Potential Synergistic Antibiotic Combinations against Fluoroquinolone-Resistant Pseudomonas aeruginosa

Abstract

The rise in multiple-drug-resistant (MDR) phenotypes in Gram-negative pathogens is a major public health crisis. Pseudomonas aeruginosa is one of the leading causes of nosocomial infections in clinics. Treatment options for P. aeruginosa have become increasingly difficult due tdo its remarkable capacity to resist multiple antibiotics. The presence of intrinsic resistance factors and the ability to quickly adapt to antibiotic monotherapy warrant us to look for alternative strategies like combinatorial antibiotic therapy. Here, we report the frequency of P. aeruginosa multidrug-resistant and extensively drug-resistance (XDR) phenotypes in a super-specialty tertiary care hospital in north India. Approximately 60 percent of all isolated P. aeruginosa strains displayed the MDR phenotype. We found highest antibiotic resistance frequency in the emergency department (EMR), as 20 percent of isolates were resistant to 15 antipseudomonal antibiotics. Presence of plasmids with quinolone-resistance determinants were major drivers for resistance against fluoroquinolone. Additionally, we explored the possible combinatorial therapeutic options with four antipseudomonal antibiotics—colistin, ciprofloxacin, tobramycin, and meropenem. We uncovered an association between different antibiotic interactions. Our data show that the combination of colistin and ciprofloxacin could be an effective combinatorial regimen to treat infections caused by MDR and XDR P. aeruginosa.

The Combination Effect of Ceftriaxone and Chloramphenicol on Staphylococcus aureus Isolate of Diabetic Gangrene

“…Antibiotic combination of CTX and CML is used to increase efficacy on gangrene diabetic infection. The combination was selected to expand the spectrum of bacteria also (Kothari et al, 2022). Actually, the aims of antibacterial combination to increase potency, extend spectrum, reduce resistance and toxicity (Alsherbiny et al, 2021;Kothari et al, 2022).…”

“…The combination was selected to expand the spectrum of bacteria also (Kothari et al, 2022). Actually, the aims of antibacterial combination to increase potency, extend spectrum, reduce resistance and toxicity (Alsherbiny et al, 2021;Kothari et al, 2022). However, incorrect selection of antibacterial combination and the dose produce therapy failure (Gilbert et al, 2010;Parkunan et al, 2019).…”

Genomic epidemiology and mechanisms of antibiotic resistance in Pseudomonas aeruginosa isolated from children’s hospital in Shenzhen, China

“…It is best known for causing lung infection among cystic brosis patients, in addition to critical infections among immunocompromised patients, patients with severe burns, catheterized and other indoor patients [2,3]. P. aeruginosa also causes blood infections, respiratory tract infections (RTI), skin infections, urinary tract infections (UTI), and surgical site infections/wound infections [4]. A restricted choice of antimicrobial agents such as cephalosporins and carbapenem has reliable activity against P. aeruginosa infections [5].…”

Quantifying combined effects of colistin and ciprofloxacin against Escherichia coli in an in silico pharmacokinetic-pharmacodynamic model

“…Colistin (CST), an old antibiotic mainly used as last resort drug against multidrug resistant Gram-negative bacteria, acts as a membrane disruptor by binding to surface molecules such as lipopolysaccharides and thus causing disintegration of bacterial membrane 3 , is expected to enhance the antibacterial effect of the co-administered drug by increasing membrane permeability and reducing efflux of the permeated antibiotics. Given the concern that CST has high incidences of nephrotoxicity at therapeutic doses 4,5 , a low CST dose would be preferred and may result in an acceptable benefit-risk balance when used in combination.The combination of CIP and CST has been found to be effective against Pseudomonas aeruginosa in vitro against multidrug resistant and persistent pathogens [6][7][8][9][10][11] , and shown to eradicate early P. aeruginosa infection in cystic fibrosis patients 12 . Recent publications reported a synergistic effect in vitro against Acinetobacter baumannii 13 and Klebsiella pneumoniae 14 .…”

“…The combination of CIP and CST has been found to be effective against Pseudomonas aeruginosa in vitro against multidrug resistant and persistent pathogens [6][7][8][9][10][11] , and shown to eradicate early P. aeruginosa infection in cystic fibrosis patients 12 . Recent publications reported a synergistic effect in vitro against Acinetobacter baumannii 13 and Klebsiella pneumoniae 14 .…”