Sisomicin: An Aminoglycoside Antibiotic that is Highly Effective against Pseudomonas

Abstract

The in vitro activity of sisomicin against Pseudomonas is two- to eight-fold greater then gentamicin or amikacin, and similar to tobramycin. Minimal inhibitory concentrations of sisomicin are usually <1.0 μg/ml. Sisomicin interacts synergistically with a variety of penicillins against many Pseudomonas, including strains resistant to gentamicin. The degree of cross-resistance between sisomicin and other aminoglycosides varies depending upon mechanism. Many strains with inactivating enzymes are resistant to sisomicin, gentamicin and tobramycin. However, due to high intrinsic potency, sisomicin is active against many strains that are resistant to other aminoglycosides as a result of impermeability. Thus sisomicin is active against 4% to 66% of strains resistant to gentamicin, tobramycin or amikacin. The ability of sisomicin to protect animals from fatal Pseudomonas infections has been assessed in 29 paired tests with tobramycin and 36 paired tests with gentamicin. The dose of sisomicin in mg/kg required to protect 50% of animals from death is, on average, 1.5 times lower than tobramycin and 3.1 times lower than gentamicin. Sisomicin also interacts synergistically with carbenicillin or ticarcillin in treatment of experimental infections in animals. The human pharmacology of sisomicin is similar to gentamicin. Rates of adverse reactions to sisomicin are comparable to those seen with gentamicin or tobramycin. Clinical trials have shown sisomicin to be as effective, and in some instances more effective, than gentamicin, tobramycin, or amikacin. In several studies, the efficacy of sisomicin, administered in lower doses than gentamicin, was equal to or greater than gentamicin. Infections caused by gentamicin-resistant Pseudomonas have responded to sisomicin. Also, several patients who failed to respond to either gentamicin or tobramycin have been successfully treated with sisomicin. In view of its high intrinsic potency both in vitro and in vivo, sisomicin may become a preferred agent for treatment of serious Pseudomonas infections due to sensitive strains.