Cheryl Guttman Krader is a contributor to Dermatology Times, Ophthalmology Times, and Urology Times.
For the first time in a decade, there are antibiotics newly approved for use in children with skin and skin structure infections that do not respond to conventional treatment.
An “Antimicrobial update” session has been a fixture at the American Academy of Pediatrics National Conference for many years, but for the first time in about a decade, the topics covered included a discussion of antibiotics newly approved for use in children.
At a session on September 17, John S Bradley, MD, FAAP, and Brian Williams, MD, FAAP, reviewed the use of ceftaroline fosamil (Teflaro; Allergan, Dublin, Ireland) and daptomycin (Cubicin; Merck, Whitehouse Station, New Jersey) for treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Information relevant to the management of other common community-acquired infections was also discussed.
Both ceftaroline and daptomycin are new to pediatricians but not to the US market. Ceftaroline was approved for use in adults in 2010. Daptomycin was first approved in 2003 and just recently came off patent.
Ceftaroline is a cephalosporin indicated in adult and pediatric patients aged 2 months and older for the treatment of the acute bacterial skin and skin structure infections caused by susceptible organisms, including MRSA. It is also approved for the treatment of community-acquired bacterial pneumonia, and although it demonstrated good activity in infections caused by MRSA, the US Food and Drug Administration (FDA) felt there were too few such cases to support an indication, said Bradley, director, Division of Infectious Diseases, Rady Children’s Hospital–San Diego, California, and professor and chief, Division of Infectious Diseases, Department of Pediatrics, University of California San Diego School of Medicine, La Jolla.
Daptomycin is a lipopeptide that is approved for complicated skin and skin structure infections in adults and pediatric patients aged 1 to 17 years. In adults, it is also indicated for S aureus bacteremia, including in adults with right-sided infective endocarditis. Daptomycin is not effective for the treatment of pneumonia because it is bound by surfactant in the lungs and rendered inactive.
At the present time, both ceftaroline and daptomycin should be reserved for use in children with MRSA skin and skin structure infections that are not responding to conventional treatment with vancomycin or clindamycin, said Bradley.
“We will be reviewing data collected over the next 1 to 2 years to see if these agents have the same efficacy and safety profiles when they are used in larger numbers of children in clinical practice as they had in clinical trials,” he stated.
Neither drug was associated with any concerning adverse effects in clinical trials. As a cephalosporin drug, ceftaroline should not be used in anyone with a history of a serious hypersensitivity reaction to a beta-lactam antibiotic.
Bradley mentioned that because daptomycin caused neurological toxicity in a neonatal animal model, clinical trials of daptomycin stopped enrolling children aged younger than 1 year.
“There has been no evidence of neurological toxicity in any child treated with daptomycin nor of myopathy that was observed in adults in early clinical studies where the drug was administered 4 times a day rather than just once daily. We will be watching for these potential [adverse] effects in postmarketing surveillance as more children are exposed to daptomycin,” Bradley said.
Williams discussed treatment approaches for intravenous, intramuscular, and oral antibiotic therapy for urinary tract infections caused by extended spectrum beta-lactamase-producing Escherichia coli, which is an increasing problem for children across the United States. In addition, atypical pneumonia and recurrent streptococcal pharyngitis were reviewed in case-based presentations.
“The management for atypical pneumonia caused by Mycoplasma pneumoniae is a subject of debate because there is a lack of data to support recommendations,” said Williams, a pediatric hospitalist at Rady Children’s Hospital–San Diego, California, and assistant clinical professor of Pediatrics and Internal Medicine, Division of Hospital Medicine, University of California San Diego.
The “Antimicrobial update” session organized by Drs. Bradley and Williams was extraordinarily timely because we face a crisis in antimicrobial resistance globally, so severe, in fact, that pediatricians sometimes have no remaining licensed antibiotics for the treatment of serious and occasionally life-threatening infections in children. Both the ubiquitous presence of antibiotics in agribusiness and overuse of antibiotics for viral infections have contributed to the crisis in antimicrobial resistance. Zealously enforced antimicrobial stewardship programs are required to reverse this trend.
As another issue, many serious infections with Staphylococcus aureus are increasingly being encountered in children, including infections caused by methicillin-resistant strains. Because methicillin resistance is mediated by alterations in penicillin-binding proteins and not by beta-lactamases, inclusion of beta-lactamase inhibitors is not helpful, and novel drugs are needed.
In this context, the emergence of ceftaroline fosamil and daptomycin for pediatric use is very welcome "good news" for pediatricians who care for children with serious infections. Ceftaroline, a "fifth-generation cephalosporin," is indicated in children aged 2 months and older for treatment of acute bacterial skin and skin structure infections caused by susceptible organisms, including methicillin-resistant Staphylococcus aureus (MRSA). This agent is also approved for the treatment of community-acquired bacterial pneumonia.
Another new agent, daptomycin, is a “first-in-class” cyclic lipopeptide that is approved for complicated skin and skin structure infections in children aged 1 to 17 years. As a note of caution, daptomycin is not effective for the treatment of pneumonia because it is bound by surfactant in the lungs and hence rendered inactive.
Drs Bradley and Williams recommended that at the present time, both ceftaroline and daptomycin should be reserved for use in children with MRSA skin and skin structure infections that are not responding to conventional treatment with vancomycin or clindamycin. I agree with the recommendation, but I also encourage pediatricians to not be hesitant to use these agents, when appropriate, as well as other novel and emerging antimicrobials we can plan on seeing for pediatric practice in the near future!
-Mark R. Schleiss, MD, is professor and director, Division of Pediatric Infectious Diseases and Immunology, University of Minnesota Medical School, Minneapolis.