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
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The Letter (BMJ 2012;344:e3369) suggests a certain course of action with regard to antibiotic stewardship and development. It does so based on an informal rating of antibiotics such that some classes are declared the 'best.' These are presumably broad-spectrum, least toxic at clinically effective concentrations, with favorable systemic pharmacokinetics and dynamics.
However, these classes of antibiotics, optimized for systemic administration and broad coverage, are only ideal from an outdated perspective. Now, with new understandings of the human microbiome, it is clear that the ideal antibiotic would be incredibly narrow spectrum and even spatially localized - perhaps to an organ system, or a wound, wherever the relevant infection is causing distress. It may be that the very same bacteria also reside elsewhere on the body beneficially; and it may be that close relatives of the pathogen are innocuous or helpful nearby. The 'best antibiotics we will ever have' would not disturb these other sites and other related organisms.
Antibiotic chemotherapy in this new mode will require not only an entirely new strategy for developing antibiotics, but also a new strategy for diagnosing infections. The detection and characterization of the pathogen must be performed with a level of specificity impossible using only the culture methods dominant over the past century. Empiric therapy will likely be completely incompatible with extremely narrow spectrum antibiotics. Our collective understanding of infection will require a significant enhancement.
This will eventually arrive. The entire system will change. When it does, antibiotic resistance will also be transformed as a problem, because only a relatively few cells will be exposed to selection pressure by the new, narrow spectrum, localized antibiotics. No longer will each patient expose the entire gut, skin, respiratory flora to each antibiotic for days on end. This will drastically slow the evolution of antibiotic resistance by reducing the effective population size under selection.
This is not an argument against stewardship of the broad spectrum antibiotics; their overuse has many other ramifications beyond the increase in resistance and they are the only effective agents we currently possess. However, there is a strong argument for funding new antimicrobial development efforts. Interestingly, though, the necessary efforts (extermely narrow spectrum, localized, paired with new diagnostics) are unlike most which are currently proposed or underway.
The existing 'silver bullets,' miraculous in their time and context, are not the primary antibiotics of a successful future. What generation of antibiotics will be 'the best we will ever have?' It is yet to come.
Competing interests: No competing interests