamydia, an obligate intracellular pathogen. More importantly, azithromycin has high tissue bioavailability and a tissue half-life of between 2 and 4 days. These pharmacokinetic properties imply that the dosing period for azithromycin can be greatly reduced while still achieving high antimicrobial activity at sites of infection. Clinical experience to date shows that a single 1 g oral dose of azithromycin is as effective as a standard 7-day twice daily regimen of doxycycline and more effective than 7 days of ciprofloxacin in eradicating uncomplicated chlamydial genital infections. As such, azithromycin is the first single-dose therapy for the treatment of urethritis and cervicitis due to C. trachomatis. Single-dose therapy for chlamydial infection, which could be administered under supervision in the clinic, would be a significant advance in the management and public health control of chlamydial infections.

Comparison of endemic and epidemic nosocomial infections.

Epidemics account for a small proportion of preventable infections acquired in hospitals, but they have been important in defining sources, modes of spread, and methods for prevention and control of nosocomial infections. To characterize hospital-based epidemics, 265 consecutive outbreaks investigated by the Center for Disease Control between 1956 and 1979 were reviewed. Pseudoepidemics were found in 11 percent of the investigations, most often resulting from errors in processing microbiologic specimens or from surveillance artifacts. In 223 actual epidemics, the pathogens most commonly involved were Staphylococcus aureus (19 percent), tribe Klebsielleae (14 percent), Salmonella (13 percent), hepatitis B virus (8 percent), enteropathogenic Escherichia coli (5 percent), Pseudomonas (4 percent) and group A streptococci (4 percent). Sites of epidemic infection were closely linked to the responsible pathogens. Gastroenteritis (21 percent), skin infection (18 percent), bacteremia (12 percent), meningitis (11 percent) and hepatitis (10 percent), infrequent causes of endemic nosocomial infections, were frequently involved in epidemics. Over the 25-year period reviewed, staphylococcal epidemics and outbreaks of gastroenteritis due to Salmonella and Esch. coli declined in frequency and those due to gram-negative bacilli and hepatitis B virus increased. Since 1970, clusters of primary bacteremia were the most frequently investigated type of epidemic. Many epidemic strains of staphylococci obtained since 1975 or Enterobacteriaceae obtained since 1970 exhibited unusual drug resistance. Specific site-pathogen combinations were closely associated with characteristic reservoirs and modes of spread.

The effect of private isolation rooms on patient care practices, Colonization and infection in an intensive care unit.

Conversion of an intensive care unit (ICU) from an open unit to isolation rooms permitted study of patient care practices, colonization and infection in both settings. Air sampling and observation of patient care practices included 99 of 410 open unit patients (168 patient-hours during nine months) and 68 of 1,022 isolation room patients matched on the basis of risk factors for infection and staff contact (113 patient-hours during 12 months). Number and type of interactions between staff and patients, and frequency of handwashing and its relationship to patient-staff interactions were recorded. All ICU patients were monitored daily for signs of and selected risk factors for infection, and material for culture for six surveillance organisms was obtained every four days. Numbers of persons interacting with a patient hour were 6.1 +/- 3.5 in the open units and 4.9 +/- 2.8 in the isolation rooms (0.05 less than P less than 0.10). Frequency of handwashing did not increase significantly in the unit providing convenient sinks, occurring in an observed to expected ratio of only 24 percent. Over-all rates of infection in the open unit and isolation rooms were 15.0 and 13.4, respectively. Half of the infections occurring in patients with complete cultures obtained on admission were caused by organisms colonizing the patient upon admission to the ICU. The isolation rooms did not appear to reduce nosocomial acquisition (P = 0.168, Mantel-Haenszel) of the six surveillance organisms. We conclude that many patient-staff interactions in an ICU are not followed by handwashing, and that the new unit design had no apparent effect upon the frequency of handwashing or over-all incidence of colonization and infection in the ICU.

The effectiveness of a clinical practice guideline for the management of presumed uncomplicated urinary tract infection in women.

PURPOSE: Acute uncomplicated urinary tract infection is a common and costly disorder in women. To reduce potentially unnecessary expense and inconvenience, a large staff-model health maintenance organization instituted a telephone-based clinical practice guideline for managing presumed cystitis in which women 18 to 55 years of age who met specific criteria were managed without a clinic visit or laboratory testing. We sought to evaluate the effects of the guideline. SUBJECTS AND METHODS: We performed a population-based, before-and-after study with concurrent control groups at 24 primary care clinics to assess the effect of guideline implementation on resource utilization and on the occurrence of potential adverse outcomes. We measured the proportion of patients with presumed uncomplicated cystitis who had a return office visit for cystitis or sexually transmitted disease or who developed pyelonephritis within 60 days of the initial diagnosis. Relative risks (RR) and 95% confidence intervals (CI) were estimated, adjusting for the effects of clustering within clinics. RESULTS: A total of 3,889 eligible patients with presumed acute uncomplicated cystitis were evaluated. As compared with baseline, guideline implementation significantly decreased the proportion of patients with presumed cystitis who received urinalysis (RR = 0.75; CI, 0.70 to 0.80), urine culture (RR = 0.73; CI, 0.68 to 0.79), and an initial office visit (RR = 0.67; CI, 0.62 to 0.73), while increasing the proportion who received a guideline-recommended antibiotic 2.9-fold (CI, 2.4 to 3.7-fold). In the prospective comparison of the 22 intervention and two control clinics, the guideline decreased the proportion of patients who had urinalyses performed (RR = 0.80; CI, 0.65 to 0.98) and increased the proportion of patients who were prescribed a guideline-recommended antibiotic (RR = 1.53; CI, 1.01 to 2.33). Adverse outcomes did not increase significantly in either comparison. CONCLUSION: Guideline use decreased laboratory utilization and overall costs while maintaining or improving the quality of care for patients who were presumptively treated for acute uncomplicated cystitis.

