Beta-Lactams Therapeutic Monitoring in Septic Children–What Target Are We Aiming for? A Scoping Review

Abstract

The antimicrobial therapy of sepsis and septic shock should be individualized based on pharmacokinetic/pharmacodynamic (PK/PD) parameters to deliver effective and timely treatment of life-threatening infections. We conducted a literature scoping review to identify therapeutic targets of beta-lactam antibiotics in septic pediatric patients and the strategies that have been applied to overcome sepsis-related altered pharmacokinetics and increase target attainment against susceptible pathogens. A systematic search was conducted in the MEDLINE, EMBASE and Web of Science databases to select studies conducted since 2010 with therapeutic monitoring data of beta-lactams in septic children. Last searches were performed on 02 September 2021. Two independent authors selected the studies and extracted the data. A narrative and qualitative approach was used to summarize the findings. Out of the 118 identified articles, 21 met the eligibility criteria. Population pharmacokinetic modeling was performed in 12 studies, while nine studies reported data from bedside monitoring of beta-lactams. Most studies were conducted in the United States of America (n = 9) and France (n = 5) and reported PK/PD data of amoxicillin, ampicillin, azlocillin, aztreonam, cefazolin, cefepime, cefotaxime, ceftaroline, ceftazidime, doripenem, meropenem and piperacillin/tazobactam. Therapeutic targets ranged from to 40% fT> MIC to 100% fT> 6 × MIC. Prolonging the infusion time and frequency were most described strategies to increase target attainment. Monitoring beta-lactam serum concentrations in clinical practice may potentially maximize therapeutic target attainment. Further studies are required to define the therapeutic target associated with the best clinical outcomes.

Safety and Efficacy of Ceftaroline in Neonates With Staphylococcal Late-onset Sepsis: A Case Series Analysis

“…In the intensive care unit, some authors recommend a target of free-C min /MIC ratio of up to 6. 8 Three of our successfully treated patients have C min /CMI below this target but maintained above 1, as suggested by some authors. The few dosages did not allow us to conclude whether lower targets could be generalized.…”

Relationship Between Real-time TDM-guided Pharmacodynamic Target Attainment of Continuous Infusion Beta-lactam Monotherapy and Microbiologic Outcome in the Treatment of Critically Ill Children With Severe Documented Gram-negative Infections

“…18 Likewise, a recent scoping review concerning betalactams TDM among septic children showed that administration by prolonged or CI was implemented only in 2 studies, even if none of these investigated the probability of attainment of aggressive PK/ PD targets or the relationship with clinical outcome. 19 The aim of this study was to explore the relationship between PK/PD target attainment and microbiologic eradication in critically ill children with severe documented Gram-negative infections treated with CI beta-lactam monotherapy.…”

“… 16 , 17 Only a few studies assessed the impact that prolonged or CI may have on PK/PD target attainment and clinical outcome among critically ill children treated with beta-lactams. 18 , 19 A cross-sectional survey on the implementation prolonged or CI of beta-lactams among neonatal sepsis patients found that only approximately 30% of respondents had access to this infusion modality. 18 Likewise, a recent scoping review concerning beta-lactams TDM among septic children showed that administration by prolonged or CI was implemented only in 2 studies, even if none of these investigated the probability of attainment of aggressive PK/PD targets or the relationship with clinical outcome.…”

“… 18 Likewise, a recent scoping review concerning beta-lactams TDM among septic children showed that administration by prolonged or CI was implemented only in 2 studies, even if none of these investigated the probability of attainment of aggressive PK/PD targets or the relationship with clinical outcome. 19 …”

Beta-Lactams in Critically Ill Children: Time to Step Up Our Game?*

“…Indeed, in critically ill adults, pharmacokinetic/pharmacodynamic targets between ƒt greater than MIC = 100% and ƒt greater than 4 × MIC = 100% are associated with better microbiological and clinical outcomes (5) and are commonly used for therapeutic drug monitoring (TDM) according to an international survey (6). However, optimal pharmacokinetic/pharmacodynamic targets still need to be better defined in children, and so far, pediatric studies have used conservative targets of ƒt greater than MIC between 40% and 50% up to aggressive targets of ƒt greater than 6 × MIC = 100% (7). Furthermore, it is unclear if identical pharmacokinetic/pharmacodynamic targets should apply to all septic children regardless of the infection source.…”