, Volume 27, Issue 6, pp 548–578 | Cite as

Sisomicin, Netilmicin and Dibekacin

A Review of their Antibacterial Activity and Therapeutic Use
  • Paul Noone
Review Article


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 I-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 aminoglycosides, streptococci are usually resistant (except when β-lactam antibiotics are used in combination) and anaerobic organisms are not sensitive. Sisomicin is closely related structurally to gentamicin C 1a, 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 3-1. 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 β-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 β-phase elimination half-lives of around 2 to 2.5 hours. As with other aminoglycosides, elimination is reduced proportionately by increasing impairment of renal function so that dosage intervals need to be extended. All patients should be monitored by assay of serum concentrations, especially those with renal failure, to ensure therapeutic levels and to minimise toxicity.

Clinical use: The 3 aminoglycosides have been used in a wide variety of infections, usually in hospitalised patients, many with immunocompromised conditions. Sisomicin has performed well in most clinical studies, including excellent results when treating compromised patients with difficult or refractory Ps. aeruginosa infections. In comparative studies, sisomicin has been shown to have a marginal advantage in efficacy when compared with gentamicin and tobramycin. Nephro- and ototoxicity have been similar or less in these studies. Unfortunately, no really large scale comparative studies have been undertaken, although it seems to be a generally more active compound than gentamicin and no more toxic. Probably the main reason for its overall lack of impact is its susceptibility to most of the enzymes which inactivate gentamicin and tobramycin.

Clinical studies with netilmicin have shown it to be a highly effective agent for life-threatening infections in immunocompromised hosts at doses similar to and greater than those normally used for gentamicin. One prospective controlled study showed netilmicin to be more efficacious in terms of eliminating pathogens than gentamicin, a difference seen most clearly with Klebsiella-Enterobacter infections and soft tissue sepsis (all pathogens being sensitive to both agents). In all carefully monitored studies, ototoxicity has been rare; in a prospective, randomised controlled trial, netilmicin was shown to be significantly less ototoxic than tobramycin. Cumulative prospective studies suggest also that netilmicin is probably less nephrotoxic than either tobramycin or gentamicin. This marginal improvement in terms of antibacterial spectrum, clinical efficacy and reduced oto- and nephrotoxicity suggests that netilmicin could well become the aminoglycoside of first choice. Netilmicin is certainly indicated wherever ototoxicity is more likely or is a less acceptable risk, e.g. dialysis patients, the blind, the elderly, neonates, and patients needing prolonged or repeated courses of aminoglycoside therapy (e.g. neutropenics and patients with malignant disease or receiving immunosuppressive therapy).

Dibekacin, in spite of its wide usage, has not been subjected to the same intensive controlled clinical studies as gentamicin, tobramycin, amikacin, netilmicin or even sisomicin. It is difficult to see, therefore, whether it offers any clear advantage over these other aminoglycosides. In general, dibekacin has to date been used at relatively low doses (in mg/kg) clinically, and perhaps better efficacy would be seen with larger doses, possibly of a similar order to gentamicin, with no greater nephrotoxicity and less ototoxicity. However, many gentamicin-, sisomicin- and tobramycin-resistant organisms are resistant to dibekacin as well, and this undoubtedly limits further intensive investigation of its clinical usefulness.


Gentamicin Aminoglycosides Amikacin Tobramycin Carbenicillin 
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Copyright information

© ADIS Press Limited 1984

Authors and Affiliations

  • Paul Noone
    • 1
  1. 1.Royal Free HospitalLondonEngland

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