Precision Drugs for Bad Bugs

Awareness is high that antibiotic resistance is a critical problem, but many still don’t appreciate the role played by antibiotics themselves in accelerating this problem’s spread.

Single antibiotics capable of killing multiple bacterial species – a class of drugs termed “broad spectrum” – have long been seen as a panacea and a cure for all bacterial infections. Today, essentially all marketed antibiotics kill multiple species of bacteria. Unfortunately bacteria that become resistant to a particular antibiotic can pass to other bacteria the genetic material conferring that resistance. The result: relatively soon after introducing a new broad-spectrum antibiotic, resistant bacteria appear widely.

Clearly, the greater the antibiotic prevalence in the bacterial environment, the more prevalent will be antibiotic-resistant bacteria. In the presence of antibiotics, bacteria are incentivized to retain any drug resistance that they acquire from other nearby microbes. Multiple antibiotic-resistance genes frequently travel and transfer linked together.

Antibiotics are nearly ubiquitous in our world, with non-human uses – mostly in animal husbandry – accounting for 75-80% of manufactured antibiotics. Antibiotics have for 70 years saved lives and limbs, providing enormous benefits. For scientific, financial and political reasons, many health organizations predict that era is on the verge of ending.

To protect human health and at least delay such a crisis, two actions are required. The first and simpler action is to markedly reduce the prevalence of antibiotics in the environment by avoiding medically unnecessary or inappropriate uses, thereby reducing selective pressures on bacteria to become and remain drug resistant. The second action – more difficult and complex – is to discover and develop new antibacterial drugs that only target the offending pathogen and do not kill other “bystander” bacteria.

Fortunately, new technologies that enable rapid, accurate diagnosis of bacterial pathogens and their drug sensitivities, combined with a simple concept to guide development of new antibacterial drugs, might together markedly change the course of emerging antibiotic resistance and stave off the impending crisis of “No Drugs for Bad Bugs.”

The simple concept is “Precision Drugs for Bad Bugs.” Why has precision medicine until now applied predominately to cancer? If bacteria other than the specifically targeted disease organism are already insensitive to a drug, there will be no selective pressure on those microbes to retain drug-resistance genes. Were the physician to know promptly the specifics of an offending bug, an appropriate, precisely targeted antibacterial agent could be prescribed – if one was available.

Precisely targeted antibacterials could confer another significant advantage. Non-target bacteria in the gut, mouth, skin and vagina, which we are learning confer important health benefits, would be insensitive to a drug aimed only at an offending bad bug. These healthful bacteria would not be unintentionally damaged or eliminated as inevitably occurs with broad-spectrum antibiotic use and misuse.

Knowing that bacteria can quickly acquire and share genetic resistance to any new broad-spectrum antibiotic, and that broad-spectrum antibiotics cause unintended, potentially harmful damage to beneficial bacteria, why would one want to encourage the development of more broad-spectrum antibiotics rather than precision drugs and accurate companion diagnostics? Many existing stakeholders still favor broad-spectrum antibiotics. Such antibiotics allow physicians to treat illness without having accurate diagnoses, pharmaceutical companies to imagine larger markets, and farmers to speed the growth of livestock.

Broad-spectrum antibiotics will certainly remain useful and necessary until a portfolio of readily available precision antibacterial agents and companion diagnostics can provide the coverage sufficient to replace traditional modes of managing bacterial infections. But the effective future of fighting bacterial infections requires that we overcome both change-resistant stakeholders and drug-resistant bacteria by turning attention to precision drugs for bad bugs.

 

David W. Martin, Jr. M.D., Chief Executive Officer, AvidBiotics

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