Effect of Berberine as efflux pump inhibitor in multidrug-resistant Klebsiella pneumoniae isolated from urinary tract infections

Abstract

The urinary tract infections with K. pneumoniae have increased over many years. The emergence of antibiotic resistance among these bacteria presents a challenging problem for the clinician regarding the management and treatment of infections. The multidrug resistance in K. pneumoniae is due to several mechanisms, one of which is the role of efflux pumps. The current study investigated the role of Efflux Pump Inhibitors Phenylalanine-Arginine β-Naphthylamide (PAβN) and Berberine as antibacterial agents with multidrug-resistant K. pneumonia isolates from urinary tract infections. The collection of study samples took place between December 2021 and completed at the end of April 2022; it included 260 urine samples collected from outpatients and inpatients suffering from urinary tract infections during this period, from both genders with ages ranging from 15 to 72 years in five hospitals in Baghdad. The results of selective media, biochemical tests, and the VITEK2 system identified 76 isolates (65.5%) as K. pneumoniae from all collected bacterial cultures. The results of the antimicrobial susceptibility test using the disc diffusion method for the isolates under study showed that K. pneumoniae clinical isolates were moderately resistant to most antibiotics tested. Most K. pneumoniae isolates were highly resistant to Amoxicillin (96.1%) and Trimethoprim (80.3%). Also, there was apparent resistance to Gentamicin and Amikacin, while the lowest percentage of resistance was for Meropenem (55.1%) and Ciprofloxacin (53.9%). The susceptibility of the strains to Ciprofloxacin was highly increased in the presence of the efflux pump inhibitor (PAβN). The PAβN reduced the minimum inhibitory concentrations (MICs) by 4- to 64-fold. The results of minimum inhibitory concentrations (MICs) of Berberine against ten K. pneumoniae isolates with multidrug resistance revealed that the range of MICs of Berberine was (3.9-500 µg/ml) and it was obvious that there is a significant effect of Berberine on the growth of K. pneumoniae at deficient concentrations. This study concluded that using Berberine as an efflux pump inhibitor and antimicrobial agent may become a new generation of urgently needed antimicrobials that can overcome bacterial resistance mechanisms. Keywords: UTI infections, MDR, Berberine, Klebsiella pneumoniae