Aminoglycoside inactivating enzyme

It is semisynthetic derivative of kanamycin. It is active against gentamicin resistant organisms e.g. Pseudomonas aeruginosa, Klebsiella, E. coli and Proteus. It is resistant to bacterial aminoglycoside inactivating enzymes. 

Between the thin murein layer and the cytoplasmic membrane is the periplasmic space (see Figure 7.1). The jS-lactamase enzymes of Ps. aeruginosa are thought to be situated in the periplasmic space [43,44]. Evidence of this comes from enzyme liberation experiments after treatment of cells in various ways [45]. A number of aminoglycoside inactivating enzymes are also thought to be located in this space [46]. 

Table 7.17. AMINOGLYCOSIDE INACTIVATING ENZYMES PRODUCED BY STRAINS OF PS. AERUGINOSA...

A second approach has been to acylate amino groups in the aminoglycoside molecule. The acylation of kanamycin with L(-)-4-amino-2-hydrox ybutyric acid has led to the synthesis of BB-K8 [222]. This compound, which is extremely active, fails to act as a substrate for any of the aminoglycoside inactivating enzymes produced by Ps. aeruginosa. However, it has recently been shown that BB-K8 is acetylated by a strain of E. coli [111]. 

The spectrum of antimicrobial activity of amikacin (amikin) is the broadest of the group. Because of its resistance to many aminoglycoside-inactivating enzymes, it has a special role in hospitals where gentamicin- and tobramycin-resistant organisms are prevalent. 

Other enzymes that may play a role clinically are AAC(2 ), important in some Providencia and Proteus species, APH(3 ), and APH(3") (71). Others that have been observed include APH(2 ), APH(5 ), APH(6), ANT(4 ), ANT(3 ), and ANT(6). It has been suggested that, for effective resistance, an organism must have both impaired aminoglycoside transport and levels of aminoglycoside inactivating enzymes such that the rate of inactivation in the cytoplasm is greater than the rate of influx (68). 

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