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Beware of backfire

Posted by Pitlik on 02 May 2013 at 07:17 GMT

In real life conditions, we have to be very cautious with this approach. Susceptible bacteria are frequently more virulent than their resistant mutants. The use of a molecule to revert resistance at the time of an active infection may actually worsen the situation.

No competing interests declared.

RE: Beware of backfire

ahakansson replied to Pitlik on 02 May 2013 at 10:35 GMT

It is true that in some instances (but far from all) antibiotic resistance can come with a fitness cost making them less virulent in the absence of antibiotics (at least when competing with susceptible strains). However, in the presence of antibiotics, susceptible bacteria will be eradicated whereas resistant bacteria ail not. This is the reason antibiotic-resistant bacteria are responsible for an increased proportion of complications and deaths associated with infection. HAMLET has the ability to sensitize antibiotic-resistant bacteria to the antibiotic they are resistant to. This does not, as Pitlik suggests, mean that HAMLET genetically alters the bacteria to make them more susceptible. The bacteria are still antibiotic-resistant and carry their antibiotic-resistance genes, with or without fitness and virulence cost. I therefore do not feel that HAMLET would worsen a clinical situation. This is especially true as HAMLET will not be used alone, but in combination with antibiotics, which has the potential to increase the efficacy and treatment success of infections with antibiotic-resistant strains. To me that can only be a good thing.

Competing interests declared: Corresponding author of this paper