Treatment of adult varicella with sorivudine: a randomized, placebo-controlled trial.

The antiviral and clinical efficacy of sorivudine in adults with varicella was evaluated in a double-blind, placebo-controlled randomized trial. A total of 186 patients were hospitalized for isolation and treatment within 96 h of rash onset. The diagnosis of varicella was confirmed in 184 patients with paired sera. Patients were randomly assigned to receive 10 or 40 mg of sorivudine or an identical placebo once a day for 5 days. Treatment with 40 mg of sorivudine (compared with placebo) shortened the mean time to 100% crusting from 6.6 to 5.8 days (P = .004) and reduced the mean days that new lesion formed from 3.9 to 3.1 (P = .014). Mean days of cutaneous viral shedding were reduced from 3.3 in the placebo group to 2.6 in the 40-mg sorivudine group (P = .002). The effectiveness of therapy was not affected by the duration of rash before initiation of therapy. Sorivudine is a promising new agent for the treatment of varicella-zoster virus infections.

Syphilis and neurosyphilis in a human immunodeficiency virus type-1 seropositive population: evidence for frequent serologic relapse after therapy.

OBJECTIVE: To describe clinical and treatment aspects of syphilis infection among patients seropositive for the human immunodeficiency virus (HIV). PATIENTS AND METHODS: Results of serologic tests for syphilis, CD4+ T-lymphocyte counts, and clinical response to therapy were retrospectively monitored in 100 HIV-infected adults with syphilis from a tertiary-care military HIV program. RESULTS: Of the 1,206 HIV-infected patients, 100 (8.3%) in the cohort had syphilis; 61 patients were treated for active syphilis. Serologic or clinical relapse eventually occurred in 10 of the 56 treated patients (17.9%) with follow-up available; 7 of the 10 who relapsed had previously received high-dose intravenous or procaine penicillin therapy. Relapse occurred more than 12 months after initial therapy in 6 of 10 patients (60%) who experienced relapse; 5 patients experienced multiple relapses. The mean CD4+ T-lymphocyte count was not predictive of relapse. Patients with reactive cerebrospinal fluid (CSF) Venereal Disease Research Laboratory (VDRL) test titers (4 of 7 patients [57%]) or the rash of secondary syphilis (4 of 14 patients [29%]) were at highest risk of subsequent relapse or treatment failure when monitored for an average of 2 years. CONCLUSION: Standard penicillin regimens, including high-dose intravenous penicillin, transiently lowered serum VDRL titers in nearly all cases, but were sometimes inadequate in preventing serologic and clinical relapse in patients infected with HIV type-1, especially among those with secondary syphilis and reactive CSF VDRL titers. Careful long-term follow-up is essential, and repeated courses of therapy may be needed for patients infected with HIV type-1 who have syphilis.

Tumor necrosis factor, interleukin-2, and interferon-gamma in adult varicella.

Adult varicella can be a severe illness complicated by pneumonia, encephalitis, or prolonged fever. This study measured levels of tumor necrosis factor (TNF)-alpha, interleukin-2 (IL-2), and interferon gamma (IFN-G) in a consecutive group of 31 adult varicella patients presenting within 24 hours of rash onset. All cytokines were assayed using an ELISA technique. TNF-alpha was detectable in 71% of patients with a mean level of 52 pg/ml. IL-2 was detectable in 29% with a mean level of 1040 pg/ml. IFN-gamma was detectable in only 9%. There was no correlation between TNF, IL-2, or IFN-G level and clinical severity as determined by duration and severity of cutaneous findings, duration of fever, frequency of hepatitis, or thrombocytopenia.

Soft-tissue infection due to Mycobacterium smegmatis: report of two cases.

Mycobacterium smegmatis is an uncommon pathogen in humans. Fourteen cases of skin or soft-tissue infection due to M. smegmatis have been previously reported. We report two cases of posttraumatic M. smegmatis infection of the lower extremity. M. smegmatis infection produces chronic cellulitis with fistula formation that is most commonly a result of direct traumatic inoculation of contaminated material. Extensive surgical debridement followed by skin grafting has been necessary for cure in the majority of cases.

Treatment of varicella in the immunocompetent adult.

Varicella in the immunocompetent adult is an infrequent but potentially serious infection. Previous studies in immunocompetent hosts and normal adults have demonstrated the value of intravenous acyclovir in the treatment of varicella-zoster virus infections. Oral acyclovir has also shown efficacy in both normal adults with zoster (shingles) and immunocompetent children with varicella. A recently completed double-blind placebo-controlled study of oral acyclovir in immunocompetent adults with uncomplicated varicella also demonstrated efficacy. Therapy within the first day reduced the time to 100% crusting of skin lesions from 7.4 to 5.6 days, and reduced the duration of fever by one-half day. Symptoms were also diminished. These benefits were observed only when therapy was initiated within 24 hours of the appearance of the rash. Adults with complicated varicella (usually symptomatic varicella pneumonia) should receive intravenous acyclovir. Several new agents for varicella-zoster therapy are being evaluated; brovavir is a new agent currently being compared to placebo in the treatment of adult varicella.

Risk of ventricular dysrhythmias during 1-hour infusions of amphotericin B in patients with preserved renal function.

