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.     

The association of maternal and fetal glucose homeostasis with fetal adiposity and birthweight

ObjectiveTo examine the association between maternal and fetal glucose levels and fetal adiposity and infant birthweight.Study designThis is a prospective study of 479 healthy, non-diabetic mother and infant pairs attending the National Maternity Hospital in Ireland. Fasting glucose was measured in early pregnancy (11.8 ± 2.3 weeks). At 28 weeks gestation a repeat fasting glucose was measured and 1 h glucose challenge testing (1 h GCT) was performed. At 34 weeks’ gestation (33 + 5–34 + 5 weeks) fetal growth and fetal anterior abdominal wall width, a marker of fetal adiposity, were measured. At delivery cord glucose was measured and neonatal anthropometry recorded.ResultsThere was a positive correlation between fasting glucose concentration during pregnancy and both infant birthweight and fetal anterior abdominal wall width at 34 weeks gestation. The incidence of macrosomia (birthweight > 4.5 kg) was significantly greater for maternal and cord blood glucose levels in the highest quartile compared to the lowest quartile (20.7% vs. 11.7%, p < 0.05 in the first trimester, 21.3% vs. 7.2%, p < 0.05, at 28 weeks, and 33.3% vs. 10%, p < 0.05, in cord blood). Maternal glucose concentrations at each time point, though not cord glucose, were related to early pregnancy maternal body mass index (r = 0.19, p < 0.001 in first trimester, r = 0.25, p < 0.001 at 28 weeks, r = 0.15, p < 0.01 with 1 h GCT).ConclusionMaternal glucose homeostasis is an important determinant of fetal size. We have shown that even small variations in fasting glucose concentrations can influence fetal growth and adiposity. This effect is seen from the first trimester and maintained until delivery.     

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.     

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.