Unexpected antibiotic susceptibility of a chronic isolate of Coxiella burnetii

Abstract

Evidence is mounting in support of the idea that different isolates of Coxiella burnetii, the etiologic agent of Q fever, are responsible for the distinct disease syndromes observed clinically. Recent studies have shown distinct antibiotic susceptibilities of different isolates of C. burnetii implicated in distinct clinical Q fever syndromes. With this in mind, we performed antibiotic susceptibility testing of the "S" isolate, a chronic-type isolate retrieved from a human patient with chronic disease. Antibiotics with differing efficacies upon the Nine Mile and Priscilla isolates were tested for their abilities to control acute and persistent "S" isolate infection of L-929 cells in vitro. The efficacies of doxycycline, rifampin, and three fluoroquinolone drugs--ciprofloxacin, ofloxacin, and norfloxacin--were tested. Compared to the chronic Q fever-implicated Priscilla isolate, which has been shown to exhibit a significant resistance to these antibiotics, the "S" isolate was much more susceptible. In persistently infected cells (greater than 300 d), the "S" isolate proved to be significantly more resistant to doxycycline, slightly more resistant to ciprofloxacin, slightly more susceptible to rifampin, and equally sensitive to ofloxacin and norfloxacin compared to the acute Q fever-implicated Nine Mile isolate. As with both the Nine Mile and Priscilla isolates, the "S" isolate was more susceptible to doxycycline, rifampin, and ofloxacin in recently infected cells (22 d) compared to cells having been persistently infected. With respect to the resistant nature of the chronic Q fever-implicated Priscilla isolate, as well as the lack of success in treating the "S" isolate in vivo, these results were unexpected. Such data supports an evolving hypothesis that the distinct C. burnetii isolates which may be responsible for the clearly different Q fever syndromes exhibit a spectrum of antibiotic susceptibility ranging from very susceptible (acute-implicate), Nine Mile isolate), to moderately susceptible (chronic-implicated "S" isolate), to moderately resistant (chronic-implicated Priscilla isolate).