Intravegetation Antimicrobial Distribution in Aortic Endocarditis Analyzed

Posted by James

Therapeutic outcomes in humans with aortic valve endocarditis remain relatively poor, particularly with virulent valvular pathogens (eg, Staphylococcus aureus and Pseudomonas aeruginosa). Aminoglyco- side-based regimens have not had a major salutary impact on the outcomes of treatment of these latter endocarditides, despite in vitro susceptibilities of these bacterial strains to such agents. This subopti- mal efficacy of aminoglycosides in human endocarditis has suggested potential impairment in either intraveg­etation penetration or distribution of these agents within cardiac vegetations.

We recently showed that the pharmacokinetic and pharmacodynamic characteristics of overall penetra­tion of an aminoglycoside (amikacin) and a B-lactam (ceftazidime) into experimental aortic valve vegeta­tions were inferior to those obtained within tricuspid valve vegetations. However, since these data involved profiles of intravegetation penetration of the antibiotics into the vegetation as a whole, we were not able to measure or calculate point concentrations of the drugs at various sections of the vegetation. The current study was designed to examine the effect of differing regi­mens of an aminoglycoside (amikacin) upon drug levels at specific regions within a typical vegetation for both human and experimentally induced aortic vegetations infected with P aeruginosa. For this investigation, we used previously defined, overall intravegetation levels of amikacin in an integrative computer-generated model to estimate concentrations of the drug in the center, as opposed to the more peripheral parts, of the aortic vegetation, and we compared these values to the in vitro MBC of the infecting bacterial strain. cialis professional