The Production of Antibiotics Must Be Reoriented: Repositioning Old Narrow-Spectrum Antibiotics, Developing New Microbiome-Sparing Antibiotics

Abstract

The development of broad-spectrum antibiotics to control multidrug-resistant bacteria is an outdated business model. This strategy has led to the introduction of highly effective antibiotics, but their widespread use has contributed to the emergence of even broader antibiotic resistance. In a strategy to combat antimicrobial resistance, we believe that the use of narrow-spectrum antibiotics should be promoted. This should involve both the repositioning of old antibiotics and the reorientation of research and development towards new narrow-spectrum antibiotics with a low ecological impact. These antibiotics could be prescribed for common conditions such as sore throats and cystitis, which account for the bulk of antibiotic use in humans. Narrow-spectrum, targeted, microbiome-sparing antibiotics could help control antibiotic resistance while being economically sustainable. Their development and production should be supported by governments, which would ultimately benefit from reduced health care costs.

Evaluation of the microbiota-sparing properties of the anti-staphylococcal antibiotic afabicin

“…To summarize, afabicin is a member of a short list of microbiota-sparing antibiotics currently in clinical development. 10 Further efforts are warranted to expand this list through reorientation of research towards highly targeted pathogen-specific antibiotics with very narrow spectrum of activity and low ecological impact; 3 , 9 , 54–56 clinical implementation of highly targeted antimicrobials should limit dysbiosis, thereby helping to control AMR.…”

High proportions of single-nucleotide variations associated with multidrug resistance in swine gut microbial populations

“…Our SDHSE MAGs are likely harboring MDR to not only CTC and TMU, but other drugs, with genetic variations hindering targeted therapeutics 135 . While there has been a call for shifting our antibiotic usage to narrow or even strain-specific antibiotics to limit further AMR with application of broad antibiotics 136 , bacterial populations with high genetic variation could minimize the success of such therapies 35 . Clearly bacterial populations, such as SDHSE bacteria, with high genetic variation are concerning as they demonstrate increased AMR and threaten further AMR through targeted antimicrobials 35 .…”

Daidzein‐Based Amphiphilic Small Molecular Antimicrobial Peptidomimetics as Novel Antimicrobial Agents with Anti‐Biofilm Activity

“…AMPs exhibit a reduced susceptibility to bacterial resistance due to their action on the lipid membrane rather than on specific proteins. [14][15] AMPs can also inhibit the formation of biofilms and disrupt mature biofilms. [16] However, the utility of AMPs as therapeutic agents is limited due to their poor pharmacological properties owing to their long synthesis times, difficulty in large-scale preparation, low stability in plasma, sensitivity to changes in salt concentrations and pH changes, as well as proteolytic enzymes, low hydrolytic stability, and high cost of production.…”

“…Peptides then bind strongly to the membrane surfaces with their hydrophobic domains anchored into the hydrophobic lipid core of the bilayer, followed by membrane penetration, pore formation or membrane disruption, which eventually leads to cell death. AMPs exhibit a reduced susceptibility to bacterial resistance due to their action on the lipid membrane rather than on specific proteins [14–15] . AMPs can also inhibit the formation of biofilms and disrupt mature biofilms [16] .…”