In patients hospitalized with pneumonia who were critically ill, a prolonged infusion of meropenem was not consistently associated with a significant clinical benefit for those who required a higher therapeutic target or those with drug-resistant or severe infections. Moreover, treatment with low-dose meropenem was found to be effective among patients with decreased creatinine clearance and increased uric acid concentration. These results, from a prospective study, were published in Infectious Diseases and Therapy.
In this prospective study conducted between January and December 2019, researchers analyzed 209 blood sample specimens from 64 patients with pneumonia who were treated with meropenem. The researchers sought to assess the pharmacokinetics (PK) andpharmacodynamics (PD) of meropenem, as well as potential benefits of prolonged infusion time. In addition, the researchers used minimum inhibitory concentration (MIC) values associated with the most commonly found pathogenic bacteria such as Enterobacter cloacae, Pseudomnoas aeruginosa, Klebsiella pnuemoniae, and Acinetobacter baumannii.
Among a total of 64 patients included in the study, 73.43% were men, the mean weight was 62.5 kg (138 lb), and the mean age was 63.5 years. Patients who were pregnant or lactating, those who were allergic to carbapenems, and those treated with concomitant sodium valproate were excluded from the study.
Among 71.86% of patients who underwent sensitivity testing for meropenem, most were infected with more than 1 type of Gram-negative bacterium. Of 80 meropenem MIC values that were collected from these patients, 53.75% were greater than 8 mg/L. In addition, A baumannii was the most commonly detected pathogen and its associated MIC values were greater than 8 mg/L, indicating resistance to meropenem. Of note, 56.3% of Gram-negative bacteria were found to be multi-drug resistant.
Creatinine clearance and uric acid concentrations were found to be significant covariates. The researchers found that a greater than 90% target attainment (fT) under a MIC of 8 mg/L was achievable for patients with a creatinine clearance and uric acid concentration of less than or equal to 60 mL/min and greater than 400 μmol/L, respectively. Similar results were observed among patients who received intravenous meropenem 500 mg every 8 hours at an infusion time of 2 hours.
The researchers found that when the MIC was less than 4 mg/L, the therapeutic effect of meropenem was increased via prolonged infusion time. No statistically significant differences in regard to the PD effects of meropenem were observed when fT was 100% greater than the MIC or when fT was 100% for a MIC of greater than 4 mg/L.
Study limitations included its small sample size, which limited the ability to assess for correlations between PK and PD targets and microbiologic outcomes, and its single-center setting. In addition, some patients refused to undergo MIC testing.
According to the researchers, “[An increased] dose [of meropenem] or alternative therapeutic strategies may be required for critically ill patients with drug-resistant or severe infections.”
Zhao YC, Zou Y, Xiao YW, et al. Does prolonged infusion time really improve the efficacy of meropenem therapy? A prospective study in critically ill patients. Infect Dis Ther. Published online November 6, 2021. doi: 10.1007/s40121-021-00551-2