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Surveillance system [NNIS]) definitions for device-associated health care-associated infection, we collected prospective data from 155,358 patients hospitalized in the consortium's hospital ICUs for an aggregate of 923,624 days. Although device utilization in the developing countries' ICUs was remarkably similar to that reported from US ICUs in the CDC's NHSN, rates of device-associated nosocomial infection were markedly higher in the ICUs of the INICC hospitals: the pooled rate of central venous catheter (CVC)-associated bloodstream infections (BSI) in the INICC ICUs, 7.6 per 1000 CVC-days, is nearly 3-fold higher than the 2.0 per 1000 CVC-days reported from comparable US ICUs, and the overall rate of ventilator-associated pneumonia (VAP) was also far higher, 13.6 versus 3.3 per 1000 ventilator-days, respectively, as was the rate of catheter-associated urinary tract infection (CAUTI), 6.3 versus 3.3 per 1000 catheter-days, respectively. Most strikingly, the frequencies of resistance of Staphylococcus aureus isolates to methicillin (MRSA) (84.1% vs 56.8%, respectively), Klebsiella pneumoniae to ceftazidime or ceftriaxone (76.1% vs 27.1%, respectively), Acinetobacter baumannii to imipenem (46.3% vs 29.2%, respectively), and Pseudomonas aeruginosa to piperacillin (78.0% vs 20.2%, respectively) were also far higher in the consortium's ICUs, and the crude unadjusted excess mortalities of device-related infections ranged from 23.6% (CVC-associated bloodstream infections) to 29.3% (VAP).

Aims To obtain comprehensive pharmacokinetic and pharmacodynamic data for artesunate (ARTS) and its active metabolite dihydroartemisinin (DHA) following i.v. and oral administration of ARTS to patients with acute, uncomplicated falciparum malaria. Methods Twenty-six Vietnamese patients with falciparum malaria were randomized to receive either i.v. ARTS (120 mg; group 1) or oral ARTS (100 mg; group 2), with the alternative preparation given 8 h later in an open crossover design. Mefloquine (750 mg) was administered at 24 h. Plasma concentrations of ARTS and DHA were determined by h.p.l.c. assay. Pharmacokinetic parameters were calculated by non-compartmental methods. The time to 50% parasite clearance (PCT 50 ) was calculated by linear interpolation of parasite density determinations. Linear least squares and multiple linear regression analyses were used to evaluate pharmacokineticpharmacodynamic relationships. Results Following i.v. bolus, ARTS had a peak concentration of 29.5 mm (11 mg l −1 ), elimination t 1/2 =2.7 min, CL=2.33 l h −1 kg −1 and V=0.14 l kg −1 .The C max for DHA was 9.3 mm (2.64 mg l . Following oral ARTS, relative bioavailability of DHA was 82%, C max was 2.6 mm (0.74 mg l −1 ), t 1/2 =39 min, and MAT=67 min. Overall, the PCT 50 and fever clearance time (FCT) were 6.5 h and 24 h, respectively. There was no correlation between PCT 50 or FCT and AUC, C max or MRT for DHA. Conclusions Despite rapid clearance of ARTS and DHA in patients with uncomplicated falciparum malaria, prompt parasite and fever clearance were achieved. High relative bioavailability of DHA following oral ARTS administration, and clinical outcomes comparable with those after i.v. ARTS, support the use of the oral formulation in the primary care setting.

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