Expert clinical pharmacological advice may make an antimicrobial TDM program for emerging candidates more clinically useful in tailoring therapy of critically ill patients

Gatti, Milo; Cojutti, Pier Giorgio; Bartoletti, Michele; Tonetti, Tommaso; Bianchini, Amedeo; Ramirez, Stefania; Pizzilli, Giacinto; Ambretti, Simone; Giannella, Maddalena; Mancini, Rita; Siniscalchi, Antonio; Viale, Pierluigi; Pea, Federico

doi:10.1186/s13054-022-04050-9

Critical Care

Table 1 Desired PK/PD target, thresholds for toxicity, and TDM-guided dosage adjustments of antimicrobials included in the expert clinical pharmacological advice (ECPA) program

From: Expert clinical pharmacological advice may make an antimicrobial TDM program for emerging candidates more clinically useful in tailoring therapy of critically ill patients

Antimicrobial	Desired target	Threshold for toxicity	Dosage adjustment
Piperacillin–tazobactam	C_ss 4–8 × MIC (for piperacillin)	C_min > 361 mg/L (neurotoxicity) [25]	Decrease 50% if C_ss > 10 × MIC 25% if C_ss 8–10 × MIC Increase 50% if C_ss < 2 × MIC 25% if C_ss 2–4 × MIC
Meropenem	C_ss 4–8 × MIC	C_min > 64.2 mg/L (neurotoxicity) [25]	Decrease 50% if C_ss > 10 × MIC 25% if C_ss 8–10 × MIC Increase 50% if C_ss < 2 × MIC 25% if C_ss 2–4 × MIC
Ceftazidime	C_ss 4–8 × MIC	NA	Decrease 50% if C_ss > 10 × MIC 25% if C_ss 8–10 × MIC Increase 50% if C_ss < 2 × MIC 25% if C_ss 2–4 × MIC
Ampicillin Ampicillin–Sulbactam	C_ss 4–8 × MIC (for ampicillin)	NA	Decrease 50% if C_ss > 10 × MIC 25% if C_ss 8–10 × MIC Increase 50% if C_ss < 2 × MIC 25% if C_ss 2–4 × MIC
Cefepime	C_ss 4–8 × MIC	C_min > 36 mg/L (neurotoxicity) [26]	Decrease 50% if C_ss > 10 × MIC 25% if C_ss 8–10 × MIC Increase 50% if C_ss < 2 × MIC 25% if C_ss 2–4 × MIC
Linezolid	C_min 2–8 mg/L	C_min > 8 mg/L (thrombocytopenia) [29, 30]	Decrease 50% if C_min > 15 mg/L 25% if C_min 8–15 mg/L Increase 50% if C_min < 1 mg/L 25% if C_min 1–2 mg/L
Levofloxacin	C_max 10 × MIC C_min < 3 mg/L	NA	Decrease every 36–48 h if C_min > 2 mg/L Increase 25% if C_max < 10 × MIC
Ciprofloxacin	C_max 10 × MIC C_min < 2 mg/L	NA	Decrease 25% if C_min > 2 mg/L Increase 25% if C_max < 10 × MIC
Fluconazole	C_min 10–20 mg/L	NA	Decrease 50% if C_min > 50 mg/L 25% if C_min 30–50 mg/L Increase 25% if C_min < 10 mg/L
Voriconazole	C_min 1–3 mg/L	C_min > 3–4 mg/L (hepatotoxicity) [28]	Decrease stop if C_min > 8–10 mg/L 25–50% if C_min 3.5–8 mg/L Increase every 6–8 h if C_min < 1 mg/L
Posaconazole	C_min 1–3 mg/L	C_min > 3 mg/L (pseudohyperaldosteronism) [31]	Decrease 25–50% if C_min > 3 mg/L Increase every 12 h if C_min < 1 mg/L
Isavuconazole	C_min 1–7 mg/L	C_min > 5.1 mg/L (gastrointestinal disorders) [27]	Decrease 25–50% if C_min > 5 mg/L Increase 25–50% if C_min < 1 mg/L
Ganciclovir/Valganciclovir	C_min 0.7–2 mg/L	NA	Decrease stop if C_min > 5 mg/L 25–50% if C_min 2–5 mg/L Increase every 6–8 h if C_min < 0.5 mg/L
Acyclovir	C_min 1–3 mg/L	NA	Decrease stop if C_min > 5 mg/L 25–50% if C_min 3–5 mg/L Increase every 6 h if C_min < 0.5 mg/L

AUC area under concentration–time curve, C_max peak concentration, C_min trough concentration, C_ss steady-state concentration, CI continuous infusion, ECPA expert clinical pharmacology advice, MIC minimum inhibitory concentration, NA not available, TDM therapeutic drug monitoring

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ISSN: 1364-8535

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