Session: Inhibitors of Bacterial and Fungal Efflux Pumps
Location:
Exhibit Hall
Session Date:
Monday, 9/27/99
Session Time:
3:00 pm - 4:30 pm
Prevalence of Efflux Pumps among Clinical Isolates of
Fluoroquinolone-Resistant Pseudomonas aeruginosa
D. Cho, J. Blais, K. Tangen, C. Ford, A. Lee, O. Lomovskaya, S. Chamberland,
G.H. Miller
Microcide Pharmaceuticals, Inc.: Mountain View, CA
Active efflux plays an important role in intrinsic and acquired resistance of Pseudomonas
aeruginosa to a wide variety of antimicrobial agents. There are three well-characterized
efflux systems involved in multidrug resistance in P. aeruginosa: MexAB-OprM,
MexCD-OprJ, and MexEF-OprN. Another efflux system, MexXY has also recently
been reported. We determined the frequency of efflux-mediated resistance in 409 recent
clinical isolates of P. aeruginosa obtained from 12 countries (USA, Japan, Thailand,
Canada, Greece, China, France, Argentina, UK, Venezuela, Turkey, and Spain). Efflux
pump profiles were based upon susceptibility to 10 antibiotics (piperacillin, carbenicillin,
ceftazidime, aztreonam, imipenem, meropenem, chloramphenicol, erythromycin,
ciprofloxacin, and levofloxacin) and response to broad-spectrum and pump-specific
efflux pump inhibitors (EPIs). 56 laboratory mutants with known genotypes and varied
pump expression were used to establish criteria for each pump profile. The MexAB
profile was the most prevalent among these isolates (296 or 72%) while the
MexAB/MexCD profile was observed in 9% (36) of the isolates. The remaining isolates
were divided as follows: 17 (4%) AB/EF, 15 (4%) AB/CD/EF, 14 (3%) CD, 9 (2%)
CD/EF, 3 (<1%) EF, and 19 (5%) other pumps (responding to a broad-spectrum EPI
only). Breakdown of profiles by geographic origin revealed significant variation in pump
profiles from region to region. For example, the MexAB profile was found in only 27%
of isolates from China but in 96% of isolates from Japan. These results show that
Mex-type efflux pumps are highly prevalent among worldwide isolates of
fluoroquinolone-resistant P. aeruginosa. |
