Short-course itraconazole in the treatment of candida vulvovaginitis: A multicentre Canadian study.

OBJECTIVE: To determine the clinical and mycological effectiveness of oral itraconazole in the treatment of acute candida vulvovaginitis. DESIGN: A prospective, randomized and single-blinded, multicentre trial of 221 women, comparing a one-day course of oral itraconazole 200 mg bid with vaginal clotrimazole 500 mg single-dose therapy. MAIN OUTCOME MEASURES: Symptoms, signs and mycological results were assessed up to two months following treatment. Adverse events were recorded and evidence of hepatotoxicity sought. RESULTS: At 10 and 30 days post-treatment, clinical and mycological cure rates were similar (61.3% clinical and 88.6% mycological 10 days after, and 67.7% clinical and 79.5 mycological 30 days after itraconazole; 64.0 clinical and 85.9% mycological 10 days after, and 62.1% clinical and 78.6 mycological 30 days after clotrimazole) with the majority of both treatment groups free from infection. A total of 69 patients reported adverse events, which were generally transient and mild. Itraconazole was more often associated with gastrointestinal or central nervous system complaints, while clotrimazole recipients more often had genitourinary symptoms. No evidence of hepatotoxicity was found. A higher incidence of relapse was noted among women on the birth control pill and among those who were symptomatic for longer than 10 days before treatment. CONCLUSIONS: A one-day course of oral itraconazole is as effective as intravaginal clotrimazole in the treatment of acute yeast vulvovaginitis. The number of patients reporting adverse events was similar for the treatment groups, although the side effect profile differed. No hepatotoxicity was observed.

Detection of Chlamydia trachomatis antigen by enzyme immunoassay: importance of confirmatory testing.

AIM--To determine when a fluorescence assay for Chlamydia trachomatis elementary bodies in the specimen buffer is of most value as a verification test for genital specimens reactive on screening enzyme immunoassay (EIA). METHOD--Genital swabs from high and medium prevalence populations were tested using EIA. Samples with absorbance values greater than the positive threshold and those within the range of 30% below this value were verified by the MicroTrak direct fluorescence assay (DFA) test. Quotients derived from the threshold value and specimen absorbances were used to establish confidence limits for the EIA. RESULTS--Of 13,283 swabs tested, 474 from the high risk group and 236 from the medium risk group were reactive on EIA and confirmed by DFA. Thirty six (5.9%) patients with confirmed reactive samples would have been missed if the kit criteria alone were followed. When confidence limits were applied to the calculated quotients, only those samples with an EIA quotient of > or = 4.0 were universally confirmed by the DFA. CONCLUSION--A scheme of testing which uses the DFA to verify EIA reactive specimens over a specified range was found to improve the sensitivity and specificity of the EIA screening test.

Diagnosis and treatment of enterococcal endocarditis.

Enterococci are frequently encountered in urinary, biliary, and gastrointestinal tract infections and are increasingly being recognized in nosocomial bacteriuria and bacteremia. Undoubtedly, however, the most serious of all enterococcal infections is endocarditis. At present, enterococci are the third most common cause of infective endocarditis (after streptococci and Staphylococcus aureus), and the incidence of the disease is likely to grow as the population ages and increasing numbers of persons are placed at risk by degenerative valve disease and by predisposition to enterococcal infections through portals such as the genitourinary tract. The case presented here exemplifies many features of enterococcal endocarditis. It also illustrates the therapeutic issues and dilemmas faced in managing this disorder. Although a transesophageal approach (Figure 1) has increased the sensitivity of echocardiography for detecting valvular abnormalities in infective endocarditis, diagnosis continues to rely on blood cultures--which raises the question of how long antimicrobial therapy should be delayed for collection of blood samples. Since enterococcal isolates are often resistant to antibiotics, therapy is based on synergistic drug combinations.

Enterococcal endocarditis.

Enterococci, most often Enterococcus faecalis, cause 5%-20% of cases of infective endocarditis (IE). Enterococcal IE is usually a disease of older men, and the most frequent source of infection is the genitourinary tract. In cases of enterococcal IE, both normal and previously damaged valves can be involved. The disease most commonly presents in a subacute fashion; clinical and laboratory features are similar to those observed with IE caused by other pathogens. Diagnosis is based on the presence of clinical criteria of IE in association with positive blood cultures. Optimal therapy entails the parenteral use of a cell wall-active agent (penicillin G, ampicillin, or vancomycin) in combination with streptomycin or gentamicin in cases caused by enterococcal strains with high-level resistance to streptomycin. A 4-week treatment course may be adequate in many cases. In patients with streptomycin-resistant strains, mitral valve disease, illness of greater than 3 months' duration, and/or relapse after previous therapy, a 6-week treatment course should probably be administered. With standard treatment and the appropriate use of valve replacement, a cure rate of approximately 85% can be expected.

Cervico-vaginal screening in an STD clinic.

