5 1. 0 g q12h resulted in adequate drug concentrations to treat the GNB that were identified. However, for TZP, doses of 4. 0 g q12h resulted in insufficient selleck bio drug levels to treat Enterobacteriaceae and P. aeruginosa, and increasing the Inhibitors,Modulators,Libraries drug dose to 4 g q8h maintained TZP concentrations largely above the target threshold of efficacy. Finally, Malone et al. showed that although a cefepime regimen of 2 g daily was sufficient to cover susceptible GNB, higher doses of up to 4 g day were necessary for bacteria with MICs of at least Inhibitors,Modulators,Libraries 8 mg L. Similarly, Matzke et al. proposed that usual doses of ceftazidime be administered to maintain drug levels above the target threshold for pathogens with high MICs.
On the basis of these findings, recent recommendations propose daily doses of 1 g q12h for MEM, 2 g q12h for CEF and 4 g q8h for TZP, with minor alterations if CVVH or CVVHDF techniques are used. However, these studies were limited by small patient cohorts, by the use of different CRRT devices and techniques, by the analysis Inhibitors,Modulators,Libraries of stable pre defined CRRT settings and by the evaluation of various MIC targets. Hence, these data are difficult to generalize to larger ICU populations, may not be relevant if CRRT settings are modified over time, which is common practice, and may not provide an adequate daily dose for the treatment of less susceptible GNB. Indeed, Seyler et al. showed that these recommended doses resulted in adequate B lactam antibiotics concentrations only for pathogens with low MICs and that increased drug doses should be considered in the treatment of less susceptible strains.
However, although such an approach may limit underdosing if P. aeruginosa or other less susceptible strains are implicated, for more susceptible pathogens, drug regimens may need to be reduced. Moreover, more than 50% of samples in our study revealed very high drug concentrations in both ET and LT phases. Drug accumulation Inhibitors,Modulators,Libraries and excessive B lactam antibiotic concentrations may lead to adverse events, including Inhibitors,Modulators,Libraries neurological toxicity. Hallucinations, confusion, and seizures have been reported as a consequence of high B lactam antibiotic concentrations, mostly in patients with renal impairment, but also in patients with normal kidney function. The mechanism of cerebral toxicity seems to be related to the drug interaction with the GABA A receptor and is concentration dependent.
Smith et al. reported a case of cefepime related seizures during CRRT in a septic shock patient with a plasma concentration of 73. 8 mg L, but cerebrospinal fluid levels of 6. 1 mg L. seizures resolved selleck chemical after drug discontinuation. Chapuis et al. described two patients who developed seizures with trough cefepime concentrations 20 mg L. We did not collect neurological data in our patients so cannot relate drug levels to neurological complications. With the high PK variability among patients, an important finding of our study is the correlation between CRRT intensity and drug CL.
Related posts:
- In some instances, maximal drug concentrations do not completely decrease the bi
- Higher concentrations of SFN trigger extensive caspase mediated a
- AZD2171 reduced drug uptake and increased drug efflux related
- It is actually adequate to supply a chemotactic response resembled erm Thus, we
- We handled these cells having a series of FCdR concentrations Su