Pharmacokinetics and pharmacodynamics of piperacillin/tazobactam during high volume haemodiafiltration in patients with septic shock.

BACKGROUND: The purpose of the study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of piperacillin and tazobactam during high-volume haemodiafiltration (HVHDF). METHODS: A single dose of piperacillin/tazobactam (4/0.5 g) was administered as 30 minute infusion during HVHDF to 10 patients with acute kidney injury due to septic shock. Arterial blood samples were collected before and at 30 or 60 min intervals over 8 h (12 samples) after study drug administration. Concentrations of piperacillin and tazobactam were determined by HPLC-MS/MS. R software was used for population PK analysis and Monte Carlo Simulation of probability of PK/PD target attainment (PTA) in 1000 subjects. RESULTS: A total of 101 samples were collected during HVHDF. The median (IQR) estimated glomerular filtration rate of the patients was 16 (11.25-27.5) ml/min/1.73 m(2) and HVHDF effluent rate was 208 (146.3-298.3) ml/kg/h. A final two-compartment population PK model predicted mean (%SE) total piperacillin clearance on HVHDF was 6.9 (6.4) l/h, volume of distribution of central compartment 9.0 (10.1) l and of peripheral compartment 11.2 (12.2) l. The PTA of 50% fT>MIC for piperacillin 4 g/tazobactam 0.5 g dosed every 8 h as 0.5-h and 4-h infusion was 84.3% and 100% for MIC of 16 mg/l respectively. Aiming 100% fT>MIC of 16 mg/l, the PTA values were 88.6% and 61.0%, for piperacillin 4 g/tazobactam 0.5 g 4-h infusion every 6 and 8 h respectively. CONCLUSIONS: For bactericidal PK/PD target attainment piperacillin/tazobactam doses of 4/0.5 g every 8 h appear appropriate in septic shock patients with minimal residual renal function during HVHDF.

Differences between women and men in serial HIV prevalence and incidence trends.

To measure trends in HIV incidence and serial prevalence by sex in a intravenous drug users (IDUs) and heterosexuals (HT) cohort recruited in a counselling centre in Valencia (1988-2005). Serial prevalence and incidence rates were calculated and modelled by logistic and Poisson regression respectively. 5948 IDUs and 13343 HT were recruited. Prevalence was higher among female IDUs (46% vs. 41%), and female HT (4.1% vs. 2%). For IDUs, an interaction (P = 0.005) between sex and calendar was detected. Age-adjusted prevalence showed faster yearly decline in men (OR = 0.87 95%CI: 0.85-0.88) than in women (OR = 0.91 95%CI: 0.88-0.93). Incidence was higher in female IDUs (9.79% p-y) than in men, (5.38% p-y) with an annual decrease for both of 11%. HIV incidence was higher in female HT (0.62% p-y) compared to men 0.23% p-y with a 21% yearly decline. Gender differences in HIV prevalence and incidence trends have been detected. Women showed an increased vulnerability to infection in a country whose HIV epidemic has been largely driven by IDUs.

Trends in HIV testing, serial HIV prevalence and HIV incidence among people attending a Center for AIDS Prevention from 1988 to 2003.

AIM: To analyse trends in HIV testing, serial HIV prevalence and HIV incidence among people who underwent voluntary testing in a Center for AIDS Prevention in Valencia, Spain. METHODS: Open cohort study including all subjects who went to the Center for AIDS Prevention from 1988 to 2003. Information on sociodemographic variables and HIV test results was collected. Serial prevalence and incidence rates were calculated, and joinpoint regression was used to identify changes in trends over time. RESULTS: 21,241 subjects were analysed; 67% men, 27% injecting drug users (IDUs), 43% heterosexuals and 13% men who have sex with men (MSM). From 1988 to 1990, IDUs accounted for 57% of clinic attenders, decreasing to 14% by 1997-2003, accompanied by an increase in heterosexuals. Overall, HIV prevalence for the whole period was 15%, dropping from 35% to <10% after 1999 and to 3% by 2003, when HIV prevalence was 26% in IDUs, 6% in MSM and 2% in heterosexuals. Total HIV incidence was 2.5%. From 1988 to 1990, HIV incidence ranged from 6% to 8%, and a gradual and progressive decline observed from 1990 onwards. From 1995 onwards, HIV incidence was <2%. The highest incidence rate is seen in IDUs, 7-12% in the first period and 4-5% at the end. Among MSM, a change in the decreasing trend is seen by 1998, and increases in incidence are detected by 2002-3. CONCLUSIONS: Serial HIV prevalence has markedly decreased from 1988 in all transmission categories, although it is still high. With regard to HIV incidence, the drop has been marked too, although a worrying increase, that requires further follow-up, has been detected in MSM in the past 2 years.

Diagnóstico de la infección por el VIH en atención primaria / Diagnosis of HIV infection in primary care

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