Among critically ill children with hospital-acquired infections due to multidrug-resistant gram-negative bacteria (MDR-GNB), meropenem administered via extended infusion (EI) resulted in an increased rate of pharmacokinetic-pharmacodynamic (PK-PD) target achievement compared with administration via intermittent bolus (IB). These findings were published in the International Journal of Infectious Diseases.

Children (N=72) receiving 3 or more doses of meropenem for MDR-GNB infections at the King Chulalongkorn Memorial Hospital in Thailand between 2020 and 2021 were enrolled in this prospective observational study. Eligible patients were aged between 1 month and 18 years and received meroponem either via EI (n=54) or IB (n=18). The PK-PD of meropenem and clinical outcomes were evaluated on the basis of meropenem administration method.

Among patients included in the analysis, the median age was 12 (IQR, 3-37) months, 55.6% were girls, 56.9% had a BMI within the reference range for their age and gender, 97.2% had comorbidities, 76.4% had sepsis or other bloodstream infections, and the median duration of meropenem treatment was 11 (IQR, 7-16) days. Patients who received an IB were more likely to have chronic cardiac disease vs those who received an EI (77.8% vs 33.3%; P <.01).


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The researchers found that the geometric mean (GM) concentrations of unbound plasma mereponem at both mid- (Cmid; GM, 17.3 vs 3.4 mg/L; P <.001) and end-dosing intervals (Ctrough; GM, 2.3 vs 0.8 mg/L; P =.005) were significantly increased among patients who received treatment via EI vs IB.

Among patients with augmented renal clearance (ARC; estimated glomerular filtration rate ³130 mL/min/1.73 m2) who received meropenem via EI, GM concentrations of plasma meropenem were decreased for Ctrough vs those without ARC (GM, 1.6 vs 3.5 mg/L; P =.04). No differences were observed for Ctrough among patients who received meropenem via IB vs EI on the basis of ARC.

Among patients in the EI (n=22) vs IB (n=5) groups for whom cultures were obtained which subsequently grew gram-negative bacteria, repeat cultures obtained between days 3 and 7 after meropenem initiation were available for 13 (59.1%) and 3 (60%) patients, respectively. Of these patients, repeat culture analysis showed that the microbiological eradiation rate was increased among those in the EI group vs those in the IB group (53.8% vs 33.3%; P =.54).

The rate of PK-PD target achievement for both a minimum inhibitory concentration (MIC) of less than 1 mg/L (71% vs 33%; P =.005) and a MIC of greater than 4 mg/L (41% vs 11%; P =.02) was increased among patients in the EI vs IB groups.

However, the median duration of survival was decreased among patients who received meropenem via EI vs those who received an IB (25 vs 29 days; P =.94).

This study was limited as it did not compare outcomes of EI vs IB methods of meropenem administered at the same dose.

According to the researchers, “a meropenem dose of 20 mg/kg given intravenously every 8 [hours] by [IB] should not be used in critically ill children,” including those without suspected central nervous system infection.

Reference

Maimongkow P, Yonwises W, Anugulruengkitt S, Sophonphan J, Treyaprasert W, Wacharachaisurapol N. Therapeutic drug monitoring of meropenem and pharmacokinetic-pharmacodynamic target assessment in critically ill pediatric patients from a prospective observational study. Int J Infect Dis. 2022;120:96-102. doi:10.1016/j.ijid.2022.04.052