Clinical indications of AMG & PK/PD optimization of Antibiotic therapy

Vancomycin induce hearing lost is controversial. Vancomycin has not been found to be ototoxic in animal models. The guideline recommends that we can consider monitoring vancomycin level for patients’ receiving additional ototoxic agents, such as aminoglycosides. To summarize the 2009 vancomycin consensus, evaluating troughs alone is suboptimal method of assessing the adequacy of vancomycin dose. Although an estimation of the AUC is recommended, but because of the difficulty of gathering the information to calculate AUC to MIC ratio, the trough level can be used as a surrogate marker of AUC.

Here is a table that might help you better understand the weight interpatient vary ability with figure to vancomycin pharmacokinetics. We have average weight, over weight, and under weight patients. We may have patient with fast or slow vancomycin elimination, which they all have their individual clearance. You can see that we might have a patient can have a trough level of only 9.5, but achieving a target AUC to MIC of 400. On the other hand, if we try to increase the dosing in order to get a trough level in the acceptable range. in this case for example, we increase the dose from 1000mg to 1500mg, in order to get the trough from 9.5 to 15.

It may not always translate to achieving a target AUC to MIC if the MIC is high. Next, let’s briefly talk about aminoglycosides. Aminoglycosides antibiotics were first discovered in 1940s. So, like vancomycin is a pretty old medication we have been using. They work by binding to ribosome RNA and thus inhibit the bacteria protein synthesis. They are bactericidal against most gram-negative pathogen, such as Acinetobacter, E. Coli, Klebsiella, and Pseudomanas. The side effects of aminoglycosides are similar to vancomycin, which included renal and auditory toxicity. And these toxicities have led to decline of their use in the 1970s-80s, because of the availability of less toxic agents with comparable efficacy, and without the need for saving job concentration monitoring.

However, today the aminoglycosides are still seen in practice, because of their high efficacy, their good successability, and their low cost. Clinical use of aminoglycosides. We will rarely see aminoglycosides use as a monotherapy because of their poor tissue penetration. Usually they are using in combination either as a double coverage for serious gram-negative infection, such as Pseudomanas’ infection. or use as a synergy infect with a beta-lactam for gram-positive infection, such as enterococcal or streptococcal infection. For example, if you remember that we commonly gives aminoglycosides in the endocarditis treatment regiment in combine with maybe a third generation Cephalosporin. That’s the synergy infect we are utilizing.