New targets for antibiotics are not so common, so the recent report from Ken Keiler's lab of small molecule inhibitors of the trans-translation pathway in bacteria is pretty noteworthy. Collaborating with Novartis, who presumably provided the library, they identified several inhibitors that are effective at low micromolar concentrations. This is about 100 times more potent than streptomycin, the first antibiotic discovered to target bacterial protein synthesis, and comparable to more modern protein synthesis inhibitors such as clindamycin.
Furthermore, the inhibitors work on a biochemical pathway that appears to be confined to bacteria, and is found in a wide variety of bacteria. Thus it appears that Keiler et al have found promising leads for a new class of broad-spectrum antibiotics.
However, I'm not altogether certain that this is good news. The current exemplar of a broad-spectrum antibiotic is vancomycin, the most-prescribed antibiotic in US hospitals. It's cheap, has clinical benefit for a wide variety of bacterial infections, and is only mildly toxic. These properties make it a default choice when the identity of the infecting bacteria is unknown. And since it usually takes 3 days to isolate and identify bacteria, it's easy for a physician to continue vancomycin therapy, even when practice guidelines indicate that a switch to a more selective agent is indicated.
The results are predictable. Enterococcus, which was once considered a commensal, has become widely vancomycin resistant and opportunistically virulent as other microbiota are wiped out. There are increasing reports of vancomycin tolerance and clinical failure in S. aureus infections.
A new class of broad-spectrum antibiotics would be welcome of course, as it would provide physicians with a tool against bacterial infections that might fail other treatments. But it would also further enable lazy prescribing practices by those doctors who are unable or unwilling to do the microbiology workup and bother to understand it. The inevitable result will be the emergence of resistance.
There probably aren't a lot of new targets out there for antimicrobial development. We can't afford to waste any of them. Yet this is precisely what will happen so long as any doctor is allowed to prescribe any antibiotic for any indication.
Posted with Blogsy
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