Edward C. Oldfield

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.

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.

Prediction of Relapse After Treatment of Coccidioidomycosis

Relapse after apparently successful treatment of coccidioidomycosis has been a problem with both amphotericin B and the azoles. We conducted a retrospective cohort study of 34 patients who required therapy for coccidioidomycosis between 1973 and 1993; 10 relapsed and 25 (one patient received two courses of therapy) did not relapse during follow-up. The mean time to relapse after completion of therapy was 7.3 months (range, 1-21 months). All 34 patients responded clinically to therapy. A fourfold or greater decrease in titers of antibody, as determined by complement fixation (CF), during therapy was seen in seven (78%) of nine patients who relapsed and 17 (85%) of 20 patients who did not relapse (P = .956). There was no significant difference between relapsers and nonrelapsers in terms of the lowest CF titer during therapy, the CF titer at the end of therapy, or the peak CF titer. The risk of relapse was increased among those with a peak CF titer of > or = 1:256 (relative risk [RR] = 4.7; 95% confidence interval [CI] = 1.4-16.1), as compared with patients who did not mount such a high antibody response. Similarly, the risk of relapse was higher among those with serially negative coccidioidin skin tests (CSTs) than those with serially positive CSTs (RR = 4.8; 95% CI = 1.2-19.5). We conclude that clinical response, lowest CF titer, end-of-therapy CF titer, and decrease in the CF titer of at least fourfold are not predictive of relapse in patients with coccidioidomycosis. Negative serial coccidioidin skin tests and a peak CF antibody titer of > or = 1:256 are independently associated with increased risk of relapse.

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.

Fulminant endocarditis due to infection with penicillinase-producing Neisseria gonorrhoeae.

Endocarditis is a rare but potentially lethal manifestation of gonococcal infection. We report the case of a patient with fulminant endocarditis secondary to infection with penicillinase-producing Neisseria gonorrhoeae (PPNG). The patient had rapid deterioration from extensive destruction of the aortic valve with abscess and fistula formation. Lifesaving emergency surgery was performed. To our knowledge this is the first reported case of gonococcal endocarditis secondary to infection with a penicillinase-producing organism.