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.

Bacteremia in young urban women admitted with pyelonephritis.

The objective of this study was to determine the rate of bacteremia in young women admitted to the hospital with presumed pyelonephritis and compare it with other published rates. The study design was a retrospective, structured chart review and a review of published reports of bacteremic pyelonephritis. An urban county teaching hospital provided the setting for the study. The patients were nonpregnant women (n = 98) 44 years of age or younger who were without bladder dysfunction and who had not been admitted to an intensive care unit. Further criteria for participation included discharge with the diagnosis of acute pyelonephritis. Blood cultures were ordered for 69 women; the results of 64 were noted in the chart. Twenty-three women (35.9% of those cultured; 23.4% of all patients) were diagnosed with bacteremia. In patients for whom blood culture results were obtained, trends developed between those patients with bacteremia and those with complicated pyelonephritis, defined as a known or newly discovered genitourinary abnormality or a risk factor (P = 0.044), those who were black (P = .044), those with higher pulses on admission (P = .050), those with more white blood cells per high-powered field after urinalysis (P = 0.007), and those whose fever lasted longer (P = 0.033). Blood culture results were positive in two patients whose urine cultures were negative. This comparatively high bacteremia rate supports routine ordering of blood cultures for urban women suspected of having pyelonephritis.

Oral atovaquone compared with intravenous pentamidine for Pneumocystis carinii pneumonia in patients with AIDS. Atovaquone Study Group.

OBJECTIVE: To test the hypothesis that the therapeutic success rate of oral atovaquone is not worse than that of intravenous pentamidine in the primary treatment of mild and moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome and to detect differences in the toxicity rates of the two treatments. DESIGN: Patients were randomly assigned to receive 21 days of open-label therapy with either atovaquone, 750 mg orally with meals three times daily, or intravenous pentamidine, 3 to 4 mg per kg body weight once daily. SETTING: Multicenter study including university and community treatment facilities. PATIENTS: Patients with human immunodeficiency virus infection and clinical presentations consistent with mild or moderate P. carinii pneumonia were eligible. For efficacy and safety analyses, patients with histologically confirmed P. carinii pneumonia were emphasized. MEASUREMENTS: Patients were monitored by clinical and laboratory evaluations for therapeutic efficacy and adverse events during the acute treatment phase and for 8 weeks after therapy was discontinued. RESULTS: As initial therapy for a histologically confirmed episode of P. carinii pneumonia, 56 patients received atovaquone and 53 received pentamidine. More patients were successfully treated with atovaquone (57%) than with pentamidine (40%), a difference of 17% (95% CI, -3% to 38%; P = 0.085), but more patients failed to respond to atovaquone (29%) than to pentamidine (17%), a difference of 12% (CI, -6% to 29%; P = 0.18). Discontinuation of original therapy because of treatment-limiting adverse events was more frequent in the pentamidine group (36%) than in the atovaquone group (4%) (difference, -32%; CI, -48% to -17%; P < 0.001). Nine patients in each treatment group died during the study. CONCLUSIONS: Oral atovaquone and intravenous pentamidine have similar rates for successful treatment of mild and moderate P. carinii pneumonia, but atovaquone has significantly fewer treatment-limiting adverse events.

Antiretroviral therapy in HIV-infected adults. Which regimens are recommended?

The current status of antiretroviral therapy is in a state of flux. Clinical and immunologic benefit of antiretroviral treatment has been demonstrated, but the duration of benefit is finite and the effect on survival uncertain. Failure of antiretroviral treatment is closely associated with development of drug resistance. Strategies that may improve treatment outcome include combining or cycling antiretroviral agents. Given the current uncertainties in antiretroviral therapy, patients should be actively involved in treatment decisions.

Computer-assisted instruction in probabilistic reasoning during the inpatient medicine clerkship.

The acceptability and utility of computer-assisted instruction in probabilistic reasoning was assessed for medicine clerkship students. After a pretest, the experimental (n = 40), but not the control students (n = 39), completed a program that we designed. The program contained the test and its answers. After program exposure, experimental students rated their knowledge of the program's content significantly higher (p = 10(-4)) than control students. On the identical posttest, experimental students also scored significantly higher than control students (p = 10(-4)) and improved their scores significantly more (p = 10(-3)). They rated ease-of-use items significantly higher than content-relevance items (p = 10(-4)). We conclude that computer-assisted instruction in probabilistic reasoning is acceptable to clerkship students, and that it may improve their knowledge and skills in this area. However, students may rate the vehicle of this instruction more highly than its content.

Use of low-dose trimethoprim-sulfamethoxazole thrice weekly for primary and secondary prophylaxis of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients.

