Before a patient even sees a treating physician, their infection is already being ‘treated’ by dozens of natural antibiotics—this is the innate immune system, explained Prof. Victor Nizet during his keynote lecture at the ECCMID 2019 meeting.
In this session, Nizet encouraged the audience to reconsider the current knowledge: do we underestimate the therapeutic potential of current FDA-approved antibiotics by evaluating them as agnostic to host innate immunity? Can drugs from other fields of medicine possess beneficial activity at the host–pathogen interface?
Nizet presented studies from his laboratory on host–pathogen interactions in extreme multidrug resistant Gram-negative strains.
In one study, the most commonly prescribed antibiotic in the USA, azithromycin (AZM), inhibited protein synthesis when Acinetobacter baumannii was cultured in tissue culture media, but not in traditional Mueller-Hinton broth. AZM induced marked structural changes in Pseudomonas (from rod to coccus), indicating a change in the cell wall integrity in an organism that was not supposed to respond to AZM.
Investigators also found that statins, which are drugs traditionally used to treat blood pressure, could enhance the S. Aureus killing efficacy of neutrophils, and this effect was observed on multiple bacterial species. The mechanism was unusual: neutrophils created NETs, DNA-based extracellular traps used for catching and killing pathogenic bacteria.
In another study, low platelet count was associated with higher mortality Staphylococcus aureus bacteraemia patients. Investigators found that platelets killed these bacteria better than neutrophils in vitro, and that these bacteria drove down platelet counts in the blood—as if the bacteria and platelets were in direct competition. The FDA-approved P2Y12 inhibitor, Ticagrelor, could block Staphylococcus aureus-mediated platelet cytotoxicity, which protected against bacteria-related mortality.
Taken together, Nizet highlighted some elegant studies at the host–pathogen interface, and suggested novel, repurposed treatment strategies for multidrug resistant Gram-negative bacteria.