Chlamydia pneumoniae infection in circulating human monocytes is refractory to antibiotic treatment

Background-Recovery of the intracellular bacterium Chlamydia pneumoniae fro m atherosclerotic plaques has initiated large studies on antimicrobial ther apy in coronary artery disease. The basic concept that antibiotic therapy m ay eliminate and prevent vascular infection was evaluated in vitro and in v ivo by examining the antibiotic susceptibility of C pneumoniae in circulati ng human monocyles, which are thought to transport chlamydiae from the resp iratory tract to the vascular wall. Methods and Results-Blood monocytes (CD14+) from 2 healthy volunteers were obtained before and after oral treatment with azithromycin or rifampin and then inoculated with a vascular C pneumoniae strain and continuously cultur ed in the presence of the respective antibiotic. Progress of infection and chlamydial viability was assessed by immunogold-labeling and detection of C pneumoniae-specific mRNA transcripts. Circulating monocytes from patients undergoing treatment with experimental azithromycin for coronary artery dis ease were examined for C pneumoniae infection by cell culture. Antibiotics did not inhibit chlamydial growth within monocytes. Electron microscopy sho wed development of chlamydial inclusion bodies, Reverse transcription-polym erase chain reaction demonstrated continuous synthesis of chlamydial mRNA f or 10 days without lysis of the monocytes. The in vivo presence of viable p athogen not eliminated by azithromycin was shown by cultural recovery of C pneumoniae from the circulating monocytes of 2 patients with coronary arter y disease, Conclusions-C pneumoniae uses monocytes as a transport system for systemic dissemination and enters a persistent state not covered by an otherwise eff ective antichlamydial treatment. Prevention of vascular infection by antich lamydial treatment may be problematic: circulating monocytes carrying a pat hogen with reduced antimicrobial susceptibility might initiate reinfection or promote atherosclerosis by the release of proinflammatory mediators.