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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 
 

Sisomicin, netilmicin and dibekacin. A review of their antibacterial activity and therapeutic use.

Sisomicin is a naturally occurring aminoglycoside antibiotic produced by Micromonospora inyoensis, while dibekacin and netilmicin are both semisynthetic aminoglycosides. Dibekacin is 3',4'-dideoxykanamycin B and netilmicin is 1-N-ethyl sisomicin. In both cases, these modifications render the agents insusceptible to some of the enzymes found in resistant strains of bacteria which inactivate the parent compounds. Antibacterial activity: All 3 drugs show bactericidal activity against a wide range of Gram-negative bacteria (including E. coli, Enterobacter, Klebsiella and Proteus spp. and Ps. aeruginosa) and also against staphylococci; however, in common with other amino-glycosides, streptococci are usually resistant (except when beta-lactam antibiotics are used in combination) and anaerobic organisms are not sensitive. Sisomicin is closely related structurally to gentamicin Cla, but in vitro studies have shown it to have superior activity to gentamicin against Ps. aeruginosa, closely paralleling the activity of tobramycin, while still possessing the high activity of gentamicin against Serratia and other Gram-negative rods. However, sisomicin is inactivated by virtually all bacterial enzymes which inactivate gentamicin and tobramycin. Nevertheless, it retains useful activity against a number of gentamicin-resistant strains of Ps. aeruginosa which are resistant by non-enzymatic (possibly permeability barrier) mechanisms; in this respect it closely resembles tobramycin. Dibekacin closely resembles tobramycin structurally and in vitro it seems to have a very similar antibacterial spectrum, including activity against some strains of Ps. aeruginosa resistant to gentamicin. Netilmicin has a generally broader antibacterial spectrum than gentamicin, tobramycin, sisomicin or debekacin and is resistant to inactivation by phosphorylating and adenylylating enzymes; however, it is inactivated by all acetylases, apart from acetylase 3-I. Its spectrum is therefore not as wide as that of amikacin against 'gentamicin-resistant' strains. Nonetheless, it is intrinsically more active than amikacin, weight-for-weight, against sensitive strains, apart possibly from Ps. aeruginosa. In fact, its activity against species of the Enterobacteriaceae and staphylococci sensitive to gentamicin is of the same order as the latter and possibly better for Klebsiella-Enterobacter species. All 3 agents show marked antibacterial synergy with a variety of beta-lactam antibiotics against a range of bacteria. Pharmacokinetically, sisomicin, netilmicin and dibekacin all behave like gentamicin. All 3 drugs are excreted in the urine unchanged and have beta-phase elimination half-lives of around 2 to[1]

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