Antimicrobial Use Guidelines (AMUG) version 21 - UW Health

piperacillin/tazobactam. There were 102 patients who received the prolonged infusion ofpiperacillin/tazobactam dosed 3.375g every 8 hours. There were 92 patients who received theconventional infusion of piperacillin/tazobactam dosed 3.375g every 4 hours (4 patients) or 6hours (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 theconventional infusion group (p=0.17). The median length of stay after sample collection was 18days 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 HealthEvaluation-II (APACHE-II) score ≥17, the prolonged infusion group (n=41) had a significantlylower 14 day mortality (12.2% vs. 31.6% [p=0.04]) and decreased median length of stay (21 daysvs. 38 days [p=0.02]) verses the conventional infusion group (n=38). However, there was not asignificant improvement in mortality (p=0.5) or median length of stay (p=0.5) in patients with anAPACHE-II score 17.A retrospective study was conducted in TLC after implementing prolonged infusions ofpiperacillin-tazobactam and meropenem. The study showed statistically significantdecreased ventilator days (16.8 days to 9.6 days, 95% CI: -12.4 to -2.4), ICU length ofstay (15.3 days to 10.7 days, 95% CI: -8.3 to -1.4), and hospital length of stay (30.9 daysto 22.4 days, 95% CI: -18.7 to -1.2) between the intermittent infusion and the prolongedinfusion 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 didn’t reach statistical significance.The use of the prolonged infusion was also associated with an estimated $10,000 costsavings for the 54 patients included in the prolonged infusion group.MeropenemMattoes et al. reviewed the pharmacodynamic data of several alternative dosing regimens formeropenem including continuous infusions, prolonged infusions, increased frequency ofadministration, and higher doses. 3 The authors reported that for severe infections caused bymeropenem susceptible pathogens with higher MICs, equivalent bactericidal activity wasachieved with 500mg every 8 hours over 3 hours, 1000mg every 8 hours over 30 minutes, and500mg every 6 hours over 30 minutes. For treatment of mild to moderate infections caused bypathogens with low MICs (such as E coli and K pneumoniae), prolonged infusions would onlyhave a slight benefit over conventional 30 minute infusions. For clinical situations with a higherrisk of antibiotic resistant, gram-negative pathogens, treatment with meropenem 1g every 8 hoursas a 3-hour infusion, or 2g every 8 hours as either a 30-minute or 3-hour infusion would optimizepharmacodynamic parameters. One study reported that for an MIC of 4mg/L, the %T>MICachieved 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 trialscomparing prolonged versus intermittent dosing for meropenem.An internal audit of organisms recovered during calendar year 2008 revealed that 85% ofcommon 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 valuesgreater than 2 mcg/ml. Pharmacokinetic and pharmacodynamic data suggest that equaloutcomes would be achieved with 500mg every 8 hours infused over 3 hours for organisms withMIC less than 2 mcg/ml. A yearly audit will continue to be conducted.