Invasive fungal infections in low-risk liver transplant recipients: a multi-center prospective observational study.

Prevention of invasive fungal infections (IFIs) in orthotopic liver transplant (OLT) recipients utilizing postoperative systemic antifungal prophylaxis, typically with fluconazole, is justified among those at high risk for IFI. Use of postoperative antifungal prophylaxis for low-risk OLT recipients is widely practiced but not universally accepted nor supported by data. We conducted a prospective observational study among 200 OLT recipients who were at low risk for IFI and did not receive postoperative antifungal prophylaxis. Patients were considered low risk if they had /=units of 40 blood products or return to the operating room for intra-abdominal bleeding; return to the operating room for anastomotic leak or vascular insufficiency; preoperative serum creatinine of >/=2 mg/dL; and perioperative Candida colonization. Patients were followed 100 d post-transplantation for evidence of IFI. Of 193 eligible patients, 7 (4%) developed an IFI. Three (2%) IFIs were due to Candida spp. and potentially preventable by standard fluconazole prophylaxis. Three patients developed invasive aspergillosis; one developed late onset disseminated cryptococcosis. Liver transplant recipients at low risk for IFI can be identified utilizing pre-determined criteria, and post-transplantation antifungal prophylaxis can be routinely withheld in these patients.

Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy.

We conducted a case study of human immunodeficiency virus (HIV)-negative patients with cryptococcosis at 15 United States medical centers from 1990 through 1996 to understand the demographics, therapeutic approach, and factors associated with poor prognosis in this population. Of 306 patients with cryptococcosis, there were 109 with pulmonary involvement, 157 with central nervous system (CNS) involvement, and 40 with involvement at other sites. Seventy-nine percent had a significant underlying condition. Patients with pulmonary disease were usually treated initially with fluconazole (63%); patients with CNS disease generally received amphotericin B (92%). Fluconazole was administered to approximately two-thirds of patients with CNS disease for consolidation therapy. Therapy was successful for 74% of patients. Significant predictors of mortality in multivariate analysis included age > or =60 years, hematologic malignancy, and organ failure. Overall mortality was 30%, and mortality attributable to cryptococcosis was 12%. Cryptococcosis continues to be an important infection in HIV-negative patients and is associated with substantial overall and cause-specific mortality.

Need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses.

Studies of invasive fungal infections have been and remain difficult to implement. Randomized clinical trials of fungal infections are especially slow and expensive to perform because it is difficult to identify eligible patients in a timely fashion, to prove the presence of the fungal infection in an unequivocal fashion, and to evaluate outcome in a convincing fashion. Because of these challenges, licensing decisions for antifungal agents have to date depended heavily on historical control comparisons and secondary advantages of the new agent. Although the availability of newer and potentially more effective agents makes these approaches less desirable, the fundamental difficulties of trials of invasive fungal infections have not changed. Therefore, there is a need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses, and this article summarizes the possible strategies in this area.

DNA fingerprinting of serial Candida albicans isolates obtained during itraconazole prophylaxis in patients with AIDS.

During a randomized double-blind placebo-controlled study testing the efficacy of itraconazole for prophylaxis of systemic and mucosal fungal infections in patients with acquired immune deficiency syndrome, 298 patients were enrolled with 295 evaluable. Of those, 46 patients were considered prophylaxis failures because of recurrent oral or esophageal candidiasis. Oropharyngeal fungal cultures were taken at the time of suspected thrush or Candida esophagitis, but not at baseline. All of the Candida spp. isolates were cultured on CHROMagar Candida medium then identified using API 20 AUX strips. Antifungal susceptibility testing was performed following the National Committee for Clinical Laboratory Standards M-27A guidelines. Sequential isolates were genotyped using randomly amplified polymorphic DNA. Polymerase chain reaction fingerprints were generated using two repetitive sequence primers, (GGA)7 and (GACA)4. The study group consisted of 23 patients, nine from the itraconazole arm and 14 from the placebo arm, who were prophylaxis failures and had more than two C. albicans isolates. Five of 23 had isolates showing a > or =4-fold reduction in susceptibility; four of these patients were in the itraconazole prophylaxis arm and one was in the placebo arm. Three of the five had yeast isolations showing changes in banding patterns over time. Such changes may indicate genetic changes in the same strain that could be linked to acquired resistance to itraconazole, or acquisition of a new strain, or emergence of a previously minor component of the original population.

