A common question I've heard when discussing the case for accelerated antibiotic susceptibility testing is "why not just use several drugs in combination?", the presumption being that one of them is sure to work. The usual answers are that there is a risk of toxicity, and that pharma companies are generally not interested in sponsoring combo therapy trials - they want to own markets, not share them.
Two articles published in CID (thx @ndm1bacteria) add a third and more compelling reason: combo therapy does not work nearly as well as one would expect. A study of Acinetobacter infections treated with colistin and rifampin, and a study of Pseudomonas infections treated with various antibiotics, showed no improvement in 30-day mortality for combination over single therapy.
This is a surprise, given the success of retroviral combination therapy, and the results of in vitro microbiological studies. Why the lack of efficacy? I can think of three factors: pharmacokinetics and biodistribution, bacterial SOS responses, and host inflammatory response. It's possible that a significant fraction of the infecting bacteria did not (at least initially) get exposed to a significant dose of both antibiotics. And when exposed to one antibiotic, bacteria (unlike retroviruses) will go into stress/shutdown modes that make them less susceptible to additional antibiotics. If the infection is not rapidly eradicated, the host inflammatory response can spiral out of control, leading to organ damage and death.
In contrast to combination therapy, appropriate antibiotic therapy was shown to improve survival. The bottom line here is not surprising: using the right antibiotic matters, and a shotgun approach to therapy is not a substitute for evidence-based medicine. The problem is with the evidence part: accelerated antibiotic susceptibility tests still don't exist. And they will continue to not exist until physicians begin to demand them and lab managers show a willingness to pay for them.
Posted with Blogsy
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