Single-dose gatifloxacin compared with ofloxacin for the treatment of uncomplicated gonorrhea: a randomized, double-blind, multicenter trial.

BACKGROUND: Treatment of gonorrhea is complicated by widespread resistance of Neisseria gonorrhoeae to antimicrobial agents of choice, including decreased susceptibility to ciprofloxacin. GOAL: To demonstrate the efficacy and safety of gatifloxacin, a novel 8-methoxy fluoroquinolone antibiotic, compared with ofloxacin in treating patients with uncomplicated gonococcal infection. STUDY DESIGN: In a double-blind, randomized (2:2:1), controlled trial, 340 men and 388 women with uncomplicated gonorrhea who were 16 years or older received a single oral dose of gatifloxacin (400 mg or 600 mg) or ofloxacin (400 mg). Primary analysis of efficacy was based on bacteriologic eradication from sites of infection. Secondary analyses examined clinical response and adverse event profiles. RESULTS: Bacteriologic eradication rates for gatifloxacin in evaluable men with urethral gonorrhea were 99% (400 mg) and 100% (600 mg) versus 100% for ofloxacin (n = 117, 122, and 55, respectively; P = ns). Eradication rates in evaluable women with endocervical gonorrhea were 99% for both 400 mg and 600 mg gatifloxacin versus 100% for ofloxacin (n = 101, 104, and 55, respectively; P = ns). Eradication rates were 100% for both rectal (n = 43) and pharyngeal (n = 31) infection across all treatment groups. All three drug regimens were well tolerated and exhibited similar clinical response profiles. CONCLUSION: Gatifloxacin is safe and effective as a single 400-mg or 600-mg dose for the treatment of uncomplicated gonorrhea. Similar efficacy rates were observed with the 400-mg and 600-mg doses. A single 400-mg dose can be recommended for treatment of uncomplicated gonorrhea.

Dendritic epidermal gamma/delta T cells (DETC) activated in vivo proliferate in vitro in response to Mycobacterium leprae antigens.

BACKGROUND: gamma/delta T-cell receptor (TCR)+ dendritic epidermal T cells (DETC) are part of a primitive defense system in the skin; they are capable of responding only to a limited number of antigens. The aim of the present study was to test whether DETC can proliferate in vitro in response to antigens of Mycobacterium leprae. METHODS: DETC were obtained from CBA mouse ear skin by trypsinization and Histopaque gradient centrifugation. The resulting epidermal cell suspension contained up to 20% DETC, as analyzed by the fluorescence activated cell sorter (FACS) after staining with anti-Thy-1 or anti-gamma/delta TCR monoclonal antibodies (mAbs). The freshly isolated cells, or DETC cultured up to 4 weeks with interleukin-2 (IL-2), were exposed in vitro for up to 6 days to varying doses of the following M. leprae antigens: (1) integral (live) M. leprae bacilli; (2) Dharmendra antigen; and (3) PGL-1 (phenolic glycolipid of M. leprae). The DETC response was assessed by tritiated thymidine (3H-TdR) incorporation. RESULTS: The freshly isolated DETC, or DETC cultured up to 4 weeks with IL-2, did not respond significantly to any of the M. leprae antigens, although at the same time they were able to respond vigorously to concanavalin A (Con A), as positive control. If, however, DETC were isolated from skin, painted 7 days before with croton oil (10 microL/cm2 to cause irritant dermatitis, they were able to respond to all M. leprae antigens by a 3-4-fold incrase in the 3H-TdR uptake. The most effective stimulator was a 1 : 1 mixture of Dharmendra and PGL-1 (0. 01 microg/mL), which was as effective as 10-fold higher doses of either antigen alone. Cell counts confirmed that increased DNA synthesis was associated with cell proliferation. Experiments employing alpha/beta-TCR CBA murine spleen cells and epidermal cell suspension treated with anti-gamma/delta or antialpha/beta mAbs + C' proved that only the gamma/delta DETC were the responder cells to M. leprae antigens. CONCLUSIONS: The results suggest that activation of DETC in vivo may make them responsive to M. leprae antigens. A significant increase in the number of class II major histocompatibility complex (MHC) positive, nondendritic cells was observed in the croton oil-treated epidermis. We hypothesize that croson oil-induced upregulation of class II MHC expression, which endows epidermal cells with antigen-presenting capabilities, might be an important factor in vivo in delivering an immunogenic signal to resident DETC in the skin.

