Author Year Type of the study Population Number of patients CrCl measurement method ARC definition Main result Evaluated and/or recommended regimens Quality grading Beta-lactams Agyeman [22 ] 2021 Randomized clinical trial In vitro study 6 P. aeruginosa isolates 130 ml/min/1.73 72-hour static concentration-time-kill study Meropenem 2 g q8hr as intermittent or continuous infusion plus ciprofloxacin 400 mg q8hr P Carrie [23 ] 2019 Retrospective study Critically ill patients with HAP/VAP 177 CrCl24h 150 ml/min/1.73 Efficacy and safety Recommended:PTZ : 20 + 2.5 g daily CI after 4 + 0.5 g LDMeropenem : 6 g daily CI or 2 g q8hr EI over 4 hrCefepime : 6 g daily CI after 2 g LD over 30 minCeftazidime : 6 g daily CI after 2 g LD over 30 min G Gerlach [24 ] 2019 Retrospective study Hospitalized patients with bacteremia or/and pneumonia due to P. aeruginosa 102 CrClCG 130 ml/minf T > MIC (>60% for cefepime and >50% for PTZ) (MIC = 8 mg/L for cefepime and 16 mg/L for PTZ) clinical curePTZ : 4.5 g q8hr as the EI over 4 hrCefepime : 2 g q8hr as the EI over 4 hr Both groups received an LD over 30 minF Besnard [25 ] 2019 Prospective study Critically ill patients 35 (36 serum concentrations) CrCl24h 150 ml/minPiperacillin unbound concentration < MIC (= 16 mg/L for P. aeruginosa ) toxic cutoff of PTZ (≥150 mg/L) PTZ : 20 + 2.5 g/day over 10 hr infusion (160 mg/ml) after 4 + 0.5 g LD over 60 minP Jacobs [17 ] 2018 Retrospective study Critically ill patients who received TDM 215 (512 drug concentrations) CrCl24h 120 ml/minf T > 4×MIC (70% for FEP/CAZ, 50% for PIP, and 40% for MEM)Meropenem (MEM) Cefepime (FEP) Ceftazidime (CAZ) Piperacillin (PIP) F Carrie [6 ] 2018 Prospective observational study Critically ill patients 79 (235 drug concentrations) CrCl24h ≥170 ml/min Rate of underdosing (<4 MIC) clinical failure PTZ : 16 + 2 g daily CI as a 12 hr infusion after an LD of 4 + 0.5 g over 60 minCefepime , ceftazidime , cefotaxime , meropenem : 6 g daily CI as an 8 hr infusion after an LD of 2 g over 60 minF Burger [10 ] 2018 Prospective observational study ICU-admitted patients 101 CrClCG ≥130 ml/min/1.73 100% f T > MIC in 90% of patients Recommended:Meropenem : 6 g daily with increased frequency of administration or duration of infusion F Andersen [9 ] 2018 Prospective study Septic patients who were treated empirically with PTZ 22 CrClCG 130 ml/min/1.73 100% and 50% fT > MIC (breakpoint MIC for P. aeruginosa : 16 mg/L) IA of 4 g piperacillin q6hr, q8hr, and q12hr, over 3 min EI of 4 g piperacillin q6hr (over 3 hr), q8hr (over 4 hr), and q12hr (over 6 hr) CI of 20 g, 16 g, and 12 g piperacillin daily after a bolus LD of 4 g F Carrie [26 ] 2018 Prospective study Critically ill patients 59 CrCl24h 130 ml/min/1.73 100% f T > MIC PTZ : comparison of two dosing regimens (20 + 2.5 g/day vs. 16 + 2 g/day) that are both 12 hr CIF Dhaese [27 ] 2018 Prospective study Critically ill patients 110 (270 plasma samples) CrCl8h 130 ml/min/1.73 100% fT > 4×MIC (MIC ≤16 mg/L for susceptible P. aeruginosa ) Piperacillin : 24 g daily as CI immediately after 4 g LDF Mahmoud [15 ] 2017 Systemic review ≥130 ml/min Recommended:Meropenem : 2 g q8hrPTZ : 4 + 0.5 g q6hr as an EI over 4 hr Hobbs [8 ] 2015 Review article Critically ill