Detection of Chlamydia trachomatis antigens in urine as an alternative to swabs and cultures

By using commercially available spectrophotometric and immunofluorescent immunoassays, Chlamydia trachomatis antigens were detected in first-void urine (FVU) sediments from 224 men attending a sexually transmitted disease clinic at a frequency of 81.6%-86.8% compared with 86.8% (33/38) positive by urethral swab culture (P less than .05). Endocervical cultures from 228 women attending a gynecology clinic yielded 92.3% (12/13) positive compared with 61.5%-76.9% for urine samples in three antigen-detection assays. Culturing urine from either gender yielded low positivity rates (23.7% for men, 15.4% for women). Defining truly infected patients as positive by culture or by any two of the three antigen tests, all assays were 100% specific. Immunodiagnostic testing of male FVU sediment appears to be a reliable, rapid, nontraumatic method for diagnosing chlamydia infection.     

Value of the gram-stained urethral smear in the management of men with urethritis

The value of the gram-stained urethral smear in clinical decision-making was assessed in a study of 250 men attending a clinic for sexually transmitted diseases. Of the 250 men, 132 (52.8%) had objective evidence of urethritis. Neisseria gonorrhoeae and/or Chlamydia trachomatis was isolated from 94 patients (37.6%). No pathogens were isolated from 38 patients (15.2%) who were diagnosed as having urethritis. Although the specificity (0.95) and positive predictive value (0.95) of the gram smear for culture-proved urethral infection was high, the relatively low sensitivity (0.66) and negative predictive value (0.63), led us to conclude that the test was of limited value in diagnosis and therapeutic decision-making when the patient was first seen. The decision to treat a patient should be based on a reliable history of dysuria and/or a urethral discharge in a patient at risk of infection, with or without an observable urethral discharge. Nevertheless, a gram smear should be done for all patients who are diagnosed presumptively as having urethritis, because it may be the only objective evidence of urethritis.     

Replicate PCR testing and probit analysis for detection and quantitation of Chlamydia pneumoniae in clinical specimens

Nucleic acid amplification of clinical specimens with low target concentration has variable sensitivity. We examined whether testing multiple aliquots of extracted DNA increased the sensitivity and reproducibility of Chlamydia pneumoniae detection by PCR. Nested and non-nested C. pneumoniae PCR assays were compared using 10 replicates of 16 serial dilutions of C. pneumoniae ATCC VR-1310. The proportion positive versus the C. pneumoniae concentration was modeled by probit regression analysis. To validate the model, 10 replicates of 26 previously positive patient specimens of peripheral blood mononuclear cells (PBMC), sputum, or nasopharyngeal swabs (NPS) were tested. The proportion of replicates that were positive varied with the concentration of C. pneumoniae in the sample. At concentrations above 5 infection-forming units (IFU)/ml, both nested and non-nested PCR assay sensitivities were 90% or greater. The nested PCR was more sensitive (median detection, 0.35 versus 0.61 IFU/ml; relative median detection, 0.58; 95% confidence interval, 0.31 to 0.99; P = 0.04). In clinical specimens, replicate PCR detected 15 of 26 (nested) versus 1 of 26 (non-nested, P < 0.001). For PBMC specimens, testing 1, 3, or 5 replicates detected 3, 5, or 9 of 10 positive specimens, respectively. Median C. pneumoniae concentrations were estimated at 0.07 IFU/ml for PBMC and at <0.03 IFU/ml for NPS specimens. We conclude that performing 5 or 10 replicates considerably increased the sensitivity and reproducibility of C. pneumoniae PCR and enabled quantitation for clinical specimens. Due to sampling variability, PCR tests done without replication may miss a large proportion of positive specimens, particularly for specimens with small amounts of target C. pneumoniae DNA present.     

Correlation between culture testing of swabs and ligase chain reaction of first void urine from patients recently treated for Chlamydia trachomatis

We assessed the correlation between ligase chain reaction (LCR) on first void urine (FVU) and cultures of urethral and cervical swabs to detect chlamydia during three post-treatment follow up visits for 10 men and 19 women with genital chlamydial infections who had been treated with azithromycin or doxcycline.     

Use of moxonidine in elderly patients with resistant hypertension

BACKGROUND: Treatment of hypertension in the elderly people reduces the risk of cardiovascular and cerebrovascular events. Effective treatment often will require the use of two or more antihypertensive agents. Elderly people are at increased risk of adverse events from medication because of physiological changes in pharmacokinetics and pharmacodynamics, polypharmacy and drug interactions. They might not tolerate conventional add-on regimens of antihypertensives as a result. OBJECTIVE: To investigate the use of the I1-imidazoline receptor agonist moxonidine as an 'add-on' agent in elderly patients with resistant hypertension. METHODS: We investigated the safety and efficacy of moxonidine (200-400 microg) in a group of elderly patients whose blood pressure (BP) control remained poor despite treatment with two or more antihypertensives. BP was assessed by ambulatory BP monitoring with Spacelabs oscillometric equipment (Model 90207) before and after 6 weeks of treatment with moxonidine used as an 'add-on' agent with the patients normal medication. RESULTS: Following treatment with moxonidine, the mean daytime systolic BP fell from 169.2 to 153.8 mmHg, a significant reduction of 15.4 +/- 8.9 mmHg (P = 0.003). The mean daytime diastolic BP fell from 91.6 to 84.2 mmHg, a reduction of 7.4 +/- 5.8 mmHg (P = 0.017). For the night-time readings, the systolic BP fell from 151.1 to 141.2 mmHg, a reduction of 9.3 +/- 9.3 mmHg (P = 0.05). The corresponding diastolic fall in BP was not significant (77.9-74.7 mmHg). The 24 h-readings showed a significant reduction in the mean systolic BP from 163.0 to 148.6 mmHg (P = 0.004). The mean diastolic BP also fell significantly from 87.2 to 80.2 mmHg (P = 0.013). Clinical BP readings also showed a significant reduction from 195.9 +/- 19.6 to 174 +/- 17.8 mmHg (P = 0.002) and 103.6 +/- 9.5 to 99.0 +/- 12.4 mmHg (P = 0.013) for systolic and diastolic readings respectively. Moxonidine was well tolerated in 11 of the14 patients. CONCLUSION: These results suggest that moxonidine might have a place as an 'add-on' treatment in elderly patients whose hypertension is poorly controlled despite treatment with two or more antihypertensive agents.     

