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This study sought to better characterize the natural history of AIDS-associated disseminated Mycobacterium avium complex (MAC) infection. Towards that end two retrospective studies were done: a case-control survival study and a MAC respiratory colonization study. Among 137 consecutive patients who had a sterile body site cultured for mycobacteria within 3 months of their first AIDS-defining episode of Pneumocystis carinii pneumonia, median survival was significantly shorter in those with disseminated MAC infection (107 days; 95% confidence interval [CI] 55-179) than those with negative cultures (275 days; 95% CI 230-318; P less than .01), even after controlling for age, absolute lymphocyte count, and hemoglobin concentration. Among 34 patients with AIDS and respiratory MAC colonization, 22 later developed disseminated infection (65% predictive value for subsequent MAC dissemination). Disseminated MAC infection was associated with significantly shorter survival for patients with AIDS, and the presence of MAC in respiratory specimens has substantial predictive value for subsequent disseminated infection.

Two cephalosporin antibiotics, cefaclor and cephalexin, were administered orally to healthy, adult male volunteers for comparison of their pharmacological properties. In doses of 250 mg orally, cefaclor produced a peak serum concentration of 6.01 + 0.55 (standard deviation [SD]) ,ug/ml compared with 9.43 + 2.36 ,g/ml for cephalexin (P < 0.01). The half-lives were 0.58 + 0.07 (SD) h and 0.80 + 0.12 (SD) h, and elimination constants were 1.22 + 0.15 and 0.88 + 0.13 h-1 for cefaclor and cephalexin, respectively (P < 0.001). Neither drug showed accumulation over the dosing period, and both were well tolerated. Procedure. The subjects were randomly divided into two groups of 10 individuals each. They were assigned to a crossover sequence of the two antibiotic regimens to be taken during two separate dosing periods. Each dosing period was 4 days in duration and separated by 1 week. Group I received 250 mg of cefaclor in capsules orally every 6 h (q6h) during the first period, followed by 250 mg of cephalexin in capsule form orally q6h during the second dosing period. Group II followed a reverse order. All subjects complied with the dosage time schedule.All subjects fasted for 8 h before each dosing period. After the first dose, a fast of 2 h was maintained before and after each subsequent dose. A control venous blood sample was drawn before the first dose and showed no detectable antibiotic activity in either of the two dosing periods. Venous blood samples for assay of plasma antibiotic concentration were obtained at 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 24.0, 36.0, 48.0, 60.0, 72.0, 72.5, 72.75, 73.0, 73.5, 74.0, 75.0, 76.0, 78.0, and 90.0 h after the initial dose. Urine samples were collected in 2-h intervals from time 0 to 6 h and from 72 to 78 h. There was a loss of up to 50% activity of cefaclor in serum samples that were left at room temperatures for 3 to 8 h. Therefore, all blood samples were immediately iced, and the serum was separated in a refrigerated centrifuge and either immediately placed in a -70°C freezer or assayed. Using these precautions, a 14.17 + 1.47 (standard deviation [SD])% loss of activity was found in 16 samples evaluated.The following tests were performed before and after each dosing period: hemoglobin, hematocrit, leukocyte count and differential, platelet estimation, urinalysis, blood urea nitrogen, glucose, sodium, potassium, chloride, bicarbonate, calcium, phosphorus, alkaline phophatase, lactic dehydrogenase, serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, cholesterol, total bilirubin, total protein, albumin, uric acid, and creatinine. Creatinine clearances were performed 157 on May 9, 2018 by guest http://aac.asm.org/ Downloaded from

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