Growth cycle-dependent pharmacodynamics of antichlamydial drugs

Chlamydiae are obligate intracellular pathogens that exhibit an extensive intracellular developmental cycle in vivo. Clinical treatment of chlamydial infection is typically initiated upon occurrence of symptomatology and is directed against an asynchronous population of different chlamydial developmental forms. Pharmacodynamics of antichlamydial drugs are predominantly characterized by MICs; however, in vitro determinations of MIC may not reflect differential susceptibilities of the developmental cycle. In this study, we correlated the antichlamydial effect of erythromycin, rifampin, doxycycline, and ciprofloxacin with the developmental stage of a fast-replicating and a slow-replicating chlamydial species. In addition, we describe the influence of concentration on killing. Extracellular elementary bodies and very-early-phase and late-phase chlamydiae were refractory to all tested antibiotics except rifampin, which was very effective against early-cycle chlamydiae. Rifampin was the most effective antibiotic overall, killed in a dose dependent matter, and exhibited moderate synergism with erythromycin. These considerations provide important information on chlamydial biology and antimicrobial susceptibility. A combinational therapy of rifampin and a macrolide should be considered in therapy-refractory infections.