One of the principal targets of HIV infection is the human peripheral blood CD4+ T cell, resulting in progressive CD4+ lymphocyte loss. Hypothesized mechanisms for this loss include apoptosis, cytolytic reactions, V-beta gene deletion of the T-cell receptor (TCR) by superantigens, CD4+ lymphocyte syncytium formation, and autoimmune reactions. In adults with HIV infection, the critical decline in CD4+ lymphocyte number that heralds the onset of AIDS-defining conditions is well characterized, whereas in infants and children the critical level of CD4+ cells predisposing to the development of AIDS-defining conditions or mortality is not fully characterized, due to an incomplete knowledge of CD4+ lymphocyte number and changes with age in normal and HIV-infected children. In a prospective study of 317 infants born to HIV-infected women, early results show that the monthly change in absolute CD4+ lymphocyte number over a 3- to 9-month period in HIV-infected infants was -109 cells/mm3 per month, at least double the rate of decline measured in HIV-noninfected infants in the study or that calculated from normal infants' values reported in the literature. In other clinical studies in HIV-infected infants and children, it was possible to study the effect of low CD4+ cell counts on clinical status and mortality. In HIV-infected pediatric patients younger than 1 year, it was possible to correlate low CD4+ cell number with advanced disease status (CDC pediatric class P-2). It was also possible to correlate extremely low CD4+ cell counts (< 200 cells/mm3) in HIV-infected children with a significant risk of mortality within the next 3 months of life. Sequential CD4+ cell analysis of HIV-high-risk infants will delineate the rate of HIV-related decline in CD4+ cells, thus facilitating the diagnosis of HIV infection and aiding in identification of HIV-infected children at high risk of disease progression or death.
Limited pharmacokinetic data for cefoperazone are available from the parturient. Because cefoperazone has a dual excretory patterni, primarily via the biliary system and secondarily via the kidney, pregnancy-induced physiologic alterations can influence its deposition and cleltrance. Twelve term parturients receiving cefoperazone prophylaxis after cesarean section were selected for study. After 2 g of cefoperazone was administered for 1 h intravenously, serial blood samples were assayed by high-pressure liquid chromatography, Plasma protein binding of cefoperazone was studied in vitro. The mean peak cefoperazone concentration ± standard deviation was 169.9 ± 60.4 ,ug/ml. The mean half4life was 152 min. Total serum clearance was 80.8 ± 30.8 ml/mhin. The steady-state volume of distribution was 14.2 ± 6.0 liters. All subjects had detectable trough levels at the end of the dosage interval, with a mean value of 6.5 + 5.2 ,ug/ml. Protein binding of cefoperazone for parturients was 74.3 ± 10.9%, comnpared with 87.7 ± 3.2% in nonpregnaimt controls (P < 0.05). These data suggest that cefoperazone deposition can be greatly influenced by pregnancy. However, unlike several other new anti-icrobial agents whose excretions are mainly renal, the cefoperazone half-lire and thus trough concentration for the parturient more closely resemble that for the nonpregnant subject.Cefoperazone has been shown to be efficacious in a variety of clinical settings by virtue of its broad range of antibacterial activity. In particular, because the obstetric patient who develops post-cesarean-section sepsis is most often infected by a polymicrobial insult, broad-spectrum antimicrobial agents have justified the single-drug approach of the clihician to therapy (4, 12). However, recognition of physiologic alterations which normally occur in the parturient is important, because these changes may directly influence the pharmacokinetic behavior of a given drug and therefore its clinical utility (10). In this regard, cefoperazone has been shown to exhibit an excretion pattern primarily via the biliary system and secondarily through the kidneys (3).Because these excretory pathways may be altered during pregnancy, a study Was undertaket to evaluate the pharrhacokinetics of cefoperazone in this select study population.MATERIALS AND METHODS Subjects. Twelve term parturients who underwent cesarean section by the obstetric service staff at Hermann Hospital, the major teaching institution for the University of Texas Medical School at Houston, were enrolled in this prospective research study. The protocol was approved by the Committee for the Protection of Human Subjects at the University of Texas Health Science Center at Houston and the University of Houston-University Park. All patients received cefoperazone for prophylaxis at the time of surgery and again 12 h postoperatively. Each subject was studied at the time of the latter drug administration period. After informed consent was obtained, 2 g of cefoperazone were administered over 60 min with an intravenou...
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