Exploring Nonantibiotic Adjuncts: Synergistic Effects of Esmolol and Carvedilol With Tigecycline

Antimicrobial resistance poses a major global health threat, and carbapenem-resistant Gram-negative bacteria such as Klebsiella pneumoniae and Acinetobacter baumannii have been classified as critical priority pathogens. Although tigecycline provides coverage against multidrug resistant organisms, its use is limited by pharmacokinetic constraints and the emergence of resistance. This study investigates the in vitro synergistic potential of tigecycline combined with two β-blockers, carvedilol and esmolol, against clinical isolates of K. pneumoniae, Proteus mirabilis, and A. baumannii.

Synergy was assessed using the disc diffusion, broth microdilution, and checkerboard methods. A total of 36 clinical isolates were tested. Esmolol and carvedilol were supplemented with tigecycline discs, and inhibition zone diameters were compared. Minimum inhibitory concentrations (MICs) and fractional inhibitory concentration indices (FICi) were calculated according to standard protocols.

Both β-blockers significantly enhanced tigecycline's antibacterial activity across all isolates, as evidenced by increased inhibition zones and synergistic FICi values (≤ 0.5). Neither carvedilol nor esmolol exhibited intrinsic antimicrobial activity at therapeutic concentrations, suggesting their synergistic role is not based on direct bactericidal effects. These findings support the hypothesis that β-blockers modulate bacterial susceptibility, possibly by interfering with quorum sensing or membrane dynamics.

Carvedilol and esmolol significantly potentiate tigecycline's efficacy against MDR Gram-negative pathogens in vitro. These results support repurposing β-blockers as nonantibiotic adjuvants in antimicrobial therapy. Further molecular studies and in vivo validation are warranted to explore their potential in clinical applications and to better understand the mechanisms underlying the observed synergy.