Grepafloxacin versus cefixime as single-dose therapy for uncomplicated gonorrhea in women.

OBJECTIVE: To compare the efficacy and tolerance of single-dose grepafloxacin with cefixime for treatment of uncomplicated gonorrhea in women. METHODS: Women attending nine sexually-transmitted-disease clinics in the United States who had suspected uncomplicated gonorrhea were enrolled in an open study. Participants were randomized to receive single oral doses of grepafloxacin (400 mg) or cefixime (400 mg), and efficacy was evaluated in those who returned for follow-up assessment 5 to 10 days later. The primary measure of efficacy was microbiological response to therapy as determined by pre- and posttreatment culture results for Neisseria gonorrhoeae. RESULTS: Of 380 patients enrolled, 124 in the grepafloxacin group and 131 in the cefixime group were evaluated for microbiological response. Cervical gonococcal infections were eradicated in 99% of patients in both treatment groups, with only one persistent infection in each group. All pharyngeal (n = 15) and rectal (n = 32) gonococcal infections treated with grepafloxacin were cured, whereas 5 of 16 (31%) pharyngeal and 1 of 38 (3%) rectal infections failed to respond to cefixime. Although a third (123 of 386) of N. gonorrhoeae pretreatment isolates were resistant to penicillin or tetracycline, this had no impact on cure rates. Both drugs were well tolerated, with vaginitis being the most common treatment-related adverse event in each group. CONCLUSIONS: This study shows that single-dose grepafloxacin is at least as effective as cefixime for treating women with uncomplicated cervical gonorrhea. Grepafloxacin also appears to be highly effective against extragenital infections.

Genital ulcer disease.

There are five major sexually transmitted diseases producing genital ulcerations. Their prevalence varies among geographic regions. Whereas genital herpes is the most frequent cause of genital ulcer in western Europe and North America, the most common cause of genital ulcer disease in developing countries appears to be chancroid. Owing to frequently atypical presentation and mixed infections, an accurate clinical diagnosis is very difficult. Successful management of genital ulcer disease depends on accurate diagnosis corroborated by performance of appropriate laboratory tests when possible.

Dermatologic manifestations of sexually transmitted diseases other than HIV.

This article focuses on the common skin manifestations of sexually transmitted diseases. A number of unusual skin lesions associated with these diseases are shown, and pathogenesis and treatment are briefly presented. This article will be most useful as a reference for the formulation of the differential diagnosis of genital area skin lesions.

Comparison of ciprofloxacin and ceftriaxone as single-dose therapy for uncomplicated gonorrhea in women.

Although women bear the brunt of gonococcal infection-related morbidity, few large studies of gonorrhea treatment in women have been conducted. In a multicenter, double-blind, placebo-controlled trial, 181 evaluable women with uncomplicated gonorrhea were treated with ciprofloxacin (250 mg orally; 94 women) or ceftriaxone (250 mg intramuscularly; 87 women). Twenty-four percent of the participants were infected with antibiotic-resistant Neisseria gonorrhoeae. Cervical gonorrhea was cured in 100% (93 of 93) of the women treated with ciprofloxacin and 99% (83 of 84) receiving ceftriaxone. All pharyngeal (n = 5) or rectal (n = 20) infections treated with ciprofloxacin were cured, as were ceftriaxone-treated patients with pharyngeal (n = 6) or rectal (n = 21) infection. Geometric mean MICs (range) for 248 pretreatment isolates were: penicillin, 0.28 (0.015 to 8.0); tetracycline, 0.46 (0.06 to 4); ciprofloxacin, 0.003 (0.002 to 0.015); and ceftriaxone, 0.004 (0.001 to 0.125) microgram/ml. Both drugs were well tolerated. Despite the high prevalence of antibiotic-resistant gonococci in these populations, 250 mg of oral ciprofloxacin was as effective as an injection of ceftriaxone.

Lepromin responses in recipients of a candidate antileprosy bacterin vaccine (WHO-IMMLEP Mycobacterium leprae killed preparation) in the USA.

