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Published on: April 18, 2019
Potential Synergistic Antibiotic Combinations against Fluoroquinolone-Resistant Pseudomonas aeruginosa
Ashish Kothari1, Neeraj Jain2,3, Shyam Kishor Kumar4
1Department of Microbiology, All India Institute of Medical Sciences Rishikesh, Rishikesh 249203, India.
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.
Insights
Multiple-drug-resistant Pseudomonas aeruginosa is a growing threat. Combinations of colistin and ciprofloxacin show promise for treating these difficult infections, offering a potential new strategy against resistant Gram-negative pathogens.
Area of Science:
- Clinical Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Multiple-drug-resistant (MDR) Gram-negative pathogens, particularly *Pseudomonas aeruginosa*, pose a significant public health challenge due to limited treatment options.
- *P. aeruginosa*'s intrinsic resistance mechanisms and adaptability to antibiotic monotherapy necessitate alternative therapeutic strategies.
- Nosocomial infections caused by MDR *P. aeruginosa* are increasingly difficult to manage in clinical settings.
Purpose of the Study:
- To determine the prevalence of MDR and extensively drug-resistant (XDR) phenotypes of *P. aeruginosa* in a tertiary care hospital in North India.
- To investigate the antibiotic resistance patterns and identify key resistance determinants.
- To evaluate potential combinatorial antibiotic therapy options against MDR and XDR *P. aeruginosa*.
Main Methods:
- Phenotypic characterization of *P. aeruginosa* isolates for multidrug resistance and extensive drug resistance.
- Antimicrobial susceptibility testing against a panel of antipseudomonal antibiotics.
- Exploration of synergistic or antagonistic interactions between colistin, ciprofloxacin, tobramycin, and meropenem.
Main Results:
- Approximately 60% of isolated *P. aeruginosa* strains exhibited MDR phenotypes.
- The highest frequency of antibiotic resistance was observed in isolates from the emergency department, with 20% resistant to 15 antipseudomonal antibiotics.
- Plasmids carrying quinolone-resistance determinants were identified as major contributors to fluoroquinolone resistance. The combination of colistin and ciprofloxacin demonstrated potential efficacy.
Conclusions:
- MDR and XDR *P. aeruginosa* are prevalent in the studied tertiary care hospital, highlighting the urgent need for effective treatment strategies.
- The combination of colistin and ciprofloxacin emerged as a promising therapeutic regimen for combating infections caused by MDR and XDR *P. aeruginosa*.
- Understanding antibiotic interactions is crucial for developing successful combinatorial therapies against challenging Gram-negative infections.
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