Aminoglycosides response

Discuss ways to promote an optimal response to therapy, how to manage adverse reactions, and important points to keep in mind when educating patients about the use of a fluoroquinolone or aminoglycoside. 

An enzymic assay involving the reaction of neomycin with aminoglycoside 4 adenyltransferase has been described l. a linear response for neomycin was observed over the range 2.5 to 20yg/ml serum. 

Similar well-shaped responses have been obtained at a gold electrode using the aminoglycoside neomycin (neomycin sulfate), which is a positively charged promoter favouring the electrostatic interaction with negatively charged proteins.36... 

Figure 3.2. A representative RND efflux pump system. This system is comprised of three essential components The RND pump (e.g., AcrD and MexX) is located on the cytoplasmic membrane and is responsible for the recognition of substrates in the cytosol, including aminoglycosides, and moving them into the periplasmic space. The membrane fusion protein (MFP) (e.g., AcrA and MexY) is responsible for moving the substrate across the periplasm the final component is the outer membrane factor (OMF) (e.g., TolC and OprM) that provides a conduit for the substrate to the extracellular region of the cell.

Like the protein and inositide kinases, the 3D structures of APHs display two distinct domains The N-terminal P-sheet region is responsible for ATP binding, and the a-helical C-terminal provides the aminoglycoside recognition site. The active site, where phosphate transfer occurs, lies at the interface of the two domains. APHs also contain the H-G/N-D-XXXX-N sequence motif, which is common among protein kinases and involved in phosphate transfer catalysis. Structural homology to protein kinases is extended to function, as it has been demonstrated that APHs have weak but measurable protein kinase activity. ... 

This difference in half-lives in serum and tissues was misinterpreted in the early literature as an accumulation of aminoglycosides in the inner ear and held responsible for their organ-specificity. Such an interpretation is, however, not tenable. Aminoglycoside antibiotics are present in the fluids (perilymph and endolymph) and the tissues of the inner ear at relatively low levels, typically at one-tenth of peak serum levels. The reason for the differential sensitivity of inner ear sensory cells may then be based on the extreme persistence of the drugs or on an intrinsic susceptibility to their actions, notably to the generation of reactive oxygen species as described later. ... 

The aminoacyl side chain of this drug, which is analogous to that of ceftazidime, is responsible for the high activity with respect to Gram-negative aerobic bacteria. The spectrum of use of aztreonam is very similar to the antimicrobial spectrum of aminoglycosides, and in the majority of cases it is a potential replacement. 

In response to the increasing prevalence of mycobacterial resistance to standard antibiotic chemotherapy, the use of aminoglycosides is increasing in patients at high risk for having resistant infections. Inhaled aminoglycosides may also have a role in patients with persistently positive sputum despite therapy. Streptomycin is useful in the initial therapy of severe or disseminated tuberculosis, which is most common in immunocompromised patients. 

B. A synergistic effect when the combination of an aminoglycoside and 3-lactam antibiotic are administered concurrently is well documented. The reasons for the synergistic response are not well documented but may be related to the actions of the 3-lactam antibiotic to raise pH and oxygen tension... 

Moore R, Lietman P, and Smith C. Clinical response to aminoglycosides Importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis 1987 155 93-99. 

Piepersberg W, Noseda V, Bock A (1979) Bacterial ribosomes with two ambiguity mutations effects of translational fidelity, on the response to aminoglycosides and on the rate of protein synthesis. Mol Gen Genet 171 23-34... 

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