Antibiotic Adjuvant Potential of Selected Essential Oil Components Against Respiratory Pathogens: From Planktonic Synergy to Early-Stage Biofilm Inhibition.

Background

Respiratory tract infections remain among the most common indications for antibiotic therapy and represent a major driver of antimicrobial resistance. The ability of respiratory pathogens to form biofilms further contributes to treatment failure and recurrence. This study aimed to evaluate the antibiotic adjuvant potential of selected essential oil components against clinically relevant respiratory bacteria and to determine whether planktonic synergistic interactions translate into early-stage antibiofilm efficacy. Thymol, eugenol, trans-cinnamaldehyde, and terpinen-4-ol were tested against Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa.

Methods

Minimum inhibitory concentrations were determined by broth microdilution. Synergistic interactions with clinically relevant antibiotics were assessed using the checkerboard method and fractional inhibitory concentration index (FICI) analysis. Selected combinations were further evaluated in a 6 h crystal violet-based early-stage biofilm model. Gram-positive strains generally exhibited higher susceptibility to the tested components than Gram-negative bacteria.

Results

Synergistic interactions (FICI ≤ 0.5) were most frequently observed between β-lactam antibiotics and phenolic components, particularly thymol and trans-cinnamaldehyde. Strong synergy was detected for vancomycin-eugenol against MRSA and for amoxicillin/clavulanic acid-cinnamaldehyde against M. catarrhalis. Importantly, synergistic combinations translated into significantly enhanced inhibition of early biofilm formation, increasing inhibition rates by 15-40% compared to antibiotic monotherapy (p < 0.05). Selected essential oil components enhanced the antibacterial activity of clinically relevant antibiotics and effectively potentiated early-stage biofilm inhibition.

Conclusions

These findings support further investigation of phytochemical-antibiotic combinations as potential adjunct strategies in respiratory infection management.