Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013;369:840–51.

Article  CAS  PubMed  Google Scholar 

Vincent J-L, Sakr Y, Singer M, Martin-Loeches I, Machado FR, Marshall JC, et al. Prevalence and outcomes of infection among patients in intensive care units in 2017. JAMA. 2020;323:1478–87.

Article  PubMed  PubMed Central  Google Scholar 

Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47:1181–247.

Article  PubMed  PubMed Central  Google Scholar 

Abdul-Aziz MH, Alffenaar J-WC, Bassetti M, Bracht H, Dimopoulos G, Marriott D, et al. Antimicrobial therapeutic drug monitoring in critically ill adult patients: a position paper. Intensive Care Med. 2020;46:1127–53.

Article  PubMed  PubMed Central  Google Scholar 

Tam VH, Chang K-T, Zhou J, Ledesma KR, Phe K, Gao S, et al. Determining β-lactam exposure threshold to suppress resistance development in Gram-negative bacteria. J Antimicrob Chemother. 2017;72:1421–8.

Article  CAS  PubMed  Google Scholar 

Alshaer MH, Maranchick N, Alexander KM, Manigaba K, Shoulders BR, Felton TW, et al. Beta-lactam target attainment and associated outcomes in patients with bloodstream infections. Int J Antimicrob Agents. 2023;61:106727.

Article  CAS  PubMed  Google Scholar 

Gatti M, Cojutti PG, Pascale R, Tonetti T, Laici C, Dell’Olio A, et al. Assessment of a PK/PD target of continuous infusion beta-lactams useful for preventing microbiological failure and/or resistance development in critically ill patients affected by documented gram-negative infections. Antibiotics. 2021;10:1311.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gatti M, Pea F. Jumping into the future: overcoming pharmacokinetic/pharmacodynamic hurdles to optimize the treatment of severe difficult to treat-Gram-negative infections with novel beta-lactams. Expert Rev Anti Infect Ther. 2023;21:149–66.

Article  CAS  PubMed  Google Scholar 

Berry AV, Kuti JL. Pharmacodynamic thresholds for beta-lactam antibiotics: a story of mouse versus man. Front Pharmacol. 2022;13:833189.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vardakas KZ, Voulgaris GL, Maliaros A, Samonis G, Falagas ME. Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials. Lancet Infect Dis. 2018;18:108–20.

Article  CAS  PubMed  Google Scholar 

Pai Mangalore R, Ashok A, Lee SJ, Romero L, Peel TN, Udy AA, et al. Beta-lactam antibiotic therapeutic drug monitoring in critically ill patients: a systematic review and meta-analysis. Clin Infect Dis. 2022;75:1848–60.

Article  PubMed  PubMed Central  Google Scholar 

Abdulla A, Ewoldt TMJ, Purmer IM, Muller AE, Gommers D, Endeman H, et al. A narrative review of predictors for β-lactam antibiotic exposure during empirical treatment in critically ill patients. Expert Opin Drug Metab Toxicol. 2021;17:359–68.

Article  CAS  PubMed  Google Scholar 

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.

Article  PubMed  PubMed Central  Google Scholar 

Guilhaumou R, Benaboud S, Bennis Y, Dahyot-Fizelier C, Dailly E, Gandia P, et al. Optimization of the treatment with beta-lactam antibiotics in critically ill patients-guidelines from the French Society of Pharmacology and Therapeutics (Société Française de Pharmacologie et Thérapeutique-SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Société Française d’Anesthésie et Réanimation-SFAR). Crit Care. 2019;23:104.

Article  PubMed  PubMed Central  Google Scholar 

Gatti M, Rinaldi M, Laici C, Siniscalchi A, Viale P, Pea F. Role of a real-time TDM-based expert clinical pharmacological advice program in optimizing the early pharmacokinetic/pharmacodynamic target attainment of continuous infusion beta-lactams among orthotopic liver transplant recipients with documented or suspected gram-negative infections. Antibiotics (Basel). 2023;12:1599.

Article  CAS  PubMed  Google Scholar 

Pea F, Viale P. The antimicrobial therapy puzzle: could pharmacokinetic-pharmacodynamic relationships be helpful in addressing the issue of appropriate pneumonia treatment in critically ill patients? Clin Infect Dis. 2006;42:1764–71.

Article  CAS  PubMed  Google Scholar 

Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.

Article  PubMed  Google Scholar 

Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919.

Article  PubMed  PubMed Central  Google Scholar 

Gatti M, Bonazzetti C, Tazza B, Pascale R, Miani B, Malosso M, et al. Impact on clinical outcome of follow-up blood cultures and risk factors for persistent bacteraemia in patients with gram-negative bloodstream infections: a systematic review with meta-analysis. Clin Microbiol Infect. 2023;29:1150–8.