Phenotypic drug susceptibility testing predicts long-term virologic suppression better than treatment history in patients with human immunodeficiency virus infection.

To assess the value of phenotypic drug susceptibility testing as a predictor of antiretroviral treatment response in human immunodeficiency virus (HIV)-infected people, drug susceptibility testing was performed retrospectively on plasma samples collected at baseline in a cohort of 86 antiretroviral-experienced, HIV-infected people experiencing treatment failure and initiating a new antiretroviral treatment regimen. Two separate criteria for reduced drug susceptibility were evaluated. In multivariate analyses, phenotypic susceptibility was an independent predictor of time to treatment failure (adjusted hazards ratio [HR], 0.70; 95% confidence interval [CI], 0.55-0.90; and adjusted HR, 0.76; 95% CI, 0.61-0.95, with reduced drug susceptibility cutoffs defined as 4.0-fold and 2.5-fold higher than reference virus IC(50) values, respectively). Previous protease inhibitor experience was also a significant independent predictor. Notably, drug susceptibility predicted on the basis of treatment history alone was not predictive of time to treatment failure. In this cohort, phenotypic testing results enhanced the ability to predict sustained long-term suppression of virus load.

Comparison of oral fluconazole and itraconazole for progressive, nonmeningeal coccidioidomycosis. A randomized, double-blind trial. Mycoses Study Group.

BACKGROUND: In previous open-label noncomparative clinical trials, both fluconazole and itraconazole were effective therapy for progressive forms of coccidioidomycosis. OBJECTIVE: To determine whether fluconazole or itraconazole is superior for treatment of nonmeningeal progressive coccidioidal infections. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 7 treatment centers in California, Arizona, and Texas. PATIENTS: 198 patients with chronic pulmonary, soft tissue, or skeletal coccidioidal infections. INTERVENTION: Oral fluconazole, 400 mg/d, or itraconazole, 200 mg twice daily. MEASUREMENTS: After 4, 8, and 12 months, a predefined scoring system was used to assess severity of infection. Findings were compared with those at baseline. RESULTS: Overall, 50% of patients (47 of 94) and 63% of patients (61 of 97) responded to 8 months of treatment with fluconazole and itraconazole, respectively (difference, 13 percentage points [95% CI, -2 to 28 percentage points]; P = 0.08). Patients with skeletal infections responded twice as frequently to itraconazole as to fluconazole. By 12 months, 57% of patients had responded to fluconazole and 72% had responded to itraconazole (difference, 15 percentage points [CI, 0.003 to 30 percentage points]; P = 0.05). Soft tissue disease was associated with increased likelihood of response, as in previous studies. Azole drug was detected in serum specimens from all but 3 patients; however, drug concentrations were not helpful in predicting outcome. Relapse rates after discontinuation of therapy did not differ significantly between groups (28% after fluconazole treatment and 18% after itraconazole treatment). Both drugs were well tolerated. CONCLUSIONS: Neither fluconazole nor itraconazole showed statistically superior efficacy in nonmeningeal coccidioidomycosis, although there is a trend toward slightly greater efficacy with itraconazole at the doses studied.

Does long-term itraconazole prophylaxis result in in vitro azole resistance in mucosal Candida albicans isolates from persons with advanced human immunodeficiency virus infection? The National Institute of Allergy and Infectious Diseases Mycoses study group.

