Nonmultiplying bacteria are profoundly tolerant to antibiotics

Bacteria survive treatments with antimicrobial agents; they achieve this in two ways. Firstly, bacteria quickly become tolerant to these agents. This tolerance is temporary, reversible, and associated with slowing of the multiplication rate. Secondly, bacteria can undergo genetic mutations leading to permanent clonal resistance to antimicrobial agents. In patients with infections, nonmultiplying bacteria, some of which may be viable but nonculturable, exist side by side with multiplying bacteria. Current antibiotics capable of killing actively multiplying bacteria have very limited or no effect against nonmultiplying bacteria. Treatment of such infections requires a regimen of multiple antimicrobial agents in order to control nonmultiplying persistent bacteria. This is especially important in tuberculosis where there is co-existence of slowly multiplying tolerant bacteria with fast growing sensitive organisms. For this reason, a prolonged length of chemotherapy, lasting 6 months, is necessary to achieve cure. This long duration of treatment is due to the slow, inadequate effect of antibiotics on nonmultiplying persistent bacteria. Similar problems with eradication of persistent bacteria are evident in the treatment of biofilms. These bacteria serve as a pool for recurrent infections. Extended courses of antibiotics increase the likelihood of genetic resistance, raise the cost of treatments, and lead to more side effects.