Upper gastrointestinal tolerability of alendronate sodium monohydrate 10 mg once daily in postmenopausal women: A 12-week,randomized, double-blind,placebo-controlled,exploratory study

Background: The dissolution profiles of generic oral bisphosphonate alendronate (ALN) sodium for the treatment of postmenopausal osteoporosis differ by formulation, suggesting potential differences in the risk for upper gastrointestinal (GI) irritation.Objective: This study compared the tolerability profile of ALN monohydrate with that of placebo, with a focus on upper GI irritation, in postmenopausal women with osteoporosis.Methods: This multicenter, double-blind, placebo-controlled estimation study enrolled postmenopausal women with osteoporosis. Patients were randomized in a 2:1 ratio to receive ALN monohydrate 10 mg or placebo once daily for 12 weeks. Tolerability was monitored throughout the study and up to 14 days after administration of the final dose. Primary end points were the proportions of patients with upper GI adverse events (AEs); upper GI AEs that were rated as serious or study drug related or that led to study discontinuation; and esophageal AEs. Between-treatment differences and associated 95% CIs were assessed using the Wilson score method.Results: Of 438 patients who were randomized, 367 (mean age, 65.5 years; history of osteoporotic fracture, 6.8%; ALN monohydrate, 237; placebo, 130) completed the study. The proportion of patients with a history of upper GI disorders at baseline was numerically greater in the ALN monohydrate group than in the placebo group (117 [40.2%] and 45 [30.6%], respectively). The proportions of patients with active baseline upper GI disease were 83 (28.5%) and 30 (20.4%) in the ALN monohydrate and placebo groups, respectively. The proportions of patients who experienced an upper GI AE during the study period were 66 (22.7%) and 30 (20.4%) (95% CI, ?6.2 to 10.0). The proportions of patients with upper GI AEs that were rated as serious or study drug related or that led to study discontinuation were 20.3% and 12.9% (95% CI, ?0.3% to 14.1%). Three serious AEs in the active-treatment group (breast cancer, 2; wrist fracture, 1) were not considered related to the study drug, nor was the 1 serious AE in the placebo group (wrist fracture). One patient (ALN monohydrate) had an esophageal AE (nonserious spasm). Approximately 8% of patients who received ALN monohydrate reported dyspepsia, compared with none who received placebo. Within each treatment group, the rates of upper GI AEs were numerically higher in patients with a history of upper GI disease.Conclusions: In these postmenopausal women who received ALN monohydrate or placebo, upper GI AEs were common (20.4%–22.7%). The proportion of patients who experienced upper GI AEs considered drug related or that led to discontinuation was appar- ently greater with ALN monohydrate compared with placebo.     

Antimicrobial activities of synthetic bismuth compounds against Clostridium difficile

Clostridium difficile is a major nosocomial pathogen responsible for pseudomembranous colitis and many cases of antibiotic-associated diarrhea. Because of potential relapse of disease with current antimicrobial therapy protocols, there is a need for additional and/or alternative antimicrobial agents for the treatment of disease caused by C. difficile. We have synthesized a systematic series of 14 structurally simple bismuth compounds and assessed their biological activities against C. difficile and four other gastrointestinal species, including Helicobacter pylori. Here, we report on the activities of six compounds that exhibit antibacterial activities against C. difficile, and some of the compounds have MICs of less than 1 microgram/ml. Also tested, for comparison, were the activities of bismuth subcitrate and ranitidine bismuth citrate obtained from commercial sources. C. difficile and H. pylori were more sensitive both to the synthetic bismuth compounds and to the commercial products than were Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis, and the last three species were markedly resistant to the commercial bismuth salts. Testing with human foreskin fibroblast cells revealed that some of the synthetic compounds were more cytotoxic than others. Killing curves for C. difficile treated with the more active compounds revealed rapid death, and electron microscopy showed that the bismuth of these compounds was rapidly incorporated by C. difficile. Energy dispersive spectroscopy X-ray microanalysis of C. difficile cells containing electron-dense material confirmed the presence of internalized bismuth. Internalized bismuth was not observed in C. difficile treated with synthetic bismuth compounds that lacked antimicrobial activity, which suggests that the uptake of the metal is required for killing activity. The nature of the carrier would seem to determine whether bismuth is transported into susceptible bacteria like C. difficile.