Evaluation of oral erythromycin and local isoniazid instillation therapy in infants with Bacillus Calmette-Guérin lymphadenitis and abscesses. Is medical therapy effective for regional lymphadenitis following BCG vaccination? Randomized, double-blind, multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiases. Needle aspiration for suppurative post-BCG adenitis. A trial of three regimens to prevent tuberculosis in Ugandan adults infected with the human immunodeficiency virus. Uganda-Case Western Reserve University Research Collaboration.
A randomized placebo-controlled prospective trial was conducted to evaluate the efficacy of erythromycin therapy in 69 patients affected with Bacillus Calmette-Guérin lymphadenitis. When patients who developed subsequent regional abscesses were excluded, erythromycin caused significantly earlier resolution of lymphadenitis (5.1 months vs. 5.7 months for placebo; P < 0.01) compared with placebo. There was no significant difference in the proportion of patients who developed subsequent regional abscesses between the 2 groups (47% for erythromycin, 60% for placebo, P = 0.14). When the entire group of 69 patients was evaluated for "duration to heal" (regardless of subsequent abscess formation), erythromycin therapy (4.1 +/- 1.5 SD months) did not differ significantly from the placebo group (3.5 +/- 1.3 months, P = not significant). Patients who developed subsequent abscess (n = 36) along with those with B. Calmette-Guérin regional abscesses at presentation (n = 27) were further studied to compare oral erythromycin therapy with that of single dose 50-mg intranodal isoniazid instillation. Local isoniazid therapy caused significantly earlier resolution of the abscesses (3.9 months) compared with erythromycin therapy (5.2 months; P < 0.001). We describe 120 patients with regional lymphadenitis following intradermal BCG vaccination. Seventy-eight of the patients were given medical therapy to prevent drainage and suppuration, and 42 patients were followed up without such treatment. The medical therapy group is divided into three subgroups: 36 were given erythromycin stearate, 21 isoniazid, and 21 isoniazid plus rifampin. No statistical difference in the incidence of spontaneous drainage and suppuration was found between the "no therapy" and the "medical therapy" groups. No significant superiority of any specific therapy was shown. If lymphadenitis develops rapidly (in two months), the incidence of spontaneous drainage and suppuration is significantly higher than in patients with slowly developing lesions. Total surgical excision is recommended to prevent spontaneous drainage and chronic suppuration in these rapidly evolving instances. Caspofungin is an antifungal agent of the novel echinocandin class. We investigated its efficacy, safety, and tolerability as therapy for oropharyngeal and/or esophageal candidiasis in a phase II dose-ranging study. Patients were randomized in a double-blind manner to receive either caspofungin acetate (35, 50, or 70 mg) or amphotericin B (0.5 mg/kg of body weight) intravenously once daily for 7 to 14 days. A favorable response required both complete resolution of symptoms and quantifiable improvement of mucosal lesions 3 to 4 days after discontinuation of study drug. Efficacy was assessed using a modified intent-to-treat analysis. No hypothesis testing of efficacy was planned or performed. Of 140 enrolled patients, 63% had esophageal involvement and 98% were infected with the human immunodeficiency virus (HIV) (median CD4 count, 30/mm(3)). A modestly higher proportion of patients in each of the caspofungin groups (74 to 91%) achieved favorable responses compared to amphotericin B recipients (63%), but there was considerable overlap in the 95% confidence intervals surrounding these point estimates. Similar trends were found in the subgroups with esophageal involvement, a history of fluconazole failure, and CD4 counts of < or =50/mm(3). A smaller proportion of patients receiving any dose of caspofungin experienced drug-related adverse events compared to patients given standard doses of conventional amphotericin B (P < 0.01). Caspofungin provided a generally well-tolerated parenteral therapeutic option for HIV-infected patients with oropharyngeal and/or esophageal candidiasis in this study. The effect of needle aspiration in suppurative post-BCG adenitis was studied. Nodes that had been aspirated (43 patients) regressed in 25 (58%) and 41 (95%) patients two and six months after aspiration. In the control group (34 patients) regression occurred in three (9%) and 22 (65%) patients. Spontaneous drainage with sinus tract formation was also significantly less in the aspirated group at six months (7% v 44%). Infection with the human immunodeficiency virus (HIV) greatly increases the risk of reactivation tuberculosis. We evaluated the safety and efficacy of three preventive-therapy regimens in a setting where exposure to tuberculosis is common.
                We performed a randomized, placebo-controlled trial in 2736 HIV-infected adults recruited in Kampala, Uganda. Subjects with positive tuberculin skin tests (induration, > or =5 mm) with purified protein derivative (PPD) were randomly assigned to one of four regimens: placebo (464 subjects), isoniazid daily for six months (536), isoniazid and rifampin daily for three months (556), or isoniazid, rifampin, and pyrazinamide daily for three months (462). Subjects with anergy (0 mm induration in reaction to PPD and candida antigens) were randomly assigned to receive either placebo (323 subjects) or six months of isoniazid (395). The medications were dispensed monthly and were self-administered.
                Among the PPD-positive subjects, the incidence of tuberculosis in the three groups that received preventive therapy was lower than the rate in the placebo group (P=0.002 by the log-rank test). The relative risk of tuberculosis with isoniazid alone, as compared with placebo, was 0.33 (95 percent confidence interval, 0.14 to 0.77); with isoniazid and rifampin, 0.40 (0.18 to 0.86); and with isoniazid, rifampin, and pyrazinamide, 0.51 (0.24 to 1.08). Among the subjects with anergy, the relative risk of tuberculosis was 0.83 (95 percent confidence interval, 0.34 to 2.04) with isoniazid as compared with placebo. Side effects were more common with the multidrug regimens, and particularly with the regimen containing pyrazinamide. Survival did not differ among the groups, but the subjects with anergy had a higher mortality rate than the PPD-positive subjects.
                A six-month course of isoniazid confers short-term protection against tuberculosis among PPD-positive, HIV-infected adults. Multidrug regimens with isoniazid and rifampin taken for three months also reduce the risk of tuberculosis.
It is unclear if oral antibiotics (isoniazid, erythromycin, or a combination of isoniazid plus rifampicin) are effective for the resolution of BCG-induced disease. Most non-suppurated lymphadenitis will resolve without treatment in 4 to 6 months. Patients with lymphadenitis abscess might benefit from needle aspiration and possibly local instillation of isoniazid could shorten recovery time. Included studies were generally small and could be better conducted. Further research should evaluate the use of needle aspiration and local instillation of isoniazid in fluctuant nodes. Therapeutic and preventive measures in HIV-infected infants could be important given the higher risk of negative outcomes in this group.