Bacterial resistance gentamicin

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. 

These depend on the fact that bacterial resistance to aminoglycosides (Chapter 13), such as gentamicin, tobramycin, amikacin, netilmicin, streptomycin, spectinomycin, etc. and chloramphenicol is frequently associated with the presence of specific enzymes (often coded for by transmissible plasmids), which either acetylate, adenylylate or phosphory-late the antibiotics, thereby rendering them inactive (Chapter 13). Aminoglycosides may be susceptible to attack by aminoglycoside acetyltransferases... 

It was once believed that gentamicin would be very unlikely to cause bacterial resistance (SED VII, p. 376). Many reports have since then appeared from hospitals in several countries on the emergence and spread of gentamicin-resistant bacteria (SED VIII, p. 618), demonstrating that the antibiotic does not constitute an exception to the general rule that widespread or indiscriminate use of an antibiotic favours the development of microbial resistance. 

Since tobramycin is a broad-spectrum antibiotic its application may be followed by bacterial colonization of the patient with resistant organisms (27 ). So far, the clinical use of tobramycin has only occasionally been reported to be followed by the development of bacterial resistance. On theoretical grounds and on the basis of a comparison with gentamicin it can be presumed that widespread or indiscriminate use of tobramycin will be associated with the risk of the development of bacterial resistance due to resistance factor coding for a number of bacterial enzymes inactivating aminoglycosides and probably other antibiotics as well. 

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 . 

Neomycin is a topical aminoglycoside widely nsed for skin wounds and in otolaryngology. Its antibacterial activity resembles that of gentamicin and tobramycin, except that P aeruginosa, S. pneumoniae, and the a-hemolytic streptococci are generally resistant. Neomycin s usefnl-ness for treating acnte bacterial conjunctivitis is limited... 

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

Amikacin is mainly of value because it is more resistant to aminoglycoside-inactivating bacterial enzymes than is gentamicin. Since it is more costly, amikacin is reserved for treatment of infections with gentamicin-resistant organisms. Peak plasma concentrations should be kept between 20-30 mg/1 and trough concentrations below 10 mg/1. 

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. 

Bacterial Endocarditis Streptomycin and penicMn in combination are synergisticaUy bactericidal in vitro against strains of enterococci, group D streptococci, and the various oral streptococci of the viridans group. A combination of penicUhn G and streptomycin may be indicated for treatment of streptococcal or enterococcal endocarditis. Streptomycin largely has been replaced by gentamicin but may still be used when the strain is resistant to gentamicin and susceptible to streptomycin. 

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-,... 

T. I. Nicas and R. E. W. Hancock, Outer membrane protein HI of Pseudomonas aeruginosa involvement in adaptive and mutational resistance to ethylenediaminetetraacetate, polymyxin B, and gentamicin, J. Bacterial, 143 (1980) 872-878. 

---