Evaluation of antibacterial activity of some non-steroidal anti-inflammatory drugs against Escherichia coli causing urinary tract infection

Abstract

Extensive use of antibiotics for urinary tract infections has led to the emergence of drug-resistant microorganisms and one solution to this problem is to search for non-antibiotic compounds that exert anti-bacterial activity through different mechanisms such as non-steroidal anti-inflammatory drugs (NSAIDs). In this study, out of 100 urine samples; 48 Escherichia coli strains were detected, 47.9% were multi-drug resistant. The antibiogram resistance pattern of the strains was carried out by agar dilution method. Diclofenac sodium, indomethacin, aspirin and ibuprofen were tested against the E. coli isolates. Diclofenac sodium showed the lowest MIC 50 and MIC 90 ; 8 and 256 g/ml, respectively. Aspirin showed MIC 50 of 64 g/ml, while both indomethacin and ibuprofen showed MIC 50 of 256 g/ml. Indomethacin, aspirin and ibuprofen showed the same MIC 90 of 1024 g/ml. The combined effects of the four NSAIDs and five antibiotics (Amoxicillin, Augmentin, Cefotaxime, Ciprofloxacin and Gentamicin) were tested on five resistant clinical E. coli strains by checkerboard dilution technique. All the tested NSAIDs significantly reduced the minimum inhibitory concentrations (MICs) of antibiotics against the tested bacteria and fractional inhibitory concentration indices (FICIs) for this combination ranged from 0.03 to 0.5. In this study, leakage of intracellular components suggests that the effect of NSAIDs on E. coli could be the formation of pores in the plasma membrane and scanning electron microscopy (SEM) observations confirmed the damage to the structural integrity of the tested bacteria. In conclusion, NSAIDs showed antibacterial activity against E. coli causing urinary tract infections (UTIs), a combination of them and antibiotics exhibited good synergism and the mechanism of their action was by damaging the bacterial cell membrane.

The Phenylacetic Acid Catabolic Pathway Regulates Antibiotic and Oxidative Stress Responses in Acinetobacter

“…Understanding the molecular basis underlying the PAA-mediated response to stress could open new avenues for drug development and research. In fact, some PAA derivatives are already part of a group of FDA-approved nonsteroidal anti-inflammatory drugs, some of which have been used to treat bacterial infections in murine models ( 47 , 48 ). The therapeutic potential of PAA or PAA derivatives in interfering with the stress response of drug-resistant bacteria is extremely relevant to the growing field of antimicrobial resistance, warranting further research into their potential effects on Acinetobacter stress tolerance and pathogenesis.…”

Diclofenac sensitizes multi-drug resistantAcinetobacter baumanniito colistin

“…Previous studies have shown that diclofenac has antibacterial activity against both Gram-negative and Gram-positive pathogens. Specifically, it has been reported that diclofenac has anti-listerial activity in vivo (56), is effective against Escherichia coli in an in vivo urinary model (33, 34), and eliminates Mycobacterium tuberculosis in an in vivo model when used as monotherapy or in combination with streptomycin (32). Moreover, diclofenac displayed antibacterial activity against the Gram-positive methicillin-resistant Staphylococcus aureus in combination with β-lactams (35).…”

“…Diclofenac functions by inhibiting cyclooxygenases, COX-1 and COX-2 in the host (31). It has been suggested that diclofenac may have antibiotic properties (32)(33)(34)(35). In this study, we explore the potential of repurposing the FDA approved PAA-derivative, diclofenac, to enhance antibiotic efficacy against MDR A. baumannii with a specific focus on the last-resort drug, colistin.…”

Repurposing: A Potentially Emerging Discipline

“…and Bacillus spp. 105 Diflunisal, an FDA-approved NSAID is reported to reduce S. aureus cytotoxicity, inhibit skeletal cell death, and prevent bone destruction during staphylococcal osteomyelitis. 107 Further, it is reported that diflunisal inhibits the growth of Helicobacter pylori, indicating its usefulness in drug repurposing.…”