Susceptibility of hamsters to infection by historic and epidemic BI Clostridium difficile strains during daily administration of three fluoroquinolones.

BACKGROUND: The recent epidemic of Clostridium difficile infection (CDI) has been attributed largely to the REA strain group BI (aka NAP1/027). Current isolates of the BI group differ from historic non-epidemic BI strains in that they have developed resistance to the newer fluoroquinolone (FQ), moxifloxacin. The acquisition of moxifloxacin resistance has been associated with the rise in frequency of CDI caused by these isolates. In order to explore the effect of FQ resistance on CDI we compared colonization and mortality in hamsters challenged with a historic (BI1 - susceptible to moxifloxacin) and a recent epidemic (BI17 - resistant to moxifloxacin) BI strain of CD during continuous administration of 3 different FQs.

METHODS: Groups of 6 hamsters were treated with a 5 day course of ciprofloxacin, levofloxacin, or moxifloxacin given orally once per day. Each hamster was then challenged with 1 × 10(4) CFU of either BI1 or BI17 on day 3 or day 5. Colonization and time to death were recorded.

RESULTS: Colonization efficiency (CE) following moxifloxacin (92%) was significantly greater than following levofloxacin (50%, p < 0.01) or ciprofloxacin (42%, p < 0.01) for both strains combined. The CE of BI17 was higher than BI1 for ciprofloxacin (67% vs 17%, p = 0.04) and levofloxacin (83% vs 17%, p < 0.01), but not moxifloxacin (100% and 83%, p = 0.48) administration. BI17 also showed a shorter time from inoculation to death than BI1 following moxifloxacin administration (1.8 days vs 3.9 days, p < 0.01). Moxifloxacin shortened the time from inoculation to death compared to ciprofloxacin in hamsters challenged with BI17 (1.8 days vs 4.0 days, p < 0.01) but not levofloxacin (1.8 days vs 2.0 days, p = NS).

CONCLUSIONS: For the epidemic BI17 strain, ciprofloxacin, levofloxacin and moxifloxacin have similar colonization rates, suggesting that the acquisition of high-level FQ resistance increases colonization rates in association with any FQ. Historic strain BI1 which does not carry high-level FQ resistance colonized efficiently only in the presence of moxifloxacin, possibly explaining lower rates of CDI historically prior to the widespread clinical use of moxifloxacin (and gatifloxacin). Current high rates and severity of CDI from 2000 to 2010 may in part be associated with the acquisition of high-level FQ resistance in BI strains and higher patient exposure rates of all FQs, especially moxifloxacin.