Resistance factors: influence on netilmicin activity

Netilmicin is active against many but not all bacterial strains that have acquired resistance to aminoglycosides. Generally, netilmicin is 1) active against strains that produce enzymes inhibiting aminoglycosides by phosphorylation or adenylation. Some of these enzymes are widely distributed in aminoglycoside resistant strains, e.g. the adenylating enzyme ANT(2") predominating in resistant Klebsiella and common in resistant Pseudomonas and Serratia strains. Netilmicin either lacks the hydroxyl groups that are the targets for these enzymes or blocks the enzymes through steric hindrance, e.g. by an ethyl group being added to an amino group of the 2-deoxystreptamine. 2) Netilmicin is active or not active against strains producing acetylating enzymes depending on the specific type of enzyme. Thus netilmicin is variably active against strains producing the frequently occurring enzymes of the AAC(3) group mainly found in Pseudomonas but also among Enterobacteriaceae. Providencia and Proteus rettgeri synthesizing AAC(2') are resistant to netilmicin. Bacteria producing enzymes that will acetylate the amino group in the 6' position may be resistant to all currently used aminoglycosides. These enzymes are mainly found in Pseudomonas, Serratia and Staphylococcus. 3) Netilmicin is not active against bacteria resistant to all other aminoglycosides due to reduced cell wall permeability.