A detailed presentation at AAP 2014 covered recent hot topics in antibiotic development, microbial resistance, pneumonia treatment, fluoroquinolone safety, and the impact of antibiotic use on the gut microbiome.
At the 2014 AAP National Conference & Exhibition in San Diego, CA, John S. Bradley, MD, provided an overview of recent advances in antibiotic research and development, and discussed the results of several recent clinical studies involving the use of newer agents to treat infectious conditions in children.
Bradley, the director of the Division of Infectious Diseases at Rady Children’s Hospital in San Diego, graduated in medicine from the University of California at Davis and became a pediatric resident at Kaiser Foundation Hospital in San Francisco. He was driven towards specializing in childhood infectious diseases after his son contracted a severe infection. Bradley subsequently gained a particular interest in antibiotic development.
In preparing his talk, he said consulted with several colleagues who are distinguished clinical pediatricians to ensure that he addressed the most current and pertinent issues for pediatric infectious diseases.
A key element of his presentation was an update on the status of three antibiotics recently approved for the treatment of adults with methycillin-resistant Staphylococcus aureus (MRSA), namely dalbavancin, oritavancin, and tedizolid. They are now under investigation in children together with the slightly more established drugs ceftaroline, daptomycin, and telavancin. Several of the newest agents in adult studies displayed some impressive characteristics, including the long half-lives of dalbavancin (14 days) and oritavancin (10 days), with high potencies and side effect profiles superior to the comparator drugs. Tedizolid, a protein synthesis inhibitor, remarkably showed virtually 100% absorption from the GI tract with a lower (and single daily) dose than the linezolid comparator. Tedizolid also exhibited less bone marrow toxicity than linezolid.
Bradley also reviewed the results of the RIVUR trial involving 607 children diagnosed with grade 2-3 reflux due to urinary tract infection (UTI) and treated with trimethoprim-sulfamethoxazole or placebo. There was antibody resistance, as expected, but no benefit from treatment as regards renal scarring possibly due to insufficient numbers or too short a follow-up.
He discussed several approaches for dealing with mycoplasma infection in pediatric community-acquired pneumonia. Amoxicillin is still the standard treatment, according to CAP guidelines, but Bradley said the question is whether penicillin should now be recommended since microorganism resistance to this classic drug seems to have greatly diminished in recent years. If mycoplasma infection is detected, azithromycin, the best tolerated macrolide, has been the treatment of choice although azithromycin resistance is still very high within pneumococcal infection. “Is there a push towards dual therapy?” Bradley asked. The problem is that there is no rapid test for mycoplasma. The PCR assay performed in reference labs has a 2-4 day turn around.
He provided an update on fluoroquinoline safety in children. There had been concerns with the 1-month levofloxacin data with respect to musculoskeletal adverse events; specifically cartilage injury. However, very thorough blinded evaluation by experts of the 5-year follow-up data was much more reassuring, with few signs of drug-induced cartilage injury. No case was categorized as “likely” or “definitely” drug-related.
Another topic Bradley addressed was variations of recurrent strep throat and the failure of penicillin V versus amoxicillin. However, it appeared that since free penicillin is the active form, the presence of pus or other proteinaceous material could have bound the drug and inactivated it. One solution might be to increase the dose of penicillin V or to use the drug only in the absence of pus.
There is a long-established OTC antiviral approved for cold sores (Abreva®; 10% docosanol cream) which has activity against HSV 1 and 2 and appears to be an effective and inexpensive alternative to topical acyclovir. However, there have been few studies of a rigorous nature published over the 20 years since it was launched.
Another topic touched on was the microbiome and the impact of antibiotic use in both humans and animals. This is a “hot new field” where there is a lot of literature but a paucity of well-controlled studies. Probiotics and prebiotics have become very popular and manage to avoid FDA regulation by placing a standard disclaimer relating to clinical indications or efficacy on the labeling.
Finally, Bradley mentioned the media obsession with the Ebola virus, noting that the US military has funded development of two biologic agents, Z-mapp and TKM-Ebola, including proof of principle testing in primates. He trusted that the FDA will do its part to accelerate the approval process while calling upon the manufacturers to ramp up production as quickly as possible without sacrificing quality.