Table 1 Characteristics of the included studies. fT > MIC and fT > 4xMIC, the proportion of the dosing interval in which the unbound concentrations of the antibiotic exceeded the minimal inhibitory concentration, or four times the minimal inhibitory concentration, respectively.
Author and year of publication | Type of study | Level of medical care | Population | Intervention | Control | Antibiotic type and MIC | Pharmacokinetic–Pharmacodynamic target | Extracted outcomes |
|---|---|---|---|---|---|---|---|---|
De Waele et al. 201315 | RCT | Medical and surgical ICU of Ghent University Hospital, Belgium | Antibiotic treatment with PTZ and/or MEM with normal renal function | Daily TDM with dose adjustment as needed | Conventional treatment: daily TDM, but the physician was blinded to result | PTZ and MEM extended infusion | 100% fT > MIC; 100% fT > 4 × MIC | Clinical cure microbiological eradication target attainment: 100% fT > MIC 100% fT > 4 × MIC treatment failure in-hospital mortality 28-day mortality ICU mortality |
n = 41 | n = 21 | n = 20 | MIC: epidemiological cutoff value of wild-type Pseudomonas species | |||||
Fournier et al. 201822 | RCT | Lausanne Burn Intensive Care, Switzerland | Burn trauma patients receiving intravenous antibiotics | Real-time TDM and online antibiotic adaptation | Dose adjustment upon clinician’s discretion | Intermittent bolus, various beta-lactams | Trough level > MIC, or above a predefined concentration | Clinical cure treatment failure ICU mortality ICU length of stay |
n = 38 | n = 19 | n = 19 | MIC: actual MIC of isolated pathogen or EUCAST clinical breakpoint for P aeruginosa and Enterobacteriaceae | |||||
Hagel et al. 202216 | RCT | 13 ICU centers in Germany | Patients with severe sepsis or septic shock | Dosing of piperacillin/ tazobactam was guided by daily TDM | Piperacillin/ tazobactam was administered without use of TDM | Continuous infusion, piperacillin/ tazobactam | 100% fT > 4 × MIC | Clinical cure microbiological eradication target attainment: 100% fT > 4 × MIC treatment failure 28-day mortality ICU length of stay hospital length of stay |
n = 249 | n = 125 | n = 124 | MIC: actual MIC of isolated pathogen | |||||
Fournier et al. 201520 | RCS | Burn ICU Vaud, Switzerland | Patients admitted to the burn ICU receiving carbapenems | Patients with real-time TDM and adjusted dosages | Patients without TDM | Intermittent bolus, meropenem and imipenem | Trough concentration > MIC, upper trough limit of 8 mg/L; 100% fT > MIC | ICU mortality ICU length of stay |
n = 109 | n = 27 | n = 82 | MIC: of causative organism; if no organism isolated, MIC of 1 mg/L; later, this was changed to 2 mg/L (per EUCAST) | |||||
McDonald et al. 201617 | RCS | Tertiary referral ICU, Brisbane, Australia | Patients with suspected or confirmed infection with either MEM or PTZ regardless of organ function | ‘High-dose group’ | ‘Licensed-dose group’ | Infusion: intermittent bolus, MEM or PTZ continuous or extended infusion in high-dose group to achieve target concentration | 100% fT > MIC | Clinical cure microbiological eradication target attainment: 100% fT > MIC treatment failure in-hospital mortality ICU length of stay hospital length of stay |
n = 93 | n = 25 MEM group n = 23 PTZ group | n = 22 MEM group n = 23 PTZ group | MIC: EUCAST clinical breakpoint | |||||
Aldaz et al. 202118 | RCS | Clínica Universidad de Navarra, Pamplona, Spain | Critically ill patients receiving meropenem | Patients who received meropenem dose adjusted by TDM | Patients who received meropenem adjusted following standard recommendations | Extended infusion, meropenem | fT > 4 × MIC | Clinical cure microbiological eradication in-hospital mortality 14-days mortality ICU length of stay hospital length of stay |
n = 154 | n = 77 | n = 77 | MIC was determined in each case when a pathogen could be identified. For empirical treat- ments and when the MIC was not available, 1 mg/L was used | |||||
Nikolas et al. 202121 | RCS | University Hospital Wuerzburg, Germany | Critically ill patients receiving PTZ | With TDM | Without TDM | continuous infusion, piperacillin/ tazobactam | Target of total piperacillin concentration: 20 mg/L if MIC ≤ 4 mg/L; 40 mg/L if 4 mg/L < MIC ≤ 8 mg/L; 80 mg/L if 8 mg/L < MIC ≤ 16 mg/L, or pathogen is unknown | ICU length of stay |
n = 160 | n = 114 | n = 46 | MIC: not reported | |||||
Kunz Coyne et al. 202219 | RCS | UF Shands Gainesville and UF Health Jacksonville academic medical center, USA | Critically ill patients with Pseudomonas aeruginosa pneumonia and bloodstream infections receiving beta-lactams* | Routine beta-lactam TDM | Nonroutine beta-lactam TDM | Extended or continuous infusion of beta-lactams | 100% fT > MIC; 100% fT > 4 × MIC | Clinical cure treatment failure in-hospital mortality ICU length of stay hospital length of stay |
n = 200 | n = 95 | n = 105 | MIC: Clinical and Laboratory Standards Institute (CLSI) breakpoint |
