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piperacillin/tazobactam. There were 102 patients who received the prolonged infusion of piperacillin/tazobactam dosed 3.375g every 8 hours. There were 92 patients who received the conventional infusion of piperacillin/tazobactam dosed 3.375g every 4 hours (4 patients) or 6 hours (88 patients). There was no difference in baseline characteristics between the two groups. The 14-day mortality rate was 8.8% in the prolonged infusion group versus 15.2% in the conventional infusion group (p=0.17). The median length of stay after sample collection was 18 days in the prolonged infusion group versus 22.5 days in the conventional infusion group (p=0.09). However, in the subgroup of patients with an Acute Physiological and Chronic Health Evaluation-II (APACHE-II) score â¥17, the prolonged infusion group (n=41) had a significantly lower 14 day mortality (12.2% vs. 31.6% [p=0.04]) and decreased median length of stay (21 days vs. 38 days [p=0.02]) verses the conventional infusion group (n=38). However, there was not a significant improvement in mortality (p=0.5) or median length of stay (p=0.5) in patients with an APACHE-II score<17. The authors suggested the differences found with respect to APACHE-II score may have been because more critically ill patients with P. aeruginosa infection are most dependent on drug exposure for good clinical outcome. The Trauma Life Center uses APACHEIV scoring for patient stratification and there is no direct correlation between APACHE-II and APACHE-IV. It is estimated that most patients in TLC who receive systemic antibiotics would have an APACHE-II score > 17. A retrospective study was conducted in TLC after implementing prolonged infusions of piperacillin-tazobactam and meropenem. The study showed statistically significant decreased ventilator days (16.8 days to 9.6 days, 95% CI: -12.4 to -2.4), ICU length of stay (15.3 days to 10.7 days, 95% CI: -8.3 to -1.4), and hospital length of stay (30.9 days to 22.4 days, 95% CI: -18.7 to -1.2) between the intermittent infusion and the prolonged infusion group. There was also a decrease in mortality in the prolonged infusion group (20.7% to 12.4%, OR 0.54 (95% CI 0.18-1.66)) that didnât reach statistical significance. The use of the prolonged infusion was also associated with an estimated $10,000 cost savings for the 54 patients included in the prolonged infusion group. Meropenem Mattoes et al. reviewed the pharmacodynamic data of several alternative dosing regimens for meropenem including continuous infusions, prolonged infusions, increased frequency of administration, and higher doses.3 The authors reported that for severe infections caused by meropenem susceptible pathogens with higher MICs, equivalent bactericidal activity was achieved with 500mg every 8 hours over 3 hours, 1000mg every 8 hours over 30 minutes, and 500mg every 6 hours over 30 minutes. For treatment of mild to moderate infections caused by pathogens with low MICs (such as E coli and K pneumoniae), prolonged infusions would only have a slight benefit over conventional 30 minute infusions. For clinical situations with a higher risk of antibiotic resistant, gram-negative pathogens, treatment with meropenem 1g every 8 hours as a 3-hour infusion, or 2g every 8 hours as either a 30-minute or 3-hour infusion would optimize pharmacodynamic parameters. One study reported that for an MIC of 4mg/L, the %T>MIC achieved with a 30-minute infusion of 500mg and 2000mg every 8 hours was 30% and 58%, respectively. Increasing the infusion time to 3 hours every 8 hours achieved a %T>MIC of 43% and 73% for the 500mg and 2000mg doses, respectively. Currently, there are no clinical trials comparing prolonged versus intermittent dosing for meropenem. An internal audit of organisms recovered during calendar year 2008 revealed that 85% of common gram-negative species had MIC values less than or equal to 2 mcg/ml to meropenem. There were 15 isolates (a single Acinetobacter, and 14 Pseudomonas) that had MIC values greater than 2 mcg/ml. Pharmacokinetic and pharmacodynamic data suggest that equal outcomes would be achieved with 500mg every 8 hours infused over 3 hours for organisms with MIC less than 2 mcg/ml. A yearly audit will continue to be conducted.