Chronic administration of nevirapine during pregnancy: impact of pregnancy on pharmacokinetics.

OBJECTIVES: To determine the impact of pregnancy on the pharmacokinetics (PK) of nevirapine (NVP) during chronic dosing in HIV-infected women and appropriate NVP dosing in this population. METHODS: Twenty-six pregnant women participating in two open-label Pediatric AIDS Clinical Trials Group studies (P1022 and P1026S) were evaluated. Each patient received 200 mg NVP every 12 h and had PK evaluations during the second or third trimester; these evaluations were repeated postpartum. Paired maternal and cord blood NVP concentrations were collected at delivery in nine patients. Ante- and postpartum comparisons were made using paired t-tests and using a 'bioequivalence' approach to determine confidence interval (CI). RESULTS: The average NVP Area Under the Curve (AUC) was 56 +/- 13 mcg(*)h/mL antepartum and 61 +/- 15 mcg(*)h/mL postpartum. The typical parameters +/- standard error were apparent clearance (CL/F)=3.51 +/- 0.18 L/h and apparent volume of distribution (Vd/F)=121 +/- 19.8 L. There were no significant differences between antepartum and postpartum AUC or pre-dose concentrations. The AUC ratio was 0.90 with a 90% CI of the mean equal to 0.80-1.02. The median (+/- standard deviation) cord blood to maternal NVP concentration ratio was 0.91 +/- 0.90. CONCLUSIONS: Pregnancy does not alter NVP PK and the standard dose (200 mg every 12 h) is appropriate during pregnancy.

Randomized trial of trovafloxacin and ofloxacin for single-dose therapy of gonorrhea. Trovafloxacin Gonorrhea Study Group.

PURPOSE: To compare trovafloxacin, a new quinolone antibiotic with enhanced activity against Neisseria gonorrhoeae, with ofloxacin as single-dose oral therapy for uncomplicated gonococcal urethritis or cervicitis. PATIENTS AND METHODS: In this multicenter, double-blind trial, 625 patients (270 men, 355 women) with uncomplicated gonococcal urethritis or cervicitis received one 100-mg tablet of trovafloxacin or two 200-mg capsules of ofloxacin as a single dose under direct supervision. RESULTS: Single-dose oral therapy with trovafloxacin was equivalent both bacteriologically and clinically to ofloxacin. Among evaluable patients, N gonorrhoeae was eradicated in 99% of trovafloxacin recipients and in 98% of ofloxacin recipients. Each treatment was well tolerated; vaginitis was the most frequently observed side effect (4% trovafloxacin, 7% ofloxacin). CONCLUSION: Based on the results presented here, trovafloxacin is a promising agent for single-dose therapy of uncomplicated gonorrhea.

Comparison of single-dose cefuroxime axetil with ciprofloxacin in treatment of uncomplicated gonorrhea caused by penicillinase-producing and non-penicillinase-producing Neisseria gonorrhoeae strains.

