Antimicrobial Effects of Antipyretics, a paper in AAC by Zimmerman & Curtis

Dear All:
 
OK, I’ll say that I’m sending this around because the title was so intriguing and reminded me of the debates we’ve had about why fever is not part of endpoint definition for clinical trials of new drugs.
 
But, this article (see weblink & abstract below) is an excellent, in-depth survey of how salicylic acid and the NSAIDs can actually have effects at concentrations that might actually be reached at times. No, I don’t think you should plan on treating a life-threatening infection with aspirin, but here’s one snippet from the paper:
 
Although many of the MICs for antipyretic drugs are above the therapeutic plasma levels normally attained, higher drug concentrations might be reached in urine, synovia, or with topical therapy. Antipyretic drugs in those situations might reach levels where they inhibit microbial growth or influence microbes by some of the other mechanisms described. Topical ibuprofen, for example, is more effective in suppressing the growth of Trichophyton than topical clotrimazole (94). Another example is that two thirds of women with uncomplicated urinary tract infections (80% with E. coli) treated with ibuprofen recover without antibiotics (95). Although this finding is considered to result from the anti-inflammatory effects of ibuprofen, it might also be attributable to the antimicrobial effects of ibuprofen, which include blocking of adherence to uroepithelial cells, reduced motility, and reduced toxin and biofilm production, as well as inhibition of growth (9, 25, 26). Diclofenac and other NSAIDs inhibit bacterial DNA synthesis (10, 91) in E. coli; this was shown to be through the inhibition of a DNA polymerase (96).
 
Who knew?!?
 
Have a good weekend, –jr
 
John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Chief Strategy Officer, CARB-X | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx
 
Reference: Petra Zimmermann and Nigel Curtis: https://journals.asm.org/doi/10.1128/AAC.02268-16
 
ABSTRACT: Antipyretics are some of the most commonly used drugs. Since they are often coadministered with antimicrobial therapy, it is important to understand the interactions between these two classes of drugs. Our review is the first to summarize the antimicrobial effects of antipyretic drugs and the underlying mechanisms involved. Antipyretics can inhibit virus replication, inhibit or promote bacterial or fungal growth, alter the expression of virulence factors, change the surface hydrophobicity of microbes, influence biofilm production, affect the motility, adherence, and metabolism of pathogens, interact with the transport and release of antibiotics by leukocytes, modify the susceptibility of bacteria to antibiotics, and induce or reduce the frequency of mutations leading to antimicrobial resistance. While antipyretics may compromise the efficacy of antimicrobial therapy, they can also be beneficial, for example, in the management of biofilm-associated infections, in reducing virulence factors, in therapy of resistant pathogens, and in inducing synergistic effects. In an era where it is becoming increasingly difficult to find new antimicrobial drugs, targeting virulence factors, enhancing the efficacy of antimicrobial therapy, and reducing resistance may be important strategies.

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