The effects of prolonged itraconazole exposure on the susceptibility of Candida albicans isolates to itraconazole and fluconazole have not been well characterized. A recent placebo-controlled study of long-term itraconazole antifungal prophylaxis in persons with advanced human immunodeficiency virus infection afforded the opportunity to address this question. Mucosal Candida sp. isolates were obtained from subjects who developed oropharyngeal or esophageal candidiasis, and in vitro susceptibilities of the last isolate obtained at removal from the study as a prophylaxis failure were compared in itraconazole and placebo recipients. More subjects in the placebo group (74 of 146 [51%]) than in the itraconazole group (51 of 149 [34%]) developed mucosal candidiasis (P = 0.004). A total of 112 isolates were recovered from 56 of the 74 (76%) subjects with mucosal candidiasis assigned to the placebo group, compared to 97 isolates from 45 of the 51 (88%) subjects in the itraconazole group. C. albicans accounted for 98% of isolates in the placebo group and 89% of isolates in the itraconazole group. The itraconazole MIC at which 50% of the isolates tested were inhibited (MIC(50)) for last-episode isolates from the itraconazole group was 0.125 microg/ml compared to 0.015 microg/ml for the placebo group subjects, P = 0.0001. The MIC(50) of fluconazole for the last isolates from the itraconazole group was 1.5 microg/ml compared to 0.5 microg/ml for the placebo subjects (P = 0.005). A lower proportion of isolates recovered from subjects on itraconazole therapy were classified as susceptible to itraconazole (63%) compared to isolates from the placebo group (96%) (P = 0.001). Similarly, a lower proportion of C. albicans isolates from subjects on itraconazole therapy were susceptible to fluconazole (78%) compared to isolates from the placebo group (96%) (P = 0.01). Also, the proportion of isolates that were not fully susceptible to itraconazole or fluconazole was greater in patients assigned to the itraconazole group than the placebo group (itraconazole susceptibility, 37 and 4%, respectively (P = 0.001); fluconazole susceptibility, 23 and 4%, respectively (P = 0.01). In conclusion, long-term itraconazole prophylaxis in patients with AIDS is associated with reduction in susceptibility to itraconazole and cross-resistance to fluconazole.

Itraconazole prophylaxis for fungal infections in patients with advanced human immunodeficiency virus infection: randomized, placebo-controlled, double-blind study. National Institute of Allergy and Infectious Diseases Mycoses Study Group.

In a prospective, randomized, double-blind trial, 149 patients with advanced human immunodeficiency virus (HIV) infection were randomized to receive itraconazole capsules (200 mg daily) and 146 to receive a matched placebo. Both groups were monitored for evidence of fungal infections. Baseline characteristics of the two groups were similar. Failure of prophylaxis occurred in 29 (19%) of the itraconazole recipients and 42 (29%) of the placebo recipients (P = .004; log-rank test). There were 6 invasive fungal infections in the itraconazole group (4, histoplasmosis; 1, cryptococcosis; 1, aspergillosis) and 19 in the placebo group (10, histoplasmosis; 8, cryptococcosis; 1, aspergillosis) (P = .0007; log-rank test). Itraconazole significantly delayed time to onset of histoplasmosis (P = .03; log-rank test) and cryptococcosis (P = .0005; log-rank test). Prophylaxis failure due to recurrent or refractory mucosal candidiasis occurred with similar frequency in the two groups (itraconazole, 15%; placebo, 16%). A survival benefit was not demonstrated. Itraconazole generally was well tolerated. Primary prophylaxis with itraconazole capsules prevents histoplasmosis and cryptococcosis in patients with HIV infection.

A comparison of itraconazole versus fluconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. National Institute of Allergy and Infectious Diseases Mycoses Study Group.