A randomized, multicenter, investigator-blind trial was conducted to compare the efficacies of cefuroxime axetil and ciprofloxacin for treatment of patients with uncomplicated gonorrhea caused by penicillinase-producing Neisseria gonorrhoeae (PPNG). A total of 832 patients (434 females and 398 males) received a single oral dose of cefuroxime axetil (1,000 mg [417 patients]) or ciprofloxacin (500 mg [415 patients]). N. gonorrhoeae was eradicated from the cervix in 114 of 118 (97%) and 118 of 119 (99%) bacteriologically evaluable females treated with cefuroxime axetil and ciprofloxacin, respectively (P = 0.213; difference, -2%; 95% confidence interval, -6 to 1%), and from the urethra in 154 of 166 (93%) and 171 of 171 (100%) bacteriologically evaluable male patients treated with cefuroxime axetil and ciprofloxacin, respectively (P < 0.001; difference, -7%; 95% confidence interval, -11 to -3%). Both treatments were effective in eradicating N. gonorrhoeae in females with rectal infections (cefuroxime axetil, 29 of 30 [97%]; ciprofloxacin, 25 of 25 [100%]; P = 1.00). In small numbers of patients, cefuroxime axetil was less effective than ciprofloxacin in treating males with pharyngeal infections (eradication in 4 of 10 and in 8 of 8 patients, respectively; P = 0.013). PPNG was eradicated from the cervix in 22 of 23 (96%) and 32 of 32 (100%) bacteriologically evaluable female patients treated with cefuroxime axetil and ciprofloxacin, respectively (P = 0.418; difference, -4%; 95% confidence interval, -13 to 4%), and from the urethra in 35 of 36 (97%) and 34 of 34 (100%) bacteriologically evaluable male patients treated with cefuroxime axetil and ciprofloxacin, respectively (P = 1.00; difference, -3%; 95% confidence interval, -8 to 3%). The incidences of drug-related adverse events were similar for the two study drugs. In summary, treatment with a single oral dose of cefuroxime axetil is as effective as treatment with a single oral dose of ciprofloxacin in eradicating PPNG from males and females with uncomplicated gonorrhea (urethral and endocervical), and both regimens are well-tolerated. However, in the present study, cefuroxime axetil was less effective than ciprofloxacin in treating urethral gonococcal infections in male patients, although both study drugs were highly effective in treating cervical gonococcal infections in female patients.

Chlamydial cervicitis and urethritis: single dose treatment compared with doxycycline for seven days in community based practises.

STUDY GOAL: To compare the efficacy and safety of single 1 g oral azithromycin with doxycycline, 100 mg twice daily for seven days for treatment of uncomplicated urogenital chlamydial infection. STUDY DESIGN: Randomised, unblinded, comparative trial, involving 597 patients demonstrating clinical evidence of genital chlamydia and a positive non-culture assay for Chlamydia trachomatis. RESULTS: Among the azithromycin- and doxycycline-treated patients 61% and 60%, respectively, were asymptomatic within one week after the first dose. At two weeks, these figures increased to 86% and 83%, respectively. Bacteriological eradication, based on a negative assay, occurred in 338 (97%) of 347 azithromycin-treated patients and 161 (99%) of 163 doxycycline-treated patients. CONCLUSION: Treatment of uncomplicated chlamydial cervicitis and urethritis with single 1 g oral azithromycin is equivalent to standard therapy with doxycycline. Drug-related adverse events were approximately twice as common as previously reported for both drugs.

Treatment of post-cesarean section endometritis with ampicillin and sulbactam or clindamycin and gentamicin.

Seventy-seven patients were prospectively enrolled in a randomized clinical trial to compare two antimicrobial regimens for the treatment of post-cesarean section endometritis. The two groups were not significantly different with respect to age, race, gravidity, parity, hours in labor, cesarean section indication, preoperative or postoperative hemoglobin/hematocrit, pretreatment white blood cell count or pretreatment temperature. Pretreatment urine, blood and endometrial cultures were obtained. One or more organisms was recovered from the endometrium in 90% of the patients using a double-lumen sampling device. The most frequent endometrial isolates were Peptostreptococcus and Bacteroides species, followed by Gardnerella vaginalis and enterococci. Thirty (81%) of 37 patients receiving ampicillin/sulbactam and 33 (83%) of 40 receiving gentamicin and clindamycin responded to therapy. There were 14 (18%) treatment failures, 7 in each group. Five (36%) of the 14 clinical failures were due to septic pelvic thrombophlebitis, 2 (14%) of the 14 failures were complications of intraabdominal abscesses, and the remaining 7 patients responded after a change in their antibiotic regimen. We conclude that ampicillin/sulbactam and clindamycin/gentamicin are similarly effective for the treatment of post-cesarean section endometritis.

Nonimmune hydrops fetalis associated with maternal infection with syphilis.

Intrauterine infection with syphilis was diagnosed by reactive maternal serologic studies, ultrasonographic findings, and exclusion of other causes in three hydropic fetuses at 31, 34, and 35 weeks' gestation. With penicillin therapy and preterm delivery all infants survived through the perinatal period. Intrauterine infection that follows syphilis is a potentially treatable cause of nonimmune hydrops.