Netilmicin Aminoglycoside

General Antibacterial Properties. In the clinical control of bacterial infectious disease, the aminoglycosides gentamicin, tobramycin, amikacin, netilmicin, and to a lesser extent, dibekacin and isepamicin are most commonly used for the treatment of serious infections involving aerobic or facultative gram-negative baciUi, especially in the compromised host. This usage is discussed in the Hterature (44—51). 

The aminoglycosides include amikacin (Amikin), gentamicin (Garamycin), kanamycin (Kantrex), neomycin (Mycifradin), netilmicin (Netromycin), streptomycin, and tobramycin (Nebcin). 

Table 1.19. Some aminoglycoside antibiotics which have gained significant therapeutic application. Producer microorganisms are listed in brackets. In addition to naturally produced aminoglycosides, a number of semi-synthetic derivatives have also found medical application. Examples include amikacin, a semi-synthetic derivative of kanamycin and netilmicin, an N-ethyl derivative of sissomicin...

The aminoglycosides include streptomycin, gentamicin, tobramycin, netilmicin, kanamycin, amikacin, sisomicin, neomycin, paromomycin and others. Those are bactericidal antibiotics. This bactericidal activity is concentration dependent in contrast to the... 

Aminoglycosides amikacin sulfate gentamicin sulfate netilmicin sulfate paromomycin sulfate streptomycin sulfate tobramycin sulfate... 

They have a synergistic effect with aminoglycosides (e.g. gentamicin or netilmicin) and hence should be given concomitantly in pseudomonas septicaemia. They should however, not be mixed in the same syringe. Owing to the sodium content, high doses may lead to hypernatremia. 

The aminoglycosides include streptomycin, neomycin, kanamycin, amikacin, gentamicin, tobramycin, sisomicin, netilmicin, and others. They are used most widely against gram-negative enteric bacteria, especially in bacteremia and sepsis, in combination with vancomycin or a penicillin for endocarditis, and for treatment of tuberculosis. 

Structures of several important aminoglycoside antibiotics. Ring II is 2-deoxystreptamine. The resemblance between kanamycin and amikacin and between gentamicin, netilmicin, and tobramycin can be seen. The circled numerals on the kanamycin molecule indicate points of attack of plasmid-mediated bacterial transferase enzymes that can inactivate this drug. , , and , acetyltransferase , phosphotransferase , adenylyltransferase. Amikacin is resistant to modification at , , , and . 

In 1991, Cite most widely used aminoglycosides in medical practice were gentamicin, tobramycin, amikacin, and netilmicin. Other aminoglycosides used to a lesser extent include dibekacin, isepamicin. neomycin, astromicin, speclinoniycin, kanamicin A, sisoinicin, and streptomycin. 

Bacterial Resistance Mechanisms. The most common resistance mechanism involves the inactivation of the aminoglycoside by reactions cat alyzed by plasmid borne enzymes. In general, amikacin and isepam icin tend to be least susceptible to inactivation by this mechanism, while netilmicin and dibekacin are intermediate and gentamicin and tobramycin are most susceptible. Less common resistance mechanisms include decreased affinity for the antibiotic by the bacterial ribosome, and decreased rate of transport into the bacterial cytoplasm. 

It is important to monitor peak and trough plasma levels (see p. 20) of gentamicin, tobramycin, netilmicin, and amikacin to avoid concentrations that cause dose-related toxicities (Figure 31.7). [Note Peak levels are defined as those obtained 1/2 to 1 hour after infusion. Trough levels are obtained immediately before the next dose.] Patient factors, such as old age, previous exposure to aminoglycosides, gender, and liver disease, tend to predispose patients to adverse reactions. The elderly are particularly susceptible to nephrotoxicity and ototoxicity. 

Netilmicin is a semisynthetic aminoglycoside which is active against some strains of bacteria that resist gentamicin and tobramycin evidence suggests that it may be less oto- and nephrotoxic. 

After administration of the recommended doses of amikacin for 10 days, renal damage probably occurs in less than 10% of cases. Limited data support the view that amikacin is less nephrotoxic than other aminoglycosides, possibly because of lower binding affinity to proximal tubular cells or reduced potential to cause phospholipidosis (SEDA-20,236). In several prospective randomized studies the liability of amikacin to cause nephrotoxicity was no greater than that of gentamicin or tobramycin (6-8). In a prospective study there was significantly lower nephrotoxicity with amikacin 15 mg/kg/day (4% toxicity) compared with netilmicin 7 mg/kg/day (12%) (9). As with other aminoglycosides, renal toxicity is reversible in most cases (10). 

With regard to this effect, neomycin is the most potent member of the group. Several deaths and cases of severe respiratory depression due to neomycin have been reported (11). Severe clinical manifestations are rare in patients treated with aminoglycosides that are administered in low doses, such as gentamicin, netilmicin, and tobramycin. In some cases the paralysis was reversed by prostigmine. 

There are interesting differences in the toxicity patterns of aminoglycosides in animals. Gentamicin and tobramycin affect the cochlear and vestibular systems to a similar extent, while amikacin, kanamycin, and neomycin preferentially damage the cochlear and streptomycin the vestibular system. Netilmicin appears to be the least toxic (26,27). 

In man, differences in the ototoxic risks of the currently used aminoglycosides are difficult to evaluate (20). There have been no prospective comparisons of more than two drugs using the same criteria in similar patient populations. However, several controlled comparisons of two aminoglycosides are available and provide some information. A survey of 24 such trials showed the following mean frequencies of ototoxicity gentamicin 7.7%, tobramycin 9.7%, amikacin 13.8%, netilmicin 2.3% (28). There was also a lower incidence of netilmicin-induced inner ear damage compared with tobramycin in two studies (29,30). 

Although aminoglycoside antibiotics are dialysable, peritoneal dialysis may not remove aminoglycosides from the blood after overdosage (171). However, hemodialysis is effective (172). In one study in eight patients hemodia-filtration removed more netilmicin than conventional hemodialysis (173). 

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