patients with ARC CrCl8h 130 ml/min/1.73 f T > MIC (60% for FEP, 50% for PTZ, and 40% for MEM)Recommended:Meropenem (MEM) : 2 g q8hr as a 3 hr infusionPTZ : 4.5 g q6hr as a 4 hr infusionCefepime (FEP) : 2 g q6-8hr as a 3 hr infusion Huttner [7 ] 2015 Observational prospective cohort study Critically ill patients 100 CrClCG 130 ml/min/1.73 Clinical response 28 days after inclusion Imipenem/cilastatin : 500 mg q6hrMeropenem : 2 g q8hrPTZ : 4 + 0.5 g q8hrCefepime : 2 g q12hrF Udy [28 ] 2015 Prospective study Critically ill patients with sepsis 48 CrCl6h 120 to 300 ml/min Clinical response PTZ : 4.5 g q6hr as an IA over 20 minF Carlier [1 ] 2013 Prospective study Critically ill patients 61 CrCl24h 130 ml/min/1.73 100% and 50% f T > MIC 3 hr infusion immediately after an LD over 30 min of the following:Meropenem : 1 g q8hrPTZ : 4 + 0.5 g q6hr F Udy [29 ] 2012 Observational study Critically ill patients who received empirical B-lactam therapy 52 trough concentrations collected for TDM CrCl8h 130 ml/min/1.73 Trough concentrations less than MIC and 4 MIC Ampicillin , dicloxacillin , penicillin , flucloxacillin , piperacillin , cephalothin , cefazolin , ceftriaxone , ceftazidime , cefepime , meropenem , ertapenem F Taccone [30 ] 2012 Case report A patient with septic shock due to XDR P. aeruginosa 1 CrCl24h >200 ml/min f T > 4×MIC Meropenem : 12 g daily (3 g q6hr as a 3 hr EI) Tröger [12 ] 2012 Case reports Septic patients 2 CrClCG and CrClCKD-EPI ≥120 ml/min Trough concentration >4×MIC Meropenem : 1 g q8hr Vancomycin Fransson [31 ] 2021 Case report 1 CrCl12h 130 ml/min/1.73 Trough concentrations between 10 and 20 mg/L Despite using doses from 1.5 g q8hr to 2 g q6hr, a stable vancomycin target level was not achieved until 1.5 g q6hr Molina [32 ] 2020 Retrospective study Traumatic ICU-admitted patients 119 CrClCG >105 ml/min Subtherapeutic trough concentration (<10 mg/L) Mean daily dose: 44 9 mg/kg/day F Mahmoud [15 ] 2017 Systemic review CrCl24h 130 ml/min/1.73 LD: 25–30 mg/kg MD: 45 mg/kg/day q8hr Chu [33 ] 2016 Retrospective study Patients who received empirical vancomycin therapy 148 CrClCG 130 ml/minSubtherapeutic trough concentration (<10 mg/L) 1000 mg q12hr F Hirai [34 ] 2016 Retrospective observational study Patients who were treated with vancomycin 292 (48 patients with ARC) CrClCG 130 ml/min/1.73 Subtherapeutic trough concentrations ( 10 mcg/mL) TDM is used for optimizing the dose of vancomycin F Hobbs [8 ] 2015 Review article Critically ill patients with ARC CrCl8h 130 ml/min/1.73 Trough concentration between 15 and 20 mg/L AUC/MIC >400 LD: 25–30 mg/kg MD: 15–20 mg/kg q8-12hr Robert [35 ] 2011 Retrospective data collection Critically ill septic patients 206 CrCl24h ml/min/1.73 Trough concentrations between 20 and 30 mg/L LD: 35 mg/kg over 180 min MD: at least 35 mg/kg/day as CI F Baptista [36 ] 2014 Two-step study (first retrospective and then prospective) Critically ill patients 104 patients in total (79 and 25 patients, respectively) CrCl8h 130 ml/min/1.73 Trough concentrations between 20 and 30 mg/L Dosing nomogram for different CrCls: LD: 1000 mg for patients with TBW 70 kg and 1500 mg for TBW >70 kg MD: 3 to 5.8 g/day as CI for a CrCl of 125 to 350 mg/ml G Teicoplanin Li [37 ] 2020 