Abstract
BackgroundMost patients with bacterial infections suffer from fever and various pains that require complex treatments with antibiotics, antipyretics, and analgaesics. The most common drugs used to relieve these symptoms are non-steroidal anti-inflammatory drugs (NSAIDs), which are not typically considered antibiotics. Here, we investigate the effects of NSAIDs on bacterial susceptibility to antibiotics and the modulation of bacterial efflux pumps.MethodologyThe activity of 12 NSAID active substances, paracetamol (acetaminophen), and eight relevant medicinal products was analyzed with or without pump inhibitors against 89 strains of Gram-negative rods by determining the MICs. Furthermore, the effects of NSAIDs on the susceptibility of clinical strains to antimicrobial agents with or without PAβN (Phe-Arg-β-naphtylamide) were measured.ResultsThe MICs of diclofenac, mefenamic acid, ibuprofen, and naproxen, in the presence of PAβN, were significantly (≥4-fold) reduced, decreasing to 25–1600 mg/L, against the majority of the studied strains. In the case of acetylsalicylic acid only for 5 and 7 out of 12 strains of P. mirabilis and E. coli, respectively, a 4-fold increase in susceptibility in the presence of PAβN was observed. The presence of Aspirin resulted in a 4-fold increase in the MIC of ofloxacin against only two strains of E. coli among 48 tested clinical strains, which included species such as E. coli, K. pneumoniae, P. aeruginosa, and S. maltophilia. Besides, the medicinal products containing the following NSAIDs, diclofenac, mefenamic acid, ibuprofen, and naproxen, did not cause the decrease of clinical strains’ susceptibility to antibiotics.ConclusionsThe effects of PAβN on the susceptibility of bacteria to NSAIDs indicate that some NSAIDs are substrates for efflux pumps in Gram-negative rods. Morever, Aspirin probably induced efflux-mediated resistance to fluoroquinolones in a few E. coli strains.
Highlights
The widespread and frequent prevalence of multidrug (MDR) efflux pumps and the associated multidrug resistance to antibacterial agents among pathogenic bacteria can make the treatment of infectious diseases difficult and ineffective [1,2,3]
The presence of Aspirin resulted in a 4-fold increase in the MIC of ofloxacin against only two strains of E. coli among 48 tested clinical strains, which included species such as E. coli, K. pneumoniae, P. aeruginosa, and S. maltophilia
The effects of PAβN on the susceptibility of bacteria to non-steroidal anti-inflammatory drugs (NSAIDs) indicate that some NSAIDs are substrates for efflux pumps in Gram-negative rods
Summary
The widespread and frequent prevalence of multidrug (MDR) efflux pumps and the associated multidrug resistance to antibacterial agents among pathogenic bacteria can make the treatment of infectious diseases difficult and ineffective [1,2,3]. Efforts have been undertaken to investigate the antibacterial activity of some compounds belonging to the group of non-steroidal anti-inflammatory drugs (NSAIDs), which are among the most commonly and frequently used medicinal products. The best studied NSAID with regards to non-antibiotic activity is diclofenac. It has antimicrobial activity against a broad spectrum of clinical species, including Escherichia coli [14,15], Klebsiella sp., Salmonella sp., Shigella sp. The mechanism of action of small molecules from the NSAIDs group, such as bromfenac, carprofen, and vedaprofen has been demonstrated [17] These NSAIDs inhibit the E. coli DNA polymerase III b subunit which disturbs DNA replication. We investigate the effects of NSAIDs on bacterial susceptibility to antibiotics and the modulation of bacterial efflux pumps
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