Existing classes of antibiotics are probably the best we will ever haveBMJ 2012; 344 doi: https://doi.org/10.1136/bmj.e3369 (Published 15 May 2012) Cite this as: BMJ 2012;344:e3369
- 1School of Medicine (General Practice and Bacteriology), National University of Ireland Galway, Galway, Republic of Ireland
Paccaud emphasises economic incentives for new antibiotic discovery to tackle antibiotic resistance.1 An ecological perspective suggests that new drug discovery may not make a major contribution.
The ideal target for antibiotic action is a crucial step in bacterial physiology with no parallel in mammalian cells—for example, penicillin targets a step in cell wall synthesis. Because there is no parallel in mammalian cells there is little dose related cellular toxicity. Because biological motifs are generally conserved in evolution, the number of ideal targets is probably limited. Many compounds (including penicillin) that disrupt crucial bacterial pathways exist naturally, so many environmental bacteria have systems to neutralise their effects.
Therefore, pre-antibiotic microbial biodiversity had two valuable aspects: the number of ideal targets was limited and most common pathogens had few antibiotic neutralisation systems because they were not needed within their animal host. These factors made it relatively easy to find the early “magic bullets.”
Human activity has resulted in a profound transformation of preindustrial microbial biodiversity. Therapeutic antibiotics, disinfectants, and biocides have generated intense selection pressures for bacteria on our body and at the interface between the body and environment (sewage systems), thus shaping pathogens with systems to protect those few ideal targets. This effect of antibacterial agents is compounded by weak or non-existent infection control, population density, environmental contamination (for example, sewage), and global travel.
We have limited expectations from a “renewable pipeline of products.” We hope for some modest success, but the existing classes of antibiotics are probably the best we will ever have. We are wary of creating an expectation that economic incentives can generate a pipeline to compensate for our squandering of this non-renewable resource.
Cite this as: BMJ 2012;344:e3369
Competing interests: None declared.