Abstract
This single-center historical cohort study investigated the effectiveness and safety of extended infusion (EI) compared with short-term infusion (STI) of meropenem in neonatal sepsis. Patient electronic health records from Peking University Third Hospital (1 December 2011–1 April 2021) were screened. Neonates diagnosed with sepsis and treated with meropenem in the neonatal intensive care unit were included (256 patients) as STI (0.5 h, 129 patients) and EI (2–3 h, 127 patients) groups. Three-day clinical effectiveness and three-day microbial clearance were considered the main outcomes. Univariate and multivariate analyses were performed. Baseline characteristics were similar in both groups. EI of meropenem was associated with a significantly higher 3-day clinical effectiveness rate (0.335 (0.180, 0.623), p = 0.001) and 3-day microbial clearance (4.127 (1.235, 13.784), p = 0.021) than STI, with comparable safety. Subgroup analyses showed that neonates with very low birth weight benefited from EI in terms of 3-day clinical effectiveness rate (75.6% versus 56.6%, p = 0.007), with no significant difference in the 3-day clinical effectiveness (85.1% versus 78.3%, p = 0.325) and microbial clearance (6% versus 5%, p > 0.999) rates between 3 h and 2 h infusions. Thus, EI of meropenem may be associated with better effectiveness and comparable safety in treating neonatal sepsis than STI. Nonetheless, historically analyzed safety evaluation might be biased, and these findings need confirmation in randomized controlled trials of larger sample sizes.
Highlights
Neonatal sepsis, a systemic inflammatory response syndrome caused by bacterial, viral, or fungal infections, was reported to be the third leading cause of neonatal death worldwide, with mortality between 11% and 19% [1,2]
Here, we conducted a historical cohort study to investigate the effectiveness and safety of extended infusion (EI) compared with short-term infusion (STI) of meropenem in neonatal sepsis based on real-world data
We initially identified 653 neonates that had been prescribed meropenem from their medical records, 397 of which were excluded since they were not diagnosed with neonatal sepsis, had comorbidities of Gram-positive cocci sepsis or purulent meningitis, or they were treated for less than 3 days (Figure 1)
Summary
A systemic inflammatory response syndrome caused by bacterial, viral, or fungal infections, was reported to be the third leading cause of neonatal death worldwide, with mortality between 11% and 19% [1,2]. Severe neonatal sepsis needs to be treated with carbapenems, among which meropenem, the most widely used agent of this group, exhibits time-dependent bactericidal activity [4]. With the widespread use of meropenem in neonatal wards, there is recognition of increasing carbapenem resistance and virulence, which are considerable challenges to antibiotic management. The optimization of EI of meropenem has been investigated using PK or population PK [6] modeling, and trials based on small sample sizes [7]. There are no guidelines or clinical studies based on large sample sizes that provide definite recommendations on the application of EI of meropenem in treating neonatal sepsis. Here, we conducted a historical cohort study to investigate the effectiveness and safety of EI compared with STI of meropenem in neonatal sepsis based on real-world data
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