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Objectives  Beta-lactam antibiotics are often subject to therapeutic drug monitoring, but breakpoints of target attainment are mostly based on expert opinions. Studies that show a correlation between target attainment and infection resolution are missing. This analysis investigated whether there is a difference in infection resolution based on two breakpoints of target attainment.    Methods  An outcome group out of 1392 critically ill patients treated with meropenem or piperacillin-tazobactam was formed due to different selection criteria. Afterwards, three groups were created: group 1=free drug concentration ( f ) was < 100% of the time ( T ) above the minimal inhibitory concentration (MIC) (< 100% fT  >    MIC  ), group 2=100% fT  >    MIC    <    4xMIC  , and group 3=100% fT  >    4xMIC  . Parameters for infection control, renal and liver function, and estimated and observed in-hospital mortality were compared between those groups. Statistical analysis was performed with one-way analysis of variance, Tukey post hoc test,  U  test, and bivariate logistic regression.    Results  The outcome group consisted of 55 patients (groups 1–3, 17, 24, and 14 patients, respectively). Patients allocated to group 2 or 3 had a significantly faster reduction of the C-reactive protein in contrast to patients allocated to group 1 ( p  = 0.033 and  p  = 0.026) .  Patients allocated to group 3 had a worse renal function, a higher Acute Physiology and Chronic Health Evaluation (APACHE II) score, were older, and had a significantly higher in-hospital mortality compared to group 1 ( p  = 0.017) and group 2 ( p  = 0.001). The higher mortality was significantly influenced by worse liver function, higher APACHE II, and higher Sequential Organ Failure Assessment (SOFA) score and norepinephrine therapy.    Conclusion  Achieving the target 100% fT  >    MIC   leads to faster infection resolution in the critically ill. However, there was no benefit for patients who reached the highest target of 100% fT  >    4xMIC  , although the mortality rate was higher possibly due to confounding effects. In conclusion, we recommend the target 100% fT  >    MIC    <    4xMIC   for critically ill patients.    Trial registration   NCT03985605Supplementary Information  The online version contains supplementary material available at 10.1186/s40560-020-00504-w.

The higher the better? Defining the optimal beta-lactam target for critically ill patients to reach infection resolution and improve outcome