Monday, October 17, 2016

Pip-Taz dosing

PulmCCM - October 14, 2016 By JE
..."There is surprisingly little data pertaining to the pharmacokinetics of pip-tazo in the critically-ill patient population. In one small investigation, trough levels of pip-tazo demonstrated significant variability in those with normal renal function. Further, in critically-ill patients with normal renal function and moderately-impaired renal function, the administration of pip-tazo 4.5 grams every 6 hours and every 8 hours, respectively, lead to insufficient plasma levels.
Pip-tazo, like other beta-lactam antibiotics, exhibit time-dependent antibacterial activity; that is, efficacy is related to the absolute duration that the antibiotic remains above the minimum inhibitory concentration [MIC] of the pathological organism of interest.
In the critically-ill, there are multiple mechanisms by which pip-tazo [and beta-lactams, in general] can fall below the MIC when dosing is intermittent. These alterations includean increase in both the apparent volume of distribution, as well as, clearance of the antibiotic. Consequently, administering beta-lactams as a continuous infusion has been shown to increase time above the MIC and amplify bacterial annihilation. Nevertheless, in ameta-analysis which included patients with non-severe sepsis [i.e. patients likely not labeled as septic by the new definition], no significant difference in mortality was found between patients who received continuous infusion versus intermittent beta-lactam dosing..."