107 Treatment of multiresistant Gram-negative non-fermentative infections in Cystic Fibrosis patients: more attention required to in vitro studies

Abstract

Due to the high degree of resistance to antimicrobial agents of Gram-negative nonfermenters bacilli isolated from CF patients, there are limited therapeutic options available. The present study evaluates the activity of the most frequently used antibacterial drugs, and the effect of combination of two antibiotic against multiresistant Gramnegative non-fermentative rods. The bactericidal effect was investigated by E-test on 48 multiresistant strains (16 P aeruginosa and 32 B. cepacia-complex) isolated over a period of 3 years from CF patients attending two Italian CF Centers. Meropenem, ceftazidime, tobramycin, were the most active inhibiting 77, 75, and 71% of strains respectively. Seventy-three out of 342 (21%) tested combinations showed a synergistic effect being meropenem + ciprofloxacin (25%) and tobramycin + ceftazidime/ticarcillin (19%) the most active associations against P aeruginosa. Ceftazidime + tobramycin (41%) and meropenem + tobramycin (34%) were the most active against B. cepacia-complex. The higher percentage of antagonistic effect was demonstrated for meropenem + cefepime/tobramycin (19%), ticarcillin + ciprofloxacin (19%) for P aeruginosa strains and cloramphenicol + cotrimoxazole (26%), meropenem + ciprofloxacin (25%), ceftazidime + tobramycin (22%) for B. cepacia-complex members. This study indicates that a choice of effective double antibiotic therapy cannot be made empirically for Gram-negative multiresistant infections. The addition of a second antibiotic was found to be potentially counterproductive, in fact 16% of tested associations resulted in antagonisms with loss of bactericidal effects. 4. Microbiology