This study was designed to compare the effectiveness of fluconazole vs. itraconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. HIV-infected patients who had been successfully treated (achieved negative culture of CSF) for a first episode of cryptococcal meningitis were randomized to receive fluconazole or itraconazole, both at 200 mg/d, for 12 months. The study was stopped prematurely on the recommendation of an independent Data Safety and Monitoring Board. At the time, 13 (23%) of 57 itraconazole recipients had experienced culture-positive relapse, compared with 2 relapses (4%) noted among 51 fluconazole recipients (P = .006). The factor best associated with relapse was the patient having not received flucytosine during the initial 2 weeks of primary treatment for cryptococcal disease (relative risk = 5.88; 95% confidence interval, 1.27-27.14; P = .04). Fluconazole remains the treatment of choice for maintenance therapy for AIDS-associated cryptococcal disease. Flucytosine may contribute to the prevention of relapse if used during the first 2 weeks of primary therapy.

Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry.

T-20, a synthetic peptide corresponding to a region of the transmembrane subunit of the HIV-1 envelope protein, blocks cell fusion and viral entry at concentrations of less than 2 ng/ml in vitro. We administered intravenous T-20 (monotherapy) for 14 days to sixteen HIV-infected adults in four dose groups (3, 10, 30 and 100 mg twice daily). There were significant, dose-related declines in plasma HIV RNA in all subjects who received higher dose levels. All four subjects receiving 100 mg twice daily had a decline in plasma HIV RNA to less than 500 copies/ml, by bDNA assay. A sensitive RT-PCR assay (detection threshold 40 copies/ml) demonstrated that, although undetectable levels were not achieved in the 14-day dosing period, there was a 1.96 log10 median decline in plasma HIV RNA in these subjects. This study provides proof-of-concept that viral entry can be successfully blocked in vivo. Short-term administration of T-20 seems safe and provides potent inhibition of HIV replication comparable to anti-retroviral regimens approved at present.

Sorivudine versus acyclovir for treatment of dermatomal herpes zoster in human immunodeficiency virus-infected patients: results from a randomized, controlled clinical trial. Collaborative Antiviral Study Group/AIDS Clinical Trials Group, Herpes Zoster Study Group.

The present randomized, double-blind, placebo-controlled, multicenter clinical trial was designed to compare the efficacy and tolerability of sorivudine [1-beta-D-arabinofuranosyl-E-(2-bromovinyl)uracil] and acyclovir for the treatment of dermatomal herpes zoster in human immunodeficiency virus (HIV)-seropositive patients. A total of 170 HIV-seropositive adults presenting with herpes zoster (confirmed by direct fluorescent-antigen testing and/or viral culture) were enrolled and randomized to receive a 10-day course of orally administered sorivudine (40 mg once daily plus acyclovir placebos) or acyclovir (800 mg five times daily plus sorivudine placebo). Patients were monitored daily to document the events of cutaneous healing, pain, zoster-related complications, and drug-related adverse events. Patients were reassessed on days 21 and 28 and then once monthly for 1 year. The primary efficacy endpoint was time to the cessation of new vesicle formation. Secondary efficacy endpoints included times to other events of cutaneous healing, resolution of pain, and frequency of dissemination and zoster recurrence. In a multivariate analysis, sorivudine was superior to acyclovir for reducing the times to the cessation of new vesicle formation (relative risk [RR] = 1.54, 95% confidence interval [CI] = 1.00 to 2.36; P = 0.049) and total lesion crusting (RR = 1.48, 95% CI = 1.07 to 2.04; P = 0.017). In a univariate analysis, there was a trend favoring sorivudine for the cessation of new vesicle formation (median of 3 versus 4 days; P = 0.07) and a significant advantage for time to total lesion crusting (median of 7 versus 8 days; P = 0.02). The time to the resolution of zoster-associated pain, the frequency of dissemination, and the frequency of zoster recurrence were not different between the two treatment groups. Both drugs were well tolerated. Sorivudine is an effective drug for the treatment of herpes zoster in HIV-infected patients and results in accelerated cutaneous healing when compared with acyclovir therapy.

Treatment of blastomycosis with higher doses of fluconazole. The National Institute of Allergy and Infectious Diseases Mycoses Study Group.