Retrospective study Critically ill patients 55 CrClCG Trough concentration ≥10 mg/L on days 2 and 4 Clinical response Adverse effects (nephrotoxicity and hepatotoxicity) LD: 400 mg or 800 mg q12hr for three doses MD: 400 mg or 800 mg q24hr, q48hr, or q72hr according to renal adjustment F Ueda [38 ] 2020 Retrospective study Patients who were treated with teicoplanin 512 (for safety), 76 (for efficacy) Estimated GFR by a formula that is developed by the Japanese Society of Nephrology Clinical response Adverse effects (nephrotoxicity and hepatotoxicity) On day 4 and the end of teicoplanin therapy LD: 12 mg/kg q12hr for four consequent doses and then 12 mg/kg once daily on day 3 MD: 6.7 mg/kg once daily F Kim [39 ] 2019 Retrospective study Patients who were treated with teicoplanin ≥72 hr 65 (124 serum concentrations) Trough concentration ≥10 mg/L and ≥20 mg/L within 10 days No LD, low LD (<9 mg/kg), and high LD ( 9 mg/kg) q12hr for three consequent doses The MD is calculated according to TDM and renal adjustment (q24hr, q48hr, or q72hr) F Byrne [40 ] 2018 Prospective study Patients with haematologic malignancy 30 CrCl24h Trough concentrations: Total 20 mg/L Unbound 1.5 mg/L On days 3 and 7 Recommended: 18–25 mg/kg for both LD (five doses with 12 hr interval) and MD (q24hr) for CrCl 130 ml/min F Cazaubon [41 ] 2017 Retrospective study Infected patients with Gram-positive cocci 98 CrClCG CrClMDRD Trough concentration 15 mg/L AUC0–24/MIC 900 AUC0–24/MIC 1800 Monte Carlo simulation F Richards et al. [11 ] 2015 Review article Critically ill patients ≥130 ml/min LD: 800 mg teicoplanin twice a day for four consequent doses MD: 400 mg q12hr Byrne [42 ] 2015 Retrospective cohort study Patients with haematologic malignancy 104 CrClCG Total trough concentration Treatment outcomes: nephrotoxicity (according to RIFLE criteria) LD: intravenous bolus injection of 600 mg (800 mg if TBW >80 kg) q12hr for three consequent doses MD: 600 mg (800 mg) once daily Recommended: LD: 12 mg/kg q12hr for 3–5 consequent doses MD: 12 mg/kg daily F Nakamura [43 ] 2015 Prospective study Critically ill patients 106 CrCl24h Trough concentration between 15 and 30 mg/L on day 3 Clinical response Adverse effects (nephrotoxicity and hepatotoxicity) LD: 12 mg/kg q12hr for five consequent doses MD: 12 mg/kg according to TDM and renal adjustment P Matsumoto [44 ] 2013 Retrospective study Critically ill patients 20 Correlation between teicoplanin LD and trough concentration on day 3 Adverse effects (nephrotoxicity and hepatotoxicity) 11–15 mg/kg q12hr for three consequent doses P Mimoz [45 ] 2006 Prospective study Critically ill patients 13 Trough concentration ≥20 mg/L LD: 12 mg/kg q12hr for four consecutive doses MD: 12 mg/kg once daily F Linezolid Barrasa [46 ] 2020 PK modeling study ICU-admitted patients 43 (136 plasma samples) CrCl10h 130 ml/min/1.73 AUC0–24/MIC > 80 fT > MIC > 85% (target MIC = 2 mg/L) 600 mg q12hr as IA (over 30 min) or CI (50 mg/hr) Recommended: 600 mg q8hr as CI (75 mg/hr) F Wang [47 ] 2020 Prospective multicenter observational study ICU-admitted patients 117 CrClCG 120 ml/min/1.73 AUC0–24/MIC >80 Trough concentration <10 mg/L (for MIC 0.5 to 4) 600 mg q12hr F Dou [48 ] 2020 PK modeling study Critically ill