Intestinal spirochetosis in homosexual men.

Previous studies have demonstrated intestinal spirochetosis in rectal biopsy specimens from 2 to 7 percent of heterosexual and 36 percent of homosexual patients, but the role of intestinal spirochetosis in the pathogenesis of intestinal disease remains unclear. To assess the clinical, histologic, and microbiologic correlates of intestinal spirochetosis in a high-risk group, rectal biopsy specimens from 130 homosexual men, 92 percent of whom had intestinal symptoms, were evaluated. All men were extensively evaluated for rectal and enteric pathogens. Intestinal spirochetosis was identified in rectal biopsy specimens from 39 (30 percent) men; 15 percent of biopsy specimens revealed intestinal spirochetosis on hematoxylin and eosin plus alcian blue staining, and positive results were found in 30 percent on silver staining. No rectal biopsy specimens from 79 control patients with a variety of gastrointestinal symptoms demonstrated evidence of spirochetosis on hematoxylin and eosin, alcian blue, or silver staining (p less than 0.0001). Fifty-six percent of rectal biopsy specimens from men with intestinal spirochetosis were normal, and no specific histologic abnormality was correlated with intestinal spirochetosis. There were no differences in the presence of or type of intestinal symptoms, sigmoidoscopic appearance of the mucosa, type of sexual practice, or prior antibiotic use in men with and without spirochetosis. Other intestinal pathogens were frequent in both groups, and only rectal gonorrhea was significantly associated with intestinal spirochetosis. It is concluded that homosexual men with intestinal symptoms have an increased prevalence of spirochetosis, often in association with Neisseria gonorrhoeae. Independent association of spirochetosis with clinical or histologic findings could not be demonstrated.

Endometrial histopathology in patients with culture-proved upper genital tract infection and laparoscopically diagnosed acute salpingitis.

To define and quantitate histologic changes in the endometrium that best correlate with documented upper genital tract infection (UGTI) and laparoscopically diagnosed acute salpingitis, we studied endometrial biopsy specimens from 69 consecutive patients with clinically suspected acute pelvic inflammatory disease (PID) who underwent microbiological evaluation for UGTI and laparoscopic examination for acute salpingitis. Both UGTI and acute laparoscopically confirmed salpingitis were present in 37 patients (54%), UGTI without salpingitis in 1 (1%), salpingitis without UGTI in 11 (16%), and neither UGTI nor salpingitis in 20 (29%). Chlamydia trachomatis or Neisseria gonorrhoeae UGTI was found in 34 women, Escherichia coli in two patients, Peptococcus magnus in one woman, and with Streptococcus agalactiae in one woman. The following features were correlated both with UGTI and with salpingitis: presence of any neutrophils in the endometrial surface epithelium; neutrophils within gland lumens; dense subepithelial stromal lymphocytic infiltration; any stromal plasma cells; and germinal centers containing transformed lymphocytes. The simultaneous presence of five or more neutrophils per X 400 field in endometrial surface epithelium, together with one or more plasma cell per X 120 field in endometrial stroma, was the best predictor of UGTI plus salpingitis. This combination had a sensitivity of 92% and a specificity of 87% for predicting the diagnosis of both UGTI and laparoscopically confirmable acute salpingitis. Prospective studies are needed to assess the usefulness of these criteria.

Chlamydia trachomatis infection as a cause of pneumonia after human marrow transplantation.

Seventy-two marrow transplant patients were studied to assess the role of Chlamydia trachomatis infection in the etiology of pneumonia in the compromised host. Sixty-four patients had pneumonia from various causes and eight died of causes other than pneumonia. Chlamydial serologies and cultures of lung tissue, or other sites, or both, were obtained from all patients. C trachomatis was recovered from a single sputum specimen obtained at the onset of pneumonia in one patient, and three patients developed sustained IgG and IgM antibody responses to chlamydiae during their pneumonia. Two of the four patients died of pneumonia. These data further confirm that C trachomatis infection occurs in immunosuppressed patients in association with pneumonia. The source of the organism and the frequency of infection remain to be determined.

Direct fluorescent monoclonal antibody stain for rapid detection of infant Chlamydia trachomatis infections.

A method of direct fluorescent antibody staining for rapid diagnosis of Chlamydia trachomatis infections in infants is described. This method utilized a fluorescein-conjugated species-specific monoclonal antibody to C trachomatis for detecting chlamydial elementary bodies in smears of the conjunctiva, nasopharynx, oropharynx, anus, and vagina. The sensitivity of direct fluorescent antibody staining was compared with isolation of the organisms in McCoy cells. Thirty-nine infants with purulent conjunctivitis were studied. Diagnosis of C trachomatis conjunctivitis was correctly made by smear in all 16 infants when inflamed eyes were sampled. Positive smears were obtained from 12/14 culture-positive and 4/16 culture-negative nasopharyngeal specimens from infants with chlamydial conjunctivitis. All nasopharyngeal cultures and smears from infants with nonchlamydial conjunctivitis were negative. These results indicate that the direct smear test is a sensitive and specific test for diagnosing C trachomatis infection of the eye and nasopharynx in infants, and this test can be completed within one hour of specimen collection.