Biofilm-Mediated Antimicrobial Resistance in Pediatric Klebsiella pneumoniae Urinary Tract Infections: A Narrative Review of Mechanisms, Clinical Challenges, and Therapeutic Strategies
Larisa Goroftei, Cristina-Mihaela Popescu, Irina Profir, Geanina-Adelina Jalba, Gabriela GurauUrinary tract infections (UTIs) caused by Klebsiella pneumoniae are an increasing challenge in pediatric practice due to the combined effects of biofilm formation, multidrug resistance (MDR), and limited therapeutic options for children. Biofilm development promotes bacterial persistence by impairing antibiotic penetration, enabling metabolic adaptation, promoting persister-cell formation, facilitating horizontal gene transfer (HGT), and inducing stress-induced mutagenesis, thereby reducing the effectiveness of conventional antimicrobial therapy. These mechanisms are further compounded by pediatric-specific challenges, including age-dependent pharmacokinetic variability, congenital urinary tract abnormalities, device-associated infections, and the limited availability of validated diagnostic tools for biofilm-associated infections. This narrative review integrates current knowledge of the molecular mechanisms underlying biofilm-mediated antimicrobial resistance with the unique diagnostic, pharmacological, and therapeutic challenges encountered in pediatric patients with K. pneumoniae UTIs. Emerging therapeutic strategies, such as optimized antibiotic combination therapy, bacteriophages, biofilm matrix-degrading enzymes, quorum-sensing inhibitors (QSIs), antimicrobial peptides (AMPs), and microbiome-directed approaches are critically evaluated with particular emphasis on their potential applicability in children. Although several anti-biofilm strategies have demonstrated encouraging results in experimental models, robust pediatric clinical evidence remains scarce. Current international guidelines continue to rely primarily on planktonic antimicrobial susceptibility testing without addressing biofilm-specific therapeutic considerations. In the absence of validated biofilm diagnostics, catheter stewardship and dosing optimization remain the most defensible clinical interventions available today. Broader translation of anti-biofilm strategies into pediatric practice will require dedicated pharmacokinetic studies, standardized biofilm diagnostics, and prospective clinical trials.