From May 1986 to March 1988, there were 3,622 "new" female clients at the Calgary Sexually Transmitted Disease (STD) Clinic of whom 2,278 registered for the first time. A cervico-vaginal (Pap) smear was obtained from those who had not had one in the previous 6 to 12 months and any history of venereal warts (VW) was recorded. 621 smears were accessed of which 611 were suitable for inclusion in this study. 65 (10.6%) smears revealed human papillomavirus (HPV) and/or cervical intraepithelial neoplasia (CIN). Any history of VW increased the likelihood of an abnormal smear by 5.3 times. Those with currently visible VW were more likely (8.8 times) to have an abnormal smear than those with a past history (3.5 times). These data re-affirm the recommendation of the first "Walton Report" that Pap smears should be obtained in STD Clinics.

Single-dose oral cefixime versus amoxicillin plus probenecid for the treatment of uncomplicated gonorrhea in men.

In this randomized study, a single 800-mg oral dose of cefixime cured 96 of 97 men with uncomplicated gonococcal urethritis, compared with 44 cures of 46 men who received standard therapy with amoxicillin (3 g) plus probenecid (1 g). Both regimens were ineffective against coexistent infection with Chlamydia trachomatis and Ureaplasma urealyticum. Cefixime was well tolerated, and all side effects were mild and self-limited.

Dose-ranging study of fleroxacin for treatment of uncomplicated Chlamydia trachomatis genital infections.

Men and women with suspected or proven genital infections caused by Chlamydia trachomatis were enrolled in a double-blind study to evaluate the efficacy and tolerability of fleroxacin. Patients received either 400, 600, or 800 mg once daily for 7 days and were monitored approximately 2, 4, and 7 weeks after initiation of therapy. In men monitored for at least 6 weeks or until failure of the therapy, fleroxacin failed to eradicate C. trachomatis in three of eight on the 400-mg regimen, in one of four on the 600-mg regimen, and in four of seven on the 800-mg regimen. All five women monitored for at least 6 weeks became culture negative. There was no association between in vitro susceptibility of C. trachomatis to fleroxacin and outcome, with MICs being 4 to 8 migrograms/ml for almost all isolates tested. Among those with positive cultures for Ureaplasma urealyticum initially, the first follow-up cultures remained positive in 8 (29%) of 28 men and 8 (50%) of 16 women. Independent of culture results, men with nongonococcal urethritis receiving 800 mg of fleroxacin were significantly more likely to show a clinical response than men receiving 400 or 600 mg (93 versus 54%). Adverse events were frequent, often severe, and dose related. Insomnia and photosensitivity reactions were the most important. The adverse reactions and unacceptably high rates of microbiologic failure resulted in premature termination of the study.

Quinolones in the treatment of sexually transmitted diseases.

Many of the new quinolone-carboxylic acids possess in vitro activity against a variety of sexually transmitted pathogens. Neisseria gonorrhoeae and Hemophilus ducreyi are particularly susceptible to those antimicrobial agents while the in vitro sensitivities of Chlamydia trachomatis and genital mycoplasmas vary widely amongst the quinolones and range from poor to modest. Clinically, single dose therapy with many of the quinolones has been highly effective in curing gonorrhea and appears to be promising in the management of chancroid. In contrast, however, the quinolones (even when used in multiple dose, 7 to 10 day regimens) have been disappointing to date in the treatment of chlamydial and nongonococcal infections. Currently there is little data available with regard to other sexually transmitted diseases but it appears that the quinolones will not be useful in the therapy of syphilis or bacterial vaginosis.

Complement activation and stimulation of chemotaxis by Chlamydia trachomatis.

The stimulus for the migration of polymorphonuclear leukocytes (PMNs) in acute chlamydial infection was studied in vitro by examining the chemotaxigenic effect of L2 and DE Chlamydia trachomatis elementary bodies (EB) upon the plasma of three healthy donors. In each individual experiment, chemotactic response was assessed with PMNs and plasma from the same respective donor, and no specific antibodies against C. trachomatis were detected in the plasma of any donor. Chemotaxis was observed in an agarose plate assay and was quantitated as the chemotactic differential, or CD (directed migration of PMNs minus random movement of PMNs). For each donor, the mean CD was significantly greater (P less than 0.005) when plasma preincubated for 2 h with L2 EB was used as the chemoattractant than when (i) plasma alone, (ii) plasma preheated to 56 degrees C for 30 min before incubation with L2 EB, or (iii) L2 EB in phosphate-buffered saline (PBS) was used as the potential chemoattractant. Similarly, in the one donor in whom DE EB were studied, the mean CD was also significantly greater (P less than 0.005) for plasma preincubated with DE EB as compared with (i) plasma alone or (ii) DE EB in PBS. Complement activation by C. trachomatis EB was assessed by radioimmunoassay for C5a des-arginine in all chemoattractant preparations used in the chemotaxis assay. Mean C5a des-arginine levels were high in plasma samples preincubated with L2 EB (171.00 +/- 10.64, 107.00 +/- 4.76, and 89.70 +/- 1.74 ng per ml) or DE EB (37.40 +/- 15.76 ng per ml) but were undetectable (less than 4.0 ng per ml) in (i) plasma alone, (ii) preheated plasma incubated with L2 EB, and (iii) PBS containing L2 EB. Thus, L2 EB and DE EB of C. trachomatis exert a chemotaxigenic effect upon normal antibody-negative plasma, and this effect is at least in part a result of complement activation and generation of the potent chemotaxin C5a.