Kanamycin, bacterial resistance

Capreomycin (capasiat) is an antimycobacterial cyclic peptide elaborated by Streptococcus capreolus. Bacterial resistance to capreomycin develops when it is given alone such microorganisms show cross-resistance with kanamycin and neomycin. Capreomycin is used only in conjunction with other appropriate drugs in treatment of pulmonary tuberculosis when bactericidal agents cannot be tolerated or when causative organisms have become resistant. 

Indiscriminate use of amikacin may lead to bacterial resistance due to R-factor coding for several enzymes inactivating aminoglycosides, including kanamycin acetyltrans-ferase (5 ). 

Antibiotic resistance profiles of the bacterial communities reflected the effects of deforestation and the land degradation (Fig. 2). The degradation was significant (p=0.05) as a source of variation for the numbers of soil bacterial cells resistant to lasalocid, penicillin, spectinomycin and trimethoprim, and marginally significant (0.50 Significant differences between two average values were observed for some antibiotics. When compared with the BG soil bacterial community, the DEF soil bacterial community had more bacterial cells resistant to dapson, kanamycin, lasalocid, nafcillin, penicillin, spectinomycin, streptomycin and trimethoprim. 

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. 

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 . 

Figure 9 Aminoglycoside antibiotic modifying enzymes. The aminoglycoside antibiotics such as kanamycin B (shown) bind to the 16 S rRNA of the bacterial ribosome impairing cognate codon-anticodon discrimination (A). Resistance occurs via acetylation (AAC), phosphorylation (APH), or adenylylation (ANT) of the antibiotic (B). A wide variety of enzymes are known with different regiospecificities of chemical modification, and the sites of some clinically important enzymes are shown in panel C.

Bacterial strain Resistance mechanism BB-K8 Kanamycin Gentamicin... 

In a leading cancer center in Houston, 24% of 758 Gram negative clinical isolates were resistant to tobramycin and 12% were resistant to amikacin (138). In 3144 bacterial isolates causing urinary tract infections in Chile, 74% were identified as Escherichia colv, 4.2% of these strains were resistant to gentamicin, and 1.3% were resistant to amikacin (139). In contrast, the resistance levels were 30% and 17% respectively, in the other enterobacterial strains. In Brazil, all isolates of methicillin-resistant S. aureus were also resistant to gentamicin, amikacin, kanamycin, neomycin, and tobramycin (140), and 97% of such strains from Spain were resistant to tobramycin (141). 

Amikacin is derived from kanamycin and has the broadest spectrum of activity of the aminoglycosides. It is less susceptible to bacterial enzyme inactivation than the other aminoglycosides, so it is usually reserved for therapy of gentamicin-resistant bacterial infections. 

As in the kanamycin series, an a-hydroxy-CO-aminoacyl group on the 1-amino moiety of a number of gentamicin—sisomicin analogues confers activity against resistant bacterial strains (169). Isepamicin (8, R = (3)-COCHOHCH2NH2) is the primary example of this type of modification. In contrast to the kanamycins, l-A/-acetyl sisomicin was resistant to inactivation by AAC(3) and ANT(2") (170). Other active l-AJ-acjiated derivatives have also been described (171,172). The naturally occurring 2 -A/-formylsisomicin is considerably less active overall than sisomicin itself (173). Guanjiation of the 1-, 3-,... 

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