Antibiotics amikacin

Singh YN, Marshall IG, Harvey AL. Some effects of the aminoglycoside antibiotic amikacin on neuromuscular and autonomic transmission BrJ Anaesth (1978) 50,109-17. 

Antibiotics Amikacin Gentamicin Netilmicin Tobramycin Chloramphenicol Vancomycin... 

The object of investigation was a chitosan (ChT) specimen produced by the company Bio progress (Russia) and obtained by acetic deacetylation of crab chitin (degree of deacetylation -84%) with M =334000. As the medicinal substance (MS) used an antibiotic amikacin (AM) quadribasic aminoglycoside, used in the form of salts sulfate (AMS) and chloride (AMCh). Chemical formulas of objects of research and their symbols used in the text are given in Table 13.1. 

A Acetylation, O-Phosphorylation, and O-Adenylylation. A/-Acetylation, O-phosphorjiation, and O-adenyljiation provide mechanisms by which therapeutically valuable aminocyclitol antibiotics, eg, kanamycia [8063-07-8] gentamicin [1403-66-3] sisomicin [32385-11-8], streptomycia [57-92-1], neomycin, or spectinomycin are rendered either partially or completely iaactive. Thus, eg, kanamycia B [4696-78-8] (50) can be iaactivated by modification at several sites, as shown. The elucidation of these mechanisms has allowed chemical modification of the sites at which the iaactivation occurs. Several such bioactive analogues, eg, dibekacia and amikacin have been prepared and are not subject to the iaactivation hence, they inhibit those organisms against which the parent antibiotics are iaeffective (96) (see Antibacterial agents, synthetic). 

Aminoglycosides. Antibiotics ia the amiaoglycoside group characteristically contain amino sugars and deoxystreptamiae or streptamiae. This family of antibiotics has frequentiy been referred to as aminocyclitol amiaoglycosides. Representative members are streptomycia, neomycin, kanamycia, gentamicin, tobramycia, and amikacin. These antibiotics all inhibit proteia biosynthesis. 

Enzymes transferring an acetyl moiety to one specific of several amino-groups of the aminocyclitol-aminoglycoside antibiotics (e.g. gentamicin, amikacin, kanamycin) are called aminoglycoside acetyltransferases... 

Fig. 5.10 Some aminoglycoside antibiotics A, streptomycin B, kanamycins C, gentamicins D, amikacin.

The most important of these antibiotics are amikacin, tobramycin, netilmicin and especially gentamicin. 

The steady-state maximum plasma concentration, Cmaxss, of gentamycin and tobramycin are 6 to 10 mcg/mL. The Cmax ss of amikacin is 25 to 30 mcg/mL. The Cmin ss of both gentamycin and tobramycin is 0.5 to 1.5 mcg/mL, while that of amikacin is 5 to 8 mcg/mL. In order for these drugs to be effective, it is important to closely monitor their therapeutic concentrations. An important observation of these antibiotics is that with prolonged therapy, the Cminsl, values increase. This increase is due to the renal impairment. In the case where Cmin ss is less than the desired Cmin ss, the dose may be insufficient. 

Newer examples of aminoglycoside antibiotics include amikacin, neomycin (Neosporin, Cortisporin), and tobramycin (TOBI, TobraDex). Injectable tobramycin is used in the treatment of serious infections at many body sites. It has also been formulated in an inhalable dosage form that has a very specific use to treat cystic fibrosis patients having Pseudomonas aeruginosa lung infections. In the form suitable for inhalation by the patient, it delivers the antibiotic directly to the site of infection. 

The range of antibiotic that can be measured is usually 0.01 to 1.00 ug antibiotic/mL and has been used for gentamicin, carbenicillin, ticarcillin and amikacin (44-46). The use of the EMIT system, to-date, has been in the clinical area and unrelated to measuring residues of antibiotics. The procedure has potential for residue analysis if interferences by non-specific factors can be overcome. 

Attaching fnnctionalities at the N-1 position of the 2-deoxystreptamine among kanamycin or neomycin class antibiotics, is one of the other most effective methods of reviving the activity against aminoglycoside resistant bacteria. This strategy has led to the development of semisynthetic amikacin that has an (5 )-4-amino-2-hydroxybutyryl (AHB) group at N-1 position. 

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... 

E. The patient has exudative pharyngitis, presumably secondary to group A streptococcus. Antibiotic treatment is indicated to reduce the duration and severity of symptoms and to prevent acute rheumatic fever. The antibiotic of first choice is penicillin V. Other reasonable alternatives are benzathine penicillin G, erythromycin, cephalosporin, clindamycin, azithromycin, and clarithromycin. Amikacin, lome-fioxacin, metronidazole, and netilmicin are not active against group A streptococcus. 

The antibioticogram analysis showed that in the long term AVL conditions, the microflora were resistant to the majority of antibiotics used and the application of these drugs were ineffective in about 50% cases, which led to the development of different broncho-pulmonary complications. The identified microorganisms showed mild resistance to amikacin, meropenem and polymyxin and total resistance to cephalosporins with exception of Staphylococcus spp. (Table 26.3). 

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 . 

The aminoglycoside antibiotics are discussed in Chapter 45. Kanamycin has been used for treatment of tuberculosis caused by streptomycin-resistant strains, but the availability of less toxic alternatives (eg, capreomycin and amikacin) has rendered it obsolete. 

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