Azlocillin was more active in vitro than ticarcillin or carbenicillin against 561 aminoglycoside-resistant strains of Pseudomonas aeruginosa collected from 74 hospitals distributed over a wide geographic area in the eastern United States. Azlocillin was compared with various other antimicrobial agents in discriminative animal models of Ps. aeruginosa pyelonephritis, osteomyelitis, endocarditis, and meningitis in a variety of mammalian species. Cefsulodin was more effective than azlocillin in reducing Ps. aeruginosa kidney concentrations in rat pyelonephritis induced by intrarenal inoculation. The mean±s.d. logl0 cfu/g kidney after three days of therapy were as follows: controls = 5.4±1.5, azlocillin = 4.4±1.8, cefsulodin = 2.6±0.9 (P < 0.01) but the MBC for the test strain was eight-fold higher for azlocillin (8 vs. 1 mg/l) and effective concentrations were maintained longer in rat serum for cefsulodin as against azlocillin. In addition, ticarcillin reduced kidney bacterial concentrations faster than azlocillin in a mouse pyelonephritis model induced by intravenous Ps. aeruginosa inoculation with subsequent iron loading. Azlocillin was less effective than tobramycin in experimental chronic Ps. aeruginosa osteomyelitis induced in rabbits by direct injection into the tibia. An azlocillin-tobramycin regimen was not more effective than tobramycin alone. After 28 days of therapy, the percentages of positive bone cultures after death were as follows: no antibiotic (controls) = 92%, azlocillin = 95%, tobramycin = 76%, azlocillin plus tobramycin = 60%. Both ticarcillin and azlocillin were less active than tobramycin in experimental Ps. aeruginosa endocarditis induced in rabbits by intravenous inoculation of 108 cfu following 1 h of catheter induced aortic valve trauma. The best results were noted with an azlocillin-tobramycin regimen. The mean±s.d. log10 cfu Ps. aeruginosa/g vegetation after five days of therapy were as follows: no antibiotic controls = 8.1 ± 1.1, tobramycin = 4.5 ±0.8, ticarcillin = 6.9 ± 0.8, azlocillin = 5.7 ± 1.5, ticarcillin phis tobramycin = 4.9 ± 1.0, azlocillin plus tobramycin = 3.3 ± 1.6. Sterile vegetations were rarely attained with any regimen. The mean percentage penetration into purulent cerebrospinal fluid (CSF) in experimental Ps. aeruginosa meningitis for azlocillin was 13.3%, comparable to many other β-lactam antibiotics. Azlocillin was the single most active (P < 0.01) agent evaluated after 8 h intravenous infusions in this model. An azlocillin-amikacin regimen was more rapidly bactericidal (P < 0.01) than either agent alone in vivo. None of the agents evaluated alone or in combination, however, produced a sterile CSF after 8 h of therapy in any anima