We conducted an open prospective clinical trial to evaluate the efficacy and toxicity of trimethoprim-sulfamethoxazole given as one double-strength tablet thrice weekly for primary and secondary prophylaxis of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus-infected (HIV+) patients. A total of 104 HIV+ patients were evaluated, with 74 being in the primary prophylaxis group and 30 being in the secondary prophylaxis group. All except six patients received concomitant zidovudine; five patients on primary prophylaxis and one patient on secondary prophylaxis refused zidovudine. There were 70 patients evaluated for the efficacy of primary prophylaxis. The mean CD4 count was 124.4 +/- 110.1 cells per microliter. The mean follow-up time was 11.8 +/- 5.8 months (median, 12 months; range, 1 to 32 months). Two noncompliant patients developed PCP after 1 and 3 months of chemoprophylaxis. The failure rate (under the intention to treat principle) was 2 of 70 patients (2.9%; 95% confidence interval, 0.35 to 10%), or 1 per 413 patient-months of observation. There were 27 patients evaluated for the efficacy of secondary prophylaxis. The mean follow-up time was 12.4 +/- 7.2 months (median, 11 months; range, 1 to 29 months). Two patients, one of whom was noncompliant, were treatment failures, developing PCP after 14 and 15 months of chemoprophylaxis; this gave a failure rate of 2 of 27 patients (7.4%; 95% confidence interval, 0.9 to 24.3%), or 1 per 167 patient-months of observation. Adverse reactions sufficient to permanently terminate therapy occurred in 9 of 104 patients (8.7%; 95% confidence interval, 4 to 15.7%) overall. The serum trimethoprim, sulfamethoxazole, and N4-acetyl-sulfamethoxazole concentrations measured by high-pressure liquid chromatography were uniformly low. One double-strength tablet of trimethoprim-sulfamethoxazole taken weekly on Monday, Wednesday, and Friday appeared to be well tolerated and efficacious for the prophylaxis of PCP in HIV+ patients at high risk and deserves further investigation.

Safety and pharmacokinetics of 566C80, a hydroxynaphthoquinone with anti-Pneumocystis carinii activity: a phase I study in human immunodeficiency virus (HIV)-infected men.

A hydroxynaphthoquinone compound (566C80) has been shown to be effective in the prevention and treatment of murine Pneumocystis carinii pneumonitis. In a phase I study, five cohorts of four human immunodeficiency virus-infected men received 100, 250, 750, 1500, and 3000 mg of the compound orally once daily for 12 days. A sixth cohort received 750 mg three times daily for 5 days, then twice daily for 16 days. Evaluation included clinical, hematologic, and biochemical studies and the pharmacokinetics of 566C80. The only drug-related adverse effect was a maculopapular rash in one patient that resolved without discontinuation of the drug. With the largest dosage tested (3000 mg) the following pharmacokinetic measures were achieved: maximum plasma concentration, 39 micrograms/ml; time to maximum plasma concentration, 8.0 h; area under plasma concentration-time curve at steady state, 1088 h.micrograms/ml; plasma half-life, 51 h; and total plasma clearance, 4.09 l/h. Compound 566C80 offers promise as a new drug class for P. carinii pneumonia.

Indigent health care: the increasing contribution of AIDS to the health care budget deficit.

With the number of AIDS cases in the United States exceeding 100,000 and rising, it is becoming more of a financial burden to take care of this population. The Regional Medical Center at Memphis, like most hospitals providing indigent care, sustains annually a large deficit for both outpatient and inpatient care of AIDS patients. With the establishment of a dedicated AIDS clinic, it is hoped to maximize outpatient care and the utilization of available financial resources. Implementation of this model may help obviate the financial disaster that is impending for the already overburdened public hospitals and their patients.

Health perceptions and medical care opinions of inner-city adults with sickle cell disease or asthma compared with those of their siblings.

Inner-city adults (n = 108) with a chronic disease (sickle cell disease or asthma) and their unaffected siblings (n = 50) were interviewed and ratings of health perceptions and opinions about medical care were compared. Persons with a chronic disease reported unfavorable ratings of their health (P less than .001). Their siblings reported moderately favorable health perceptions but much worry and concern about their health. When compared with the asthma subgroup, persons with sickle cell disease reported more adverse ratings of health outlook susceptibility to illness, sickness orientation, humaneness of medical care, and satisfaction with medical care (P less than .05). These observations demonstrate low health perceptions in adults with two chronic medical conditions and more negative perceptions in persons with sickle cell disease. They indicate possible opportunities for improving medical care for patients with these conditions to achieve better perceptions of health, outlook, and medical services.