Gram Negative Enterococcal And Myobacterial Infection Diseases Biology Essay

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Their isolation causes a great revolution against sever bacterial infections and their treatment. But their toxic effect was limiting their use and always make their use according to the risk benefit ratio as the aminoglycosides known to cause nephrotoxicity and ototoxicity specially when use for long term treatment. Due to the aminoglycosides low prices and their bactericidal value they are prescribed the most all over the world (10). While their toxic effect still considerable as they cause for 15-20% of patients deaf (10), and occurrence of renal damage from 5-15% of cases (5).

The most common aminoglycosides used in infection treatment which cause the significant toxicity are Amikacin, Gentamicin, Neomycin, Streptomycin and Tobramycin. They generally cause damage for vestibular and cochlear cells of the ear, kidneys proximal tubular dysfunction and also neuromuscular receptors obstruction if given to the patient fast in the artery (1).

The previous harmful effects of aminoglycosides did not prevent their use even though there are several drugs which consider safer but those other antibacterial drugs with the extended therapy cases a resistance produced against these drugs and make the importance of aminoglycosides increased and the search for reduction of their toxicity become superior (7). So in order to achieve better infection treatment with the minimum risk there are new ways and method of treatments are used when it deals with the aminoglycosides. So the aminoglycosides mechanism of toxicity can be the way to prevent and avoid their harm effect as they still have significant antibacterial effect.

The aminoglycosides are group of agents that consist of sugar part (amino sugar) and non sugar part (hexose nucleus) coupled together by glycosidic link (5). This structure of the aminoglycosides is the reason for the hydrophilic character of them which make the aminoglycosides have high affinity to the nucleic acids. Ginpaolo Perletti and his coauthors said in their article that the aminoglycosides antibiotics depend on their action on the induction of mutations of translation of the bacerial DNA by incorrect coupling of non-cognate TRNAs of the bacteria (5). There were new agents that was proved as non toxic or without the aminoglycosides sever side effects and with a wide therapeutic window against bacteria with the advantages of good absorption from the gastrointestinal tract when given orally. These new agents as floroquinolones change the aminoglycosides clinical use as antibiotics of choice for treatment and that minimize their toxic manifestation ( 7). But the use of floroquinolones and the other new drugs did not stop totally the use of aminoglycosides, the resistance of the bacteria and severity of the infections which back the light spot again for the aminoglycosides. (7).

The aminoglycosides mechanism of action on the bacteria as they suppress the protein formation by interfere with the translation ansd transcription of the double non-cognate tRNAs of the bacteria what make the aminoglycosides able for that the hydrophilic parts of the structure of these compounds make them act as weak alkaline at PH of the host body that leads to a high empathy for the nucleic acid and 16S ribosomal RNA (7). For that activity aminoglycosides and their concentration charge outcome they still show successful bactericidal action against serious gram negative enteriococcal and myobacteria strains of these microorganisms. Also they are useful when shared with other b-lactams for infections reach by the blood. The use of them alone can be effective in cases of the urinary tract infection. Another goal that aminoglycosides done they show major treatment result of multi drug resistant microorganism as multi drug resistance tuberculosis. (7)

As mentioned before the aminoglycosides have main toxic side effects which bound their utilization. The main harmful consequences of them are the production of liability of loss hearing and damage of the kidney and these destructive actions of aminoglycosides lead to a significant harmful un comfortable health of the patients and notable abnormal life style according to the effect of the treatment even the use of mechanical aid for hearing or precaution should be considered with the patient who suffer from the renal damage.

Ototoxicity one of the major problems caused as side effects of some drugs frequently used for clinical treatment. The most drugs that bring the hearing loss or hearing cells injury are aminoglycosides, salicylates, loop diuretics and quinines (4). From all these drugs the most ototoxic are the aminoglycosides, the sub-types of aminoglycosides that most frequency cause the damage for hair cells are kanamycin, amikacin, neomycin and dihydrostreptomycin mainly cause cochlear cell damage. The drugs affect the vestibular cells are streptomycin, tobramycin and netilmicin. While the drug which affect both is gentamycin. The reason for that aminoglycoside cause 66% of cases to have hearing-impaired, 33% of cases have significant hearing changes for worse and 4% of vestibular toxicity even after one dose of treatment that the slow removal of the aminoglycosides present at the inner ear (4,7). As they remain at the inner ear for 4-6 months after cutting of treatment, so their effect on the haring cells can be less danger if the exposure of them was fast ended but that reason what increase their rate of toxicity (3,4,7).

The aminoglycosides (AGs) induced toxicity mainly caused due to the high dose and long time of contact at the inner ear even after the therapy end. The presences of the AGs cause activation of apoptosis of the inner ear cells. The free radicals generated by the AGs are the primarily reason for toxicity, as the oxygen and nitrogen free radicals push the cell to different pathways of apoptosis. The first way by liberating the apoptogenic factors from the mitochondria into the cell to activate caspases. While the second way is attaching of the free radicals to the death receptors; Fas and TNFR1. (3, 7). Other study showed that the Gentamicin cause restriction of the nuclei of the outer auditory cells causing rupture of the mitochondria. This way is induced by the oxygen free radicals generated from AGs and protein. The gentamycin increase the calcium inside the cells which also bring on the death of the cell. (3). The topical AGs, in case of infection of the round window membrane the permeability due to the toxins of the bacteria, so the absorption of the topical AGs increased so toxicity increased(3).

The AGs toxicity vary from person to person, some persons the long course of treatment cause damage of the hair cells while others the single dose can lead to deaf. The individuals with risk factors that control the toxic effect of AGs are those with renal problems as their clearance rate is decreased than the normal individuals also the elderly persons whose their organs are at their age are insufficient producing their functions(4). Also the persons with hearing problems history and the hypertension patients treated with loop diuretics or any other drugs having harmful effect on the kidney(4).

Because of the permanent harmful effect of the AGs the early detection of these effects can prevent further complications which finally lead to hearing loss. The patient who is liable for the toxic effect of AGs suffer from symptoms begins with lower frequency and whispers hearing loss and if the toxicity not determined the loss increased till deaf. The vestibular toxicity characterized of unclear vision with loses of the ability to balance the body while moving specially at dark. These are the early symptoms which indicate the toxic effect of AGs. (4)