Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a 1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CL(CR)), such that a 30-ml/min increase in the estimated CL(CR) would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every 8 h as a 4-h infusion is optimal for patients with a CL(CR) of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CL(CR) of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved.
Health-care-associated infections (HAIs) are considered a serious public health issues that contribute substantially to the global burden of mortality and morbidity with respect to infectious diseases. The aim is to assess the burden of health-care-associated infections by collation of available data from published point prevalence surveys (PPS) on HAIs to give future guidance. Study protocol and methodology were designed according to preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Published research papers that conducted a point prevalence survey of HAIs in hospital settings by following the structured survey methodology employed by European Centre of Disease Prevention and Control (ECDC) were included. Of 1212 articles, 67 studies were included in the final analysis conducted across different countries. Overall, 35 studies were conducted in Europe, 21 in Asia, 9 in America, and 2 in Africa. The highest prevalence of HAIs was recorded in a study conducted in adult ICU settings of 75 regions of Europe (51.3%). The majority of the studies included HAI data on urinary tract infections, respiratory tract infections, and bloodstream infections. Klebsiella pneumonia, Pseudomonas aeruginosa and E. coli were the most frequent pathogens responsible for HAIs. PPS is an useful tool to quantify HAIs and provides a robust baseline data for policymakers. However, a standardize surveillance method is required. In order to minimize the burden of HAIs, infection prevention and control programs and antibiotic stewardship may be effective strategies to minimize the risk of HAIs.