Can treatments with bacteriostatic drugs produce persisters?

Antibiotics, in general, can be divided into bactericidal and bacteriostatic drugs, depending on their mechanism of action. Bactericidal drugs like penicillin, aminoglycosides etc., act by killing the bacteria whereas bacteriostatic drugs like tetracycline, chloramphenicol, macrolides etc., act by inhibiting bacterial growth. However, it is difficult to classify antibiotics into true bactericidal or bacteriostatic antibiotics (Pankey and Sabath 2004). Under certain conditions, bactericidal drugs may only inhibit the growth of bacteria. Similarly, bacteriostatic drugs also kill bacteria depending on the concentration of antibiotic, total time of incubation and the sensitivity of the organism. Many bacteriostatic drugs kill 90-99% of the bacteria after 18-24 h, but do not kill 99.9% of them to be termed as bactericidal drugs (for a detailed review of the clinical significance of bactericidal and bacteriostatic antibiotics, see Pankey and Sabath 2004). Here again, the survivors remain in a dormant stage in the presence of the bacteriostatic antibiotic but may regrow once the antibiotic is removed. Are those 1-10% or more of the survivors persisters? If they are, will it be easy to isolate persisters after treatment with bacteriostatic drugs? If they are not, how can we distinguish the survivors following treatment with bactericidal and bacteriostatic antibiotics? Or in other words, why are the survivors following bactericidal drugs persisters and those following bacteriostatic drugs not?

Even though the static drugs, in general, do not kill 99.9% of bacteria after 18-24 h of incubation, they are powerful antibiotics widely used in treatment of many bacterial infections. If persisters are responsible for recurrent infections, one has to assume that the use of bacteriostatic drugs almost always carries the risk of chronic or recurrent infections. Is it safe to use bacteriostatic antibiotics since they carry the risk of chronic infections?

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

Pankey, G. A., and Sabath, L. D. (2004). Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of Gram-positive bacterial infections. Clin Infect Dis 38(6), 864-70.