Pharmacokinetics and safety of recently approved drugs used to treat methicillin-resistant Staphylococcus aureus infections in infants, children and adults

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) remains a significant cause of morbidity in hospitalized infants. Over the past 15 years, several drugs have been approved for the treatment of S. aureus infections in adults (linezolid, quinupristin/dalfopristin, daptomycin, telavancin, tigecycline and ceftaroline). The use of the majority of these drugs has extended into the treatment of MRSA infections in infants, frequently with minimal safety or dosing information. Only linezolid is approved for use in infants, and pharmacokinetic data in infants are limited to linezolid and daptomycin. Pediatric trials are underway for ceftaroline, telavancin, and daptomycin; however, none of these studies includes infants. Here, we review current pharmacokinetic, safety and efficacy data of these drugs with a specific focus in infants.

Keywords::

• ceftaroline
• dalfopristin
• daptomycin
• linezolid
• neonate
• quinupristin
• sepsis
• tigecycline

Financial & competing interests disclosure

D Gonzalez is funded by training grant T32GM086330 from the National Institute of General Medical Sciences. PB Smith receives salary support for research from the National Institutes of Health (NIH), the U.S. Department of Health and Human Services, and the National Center for Advancing Translational Sciences of the NIH (DHHS-1R18AE000028-01, HHSN267200700051C, HHSN275201000003I, and UL1TR001117); he also receives research support from industry for neonatal and pediatric drug development ( www.dcri.duke.edu/research/coi.jsp ). M Cohen-Wolkowiez receives support for research from the National Institutes of Health (NIH) (1K23HD064814), the National Center for Advancing Translational Sciences of the NIH (UL1TR001117), the Food and Drug Administration (1U01FD004858-01), the Biomedical Advanced Research and Development Authority (BARDA) (HHSO100201300009C), the nonprofit organization Thrasher Research Fund ( www.thrasherresearch.org ) and from industry for drug development in adults and children (www.dcri.duke.edu/research/coi.jsp). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The proportion of staphylococcal isolates that are methicillin-resistant Staphylococcus aureus has increased, and the incidence of methicillin-resistant S. aureus infection has increased 10-fold.

• Antibacterial agents that have been approved in adults over the past 15 years for the treatment of skin and skin structure infection caused by staphylococcal bacteria include linezolid, daptomycin, quinupristin/dalfopristin, ceftaroline, telavancin and tigecycline.

• Of the six recently approved antibiotics, linezolid is the only antibiotic to be labeled for use in infants and premature infants.

• Clinical studies for ceftaroline, telavancin and daptomycin are underway for pediatric patients. However, none of these studies is examining the drug in the infant population.

• Extrapolation of efficacy data from well-controlled adult trials is a possible method to accelerate drug labeling in infants and other pediatric populations.

• Antibiotics in Phase III of development include tedizolid, dalbavancin, oritavancin and omadacycline. Few clinical trials have been completed for these medications in the pediatric population. No trials in infants are underway or have been completed for any of these drugs.