Gentamicin resistance

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. 

The purpose of this study was to adopt a systematic approach to optimize formulation and to characterize the properties of tobramycin-PMMA implants. Tobramycin was selected as it is active against both Gram-positive and Gram-negative bacteria, including gentamicin-resistant Pseudomonas. The specific aims of the study were... 

The evolution of MRSA strains is not fully understood, but the same mechanisms of mutation and gene transfer that exist in other species provide a likely reason. The emergence of gentamicin resistance plasmids illustrates the evolutionary potential of translocatable elements [186], MRSA strains which are also resistant to this aminoglycoside antibiotic are referred to as MGRSA. This evolutionary progression is also responsible for the formation of the -lactamase-heavy metal resistant plasmids [250]. Some MRSA isolates are penicillin-resistant by virtue of the enzyme /J-lactamase, which pre-dates the use of /8-lactams [251], However, the spread of the phenotype has probably arisen as a result of selection caused by the widespread usage of methicillin in hospitals. 

Increasing numbers, world-wide, of nosocomical (hospital-acquired) infections are caused by MRSA strains [255], Such strains particularly affect patients in intensive-care units [246], In the UK, gentamicin resistance suddenly appeared in 1976 and MGRSA strains caused severe major hospital outbreaks. It has been proposed [186, 227, 229] that, since resistance to nucleic acid-binding (NAB) compounds, such as chlorhexidine, amidines,... 

QACs, ethidium bromide and acridines was prevalent in the staphylococcal population long before gentamicin resistance emerged, then antiseptic resistance could be of particular significance in terms of the potential for the survival of these strains in the hospital environment. This aspect is considered later (see p. 181). 

An association between antibiotic resistance and chlorhexidine and QAC resistance in Providencia stuartii and Proteus has been observed, but no evidence of a plasmid link obtained [25, 73, 287,288]. Chlorhexidine hypersensitivity has been noted in ciprofloxacin-resistant variants of Ps. aeruginosa [289] and vancomycin- and gentamicin-resistant strains of E. faecium retained sensitivity to the /usbiguanide [289, 290] and to other biocides [270-272], Anderson et al. [272] studied the inactivation kinetics of VRE and vancomycin-sensitive enterococci (VSE) exposed to environmental disinfectants at concentrations well below (extended dilutions) the recommended use-dilutions and found no differences in susceptibility of VRE and VSE. This type of approach is much more relevant than the widespread usage of MICs to measure responses to biocides. 

Interaction between -lactamase and intrinsic resistance Resistance to aminoglycosides Resistance to kanamycins Resistance to neomycins Resistance to streptomycin Resistance to gentamicin Resistance to lividomycin Resistance to tobramycin Resistance to BB-K8 Resistance to chloramphenicoi... 

A recent report [195a] describes gentamycin adenyltransferase activity as a cause of gentamicin resistance in clinical isolates of Ps. aeruginosa. The enzyme appears to be similar to the adenylating enzyme isolated from Klebsiella and E. coli strains. 

Although many workers have reported that gentamicin resistant strains of Ps. aeruginosa are sensitive to tobramycin [170,218,219], complete cross-resistance between the two antibiotics was found in 1972 [220]. 

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. 

Kuhberger R, Piepersberg W, Petzet A, Buckel P, Bock A, Alteration of ribosomal protein L6 in gentamicin-resistant strains of Escherichia coli effects on fidelity of protein synthesis, Biochem, 1979,18(1) 187-92. 

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. 

Tobramycin is structurally related to kanamycin and has four times the activity of gentamicin against Pseudomonas spp. It is an extremely expensive drug. Its use in animals is usually limited to the topical treatment of melting comeal ulcers caused by gentamicin-resistant Pseudomonas spp. using the ophthalmic solution approved for use in humans. 

Wells VD, Wong ES, Murray BE, et al. Infections due to beta-lactamase-producing, high-level gentamicin-resistant Enterococcus faecalis. Ann Intern Med 1992 116 285-292. 

Netilmicin is useful for serious infections owing to susceptible Enterobacteriaceae and other aerobic gram-negative bacilli. It is effective against some gentamicin-resistant pathogens, with the exception of enterococci. 

The presence of diphtheroid-like gram-positive rods in the cerebrospinal fluid smear of an 82-year-old patient is indicative of the presence of Listeria monocytogenes. In addition to their role as a potential causative agent in neonatal meningitis, listeria infections are more common in elderly patients and in those who have been treated with immunosuppressive agents. Treatment consists of ampicillin with or without gentamicin. Resistant strains are rare. The answer is (A). 

Tobramycin is one component (factor 6) of a mixture produced by fermentation of Streptomyces tenebrarius. Lacking the C-3 hydroxyl group, it is not a substrate for APH(3 )-1 and APH(3 )-II and so has an intrinsically broader spectrum than kanamycin. It is a substrate, however, for adenylation at C-2 by ANT(2 ) and acetylation at C-3 by AAC(3)-I and AAC(3)-II and at C-2 by AAC(2 ) (Fig. 38.26). It is widely used parenterally for difficult infections, especially those by gentamicin-resistant Pseudomonas aeruginosa. It is believed by some clinicians to be less toxic than gentamicin. 

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