Article  PubMed  Google Scholar 

Wong G, Briscoe S, McWhinney B, Ally M, Ungerer J, Lipman J, et al. Therapeutic drug monitoring of β-lactam antibiotics in the critically ill: direct measurement of unbound drug concentrations to achieve appropriate drug exposures. J Antimicrob Chemother. 2018;73:3087–94.

Article  CAS  PubMed  Google Scholar 

Carrié C, Petit L, d’Houdain N, Sauvage N, Cottenceau V, Lafitte M, et al. Association between augmented renal clearance, antibiotic exposure and clinical outcome in critically ill septic patients receiving high doses of β-lactams administered by continuous infusion: a prospective observational study. Int J Antimicrob Agents. 2018;51:443–9.

Article  PubMed  Google Scholar 

Abdulla A, Dijkstra A, Hunfeld NGM, Endeman H, Bahmany S, Ewoldt TMJ, et al. Failure of target attainment of beta-lactam antibiotics in critically ill patients and associated risk factors: a two-center prospective study (EXPAT). Crit Care. 2020;24:558.

Article  PubMed  PubMed Central  Google Scholar 

Al-Shaer MH, Rubido E, Cherabuddi K, Venugopalan V, Klinker K, Peloquin C. Early therapeutic monitoring of β-lactams and associated therapy outcomes in critically ill patients. J Antimicrob Chemother. 2020;75:3644–51.

Article  CAS  PubMed  Google Scholar 

Taccone FS, Bogossian EG, Tironi RM, Antonucci E, Hites M, Knoop C, et al. Early β-lactam concentrations and infectious complications after lung transplantation. Am J Transpl. 2021;21:2489–97.

Article  CAS  Google Scholar 

Chua NG, Loo L, Hee DKH, Lim TP, Ng TM, Hoo GSR, et al. Therapeutic drug monitoring of meropenem and piperacillin-tazobactam in the Singapore critically ill population—A prospective, multi-center, observational study (BLAST 1). J Crit Care. 2022;68:107–13.

Article  CAS  PubMed  Google Scholar 

Zhao Y, Xiao C, Hou J, Wu J, Xiao Y, Zhang B, et al. C/MIC > 4: a potential instrument to predict the efficacy of meropenem. Antibiotics (Basel). 2022;11:670.

Article  CAS  PubMed  Google Scholar 

Alshaer MH, Maranchick N, Bai C, Maguigan KL, Shoulders B, Felton TW, et al. Using machine learning to define the impact of beta-lactam early and cumulative target attainment on outcomes in intensive care unit patients with hospital-acquired and ventilator-associated pneumonia. Antimicrob Agents Chemother. 2022;66:e0056322.

Article  PubMed  Google Scholar 

Gatti M, Rinaldi M, Bonazzetti C, Gaibani P, Giannella M, Viale P, et al. Could an optimized joint pharmacokinetic/pharmacodynamic target attainment of continuous infusion ceftazidime-avibactam be a way to avoid the need for combo therapy in the targeted treatment of deep-seated DTR Gram-negative infections? Antimicrob Agents Chemother. 2023;67:e0096923.

Article  PubMed  Google Scholar 

Gatti M, Rinaldi M, Tonetti T, Siniscalchi A, Viale P, Pea F. Could an optimized joint pharmacokinetic/pharmacodynamic target attainment of continuous infusion piperacillin-tazobactam be a valuable innovative approach for maximizing the effectiveness of monotherapy even in the treatment of critically ill patients with documented extended-spectrum beta-lactamase-producing enterobacterales bloodstream infections and/or ventilator-associated pneumonia? Antibiotics (Basel). 2023;12:1736.

Article  CAS  PubMed  Google Scholar 

Udy AA, Varghese JM, Altukroni M, Briscoe S, McWhinney BC, Ungerer JP, et al. Subtherapeutic initial β-lactam concentrations in select critically ill patients: association between augmented renal clearance and low trough drug concentrations. Chest. 2012;142:30–9.

Article  CAS  PubMed  Google Scholar 

Hites M, Taccone FS, Wolff F, Cotton F, Beumier M, De Backer D, et al. Case-control study of drug monitoring of β-lactams in obese critically ill patients. Antimicrob Agents Chemother. 2013;57:708–15.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Alobaid AS, Brinkmann A, Frey OR, Roehr AC, Luque S, Grau S, et al. What is the effect of obesity on piperacillin and meropenem trough concentrations in critically ill patients? J Antimicrob Chemother. 2016;71:696–702.

Article  CAS  PubMed  Google Scholar 

Damen C, Dhaese S, Verstraete AG, Stove V, De Waele JJ. Subtherapeutic piperacillin concentrations in neurocritical patients. J Crit Care. 2019;54:48–51.

Article  CAS  PubMed  Google Scholar 

Dhaese SAM, Thooft ADJ, Farkas A, Lipman J, Verstraete AG, Stove V, et al. Early target attainment of continuous infusion piperacillin/tazobactam and meropenem in critically ill patients: a prospective observational study. J Crit Care. 2019;52:75–9.

Article  CAS