Antibiotic Toxicity, Critical Illness, Sepsis, Septic Shock
Conditions
Keywords
therapeutic drug monitoring
Brief summary
Although alternative dosing strategies can improve antimicrobial exposure in critically ill patients, the high PK variability in this population means that some may still receive sub-optimal antibiotic exposure leading to unfavourable clinical outcomes. Therapeutic drug management (TDM) guided dosing is the only safe and effective way to ensure that all critically ill patients achieve therapeutic antimicrobial exposures and to minimise the likelihood of toxicity. For experts, TDM should be a standard of care, in particular for β-lactams. Nevertheless, because of the assay method for β-lactams and the need for bioanalytical experts, delays in obtaining results frequently occurred. These barriers, combined with difficulties in the interpretation of TDM results, need to be addressed in order to increase its routine utilization. Consequently, study aiming at identify which subgroup of patients or infection are more likely to benefit from TDM are urgently warranted This prospective observational study aimed at evaluating target attainment of piperacillin/tazobactam (PIP/TAZ) and cefepim (CEF) with the use of a Therapeutic Drug Monitoring (TDM) in critically patients during the routine care
Interventions
OTHERdosage of concentration of piperacillin and cefepim
Dosage of total plasma concentration of piperacillin and cefepim at different timepoints
Sponsors
Central Hospital, Nancy, France
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Minimun age limits 18 years * Critically ill patient receiving piperacillin or cefepim administered continuously
Exclusion criteria
* Beta lactam allergy * Pregnancy * Age less than 18 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| to determine the percentage of patients who met the PK/PD targets at 24 hours | Day 1 | PK/PD target was defined as follows: Concentration of piperacillin or cefepim between a lower and a upper limit: * The lower limit was defined as estimated free concentration above 4 times the epidemiological cut-off value of suspected bacteria * The upper limit was based on known limit of neurotoxicity, namely 35 and 160 mg/L for cefepim and piperacillin, respectively Consequently : * for piperacillin : the PK/PD target is considered to be reach if the free concentration of PIPERACILLIN/TAZOBACTAM is between 32 and 160 mg/l * for cefepim : the PK/PD target is considered to be reach if the free concentration of CEFEPIM is between 4 and 35 mg/l |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| to determine the percentage of patients who met the PK/PD targets exposure at 24 hours | Day 1 | PK/PD target exposure take into account only the the lower limit was defined as estimated free concentration above 4 times the epidemiological cut-off value of suspected bacteria Consequently : * for piperacillin : the PK/PD target is considered to be reach if the free concentration of PIPERACILLIN/TAZOBACTAM is above 32 mg/l * for cefepim : the PK/PD target is considered to be reach if the free concentration of CEFEPIM is above 4 mg/l |
| factors associated with target attainment at day 1 | Statistical analysis after 2 years of inclusion | effect of age on antibiotic concentration |
| factors associated with dose changing | Statistical analysis after 2 years of inclusion | effect of presence of septic shock on number of dose changing after analyse of antibiotic concentration |
Countries
France
Outcome results
None listed