CA Data last updated: Tue Mar 15
However, both intrinsic and acquired mechanisms of resistance to aminoglycosides have occurred. Aminoglycoside resistance among gram-negative organisms can occur through acquisition or upregulation of genes that encode inactivating enzymes or efflux systems. The resistance of gram-negative organisms to aminoglycosides occurs by two major mechanisms: Bacterial production of inactivating enzymes.
Methylation of 16S ribosomal RNA. This effect is mediated by an enzyme encoded by the rmtA gene and has been associated with high-level resistance to all parenteral aminoglycosides in current use.
Binding to the aminoacyl site on 16S ribosomal RNA is the mechanism by which aminoglycosides normally interfere with protein synthesis.
Enterococci are intrinsically resistant to low to moderate levels of aminoglycosides. However, the potential for synergy exists when enterococci with low-level resistance to an aminoglycoside are exposed to a combination of the aminoglycoside with a cell wall active agent, such as penicillin or vancomycin.
The significance of such high-level resistance is that it eliminates the synergism expected between an aminoglycoside and a cell wall active agent. Different genetic mutations are responsible for high-level resistance to different aminoglycosides. While cross-resistance between the specific aminoglycoside agents does occur, it is incomplete.
Therefore, individual agents should be tested for susceptibility against the isolated pathogen whenever possible. Dose adjustments need to be made in a variety of special populations. Renal Impaired Patients Peritoneal dialysis Gentamicin and tobramycin are frequently used for empiric treatment of continuous ambulatory peritoneal dialysis CAPD related peritonitis.
Patients Acc 206 week 1 dq 2 systemic illness may receive an intravenous loading dose. Therefore, patients undergoing intermittent hemodialysis generally require supplemental doses of gentamicin or tobramycin after each dialysis depending on the time lapsed after the first dose and characteristics of the dialysis delivered.
Continuous AV hemofiltration Similar to that observed in patients with intermittent hemodialysis, significant inter-patient variability exists among patients undergoing continuous arteriovenous AV hemofiltration. Empiric initial daily gentamicin or tobramycin doses of 2.
Cystic Fibrosis Patients Both the volume of distribution and clearance of aminoglycosides are greatly increased in patients with cystic fibrosis, necessitating higher starting doses with both traditional intermittent and extended-interval dosing to achieve target serum concentrations.
Burn Patients Patients with significant burns may exhibit larger volumes of distribution when compared with most patient populations.
As a result, larger maintenance doses of gentamicin and tobramycin per day in divided doses may be needed to attain therapeutic serum aminoglycoside concentrations. Serum concentration monitoring and individualized dosing correlates with survival in this patient population.
Septic Patients Septic patients undergoing aggressive fluid resuscitation in the setting of resolving or evolving acute renal failure often warrant especially close monitoring.
Some suggest individualized monitoring for such patients. Peak concentrations of aminoglycosides may be affected by high volumes of intravenous fluids or extravascular fluid shifts, requiring adjustments in the determination of pharmacokinetic parameters such as volume of distribution.
Reduced muscle mass and the resulting reductions in serum creatinine concentration in the elderly may result in overestimation of renal function when formulas such as the Cockcroft-Gault equation are utilized.
Therefore, a relatively normal serum creatinine may be associated with a substantial loss of renal function in this patient population. Synergy for Gram-Positive Infections Lower concentrations of aminoglycosides are targeted when used in combination with other agents to treat serious gram-positive infections, whether traditional intermittent or extended-interval dosing intervals are used.
Ideal body weight IBW also may be used to determine doses for patients who are neither underweight nor obese. Hepatic Impairment No dosage adjustment for aminoglycosides is necessary since they do not undergo hepatic metabolism. Administration Administer by intermittent infusion over 30 to 60 minutes.
Higher doses are generally administered over 60 minutes. Flush line with appropriate solution both before and after administration of the aminoglycoside.
Inject deep IM into large muscle mass, e. The first steps in aminoglycoside administration include determination of the dosing weight and estimation of renal function.
Parenteral aminoglycosides can be administered using a traditional intermittent dosing strategy which uses smaller doses given several times each day or an extended-interval dosing strategy which uses high doses administered at an extended interval. These two strategies have comparable efficacy and safety.
High dose extended-interval administration takes advantage of the pharmacodynamic properties of aminoglycosides and offers greater ease of preparation, administration and monitoring. For most patients with suspected or documented moderate to severe infections due to gram-negative aerobic bacteria in whom an aminoglycoside is being used and who are expected to exhibit more predictable aminoglycoside pharmacokinetics, extended-interval rather than traditional intermittent dosing is preferred.
Certain patient groups may exhibit altered aminoglycoside pharmacokinetics that could render extended-interval dosing less useful or effective.SOC SOC Week 3 Quiz ANSWERS. Secularism: Since the s, the highest percentage of immigrants to the United States have come from: In a presidential system:vetconnexx.com · reviews of Ashford University written by vetconnexx.com Collaborating doctor list List of collaborating doctors likely to be open to working with a reproductive immunologist.
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