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New ways of using old antibiotics in pediatrics: Focus on fosfomycin
1Children's Health of Orange County (CHOC), Orange, California, USA.
Abstract:
Fosfomycin, originally named phosphonomycin when it was first isolated from fermentation broth of Streptomyces species and synthesized at Merck in 1969. The phosphonic acid containing a structurally strained and reactive epoxide ring confers broad spectrum, bactericidal activity against gram-positive and gram-negative bacteria. Fosfomycin's small size and hydrophilicity permits broad tissues penetration. Although only fosfomycin tromethamine oral is approved for urinary tract infections (UTI) in the United States since 1996, the intravenous form has been utilized worldwide for over four decades. The increasing rates of multidrug-resistant (MDR) infections with few novel treatment options available has spurred the recent interest in fosfomycin. Fosfomycin's high urinary concentration, broad spectrum of activity against MDR pathogens, and favorable safety profile offers a valuable oral option for treating UTI, one of the most common bacterial infections in childhood. The ability of fosfomycin to penetrate biofilm and reported activity against intracellular pathogens may further its importance in childhood diseases such as Chronic Granulomatous Disease, Salmonellosis, and Listeriosis. More data are needed to further define optimal Pharmacodynamic target, as well as Pharmacokinetic, safety and outcomes for repeated oral and intravenous dosing of fosfomycin in infants and children in systemic infections.
Insights
Fosfomycin is a broad-spectrum antibiotic effective against multidrug-resistant bacteria, offering a valuable treatment for urinary tract infections (UTIs) and other childhood diseases. Further research is needed to optimize its use in pediatric systemic infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Fosfomycin, discovered in 1969, is a phosphonic acid antibiotic with a unique epoxide ring structure.
- It exhibits broad-spectrum bactericidal activity against Gram-positive and Gram-negative bacteria, including multidrug-resistant (MDR) strains.
- Despite decades of intravenous use globally, only oral fosfomycin tromethamine is approved for urinary tract infections (UTIs) in the US since 1996.
Purpose of the Study:
- To review the potential of fosfomycin as a treatment option for childhood bacterial infections, particularly UTIs.
- To highlight the renewed interest in fosfomycin due to rising rates of MDR infections and limited novel therapeutic options.
- To identify areas requiring further research regarding fosfomycin's use in pediatric populations.
Main Methods:
- Literature review of fosfomycin's properties, clinical use, and emerging applications.
- Analysis of fosfomycin's pharmacokinetic and pharmacodynamic profiles.
- Evaluation of safety and efficacy data for pediatric use.
Main Results:
- Fosfomycin demonstrates broad-spectrum activity against MDR pathogens and excellent urinary concentration, making it a promising oral option for UTIs.
- Its ability to penetrate biofilms and activity against intracellular pathogens suggest potential utility in diseases like Chronic Granulomatous Disease, Salmonellosis, and Listeriosis.
- Fosfomycin possesses a favorable safety profile, though specific data for infants and children are limited.
Conclusions:
- Fosfomycin is a valuable antibiotic for treating UTIs in children, especially given its activity against MDR bacteria.
- Its potential extends to other childhood infections due to biofilm penetration and intracellular pathogen activity.
- Further clinical studies are essential to establish optimal dosing, safety, and efficacy for repeated oral and intravenous administration in pediatric systemic infections.
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