Tackling multidrug-resistant Gram-negative infections in children globally: current therapeutic options and...

Area of Science:

• Pediatric Infectious Diseases
• Antimicrobial Resistance
• Pharmacology

Background:

• Rising global burden of multidrug-resistant organisms (MDROs), especially Gram-negative bacteria (MDR-GNB), poses significant challenges in pediatric healthcare.
• Hospital-acquired MDR-GNB infections in children are difficult to manage due to limited treatment options and scarce pediatric pharmacokinetic data.
• Newer antibiotics, including beta-lactams with beta-lactamase inhibitors, offer promise but require further evaluation for optimal pediatric use.

Purpose of the Study:

• To review potential treatment strategies for MDR-GNB infections in children.
• To focus on pathogens identified on the World Health Organization (WHO) priority list.
• To assess the role and applicability of traditional and novel antibiotics in pediatric clinical practice.

Main Methods:

• Literature review focusing on antimicrobial agents for MDR-GNB.
• Examination of pharmacological properties and clinical applicability of antibiotics in pediatric populations.
• Analysis of treatment guidelines and expert opinions on MDR-GNB infections in children.

Main Results:

• Newer beta-lactam/beta-lactamase inhibitor combinations (e.g., ceftazidime-avibactam, meropenem-vaborbactam) are emerging as key options for carbapenem-resistant Gram-negative infections.
• Treatment decisions should be informed by pathogen identification and specific resistance mechanisms, as susceptibility varies.
• Older antibiotics (colistin, fosfomycin, nitrofurantoin, aminoglycosides) remain relevant, particularly in resource-limited settings, despite safety concerns.

Conclusions:

• Optimal management of pediatric MDR-GNB infections requires careful consideration of pathogen-specific resistance patterns and antibiotic pharmacokinetics.
• Newer agents provide valuable therapeutic options, but their use in children needs further research and validation.
• A combination of novel and older antibiotics, guided by susceptibility data and clinical context, is essential for effective treatment of pediatric MDR-GNB infections.