Recent clinical data suggest that fluconazole at daily doses of 200 to 400 mg for at least 6 months is moderately effective therapy for non-life-threatening blastomycosis. To examine the usefulness of higher doses of fluconazole therapy for this disorder, we conducted a multicenter, randomized, open-label study to determine the efficacy and safety of two different daily doses of fluconazole (400 and 800 mg) in the treatment of non-life-threatening blastomycosis. Of 39 patients evaluable for efficacy analysis, 34 (87%) were successfully treated, including 89% and 85% of patients who received 400 and 800 mg, respectively. Five (83%) of six patients for whom prior antifungal therapy had failed were successfully treated. The mean duration of therapy was 8.9 months for successfully treated patients. Nineteen patients (48%) reported adverse events, although most were minor. We conclude that fluconazole at daily doses of 400 to 800 mg for at least 6 months is effective therapy for non-life-threatening blastomycosis.

Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group.

BACKGROUND: Treatment with low-dose amphotericin B (0.4 mg per kilogram of body weight per day) or oral azole therapy in patients with the acquired immunodeficiency syndrome (AIDS) and cryptococcal meningitis has been associated with high mortality and low rates of cerebrospinal fluid sterilization. METHODS: In a double-blind multicenter trial we randomly assigned patients with a first episode of AIDS-associated cryptococcal meningitis to treatment with higher-dose amphotericin B (0.7 mg per kilogram per day) with or without flucytosine (100 mg per kilogram per day) for two weeks (step one), followed by eight weeks of treatment with itraconazole (400 mg per day) or fluconazole (400 mg per day) (step two). Treatment was considered successful if cerebrospinal fluid cultures were negative at 2 and 10 weeks or if the patient was clinically stable at 2 weeks and asymptomatic at 10 weeks. RESULTS: At two weeks, the cerebrospinal fluid cultures were negative in 60 percent of the 202 patients receiving amphotericin B plus flucytosine and in 51 percent of the 179 receiving amphotericin B alone (P=0.06). Elevated intracranial pressure was associated with death in 13 of 14 patients during step one. The clinical outcome did not differ significantly between the two groups. Seventy-two percent of the 151 fluconazole recipients and 60 percent of the 155 itraconazole recipients had negative cultures at 10 weeks (95 percent confidence interval for the difference in percentages, -100 to 21). The proportion of patients who had clinical responses was similar with fluconazole (68 percent) and itraconazole (70 percent). Overall mortality was 5.5 percent in the first two weeks and 3.9 percent in the next eight weeks, with no significant difference between the groups. In a multivariate analysis, the addition of flucytosine during the initial two weeks and treatment with fluconazole for the next eight weeks were independently associated with cerebrospinal fluid sterilization. CONCLUSIONS: For the initial treatment of AIDS-associated cryptococcal meningitis, the use of higher-dose amphotericin B plus flucytosine is associated with an increased rate of cerebrospinal fluid sterilization and decreased mortality at two weeks, as compared with regimens used in previous studies. Although consolidation therapy with fluconazole is associated with a higher rate of cerebrospinal fluid sterilization, itraconazole may be a suitable alternative for patients unable to take fluconazole.

Fluconazole therapy for histoplasmosis. The National Institute of Allergy and Infectious Diseases Mycoses Study Group.

We assessed the efficacy of oral fluconazole (200-800 mg daily) in the treatment of non-life-threatening acute pulmonary histoplasmosis, chronic pulmonary histoplasmosis, or disseminated histoplasmosis in patients without human immunodeficiency virus infection. Of 27 evaluable patients, two had progressive acute pulmonary histoplasmosis, 11 had chronic pulmonary histoplasmosis, and 14 had disseminated histoplasmosis. Median durations of treatment in each of the three groups were 6 months, 7 months, and 11 months, respectively. Nineteen patients were treated with 400 mg of fluconazole daily (two of these patients received 800 mg daily for a portion of their treatment courses), seven were treated with 200 mg daily, and one was treated with 800 mg daily. Treatment was successful in 17 (63%) of 27 cases. Both of the patients with acute pulmonary infection responded to therapy, as did five (46%) of 11 patients with chronic pulmonary infection and 10 (71%) of 14 patients with disseminated infection. No substantial toxicity was observed. We conclude that fluconazole therapy for histoplasmosis is only moderately effective and should be reserved for patients who cannot take itraconazole.

