Optimal Dose Of Meropenem For The Treatment Of Neonatal Sepsis:Dosing Guideline Variation And Clinical Practice Deviation

Neonatal sepsis is a major disease that threatens the life of newborns,not only has a high incidence rate,but also has a high mortality rate,and even poor survival of children.After the diagnosis of neonatal sepsis,the rational use of antibiotics is the primary treatment measure.Due to the unique physiological characteristics of newborns,the prescription and the treatment of newborns are challenging.Maturational changes in physiology can affect PK/PD profiles.Such changes during the neonatal period address the need to define regular neonatal doses.Several studies have been published highlighted significant variations and non-compliance with current dosing recommendations in neonates.Such variations in current dosing recommendations may have impact in clinical practice deviation and on PK/PD profiles in neonates.Thus,the purpose of this study was to evaluate the impact of variations of dosing guidelines and deviations of clinical practice in percentage target attainment(PTA)of meropenem for the treatment of neonatal sepsis using PK/PD modeling and simulation techniques.Data was collected from NICU of Shandong QIanfoshan Provincial Hospital.The validation set was collected from Beijing Children's Hospital.Total 13 dosing guidelines and 2 label dose information added in the final analysis.Monte Carlo simulations used to calculate PTA of all guidelines and prescriptions in clinical practice.The mean MAPE and MPE values were 4.6%and 12.6%,respectively,while the percentage of the number of patients with MPE and MAPE within the range of ± 20 and ± 30%were 81%and 96%respectively.Large variations in dose and dosing interval observed ranges from 10mg/kg,20mg/kg,30mg/kg and 40mg/kg and q8h and q12h respectively.Four guidelines and labeled doses(NICE,PDR,Medfacts,Medscap,FDA,EMA)were included in the model-based PTA analysis after excluding similar dosing recommendation in guidelines.For MIC of 2 mg/L,the PTA of 70%fT>MIC ranged from 90%to 99%and PTA of 100%fT? MIC ranged from 66%to 90%.For MIC of 8 mg/L,the PTA of 70%fT? MIC ranged from 63%to 90%and PTA of 100%fT>MIC ranged from 33%to 66%.For MIC of 2mg/L,the prescribed dosing regimen resulted 93%and 73%of neonates achieving the PD targets of 70%and 100%fT>MIC,respectively.For MIC of 8mg/L,the prescribed dosing regimen resulted 70%and 36%of neonates achieving the PD targets of 70%and 100%fT>MIC.The PTA of prescribed dosing regimen in clinical practice was less than the FDA recommendation.