Background Extended infusion of beta-lactam antibiotics is aimed at achieving microbiological eradication and clinical resolution of complicated bacterial infections. For meropenem, the best predictor of bacterial killing is the time over which free-drug concentration exceeds 4–6xMIC of the microorganism (desirable 40% fT >MIC).
Purpose To describe the course and monitoring of prolonged treatment with meropenem by extended infusion of 4 hours in a neonate with ventriculitis due to ESBL-producing Klebsiella pneumoniae.
Material and methods We present the case of a 25 weeks’ preterm newborn, who presented with a septic episode with clinical, laboratory and ultrasonographic signs of ventriculitis at 93 days of age, in February 2018.Treatment was started with meropenem 40 mg/kg/8 hour, in an extended infusion of 4 hours. Concentrations of meropenem were determined in plasma and CSF samples before the administration of a dose (Cmin), once steady-state equilibrium was reached. For the quantification of the levels, high-performance liquid chromatography validated techniques were used.
Results ESBL-producing Klebsiella pneumoniae sensitive to carbapenems (MIC Meropenem <1 mg/L) was isolated from CSF cultures. From the beginning of meropenem treatment, CSF showed progressive improvement in inflammatory parameters, and the microorganism was not isolated after 2 days of treatment. Meropenem levels in plasma and CSF were determined at 4 weeks of treatment, which were 7.6 mg/L (pre-dose) in plasma and 4.7 mg/L in CSF. These levels showed an excellent penetration of the antibiotic in CSF (CSF/plasma concentration ratio of 0.62), ensuring a time above MIC>100% in both plasma and CSF. Likewise, no potentially toxic levels were observed despite a prolonged and extended infusion strategy. The patient continued treatment until completing 8 weeks. The ventricular drain was replaced by a ventriculo-peritoneal shunt after 62 days. Clinically, the patient showed progressive improvement in neurological status. However, in view of the risk of neurodevelopmental impairment, the infant is currently under outpatient follow-up.
Conclusion With the dosing strategy used, optimal concentrations of meropenem were achieved, which allowed reaching the PK/PD index of time >4 times the MIC during 100% of the dose interval, both in plasma and in CSF.
The extended infusion of meropenem in 4 hours in our patient showed criteria of efficacy and the safety of prolonged treatment.
Reference and/or acknowledgements Conventional versus prolonged infusion of meropenem in neonates with gram-negative late-onset sepsis: a randomized controlled trial. Pediatr Infect Dis J 2017;36.
No conflict of interest.
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