Can we use MIC99 or MBC 99 in determining the extent of persister killing?

MIC and MBC are the major pharmacodynamics parameters used to quantify antibiotic activity against bacteria. MIC is defined as the minimum concentration of antibiotic that inhibit the growth of at least 99% of the population whereas MBC is the minimum concentrations of antibiotic required to kill at least 99% of the population. However, Keren et al. (2004) argues that MBC do not take into account of persisters which constitute less than 1% of the population since persisters will not be reported in conventional MBC tests as it do not fall within the above accepted range.

Byrne et al. (2007) reported that diethyldithiocarbamate (DETC) and pyrrolidine dithiocarbamate (PDTC) are active against growing and non-growing persisters of Mycobacterium tuberculosis. The activities of above agents were determined using the conventional methods of determining MIC99 and MBC99. They also found that DETC and PDTC enhanced the activities of antituberculosis drugs against both young and old cultures. They noticed a reduction in colony forming units when antituberculosis drugs were used in combination with DETC and PDTC.

However, what is the basis of using MBC99 in determining the activities of those agents against persisters? By using MBC99, aren’t they missing the same persisters they are supposed to kill? Similarly, the combination of the above agents with antituberculosis drugs has only reduced the number of CFU, but has not completely killed all the bacteria. How can it be concluded that the above agents are active against persisters?

To me, that article only indicates that DETC and PDTC enhance the killing activities of antituberculoss drugs, but does not give any indication of their activities against persisters.

Next- What difference it will make if the number of persisters is 10⁵ or 10⁶?

Keren et al. (2004). Persister cells and tolerance to antimicrobials. FEMS Microbiol Lett 230(1), 13-8.

Byrne et al. (2007). Pyrrolidine dithiocarbamate and diethyldithiocarbamate are active against growing and nongrowing persister Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy 51(12):4495-4497.