BACKGROUND: Identification of the nine-banded armadillo as a potential source of massive numbers of Mycobacterium leprae led to the development of a candidate bacterin vaccine for possible immunoprophylaxis. METHODS: Volunteers were from a leprosy-hypoendemic, nonBCG-using area (USA). They had been vaccinated intradermally 3 years earlier with a candidate antileprosy bacterin vaccine of irradiated and autoclaved Mycobacterium leprae obtained from experimental nine-banded armadillos. They were tested for dermal responsiveness to standard lepromin A. RESULTS: Values for induration and erythema appeared slightly greater for the vaccinated group; however, the differences were not statistically significant, indicating no appreciable 'anamnestic' effect on either Fernandez (early) or Mitsuda (late) reactions after 3 years. CONCLUSIONS: Because previous studies had demonstrated that administration of this bacterin produced no humoral changes, it now appears less probable that laboratory methods will be of much help in assessing even possible effectiveness of such vaccination.

Lepromin skin testing in the classification of Hansen's disease in the United States.

Hansen's disease, or leprosy, although a relatively uncommon disease in the United States, continues to be important because of its implications--physical, psychological, and social--for the patient. Prognosis and treatment of the disease are based largely on clinical classification, which ranges from the multibacillary "lepromatous" to the paucibacillary "tuberculoid" forms, depending on the patient's specific immune capabilities. Traditionally, skin testing with lepromins--suspensions of the etiologic agent of Hansen's disease, Mycobacterium leprae--have been used as adjuncts to clinical parameters for classification in endemic areas. However, these have not been systematically studied in the United States. This report describes the results obtained from skin testing 38 volunteers (22 patients and 16 uninfected persons) with standard lepromin preparations. These results support the adjunctive value of lepromins for clinically classifying Hansen's disease in our "hypoendemic" population.

Treatment of gonococcal infections with a single 250 mg intramuscular injection of trospectomycin sulphate vs ceftriaxone sodium.

Trospectomycin sulphate is a new, more potent analog of spectinomycin, which is active in vitro against penicillin-sensitive and penicillin-resistant strains of Neisseria gonorrhoeae. This study was designed to determine the bacteriologic and clinical efficacy as well as safety of a single intramuscularly administered 250 mg dose of trospectomycin sulphate in the treatment of uncomplicated gonorrhoea (cervical, urethral, pharyngeal and anal). Ceftriaxone sodium was used as a comparator antibiotic in a single 250 mg intramuscular dose. Seventy-four patients (36 women and 38 men) were evaluable in the trospectomycin treated group and 40 patients (22 women and 18 men) in the ceftriaxone treated group. The overall bacteriologic cure rate was 98.6% (73/74) for trospectomycin and 95% (38/40) for ceftriaxone. Bacteriologic failures were observed among women 1/36 (2.8%) treated with trospectomycin and 2/22 (9.1%) treated with ceftriaxone. The overall clinical success rate (clinically cured plus clinically improved) was 90.5% for trospectomycin and 100% for ceftriaxone. Adverse events were reported rarely in both groups. Less than 10% of patients complained of pain and/or tenderness at the injection site for both drugs; one patient developed a generalized, pruritic rash which occurred three days after administration of trospectomycin and resolved within six days. In conclusion, a single dose of 250 mg i.m. trospectomycin appears to be at least as effective and safe as a single dose of ceftriaxone in the treatment of uncomplicated gonorrhoea.

A controlled trial of a single dose of azithromycin for the treatment of chlamydial urethritis and cervicitis. The Azithromycin for Chlamydial Infections Study Group.

BACKGROUND: Currently, there is no single-dose therapy that is effective in the treatment of urethral or endocervical infections with Chlamydia trachomatis. Azithromycin is a new azalide antibiotic that has substantial activity against C. trachomatis, is concentrated intracellularly, and has a long half-life in serum and tissue. METHODS: We conducted a trial in which 299 female patients and 158 male patients with uncomplicated genital infection and a positive C. trachomatis antigen test were randomly assigned to receive either azithromycin (1 g once orally) or doxycycline (100 mg orally twice daily for seven days). Only patients subsequently determined to have a culture positive for C. trachomatis at base line were included in the evaluation of efficacy. RESULTS: Among the patients who could be evaluated, 5 of the 141 patients (4 percent) treated with azithromycin did not respond to treatment, as compared with 3 of the 125 patients (2 percent) treated with doxycycline (difference between groups, 2 percent; 95 percent confidence interval, 0 to 6 percent). Of the patients evaluated 21 to 35 days after treatment, none of 112 treated with azithromycin and 1 of 102 treated with doxycycline had a positive culture. The rates of bacteriologic cure were similar for the 98 female patients (97 percent) and the 43 male patients (95 percent) treated with azithromycin. Seventeen percent of the patients who received azithromycin and 20 percent of those treated with doxycycline had mild-to-moderate drug-related side effects, mainly gastrointestinal symptoms. CONCLUSIONS: A single 1-g dose of azithromycin is as effective for the treatment of uncomplicated genital chlamydial infections as a standard seven-day course of doxycycline.