Risk for gonococcal and chlamydial cervicitis in adolescent females: incidence and recurrence in a prospective cohort study.

PURPOSE: This study attempted to determine the incidence and risk for gonococcal and chlamydial cervicitis among sexually active urban adolescent females. METHODS: The study design is a prospective cohort study. A cohort of 216 sexually active females were followed with repeat sexually transmitted diseases screening for 12-24 months. Subjects positive on any retest (FU) were compared with those who remained negative on all FU. Subjects were interviewed for history and screened for endocervical gonococcal and chlamydial infection. RESULTS: The number of visits per patient ranged from 2 to 9 (median, 3). The initial Chlamydia trachomatis and Neisseria gonorrhoeae rates were 23.2 and 11.6%, respectively. The cumulative FU positive rates were 20.8% for C. trachomatis and 17.1% for N. gonorrhoeae. Although the initial gonococcal infection was a significant risk for a subsequent infection by C. trachomatis (p = .05) and N. gonorrhoeae (p = .001), the initial C. trachomatis status was not predictive of subsequent infections. The number of partners was not predictive of subsequent infections with either. In the entire study period, 86 patients had at least one episode of C. trachomatis and N. gonorrhoeae infection was confirmed in 52; 20 patients had recurrent cervicitis. During the study, 101 episodes of C. trachomatis and 68 episodes of N. gonorrhoeae infections were identified. Those with recurrent cervicitis (9.3%) were responsible for 33% of all cervicitis episodes identified during the study. CONCLUSIONS: Adolescents in our study were at high risk for cervicitis, particularly as a result of C. trachomatis. Risk for subsequent C. trachomatis cervicitis was the same among initially positive and negative groups. Our data underscore the importance of repeat screening for sexually transmitted infections and treatment of contacts of adolescent females.

Is it ever safe to stop azole therapy for Coccidioides immitis meningitis?

OBJECTIVE: To determine 1) whether patients with coccidioidal meningitis who had achieved remission with oral azole therapy were cured and 2) when oral azole therapy could be discontinued in these patients. DESIGN: Data were gathered on patients with coccidioidal meningitis who had successfully responded to azole therapy in previous clinical trials. SETTING: Referral centers, including university, county, and veterans' hospitals and clinics. PATIENTS: 18 patients in whom azole therapy for meningitis had been discontinued, usually because of a presumption of cure. MAIN OUTCOME MEASURES: Clinical and cerebrospinal fluid relapse. RESULTS: 14 of 18 patients (78% [95% CI, 52% to 94%]) had relapse with disseminated disease after discontinuation of therapy, for a total of 1 nonmeningeal and 15 meningeal relapses to date. Relapse occurred both soon and late (range, 0.5 to 30 months) after therapy was discontinued. The characteristics of patients who did not have relapse, including the particular azole used, the duration of therapy, the reason therapy was discontinued, and the cerebrospinal fluid indices before discontinuation, were similar to the characteristics of patients who had relapse. Relapse had serious consequences in some patients; 3 patients died. CONCLUSION: Our data suggest 1) that disease is only suppressed in patients with meningitis who achieve remission while receiving azole therapy and 2) that discontinuing azole therapy is unsafe. The alternative is lifelong treatment with azoles; this appears to be acceptable, because toxicity is uncommon with triazole therapy, even long-term triazole therapy.

Cerebrospinal fluid antibodies detected by ELISA against a 33-kDa antigen from spherules of Coccidioides immitis in patients with coccidioidal meningitis. The National Institute of Allergy and Infectious Diseases Mycoses Study Group.