septic patients 52 CrClCG AUC0–24/MIC of 100 (to provide a bacterial eradication rate of 80% in septic patients) Safety (thrombocytopenia) Recommended: 800 mg q12hr F Morata [49 ] 2013 Retrospective study Patients who received linezolid 78 CrClMDRD 80 ml/minTrough concentration <2 mg/L 600 mg q12hr P Colistin Fujii [50 ] 2020 Review article Critically ill patients Recommended: combination therapy with following high-dose colistin in patients with CrCl >80 ml/min/1.73 LD: 9 mIU MD: 360 mg (11 mIU) daily q12hr, 12 hr after the LD Aitullina [51 ] 2019 Retrospective study ICU-admitted patients with MDR Gram-negative bacterial infection and at least 72 hr colistin therapy 100 CrClCKD-EPI 108 ml/min/1.73 Efficacy Nephrotoxicity LD: 9 mIU LD MD: 3 mIU q8hr F Nation [52 ] 2017 Four-center observational study Adult critically ill patients 214 CrClCG 90 ml/min/1.73 PTA >80% and <30% for average steady-state concentration of colistin ≥2 and ≥4 mg/L, respectively. An algorithm for colistin dosing in different CrCls: 360 mg (11 mIU) daily for patients with CrCl >90 ml/min/1.73 q12hr F Dalfino [53 ] 2015 Prospective observational study Patients with severe sepsis or septic shock who received colistin >72 hr 70 CrClCKD-EPI 130 ml/min/1.73 Nephrotoxicity Steady-state concentration (target = 2.5 mg/L) Recommended: LD: 9 mIU MD: 9 mIU/day for CrCl 60–130 ml/min/1.73 and 12 mIU/day for CrCl 130 ml/min/1.73 q12hr, 12 hr after an LD F Aminoglycosides Carrie [54 ] 2020 Retrospective study Critically ill patients who received amikacin and underwent TDM 70 (179 serum concentrations( CrClCG 130 ml/min/1.73 Cmax/MIC 8 AUC0–24/MIC ≥75 Trough concentration <2.5 mg/L (toxic cutoff) Monte Carlo simulations F Fujii [50 ] 2020 Review article Critically ill patients Cmax/MIC 8–10 Amikacin : 30 mg/kg/day q24hrGentamycin : 8 mg/kg/day q24hrTobramycin : 10 mg/kg/day q24hr Tängdén [20 ] 2017 Review article Critically ill patients with severe infections Amikacin: Cmax/MIC ≥ 8–10, AUC/MIC >70, Cmin <2 mg/L Gentamycin and tobramycin: Cmax/MIC ≥10, AUC/MIC >70, Cmin <0.5 mg/L Initial empirical dosage:Amikacin : 30 mg/kg q24hrGentamycin and tobramycin : 7–10 mg/kg q24hr MD: adjusted doses according to TDM Hobbs [8 ] 2015 Review article Critically ill patients with ARC CrCl8h >130 ml/min Cmax/MIC = 8–10 7 mg/kg/day for gentamycin and tobramycin Najmeddi [55 ] 2014 Randomized clinical trial Septic patients who received empirical treatment, including amikacin, against Gram-negative bacteria 40 Cmax >40 and fT > MIC >60% Nephrotoxicity Amikacin : 12.5 mg/kg q12hr instead of 25 mg/kg q24hrG Fluoroquinolones Mahmoud [15 ] 2017 Review article ≥130 ml/min Recommended:Levofloxacin : 750–1000 mg/day Tängdén [20 ] 2017 Review article Critically ill patients with severe infections Ciprofloxacin: AUC/MIC ≥125 and Cmax/MIC ≥ 8 Levofloxacin: AUC/MIC ≥80 Recommended:Levofloxacin : 750 mg daily or 500 mg q12hrCiprofloxacin : 400 mg q8hr or 600 mg q12hr Given as initial empirical dosage Robert [56 ] 2016 Observational pharmacokinetic study 35 CrClCG AUC/MIC 80 Monte Carlo simulations F Hobbs [8 ] 2015 Review article Critically ill patients with ARC CrCl8h >130 ml/min AUC/MIC ≥125 Recommended:Ciprofloxacin : 400 mg q8hrLevofloxacin : 750 mg daily