Synergistic Effects of Phytochemical Extracts and Conventional Antibiotics against Multidrug-Resistant Clinical Bacterial Isolates Recovered from Urinary Tract Infections at Tikrit Teaching Hospital
TL;DR
Phytochemical–antibiotic combinations, particularly green tea extract with fluoroquinolones, may restore antibacterial efficacy against MDR uropathogens and merit further in vivo and clinical evaluation.
Abstract
Background: The global rise of multidrug-resistant (MDR) uropathogens, particularly Escherichia coli and Klebsiella pneumoniae, has narrowed therapeutic options for urinary tract infections (UTIs) and renewed interest in plant-derived antimicrobial adjuvants. Objective: To evaluate the in vitro synergistic activity of three phytochemical extracts pomegranate peel (Punica granatum), garlic (Allium sativum), and green tea (Camellia sinensis) combined with conventional antibiotics against MDR clinical isolates recovered from UTI patients attending Tikrit Teaching Hospital. Methods: Ninety MDR isolates (54 E. coli, 36 K. pneumoniae) were collected, identified, and screened for antimicrobial susceptibility by the Kirby–Bauer disc diffusion method against a 13-agent panel, with MDR classified according to Magiorakos et al., criteria. Minimum inhibitory concentrations (MIC) of ethanolic extracts were determined by broth microdilution, and interactions with ciprofloxacin, ceftazidime, gentamicin, and trimethoprim–sulfamethoxazole were assessed by the checkerboard method, expressed as the fractional inhibitory concentration index (FICI). A time-kill assay verified the most active combination. Results: Isolates showed high resistance to ampicillin (94–98%), amoxicillin–clavulanate (79–86%), and third-generation cephalosporins (72–83%), with lower resistance to meropenem and amikacin. All three extracts showed synergistic or additive interactions with the tested antibiotics; green tea extract combined with ciprofloxacin produced the strongest synergy (mean FICI 0.18–0.24; 100% synergy rate) and an 8–11-fold reduction in antibiotic MIC, followed by pomegranate peel and garlic extracts. Time-kill assays confirmed complete eradication of the test inoculum within 24 hours with the green tea–ciprofloxacin combination, versus partial inhibition with either agent alone. Conclusion: Phytochemical–antibiotic combinations, particularly green tea extract with fluoroquinolones, may restore antibacterial efficacy against MDR uropathogens and merit further in vivo and clinical evaluation.