Evaluation of evidence for pharmacokinetics-pharmacodynamics-based dose optimization of antimicrobials for treating Gram-negative infections in neonates
Nusrat Shafiq1, Samir Malhotra1, Vikas Gautam2, Harpreet Kaur3, Pravin Kumar4, Sourabh Dutta4, Pallab Ray2, Nilima A Kshirsagar5
1 Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
3 University School of Business Studies, Punjab University, Chandigarh, India
4 Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
5 National Chair of Clinical Pharmacology, Indian Council of Medical Research, New Delhi, India
Nilima A Kshirsagar
National Chair Clinical Pharmacology (ICMR), ICMR- National Institute for Research in Reproductive Health, J. M. Street Rd, Parel, Mumbai 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
Background & objectives: Neonates present a special subgroup of population in whom optimization of antimicrobial dosing can be particularly challenging. Gram-negative infections are common in neonates, and inpatient treatment along with critical care is needed for the management of these infections. Dosing recommendations are often extrapolated from evidence generated in older patient populations. This systematic review was done to identify the knowledge gaps in the pharmacokinetics-pharmacodynamics (PK-PD)-based optimized dosing schedule for parenteral antimicrobials for Gram-negative neonatal infections.
Methods: Relevant research questions were identified. An extensive electronic and manual search methodology was used. Potentially eligible articles were screened for eligibility. The relevant data were extracted independently in a pre-specified data extraction form. Pooling of data was planned.
Results: Of the 340 records screened, 24 studies were included for data extraction and incorporation in the review [carbapenems - imipenem and meropenem (n=7); aminoglycosides - amikacin and gentamicin (n=9); piperacillin-tazobactam (n=2); quinolones (n=2); third- and fourth-generation cephalosporins (n=4) and colistin nil]. For each of the drug categories, the information for all the questions that the review sought to answer was incomplete. There was a wide variability in the covariates assessed, and pooling of results could not be undertaken.
Interpretation & conclusions: There is a wide knowledge gap for determining the doses of antimicrobials used for Gram-negative infections in neonates. A different profile of newborns in the developing countries could affect the disposition of antimicrobials for Gram negative infections, necessitating the generation of PK-PD data of antimicrobials in neonates from developing countries. Further, guidelines for treatment of neonatal conditions may incorporate the evidence-based PK-PD-guided dosing regimens.