Older antibiotics still work for most common infections

AAP 2011 National Conference

BOSTON — Choosing the safest of all the effective antibiotics is most important when prescribing antibiotics for children, according to a presenter here today at the American Academy of Pediatrics 2011 National Conference and Exhibition.

John S. Bradley, MD, of the University of California at San Diego and Rady Children’s Hospital, provided a rundown of antibiotics and their effectiveness with various infections, including methicillin-resistant Staphylococcus aureus (MRSA), respiratory tract infection and urinary tract infections (UTIs).

John S. Bradley

He also stressed during his presentation that older antibiotics can often meet with challenge of newly resistant pathogens with increased frequency of dosing.

“For the beta-lactam antibiotics like cephalosporins and penicillins, it’s not how high you are with the dose, but it’s how long you are above the MIC; staying above MICs 40% time will generally kill the bug and the older beta-lactam drugs can often do that with either high doses, or more frequent doses,” he said, adding that many of these older agents never studied against resistant pathogens — even if they are active — so no package labeling exists.

“Although there’s no FDA approval, we’ve got some published data that suggest that these drugs working,” he explained. “It’s not that the FDA doesn’t think these drugs are bad, it’s not that no one has given the FDA information on which they can judge whether the drug works for the indication.”

Regarding MRSA, clindamycin and trimethoprim-sulfamethoxazole (TMP-SMX) are still the oral drugs of choice, even though each drug has its shortcomings. In addition, vancomycin remains the preferred intravenous (IV) antibiotic for serious MRSA infections.

“Clindamycin susceptibility in MRSA varies widely in regions across the USA, and in addition, varies in strains from the community compared with strains isolated from children in intensive care units,” Bradley said, who urged the audience members to get from their microbiology laboratories data on clindamycin susceptibility for their cities. “It’s very interesting and more complicated than we originally suspected.”

Respiratory infections

Oral amoxicillin and IV ampicillin have emerged as the preferred agents for routine community-acquired pneumonia, as outline by the recent clinical practice guidelines released by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. One of the three following doses are recommended for outpatient empiric therapy with amoxicillin: 90 mg/kg/day divided twice daily; or 40 mg/kg/day to 45 mg/kg/day divided three times daily (TID); or 90 mg/kg/day divided TID. Inpatient empiric therapy with ampicillin should be 150 mg/kg/day to 200 mg/kg/day divided every 6 hours. Penicillin G may also be used.

For the treatment of UTIs, the Bradley recommended a second- or third-generation cephalosporin to reach successful symptom resolution in about 95-98% of children. This is because resistance to ampicillin is between 40% and 50% and resistance to TMP-SMX is reportedly between 20% and 30%. Per the AAP Guidelines just published October 1st , other antibiotics, including TMP-SMX, and first generation cephalosporins, may also provide effective therapy. For prophylaxis of UTI, Bradley prefers to use antibiotics that are not used to treat systemic infections, such as nitrofurantoin. Even if organisms develop resistance to all the orally available antibiotics, pediatricians do not need to worry about lack of treatment for more serious infections, and virtually all current strains remain susceptible to IV meropenem and IV gentamicin.

For use of fluoroquinolones, Bradley, said they can be used, but the benefits must outweigh the risks, according to the recommendation released recently by the AAP regarding the use of quinolones in children.

“We in pediatrics have avoided quinolones for so long because of the data in beagle pups. We have now 5-year follow-up data on levofloxacin derived from otitis media and pneumonia studies. At the request of the FDA, the sponsor followed these children to find any type of bone or joint abnormalities, and even though some of the children were lost to follow-up, the sponsor found that there was no signal for toxicity,” he said. “

Antibiotic pipeline

As for antibiotics in the pipeline for use in pediatrics, Bradley said for the treatment of MRSA there are studies of fifth-generation cephalosporins (ceftaroline) underway, along with glycopeptides/glycolipopetides (dalbavancin, oritavancin and telavancin) and oxazolidinones, torezolid which is similar to linezolid.

In contrast to the antibiotics pipeline for MRSA, there are no new drugs that have even entered pediatric phase 1 (pharmacokinetic trials) in the works for gram-negative bacilli.

“For the first time since antibiotics became available, adults are dying of multi-resistant bacteria,” Bradley said, adding that some clinical strains of Klebsiella are now resistant to imipenem, ceftriaxone, ciprofloxacin, gentamicin, TMP-SMX and colistin.

“We [researchers] need to partner with the FDA, pharmaceutical companies and the NIH to develop safer, more effective therapy is needed for neonates, infants and children,” Bradley said during his presentation.— by Cassandra A. Richards

Sheldon Kaplan

John Bradley has emphasized the importance of proper dosing of antibiotics and how appropriate dosing of older well established antibiotics using pharmacokinetic and pharmacodynamic information can result in effective treatment of infections due to antibiotic-resistant bacteria. The new community-acquired pneumonia guidelines that John and others recently authored emphasize the proper dosing of penicillins and how these agents remain efficacious in treating pneumonia due to almost all isolates Streptococcus pneumoniae currently being encountered. The most serious concerns now focus on multidrug-resistant gram-negative bacilli, some of which are resistant to all antibiotics including, colistin, an older quite toxic agent. Minimizing the barriers to the develop new agents to combat these organisms is a priority for all of us.

Sheldon Kaplan, MD
Infectious Diseases in Children Editorial Board member

Disclosure: Dr. Kaplan reports receiving grant funding from Pfizer.

For more information:

• Bradley JS. #S1101. Antibiotic update for the pediatrician. Presented at: AAP 2011 National Conference and Exhibition. Oct. 15-18, Boston.

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