Objective To investigate the pharmacokinetic/pharmacodynamic (PK/PD) and therapeutic efficacy of extended 4 hour infusion of meropenem in patients with severe pneumonia, and to provide a better dosing regimen.

Methods The in vitro drug stability of meropenem at 0, 1, 3, 4, 8, and 24 hours was determined, and the minimum inhibitory concentration (MIC) of the drug solution after different storage times was compared. High-performance liquid chromatography was used to measure the drug concentrations in blood and sputum, and PK/PD parameters were calculated. The clinical efficacy was compared between the PK/PD analysis group (receiving extended 4-hour infusions of meropenem at 1 g per infusion, every 8 hours) and the clinical efficacy comparison group (receiving 0.5 hour infusions of meropenem at 1 g per infusion, every 8 hours).

Results Meropenem maintained more than 97% of its initial concentration after being stored for 4 hours, and there was no significant difference in the minimum inhibitory concentration (MIC) within 24 hours. During extended infusion, the maximum concentrations in plasma and sputum were (9.65 ± 0.78) µg/mL and (5.29 ± 0.54) µg/mL, respectively. The area under the concentration-time curve from 0 to 8 hours was (48.75 ± 4.27) h·µg·mL^–1 and (26.36 ± 1.34) h·µg·mL^–1, with an average lung penetration rate of 54.07%. In both plasma and sputum, when MIC was ≤2 µg/mL, the probability of target attainment (PTA) was ＞90.00%. When MIC increased to 4 µg/mL, PTA was mostly ＜90.00%. The all-cause mortality and pan-drug resistance rates were lower in the extended 4-hour infusion group compared to the 0.5-hour infusion group, but the differences were not statistically significant (P ＞ 0.05).

Conclusions Compared with 0.5 hour infusion of meropenem, extended 4 hour infusion has better therapeutic efficacy.