Isepamicin is a semi-synthetic aminoglycoside antibiotic, which was developed by the addition of the (S)-3-amino-2-hyroxypropionyl side chain into the 1-amino group of gentamicin B. 

Clinically, the drug is used as a sulfate. Isepamicin has similar in vitro antibacterial spectrum to amikacin, and it is active against a small proportion of amikacin-resistant Gram-negative bacilli. Thus, it may be occasionally indicated as an alternative to amikacin for the treatment of infections caused by amikacin- and gentamicin-resistant but isepamicin-susceptible Gram-negative organisms.

Drug interactions

Isepamicin is inactivated less than gentamicin by high concentration of various penicillins and beta-lactamase inhibitors. It was found to be as stable as amikacin against inactivation by these beta-lactam compounds and beta-lactamase inhibitors. The in vivo inactivation by piperacillin of isepamicin was compared with gentamicin in patients on chronic hemodialysis. The pharmacokinetics of isepamicin was not altered during combination dosing with piperacillin. The terminal elimination half-life for isepamicin (47.9 vs 45.1 hours) was not significantly altered by concomitant administration with pipercacillin, whereas the values for gentamicin were significantly reduced by the presence of piperacillin from 47.7 to 35.7 hours. Such patients receiving combinations of isepamicin and various penicillins and beta-lactamase inhibitors will not require further dose adjustment.

Clinical Uses

Isepamicin, either alone or in combination with a beta-lactam antibiotic, has been used to treat severe infections, such as pyelonephritis, peritonitis, pulmonary infections, septicemia, and skin and soft-tissue infection caused by amikacin-susceptible Gram-negative bacilli and S. aureus. Efficacy and safety of treatment with isepamicin are similar to those with amikacin. However, the same efficacy concerns for monotherapy of gentamicin outside of urinary tract infections compared with beta-lactams may also apply to isepamicin. 

The development of isepamicin was fostered by the increasing frequency of AAC-6u-I-modifying enymes in Enterobacteriaceae that may be a result of increased use of amikacin in some areas. The incidence of these strains in Belgium, France, and Greece account for 39–73% of aminoglycoside resistance in Enterobacteriaceae in these countries. These strains are also common in South America, Latin America, and Japan . Isepamicin would be an attractive alternative for treating such infections in these countries. However, as some of these strains are still susceptible to gentamicin, most clinicians prefer to use the more familiar, and usually less expensive, gentamicin for the treatment of these infections. Nevertheless, on occasion, isepamicin may have a place in therapeutics as an alternative for the treatment of those infections caused by amikacin-resistant Gram-negative bacilli.