If persisters can be killed by a second dose of antibiotic, what is their clinical significance?

The experiments demonstrating phenotypic shift have used only a static approach; i.e., a culture of bacteria incubated with a single dose and a single concentration of antibiotic for a relatively small period of time. However, this static approach has a number of disadvantages and is not a true reflection of in vivo conditions. In vivo, antibiotics are administered as multiple doses for several days. Antimicrobial efficacy results from the exposure of bacteria to variable antibiotic concentrations. Thus, in vitro conditions with a single dose and concentration of antibiotics may not reflect the true dynamic situation in the target organ and hence the result can not be extrapolated as such to in vivo conditions.

As reviewed by Lewis (2007), it may be possible to sterilize an infection by using a simple approach:

“A disarmingly simple approach to sterilize an infection was first proposed by Bigger in 1944. The proposal is to kill bacterial cells with a high dose of an antibiotic, then allow the antibiotic concentration to decrease, which will enable persisters to resuscitate and start to grow. If a second dose of antibiotic is administered shortly after persisters start to grow, a complete sterilization might be achieved. This approach is successful in vitro, and a P. aeruginosa biofilm can essentially be sterilized with 2 consecutive applications of a fluoroquinolone (K. L., unpublished observations). Perhaps understandably, this approach has not been received with enthusiasm by specialists in clinical microbiology.”

Is this not the same ‘approach’ we follow during the treatment of bacterial infections with antibiotics? After the first dose of the antibiotic, the concentration of the antibiotic decreases depending on its half-life and is followed by the next dose. In clinical infections, most antibiotics are administered as multiple doses for several days. If a P. aeruginosa biofilm can essentially be sterilized with 2 consecutive applications of a fluoroquinolone or if a second dose of antibiotic can kill all persisters and achieve complete sterilization, what is the clinical significance of persisters?

Next- Is it possible to treat persister infections serendipitously?

Lewis, K. (2007). Persister cells, dormancy and infectious diseases. Nat Rev Microbiol. 5(1): 48-56.