The anti-inflammatory non-antibiotic helper compound diclofenac: an antibacterial drug target

Abstract

Diclofenac sodium (Dc) was found to possess antibacterial activity against both drug-sensitive and drug-resistant clinical isolates of Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Mycobacterium spp., in addition to its potent anti-inflammatory activity. The time-kill curve study indicates that this non-steroidal drug exhibits bactericidal activity against Listeria, E. coli, and M. tuberculosis. The antibacterial activity of Dc comes, in part, from its ability to inhibit the DNA synthesis of E. coli and L. monocytogenes. Dc could protect murine listeriosis, salmonellosis, and tuberculosis at doses ranged within its maximum recommended human or non-toxic ex-vivo dose. Dc possesses anti-plasmid activity and acts as a 'helper compound' in synergistic combination with streptomycin against E. coli and Mycobacterium or gentamicin against Listeria. This review focuses on the possible use of Dc, a non-antibiotic helper compound, in infections and inflammatory conditions, rationalized on the basis of the activities of the compounds.

NSAIDs: can the presence of infectious agent influence the choice of analgesic drug?

“…Within our study ketorоlaс and ibuprofen showed no antimicrobial activity against S. mutans (the latter, according to our data, in general, was less sensitive to the inhibitory effects of NSAIDs), but were effective (more pronounced for ibuprofen) against S. pyogenes, which is known to have a high sensitivity to antimicrobial agents of different groups and slowly develop resistance to them. According to the reference sources sodium diclofenac showed antibacterial activity against antibiotic-sensitive and antibiotic-resistant strains of listeria and mycobacteria, explained with impaired DNA synthesis of sensitive flora [2]. Use of 30-50 mg/20 g diclofenac for mice reliably protected them from infection caused by gram-negative Salmonella typhimurium [8]; under conditions of our experiment it had practically no effect on gram-negative flora.…”

“…On the one hand, acceleration of progression of soft tissue infections of streptococcal etiology (group A) at the application of certain non-selective (ketorolac, ibuprofen and indomethacin), but not COX-2 selective NSAIDs and reduction of efficiency of etiotropic antibiotic therapy were found [1]. On the other hand, in vitro, sodium diclofenac was detected to show antibacterial activity against antibiotic-sensitive and antibiotic-resistant strains of microorganisms, including mycobacteria, associated by the authors with the violation of the DNA synthesis of sensitive flora [2], in addition, antimycobacterial properties of diclofenac have been confirmed in an experiment in vivo [3]. It is also known, that NSAIDs have direct membranotropic effects, due to which, it seems to us, they can have their own antimicrobial activity, by analogy with membranotropic antibiotics, and also modulate the action of antimicrobial agents (stimulate or weaken) [4].…”

Studies on Anti microbial Potential of Non-antibiotics on Resistant Bacteria – A Review

“…Methodical searching from the mid-1960s, notably by scientists 12,13 gave real evidences to the fact that many eukaryote-directed drugs have antimicrobial, anti-pathogenic and anti-virulence properties. Such pharmaceutical compounds developed as drugs to treat non-infectious diseases but having antimicrobial activities are called non-antibiotics.…”

“…The above non antibiotics can effectively manage the microbial infections of many viruses, mycoplasma, gram-negative and gram-positive bacteria, mycobacterium, yeasts, protozoa, plasmodia, leishmania, trypanosomes, and helminthes. 9,12,13 Many of these are capable of modifying cellular permeability, inhibiting efflux pumps, synergize with various antibiotics, especially for reversal of antibiotic resistance and thus acting as helper compounds. Prontosil, a sulfonamide group exhibits their additional antimicrobial activity.…”

Avaliação das atividades antimicrobiana, antisséptica e esterilizante de extratos e metabólitos de Baccharis dracunculifolia D. C. e Pinus elliottii Engelm

“…tanto associados entre si, na forma de extratos ou como óleos essenciais extraídos de espécies vegetais quando associados com antibióticos de alta potência disponíveis no mercado (BUSH et al, 2011;EJIM et al, 2011;MAZUMDAR, 2009;AL-BAYATI, 2008;LEHTINEN, 2007;SAKAGAMI, 2005 CHUNG et al, 2011).…”