AMIKACIN, CEFTAZIDIME, AND FLUCLOXACILLIN AGAINST SUSPENDED AND ADHERENT PSEUDOMONAS-AERUGINOSA AND STAPHYLOCOCCUS-EPIDERMIDIS IN AN INVITRO MODEL OF INFECTION

Bacterial inocula were exposed as suspended cultures or as adherent biofilms on glass beads in a novel in vitro model of infection to oscillating drug concentrations mimicking human serum kinetics during clinical treatment. Amikacin was given once or thrice daily alone or in combination with ceftazidime or flucloxacillin against Pseudomonas aeruginosa or Staphylococcus epidermidis. Killing of adherent bacteria was significantly reduced during single-drug treatment compared with suspended bacteria (P < .001), and beta-lactams were more active than amikacin against both suspended and adherent bacteria (P < .01). Amikacin-beta-lactam combinations killed the inocula more rapidly and were consistently bactericidal against both suspended and adherent pathogens (P < .05). Once-daily dosing of amikacin produced greater initial killing than thrice daily dosing (P < .05), but both regimens were similarly effective after 48 h. The differences in antibiotic activity against suspended and adherent bacteria may relate to clinical failures in the treatment of foreign-body infections by bacteria sensitive to the administered antibiotics, as determined by standard susceptibility tests.