The expert clinical pharmacological advice program for tailoring on real-time antimicrobial therapies with emerging TDM candidates in special populations: how the ugly duckling turned into a swan

Gatti, Milo; Pea, Federico

doi:10.1080/17512433.2023.2274984

Cited by 3 publications

(2 citation statements)

References 142 publications

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“…Scheduled timing for assessing aggressive PK/PD target attainment of beta-lactams may be crucial, especially in case of severe infections. Some guidance recommended that aggressive PK/PD target attainment should be assessed promptly when dealing with patients having sepsis and/or septic shock [ 14 , 39 ]. In this regard, it should be noticed that almost two-thirds of the studies included in PICO 1 fully fulfilled with this recommendation by assessing first aggressive PK/PD target attainment of beta-lactams within 72 h from starting treatment.…”

Section: Discussionmentioning

confidence: 99%

Impact of attaining aggressive vs. conservative PK/PD target on the clinical efficacy of beta-lactams for the treatment of Gram-negative infections in the critically ill patients: a systematic review and meta-analysis

Gatti,

Cojutti,

Pea

2024

Crit Care

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Background To perform a systematic review with meta-analysis with the dual intent of assessing the impact of attaining aggressive vs. conservative beta-lactams PK/PD target on the clinical efficacy for treating Gram-negative infections in critical patients, and of identifying predictive factors of failure in attaining aggressive PK/PD targets. Methods Two authors independently searched PubMed-MEDLINE and Scopus database from inception to 23rd December 2023, to retrieve studies comparing the impact of attaining aggressive vs. conservative PK/PD targets on clinical efficacy of beta-lactams. Independent predictive factors of failure in attaining aggressive PK/PD targets were also assessed. Aggressive PK/PD target was considered a100%fT>4xMIC, and clinical cure rate was selected as primary outcome. Meta-analysis was performed by pooling odds ratios (ORs) extrapolated from studies providing adjustment for confounders using a random-effects model with inverse variance method. Results A total of 20,364 articles were screened, and 21 observational studies were included in the meta-analysis (N = 4833; 2193 aggressive vs. 2640 conservative PK/PD target). Attaining aggressive PK/PD target was significantly associated with higher clinical cure rate (OR 1.69; 95% CI 1.15–2.49) and lower risk of beta-lactam resistance development (OR 0.06; 95% CI 0.01–0.29). Male gender, body mass index > 30 kg/m2, augmented renal clearance and MIC above the clinical breakpoint emerged as significant independent predictors of failure in attaining aggressive PK/PD targets, whereas prolonged/continuous infusion administration of beta-lactams resulted as protective factor. The risk of bias was moderate in 19 studies and severe in the other 2. Conclusions Attaining aggressive beta-lactams PK/PD targets provided significant clinical benefits in critical patients. Our analysis could be useful to stratify patients at high-risk of failure in attaining aggressive PK/PD targets.

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Section: Discussionmentioning

confidence: 99%

Impact of attaining aggressive vs. conservative PK/PD target on the clinical efficacy of beta-lactams for the treatment of Gram-negative infections in the critically ill patients: a systematic review and meta-analysis

Gatti,

Cojutti,

Pea

2024

Crit Care

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“…Simultaneously, especially for challenging bacteria (e.g., Pseudomonas, Enterococcus) [5,6], studies on combination therapy (typically involving fosfomycin-containing regimens) have revealed exciting potential. The role of therapeutic drug monitoring is gaining prominence [7], not only in determining if pharmacological levels are adequate but also in revising drug dosages, potentially minimizing adverse effects. Discussing special clinical situations in infectious diseases allows us to review current clinical practices in light of advancing knowledge.…”

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confidence: 99%

Antibiotics Usage in Special Clinical Situations

Di Bella

2023

Antibiotics

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Pharmacokinetic/pharmacodynamic issues for optimizing treatment with beta-lactams of Gram-negative infections in critically ill orthotopic liver transplant recipients: a comprehensive review

Gatti,

Pea

2024

Front. Antibiot.

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Orthotopic liver transplant (OLT) represents the standard of care for managing patients affected by end-stage and life-threatening liver diseases. Although a significant improvement in surgical techniques, immunosuppressant regimens, and prompt identification of early post-transplant complications resulted in better clinical outcome and survival in OLT recipients, the occurrence of early bacterial infections still represents a remarkable cause of morbidity and mortality. In this scenario, beta-lactams are the most frequent antimicrobials used in critical OLT recipients. The aim of this narrative review was to provide a comprehensive overview of the pathophysiological issues potentially affecting the pharmacokinetics of beta-lactams and to identify potential strategies for maximizing the likelihood of attaining adequate pharmacokinetic/pharmacodynamic (PK/PD) targets of beta-lactams in critically ill OLT recipients. A literature search was carried out on PubMed-MEDLINE database (until 31st March 2024) in order to retrieve clinical trials, real-world observational evidence, and/or case series/reports evaluating the PK/PD of traditional and novel beta-lactams in settings potentially involving critically ill OLT recipients. Retrieved evidence were categorized according to the concepts of the so-called “antimicrobial therapy puzzle”, specifically assessing a) beta-lactam PK/PD features, with specific regard to aggressive PK/PD target attainment; b) site of infection, with specific regard to beta-lactam penetration in the lung, ascitic fluid, and bile; and c) pathophysiological alterations, focusing mainly on those specifically associated with OLT. Overall, several research gaps still exist in assessing the PK behavior of beta-lactams in critical OLT recipients. The impact of specific OLT-associated pathophysiological alterations on the attainment of optimal PK/PD targets may represent an important field in which further studies are warranted. Assessing the relationship between aggressive beta-lactam PK/PD target attainment and clinical outcome in critical OLT recipients will represent a major challenge in the next future.

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The expert clinical pharmacological advice program for tailoring on real-time antimicrobial therapies with emerging TDM candidates in special populations: how the ugly duckling turned into a swan

Cited by 3 publications

References 142 publications

Impact of attaining aggressive vs. conservative PK/PD target on the clinical efficacy of beta-lactams for the treatment of Gram-negative infections in the critically ill patients: a systematic review and meta-analysis

Impact of attaining aggressive vs. conservative PK/PD target on the clinical efficacy of beta-lactams for the treatment of Gram-negative infections in the critically ill patients: a systematic review and meta-analysis

Antibiotics Usage in Special Clinical Situations

Pharmacokinetic/pharmacodynamic issues for optimizing treatment with beta-lactams of Gram-negative infections in critically ill orthotopic liver transplant recipients: a comprehensive review

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