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

Abstract

Introduction: Over the past two decades, the global burden of multidrug-resistant organisms has grown steadily, representing a major concern in pediatric healthcare. Among these, hospital-acquired infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) are particularly challenging to manage in children, due to limited therapeutic options and the scarcity of pharmacokinetic data in the pediatric population. Although several new antibiotics - especially β-lactams combined with β-lactamase inhibitors - have become available, uncertainties remain regarding their optimal use in pediatric populations.

Areas covered: This review explores potential treatment strategies for MDR-GNB infections in children, with a focus on pathogens listed in the WHO priority list. It examines the pharmacological properties of both traditional and newly approved antibiotics, assessing their role and applicability in pediatric clinical practice.

Expert opinion: New β-lactam antibiotics, alone or in combination with β-lactamase inhibitors - such as ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol - have emerged as preferred options for treating carbapenem-resistant and difficult-to-treat Gram-negative infections. Therapy should be guided by pathogen identification and resistance mechanisms, as susceptibility profiles vary widely based on the resistance-mechanism. Older agents like colistin, fosfomycin, nitrofurantoin, and aminoglycosides remain important, particularly in resource-limited settings, despite concerns over toxicity and safety.

Keywords: CRO; ESBL; Extended spectrum β-lactamase; MDR-GNB multidrug-resistant organism; MDRO; carbapenem resistant organism; difficult to treat infections; multi-drug-resistant Gram-negative bacteria.