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This study evaluates PK/PD of an extended-infusion protocol of meropenem, piperacillin-tazobactam and cefepime, in the early phase of septic shock.
Beta Lactams are the keystones of shock septic treatment. Early phase of septic shock is a period of disturbed pharmacokinetics, with augmented renal clearance and distribution volume of hydrophilic drugs as Beta Lactams. Consequently, early phase of septic shock is a period at risk of underdosing Beta Lactam, which could increase the risk of clinical failure an mortality.
Data are available concerning underdosing of MEROPENEM, PIPERACILLIN-TAZOBACTAM and CEFEPIME, when administered in bolus.
No data exist concerning the achievement of a target of 100% of the whole interval above 4 time the superior breakpoint of Pseudomonas Aeruginosa according to EUCAST (European Committee on Antimicrobial Susceptibility Testing), during the 48 first hours of treatment of septic shock, when Beta Lactam are administered in extended infusion.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MEROPENEM | Active Comparator | After enrollment, patients of MEROPENEM arm will receive an initial 2g bolus of MEROPENEM and 2g infusion over 3 hours every eight hours, during 48 hours, without modification of rhythm and dose according to renal function. |
|
| PIPERACILLIN-TAZOBACTAM | Active Comparator | After enrollment, patients of PIPERACILLIN - TAZOBACTAM arm will receive an initial 4g bolus of PIPERACILLIN - TAZOBACTAM and a 16g continuous infusion per day, during 48 hours, without modification of rhythm and dose according to renal function. |
|
| CEFEPIME | Active Comparator | After enrollment, patients of CEFEPIME arm will receive an initial 2g bolus of CEFEPIME and a 6g continuous infusion per day, during 48 hours, without modification of rhythm and dose according to renal function. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MEROPENEM | Drug | Administration of MEROPENEM according to a protocol of extended infusion defining dose and duration of infusion. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of patients achieving the PK/PD target | Proportion of patients achieving the target of 100% of 48 first hours of treatment above 4 time the upper critical breakpoint for Pseudomonas Aeruginosa | First 48 hours |
| Measure | Description | Time Frame |
|---|---|---|
| All cause mortality | 28th day |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chu Besancon | Besançon | 25000 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20594297 | Result | Taccone FS, Laterre PF, Dugernier T, Spapen H, Delattre I, Wittebole X, De Backer D, Layeux B, Wallemacq P, Vincent JL, Jacobs F. Insufficient beta-lactam concentrations in the early phase of severe sepsis and septic shock. Crit Care. 2010;14(4):R126. doi: 10.1186/cc9091. Epub 2010 Jul 1. | |
| 34768176 | Derived | Winiszewski H, Despres C, Puyraveau M, Lagoutte-Renosi J, Montange D, Besch G, Floury SP, Chaignat C, Labro G, Vettoretti L, Clairet AL, Capellier G, Vivet B, Piton G. beta-lactam dosing at the early phase of sepsis: Performance of a pragmatic protocol for target concentration achievement in a prospective cohort study. J Crit Care. 2022 Feb;67:141-146. doi: 10.1016/j.jcrc.2021.10.023. Epub 2021 Nov 9. |
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| ID | Term |
|---|---|
| D012772 | Shock, Septic |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
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| ID | Term |
|---|---|
| D000077731 | Meropenem |
| D000077725 | Piperacillin, Tazobactam Drug Combination |
| D000077723 | Cefepime |
| ID | Term |
|---|---|
| D013845 | Thienamycins |
| D015780 | Carbapenems |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 |
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| PIPERACILLIN-TAZOBACTAM | Drug | Administration of PIPERACILLIN-TAZOBACTAM according to a protocol of continuous infusion defining dose and duration of infusion. |
|
| CEFEPIME | Drug | Administration of CEFEPIME according to a protocol of continuous infusion defining dose and duration of infusion. |
|
| D010335 |
| Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
| Amides |
| D009930 | Organic Chemicals |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D000078142 | Tazobactam |
| D010397 | Penicillanic Acid |
| D010406 | Penicillins |
| D010878 | Piperacillin |
| D000667 | Ampicillin |
| D010400 | Penicillin G |
| D013457 | Sulfur Compounds |
| D013450 | Sulfones |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D002511 | Cephalosporins |
| D013843 | Thiazines |