In order to assess the safety of 1-h infusions of amphotericin B (AMB), we prospectively monitored 213 1-h infusions of AMB (dose range, 0.27 to 0.89 mg/kg of body weight) in 27 patients with creatinine clearances of > 25 ml/min. Holter monitor tracings during 1-h infusions were compared with those during a 4-h baseline period of monitoring. There were no ventricular dysrhythmias during 1-h infusions of AMB that were not present during baseline monitoring. Nausea and/or rigors were noted for 32 (15%) infusions in six (22%) patients. No patient exhibited a temperature rise of > 1 degree C. We conclude that, in doses of up to 0.9 mg/kg, AMB does not appear to induce asymptomatic ventricular dysrhythmias when administered over 1 h to patients with creatinine clearances of > 25 ml/min.

Detection of varicella-zoster virus DNA in the oropharynx and blood of patients with varicella.

The polymerase chain reaction (PCR) was used to detect varicella-zoster virus (VZV) DNA in respiratory epithelial cells and in peripheral blood leukocytes from adults with varicella. VZV DNA was detected in oropharyngeal epithelium in 62% of patients early in the course of varicella; the amount of VZV DNA declined with time and was detectable in only 22% of patients for greater than 6 days. VZV DNA was also detected in peripheral blood leukocytes in 74% of patients early in disease and was detected in both polymorphonuclear and mononuclear leukocytes. PCR demonstrated the presence of VZV DNA in the oropharynx and blood of most patients during varicella, in contrast to the ability to detect VZV in these tissues by viral culture.

Treatment of adult varicella with oral acyclovir. A randomized, placebo-controlled trial.

OBJECTIVE: To assess the efficacy of oral acyclovir in treating adults with varicella and to describe the natural history of adult varicella. DESIGN: Double-blind, placebo-controlled randomized trial. SETTING: A naval hospital. PATIENTS: One hundred forty-eight of 206 consecutive adult active duty Navy and Marine Corps personnel who were hospitalized for isolation and inpatient therapy of varicella and who could be treated within 72 hours of rash onset completed the study. The diagnosis of varicella was confirmed by acute and convalescent serology in 143 of 144 patients with available paired sera. INTERVENTION: Patients were randomly assigned to receive either acyclovir, 800 mg orally five times per day for 7 days, or an identical placebo. Separate randomization codes were used for patients presenting within 24 hours of rash onset and for those presenting 25 to 72 hours after rash onset. MEASUREMENTS: Daily lesion counts, symptom scores, temperature measurements, and laboratory tests were used to monitor the course of the illness. RESULTS: Early treatment (initiated within 24 hours of rash onset) reduced the total time to (100%) crusting from 7.4 to 5.6 days (P = 0.001) and reduced the maximum number of lesions by 46% (P = 0.04). Duration of fever and severity of symptoms were also reduced by early therapy. Late therapy (25 to 72 hours after rash onset) had no effect on the course of illness. Only four patients had pneumonia, and no encephalitis or mortality was noted. CONCLUSIONS: Early therapy with oral acyclovir decreases the time to cutaneous healing of adult varicella, decreases the duration of fever, and lessens symptoms. Initiation of therapy after the first day of illness is of no value in uncomplicated cases of adult varicella. The low frequency of serious complications of varicella (pneumonia, encephalitis, or death) precluded any evaluation of the possible effect of acyclovir on these outcomes.

Gastrointestinal side effects of intravenous erythromycin: incidence and reduction with prolonged infusion time and glycopyrrolate pretreatment.

OBJECTIVE: To determine the frequency of gastrointestinal toxicity due to intravenous (IV) erythromycin and to attempt to decrease this toxicity by prolonging the infusion time of erythromycin and/or pretreating with the peripheral anticholinergic, glycopyrrolate 0.1 mg IV. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: General medical wards of a tertiary medical center. PATIENTS: A total of 51 hospitalized patients 18 years of age or older who were prescribed IV erythromycin lactobionate (EMLB) 500 mg every 6 hours by their attending physicians. INTERVENTIONS: Each of eight consecutive infusions of EMLB was randomly assigned to one of four groups: control--30-minute infusion/placebo pretreatment; 60/P--60-minute infusion/placebo pretreatment; 30/G--30-minute infusion/glycopyrrolate pretreatment; and 60/G--60-minute infusion/glycopyrrolate pretreatment. MAIN OUTCOME MEASURES: Each infusion was accompanied by a questionnaire in which patients rated the magnitude of nausea and vomiting on a scale of 1 (no toxicity) to 9 (severe toxicity). Scores for both nausea and vomiting were added together for a total toxicity score ranging from 2 to 18. A total score of greater than 8 was defined as clinically important. RESULTS: The 51 patients received a total of 356 infusions with gastrointestinal toxicity occurring in 27 of 51 (53%) patients. Among patients under the age of 40, 22 of 33 (67%) experienced toxicity compared with only five of 18 patients (28%) over the age of 40 (p = 0.018). Clinically important toxicity was seen in 19 of 51 patients (37%), including five who withdrew during the study because of severe nausea and vomiting. In this group, the combination of a 60-minute erythromycin infusion and glycopyrrolate pretreatment decreased clinically important toxicity by 79% from 47% to 10%, a statistically and clinically significant 37% (95% CI, 14% to 60%) difference (p = 0.007). CONCLUSIONS: Gastrointestinal toxicity associated with the IV infusion of erythromycin is common and is more likely to occur in younger patients. A 1-hour infusion of erythromycin combined with pretreatment with glycopyrrolate, 0.1 mg IV, is effective in reducing this toxicity.