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Table 1 Characteristics of included studies in the meta-analysis

From: Efficacy of therapeutic drug monitoring-based antibiotic regimen in critically ill patients: a systematic review and meta-analysis of randomized controlled trials

First author, year, country

Study settings, period

Study population (TDM/control)

APACHE II score (TDM/Control)1)

Major focus of infection

Antibiotics type

Target for intervention

Primary outcome/mortality follow-up

Bartal, 2003, Israel

Single ICU, 1999–2000

N = 81; nonsurgical sepsis patients with suspected or documented Gram-negative infection (43/38)

20/18 (amikacin) and 10/11 (gentamicin)

Urinary tract (24.7%)

Aminoglycoside

Target peak; 20 μg/mL (gentamicin) or 60 μg/mL (amikacin), target trough; < 1 μg/mL

Nephrotoxicity/28-day mortality

Waele, 2014, Belgium

Single ICU, 2011–2012

N = 41; ICU patients who needed for antibiotic treatment with piperacillin/tazobactam and/or meropenem and the presence of an arterial catheter (21/20)

19/17

Pneumonia (78%), peritonitis (12%)

Piperacillin/tazobactam and/or meropenem extended infusion

Target trough; > 64 mg/L (piperacillin/tazobactam) or > 8 mg/L (meropenem) (> 4 × MIC) and 100%fT > 4 × MIC2)

Target attainment defined as 100%fT > MIC and 100%fT > 4MIC within the first 24 h and 72 h of treatment/hospital and 28-day mortality

Ewoldt, 2022, Netherland

8 ICUs, 2018–2021

N = 388; ICU patients who expected to receive the target antibiotics for at least 2 days (189/199)

71/70 (APACHE IV)

Pulmonary (65.2%), intra-abdominal infection (16.0%)

Beta-lactam and ciprofloxacin

Target; 100%fT > MIC (beta-lactam) or AUC0–24 h / MIC > 125 (ciprofloxacin)3), above target trough; > 10 × MIC (beta-lactam) or AUC0–24 h/MIC > 500 (ciprofloxacin)

ICU length of stay/28-day mortality, ICU mortality, hospital mortality, 6-month mortality

Hagel, 2022, Germany

13 ICUs, 2017–2019

N = 249; sepsis patients (125/124)

23/22

Pneumonia (62.2%), intra-abdominal infection (19.7%), urinary tract (12.9%)

Piperacillin/tazobactam as continuous infusion

Target concentration: > 4 × MIC

Sepsis-related organ dysfunction, discharge from the ICU or death/ 28-day mortality

Roggeveen, 2022, Netherland

2 ICUs, 2018–2020

N = 252; intensive care patients who received antibiotics for a suspected or confirmed infection and had a suspected or measured serum lactate greater than 2 mmol/L or a requirement for vasopressor support (132/120)

No severity score

No information for focus of infection

Vancomycin, ciprofloxacin, meropenem, and ceftriaxone

AUC0-24/MIC > 400 (vancomycin), AUC0-24/MIC > 125 (ciprofloxacin), 100%fT > 4 × MIC (beta-lactam)

PK target attainment during the first 24 h following randomization/ ICU, hospital, 28-day and 6 months mortality

  1. 1APACHE, Acute Physiology and Chronic Health Evaluation; values are described by mean or median
  2. 2fT > MIC, time during a dosing interval that the free drug concentration of antibiotics exceeded the MIC
  3. 3AUC0-24 h/MIC, area under the drug serum concentration–time curve over 24 h to the MIC
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Journal of Intensive Care

ISSN: 2052-0492