Aminoglycosides Aminoglycoside antibacterials

Mechanism of Action An aminoglycoside antibacterial that irreversibly binds to protein on bacterial ribosomes. Therapeutic Effect Interferes with protein synthesis of susceptible microorganisms. 

Mechanism of Action An aminoglycoside antibacterial that binds to bacterial microorganisms. Therapeutic Effect Interferes with bacterial protein synthesis. Pharmacokinetics Poorly absorbed from the GI tract following PO administration. Protein binding Low. Primarily eliminated unchanged in the feces minimal excretion in urine. Removed by hemodialysis. Half-life 3 hr. 

Clinical Use. Paromomycin (Humatin) is an aminoglycoside antibacterial (see Chapter 33) that is used primarily to treat mild to moderate intestinal infections (amebiasis).51 This drug may also be used as an adjunct to other amebicides during the treatment of more severe protozoal infections. Paromomycin is also effective against some bacteria and tapeworms, and may be used as a secondary agent in certain bacterial or helminthic infections. This drug is administered orally. 

There is an in vitro interaction between aminoglycoside antibiotics and carbenicUhn or ticarciUin, leading to a significant loss of aminoglycoside antibacterial activity if these antibiotics are mixed in the same infusion bottle (184). The extent of inactivation depends on the penicUhn concentration, the contact time, and the temperature. Azlocillin and mezlocUhn inactivate aminoglycosides in a similar manner to that described for carbenicUhn (185,186). Aminoglycosides should not be mixed with penicillins or cephalosporins in the same infusion bottle. 

The aminoglycoside antibacterials possess neuromuscular blocking activity. Appropriate measures should be taken to accommodate the increased neuromuscular blockade and the prolonged and potentially fatal respiratory depression that can occur if these antibacterials are used with conventional neuromuscular blocking drugs. 

The renal toxicity of cisplatin is potentiated by aminoglycoside antibacterials such as gentamicin and tobramycin. Extra care is required in patients treated with cisplatin requiring these antibacterials. In one retrospective analysis in patients taking cisplatin, hearing loss was not associated with the concurrent use of ototoxic drugs, including tobramycin. 

Cisplatin is nephrotoxic and it would appear that its damaging effects on the kidney are additive with the nephrotoxic effects of the aminoglycoside antibacterials. Both gentamicin and cisplatin may cause ototoxicity. Previous exposure to cisplatin caused a significant decrease in gentamicin clearance in rats. 

Not fully understood, but one suggestion is that any fall in blood calcium levels brought about by the use of clodronate is normally balanced to some extent by the excretion of parathyroid hormone, which raises blood calcium levels. However, the aminoglycoside antibacterials can damage the kidneys, not only causing the loss of calcium, but of magnesium as well. 

General Antibacterial Properties. In the clinical control of bacterial infectious disease, the aminoglycosides gentamicin, tobramycin, amikacin, netilmicin, and to a lesser extent, dibekacin and isepamicin are most commonly used for the treatment of serious infections involving aerobic or facultative gram-negative baciUi, especially in the compromised host. This usage is discussed in the Hterature (44—51). 

Members of the aminoglycoside class of antibacterial antibiotics retain an important role in the control of bacterial infectious disease, especially in... 

Norfloxacin (1, R = C2H5, R = H), a typical example, exhibits broad-spectrum activity and is useful in the treatment of upper respiratory tract and urinary infections [7] Lomefloxacin (2), a very recent introduction, is a third-generation product that, given once daily, is especially useful against pathogens resistant to cephalosponns, penicillins, and aminoglycosides [4] Floxacillin (J) is a stable, orally active antibacterial with improved activity over thenonfluonnated product (cloxacillin) [5]... 

The in vivo protective activity of rifaximin was studied in mice, infected experimentally by intraperitoneal inoculation of S. aureus Colliva and compared to that of rifampicin (a systemic rifamycin) and gentamicin (a poorly absorbed aminoglycoside) [74]. After oral administration, only rifampicin was effective whereas the other two compounds were inactive at doses up to 10 mg/kg. However, when injected subcutaneously, rifaximin displayed a good therapeutic efficacy (table 2). While confirming its antibacterial activity, these results clearly indicate that rifaximin, like gentamycin, is poorly absorbed after oral administration. 

Tetracyclines, macrolides, and aminoglycosides are important classes of antibacterials... 

The discovery of a novel structural class of antibacterials is notable, as these are few and far between. The sulfa drugs, p-lactams, quinohnes, tetracyclines, macrohdes, and aminoglycosides have been around for decades. Multiple improvements have been made over time in each of these classes but without breaking out into new structural classes. There are two notable, recent examples of new stractural classes of antibacterials and these are worth knowing about. 

Other key classes of antibacterials include the tetracyclines (Aureomycin, Terramycin), macrolides (erythromycin, Zithromax, Biaxin), and aminoglycosides (streptomycin, amikacin, neomycin). These antibacterials are protein synthesis inhibitors. 

Aminoglycoside a structurally complex antibacterial that works as bacterial protein synthesis inhibitor. 

The quinolone antibiotics feature as the one main gronp of antibacterial agents that is totally synthetic, and not derived from or based upon natural products, as are penicillins, cephalosporins, macrolides, tetracyclines, and aminoglycosides. The first of these compounds to be employed clinically was nalidixic acid more recent drugs in current use include ciprofloxacin, norfloxacin, and ofloxacin... 

The biochemical mode of action of the aminoglycosides as antibacterials has long been a topic of great interest. Early experiments carried out soon after the introduction of streptomycin suggested a variety of modes of action, but these conclusions were based largely on symptomatic analyses of antibiotic-treated bacterial cultures. One important experiment done in 1948 showed that streptomycin blocks enzyme indnction in susceptible bacteria this was the closest that anyone came to identifying the mechanism of action at the time. 

Aminoglycoside resistance has been a powerful impediment to the continued use of these potent antibacterial agents. The myriad of strategies that confer resistance... 

AND ANTIBACTERIAL ACTIVITY OF KANAMYCIN AND NEOMYCIN CLASS AMINOGLYCOSIDE ANTIBIOTICS... 

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