Table 1.
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Definitions used for PK/PD endpoints and clinical outcome variables

Primary PK/PD endpointsa,bDefinition
50% fT>MICfree drug concentration maintained above the MIC for the pathogen for at least 50% of the dosing interval
50% fT>4×MICfree drug concentration maintained >4× the MIC for the pathogen for at least 50% of the dosing interval
100% fT>MICfree drug concentration maintained above the MIC for the pathogen throughout the dosing interval
100% fT>4×MICfree drug concentration maintained >4× the MIC for the pathogen throughout the dosing interval
Secondary endpointsDefinition and description
Clinical response
 clinical curecompletion of treatment course without change or addition of antibiotic therapy, and with no additional antibiotics commenced within 48 h of cessation
 clinical failureany clinical outcome other than clinical cure
30 day survivalsurvival at day 30 following entry to the study
Primary PK/PD endpointsa,bDefinition
50% fT>MICfree drug concentration maintained above the MIC for the pathogen for at least 50% of the dosing interval
50% fT>4×MICfree drug concentration maintained >4× the MIC for the pathogen for at least 50% of the dosing interval
100% fT>MICfree drug concentration maintained above the MIC for the pathogen throughout the dosing interval
100% fT>4×MICfree drug concentration maintained >4× the MIC for the pathogen throughout the dosing interval
Secondary endpointsDefinition and description
Clinical response
 clinical curecompletion of treatment course without change or addition of antibiotic therapy, and with no additional antibiotics commenced within 48 h of cessation
 clinical failureany clinical outcome other than clinical cure
30 day survivalsurvival at day 30 following entry to the study

aThe PK/PD exposure targets have all been identified in clinical studies recruiting critically ill patients in which achieving these targets would increase the probability of clinical efficacy.

bActual MIC values, provided by the local microbiology laboratory, were used when available. Where a pathogen was isolated, but the MIC was unavailable, the ‘surrogate’ MIC was defined by EUCAST MIC90 data. Where no pathogen was formally identified, the MIC breakpoints for Pseudomonas aeruginosa (16 mg/L for piperacillin/tazobactam and 2 mg/L for meropenem) were inferred as the surrogate MIC, which reflects the least susceptible pathogen that could be encountered during β-lactam therapy.

Table 1.
Open in new tab

Definitions used for PK/PD endpoints and clinical outcome variables

Primary PK/PD endpointsa,bDefinition
50% fT>MICfree drug concentration maintained above the MIC for the pathogen for at least 50% of the dosing interval
50% fT>4×MICfree drug concentration maintained >4× the MIC for the pathogen for at least 50% of the dosing interval
100% fT>MICfree drug concentration maintained above the MIC for the pathogen throughout the dosing interval
100% fT>4×MICfree drug concentration maintained >4× the MIC for the pathogen throughout the dosing interval
Secondary endpointsDefinition and description
Clinical response
 clinical curecompletion of treatment course without change or addition of antibiotic therapy, and with no additional antibiotics commenced within 48 h of cessation
 clinical failureany clinical outcome other than clinical cure
30 day survivalsurvival at day 30 following entry to the study
Primary PK/PD endpointsa,bDefinition
50% fT>MICfree drug concentration maintained above the MIC for the pathogen for at least 50% of the dosing interval
50% fT>4×MICfree drug concentration maintained >4× the MIC for the pathogen for at least 50% of the dosing interval
100% fT>MICfree drug concentration maintained above the MIC for the pathogen throughout the dosing interval
100% fT>4×MICfree drug concentration maintained >4× the MIC for the pathogen throughout the dosing interval
Secondary endpointsDefinition and description
Clinical response
 clinical curecompletion of treatment course without change or addition of antibiotic therapy, and with no additional antibiotics commenced within 48 h of cessation
 clinical failureany clinical outcome other than clinical cure
30 day survivalsurvival at day 30 following entry to the study

aThe PK/PD exposure targets have all been identified in clinical studies recruiting critically ill patients in which achieving these targets would increase the probability of clinical efficacy.

bActual MIC values, provided by the local microbiology laboratory, were used when available. Where a pathogen was isolated, but the MIC was unavailable, the ‘surrogate’ MIC was defined by EUCAST MIC90 data. Where no pathogen was formally identified, the MIC breakpoints for Pseudomonas aeruginosa (16 mg/L for piperacillin/tazobactam and 2 mg/L for meropenem) were inferred as the surrogate MIC, which reflects the least susceptible pathogen that could be encountered during β-lactam therapy.

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