Combined Resistance to Quinolones and Beta-lactams After in Vitro Transfer on Single Drugs

Single and combined resistance to quinolones and beta-lactams was determined after serial transfers of 18 selected strains of Pseudomonas aeruginosa (5), Acinetobacter calcoaceticus (3) and beta-lactamase producing enterobacterial strains (10), in broth dilutions of 4 quinolones and 8 beta-lactams. Two definitions for resistance were used: (I) 8-fold MIC increase and stability of acquired resistance after five transfers in drug-free broth; and (II) 8-fold MIC increase over the breakpoint level. Using definition I, after transfers on a beta-lactam, resistance to one or more beta-lactams was noted in 45%, to one or more quinolones in 7% of strains. After transfers on a quinolone, the frequency of resistance to quinolones was 82%, to beta-lactams 26%. When all tests were counted separately, the resistance percentages were lower, but they showed the same trend. Calculation according to definition II showed quinolone resistance in 5.4% of all tests after transfer on a beta-lactam and beta-lactam resistance in 23% after transfer on a quinolone. Serial transfers on imipenem led to fewer cases of resistance (13%) to beta-lactams than transfers on any other beta-lactam (19-39%). There were no conclusive differences between the 7 other beta-lactams.