Common nonvenereal genital lesions.

There are a wide variety of local and systemic skin diseases that produce lesions in the genitoanal region. These lesions may resemble those produced by sexually transmitted microorganisms. The purpose of this article is to make physicians aware of the common skin diseases that produce lesions on the genitalia to avoid the inappropriate diagnosis of a sexually transmitted disease.

[Immunotypes of Chlamydia trachomatis and the clinical picture of non-gonorrheal urethritis in men and cervicitis in women]. / Immunotypy Chlamydia trachomatis a obraz kliniczny ngu u mezczyzn i zapalenia szyjki macicy u kobiet.

102 Chlamydia trachomatis isolates obtained from pregnant women and 42 isolates from man-consorts of women with chlamydial infection of cervix were immunotyped using a microimmunofluorescence (micro IF) with monoclonal antibodies kit (Washington Research Foundation, Seattle, USA). In both groups of patients the most common serovars were: E (37.3%) and D (24.6%) belonging to B-complex. Additional serovars noted were: F (11.3%), J (11.3%), I' (4.5%), I (3.5%, K (3.5%), G (2.8%) and H. Ba (both 0.2%). N. gonorrhoeae and/or T. vaginalis infections were more frequent from patients with B-complex Ch. trachomatis serovars (28/75 that is 37%) than C-complex Ch. trachomatis serovars (3/25 that is 12%).

Fine-tuning the fluorescent antibody test for chlamydial infections in pregnancy.

Endocervical specimens from 168 asymptomatic women in the second trimester of pregnancy were screened for Chlamydia trachomatis infection with both standard tissue culture methods and a direct fluorescein-conjugated monoclonal antibody assay (MicroTrak). Based on tissue culture results, the prevalence of Chlamydia trachomatis was 26.2% in this population. Compared with tissue culture, the monoclonal antibody assay's sensitivity, specificity, and positive predictive value varied depending upon how many elementary bodies were used to define a positive test. Specifically, if a cutoff of ten elementary bodies was used (as per the manufacturer's instructions), the sensitivity, specificity, and positive predictive value of this test were 86.3, 98.4, and 95.0%, respectively. At the other extreme, a cutoff of one elementary body produced a more sensitive but less specific test, with parameters of 93.2, 89.5, and 75.9%, respectively. Based on these data and operating characteristic analysis, the cutoff value defining a positive test was appropriately set at two or more elementary bodies, at least for this study population. This resulted in a sensitivity, specificity, and positive predictive value of 93.2, 95.2, and 87.2%, respectively. This monoclonal antibody assay appears to be a reasonable substitute for cell culture for Chlamydia trachomatis. However, because of varying magnitudes and implications of false-positive and false-negative tests, clinicians are urged to determine the appropriate breakpoint for their individual laboratories and patient populations before substituting the direct fluorescent antibody test for tissue culture.

Preliminary study of a Mycobacterium leprae bacterin vaccine in a human volunteer population in a nonendemic area.

Seventeen volunteers who had never resided in areas with significant transmission of leprosy (Hansen's disease) were inoculated intradermally with 1.5 X 10(8) killed, purified armadillo-derived Mycobacterium leprae in a standardized preparation being tested for possible vaccine use. The peak of local skin responses, consisting of induration with or without ulceration similar to the post-lepromin Mitsuda reaction, occurred between the 21st and 28th days after injection. The maximum mean induration diameter was 17.2 mm, the minimum, 6.1 mm. Sera tested with the ELISA technique revealed no humoral response to either the sonicated bacilli, M. leprae-specific phenolic glycolipid I antigen, or three semi-synthetic analogues reactive with lepromatous patients' sera. The dose of M. leprae inoculated appeared to be safe and without unacceptable reactions at the injection site. One volunteer developed a generalized skin rash parallel to the local reaction, but the relationship of the former to the inoculation was unclear.