Compound A49759, the 3-O-demethyl derivative of fortimicin A: in vitro comparison with six other aminoglycoside antibiotics

O-Demethylfortimicin A (compound A49759) was tested against 445 bacteria, and the results were compared with those obtained with fortimicin A, amikacin, gentamicin, netilmicin, sisomicin, and tobramycin. A49759 was found to be active and bactericidal against the Enterobacteriaceae, nonfermentative gram-negative bacilli, and Staphylococcus aureus. A49759 was two- to fourfold more active than fortimicin A against most species tested, but generally fourfold less active than amikacin against this population of Pseudomonas aeruginosa (85% inhibited at less than or equal to 16 microgram of amikacin per ml and 85% inhibited at less than or equal to 64 microgram of A49759 per ml). Only amikacin and A49759 were resistant to most aminoglucoside-inactivating enzymes and also had significant antipseudomonal activity. Amikacin was inactivated by aminoglycoside 6'-acetyltransferase, and A49759 was inactivated by aminoglycoside 3-acetyltransferase. The minimal inhibitory concentrations of all tested aminoglycosides were increased by augmenting the inoculum size.