Less Is More: Single Antibiotic as Effective, But Safer Than Combo Therapy to Treat Childhood Bloodstream Infection
Children with invasive bloodstream infections treated with a single antibiotic are just as likely to overcome their infections as those who get two-drug therapy, but at half the risk of drug-induced kidney damage, according to results of a Johns Hopkins Children’s Center study.
A report on the research, believed to be the first of its kind in pediatric patients, is published online Aug. 5 in JAMA Pediatrics.
“Many pediatricians continue to prescribe combination-drug regimens under the false assumption that two is better than one, but our study suggests otherwise — one is often just as good as two and a lot safer,” says study lead investigator and infectious disease specialist Pranita Tamma, M.D., M.H.S.
Tamma and her team say their finding that children treated with the two-drug approach had twice the risk of kidney damage at no additional clinical benefit challenges the common practice of preemptively and liberally prescribing combination drug treatments for children with bloodstream infections.
Part of the dual regimen includes a class of antibiotics known as aminoglycosides, well-known for their toxic effects on the kidney but, the researchers point out, the benefits of such treatment outweigh the risks in critically ill patients or in patients suspected to be infected with highly drug-resistant organisms. However, they caution, the need for continued dual therapy should be re-assessed as soon as bacterial cultures reveal what antibiotics the infectious organisms are susceptible to — usually within 48 to 72 hours of diagnosis.
“The aminoglycoside portion of the regimen should be continued only in cases of highly drug-resistant infections,” Tamma says.
For their analysis, investigators reviewed 879 cases of children treated at Johns Hopkins Children’s Center between 2002 and 2011 for bloodstream infections caused by a group of pathogens collectively known as Gram-negative bacteria. Gram-negative organisms encompass more than 80 types of infection-causing bacteria, including bacteria that commonly live in the gut, such as E. coli.
Of the 879 patients, 537 (61 percent) received combination treatment. Patients on dual and single treatment had a similar risk of death, with 7.6 percent of patients in the combo therapy dying, compared with 6.7 percent in the single-drug group. However, patients who got the combo therapy were twice as likely to suffer kidney damage: One-quarter of those on the dual-antibiotic regimen developed kidney damage, compared with 10 percent of those getting the single-drug treatment.
The research was funded by the Thomas Wilson Sanitarium for Children of Baltimore City and by the National Institutes of Health under grant number K24AIO79040.
Co-investigators included Alison Turnbull, Aaron Milstone, Alice Hsu and Sara Cosgrove, all of Johns Hopkins, and Anthony Harris, of the University of Maryland.
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