Antibodies against a 33-kDa antigen from Coccidioides immitis were detected by ELISA in patients' cerebrospinal fluid (CSF). Anti-33-kDa antibodies were detected at dilutions > 1:80 in only 1 (1.4%) of 73 patients without coccidioidal meningitis but in 74 (71.8%) of 103 with meningitis. Anti-33-kDa antibodies were detected in 53 (91.4%) of 58 patients whose anti-coccidioidal complement-fixing (CF) antibodies were detectable and in 21 (46.7%) of 45 patients whose CSF was negative by CF test (positive predictive value, 99%; negative predictive value, 71%; sensitivity, 72%; specificity, 99%). Anti-33-kDa antibodies, among which IgG1 was the dominant subclass, increased when infections worsened and decreased when patients' conditions improved. Antibody concentration appeared to be independent of most baseline findings, although only 1 of 5 patients coinfected with human immunodeficiency virus had initially detectable antibodies. Measurement of anti-33-kDa antibodies is a sensitive indicator of coccidioidal meningitis and of its clinical course.

Sexual contact tracing outcome in adolescent chlamydial and gonococcal cervicitis cases.

BACKGROUND AND OBJECTIVE: Treatment of sex partners is an essential part of sexually transmitted diseases (STD) control. This study examined the efficacy of contact tracing via patient self-referral in gonococcal and chlamydial cervicitis cases among adolescents, compared with the effectiveness of provider-referral. STUDY DESIGN: Adolescent females with culture-proven chlamydial or gonococcal cervicitis were the study subjects. This cohort study was done in an urban non-STD clinic setting. The subjects chose either provider-notification or self-notification method to inform their sex partner(s) in 2 months preceding the interview date. RESULTS: Two hundred and sixty-five eligible subjects (91% African-American, 9% white) were identified. One hundred and ninety-eight sex contacts were reported by 165 (62%) cases; no contact was elicited in the remaining 100 (38%). The follow-up data revealed that 129/198 (66%) contacts were informed: 63 contacts by 61 index cases, 54 contacts of 47 cases by the case manager, 9 by both methods, and 3 by unspecified means. History of treatment was obtained in 54 contacts, including 37% (23/63) of patient-notified contacts and 50% (27/54) of provider-notified contacts; these 54 contacts constituted 42% of informed contacts, or 27% of all named contacts. The mean number of sexual contacts treated per index case was 0.58 (27/47) for the provider-referral groups and 0.38 (23/61) for the self-referral groups. Successful contact tracing was documented in 19.3% (51/265) of all index cases, resulting in treatment of 54 contacts. CONCLUSION: This study demonstrates the need for more effective partner treatment strategies in adolescent STD cases.

Treatment of lymphocutaneous and visceral sporotrichosis with fluconazole.

Thirty patients with documented sporotrichosis were treated with 200-800 mg of fluconazole daily. Fourteen patients had lymphocutaneous infection; only five (36%) of these patients had any underlying illnesses. Sixteen patients had osteoarticular or visceral sporotrichosis; 12 (75%) of these patients had underlying diseases, mostly alcoholism, diabetes mellitus, and chronic obstructive pulmonary disease. Eleven of the 30 patients had relapsed after prior antifungal therapy. Most patients were treated with 400 mg of fluconazole; however, four received 200 mg of fluconazole daily for the entire course, and four received 800 mg of fluconazole daily for a portion of their therapy or for the entire course of therapy. Fluconazole therapy cured 10 (71%) of 14 patients with lymphocutaneous sporotrichosis. However, only five (31%) of 16 patients with osteoarticular or visceral sporotrichosis responded to therapy; the conditions of two of these five patients improved only, and there was no documented cure of their infections. With the exception of alopecia in five patients, toxic effects were minimal. Fluconazole is only modestly effective for treatment of sporotrichosis and should be considered second-line therapy for the occasional patient who is unable to take itraconazole.