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In vitro tests were performed with Sch 21420 and Sch 22591 to determine (i) their activity in comparison to six other aminoglycosides against 343 clinical isolates, and (ii) whether synergy with penicillin G could be demonstrated with enterococci. In broth dilution tests, Sch 22591 was more active than the seven other aminoglycosides against Staphylococcus aureus, Enterobacteriaceae, and most nonfermenting gram-negative bacilli. Sch 22591 was as active as tobramycin against Pseudomonas aeruginosa. The activity of Sch 21420 was comparable to gentamicin, sisomicin, netilmicin, and tobramycin but greater than amikacin or kanamycin against S. aureus and most genera of Enterobacteriaceae. Sch 21420, amikacin, and kanamycin were (i) more active than the other five aminoglycosides against Proteus rettgeri and Providencia stuartii, but (ii) less active than the other five aminoglycosides against Neisseria gonorrhoeae, enterococci, most nonfermenting gram-negative bacilli, Proteus mirabilis, and Proteus morganii. Studies on the bactericidal activity of Sch 22591 with penicillin indicated a synergistic interaction against enterococci, including strains highly resistant to streptomycin and kanamycin. This could be demonstrated with combinations containing 3.0 to 6.0 mug of Sch 22591 per ml and was comparable to that observed with penicillin/gentamicin. Penicillin plus Sch 21420 (25 mug/ml) also demonstrated synergy against enterococci, including strains highly resistant to streptomycin. However, synergy did not occur against strains highly resistant to kanamycin. These latter results were similar to those obtained in tests with penicillin/kanamycin.

In Vitro Studies with Sch 21420 and Sch 22591: Activity in Comparison with Six Other Aminoglycosides and Synergy with Penicillin Against Enterococci