From Therapeutic Drug Monitoring to Model‐Informed Precision Dosing for Antibiotics

Clinical Pharmacology & Therapeutics, Journal Year: 2021, Volume and Issue: 109(4), P. 928 - 941

Published: Feb. 10, 2021

Therapeutic drug monitoring (TDM) and model‐informed precision dosing (MIPD) have evolved as important tools to inform rational of antibiotics in individual patients with infections. In particular, critically ill display altered, highly variable pharmacokinetics often suffer from infections caused by less susceptible bacteria. Consequently, TDM has been used individualize this patient group for many years. More recently, there increasing research on the use MIPD software streamline process, which can increase flexibility dose individualization but also requires adequate model validation re‐evaluation existing workflows. parallel, new minimally invasive noninvasive technologies such microneedle‐based sensors are being developed, which—together software—have potential revolutionize how dosed antibiotics. Nonetheless, carefully designed clinical trials evaluate benefit approaches still sparse, needed justify implementation practice. The present review summarizes pharmacology antibiotics, conventional approaches, evidence value TDM/MIPD aminoglycosides, beta‐lactams, glycopeptides, linezolid, recommended.

Language: Английский

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Effect of therapeutic drug monitoring-based dose optimization of piperacillin/tazobactam on sepsis-related organ dysfunction in patients with sepsis: a randomized controlled trial

Intensive Care Medicine, Journal Year: 2022, Volume and Issue: 48(3), P. 311 - 321

Published: Feb. 1, 2022

Insufficient antimicrobial exposure is associated with worse outcomes in sepsis. We evaluated whether therapeutic drug monitoring (TDM)-guided antibiotic therapy improves outcomes. Randomized, multicenter, controlled trial from January 2017 to December 2019. Adult patients (n = 254) sepsis or septic shock were randomly assigned 1:1 receive continuous infusion of piperacillin/tazobactam dosing guided by daily TDM piperacillin a fixed dose (13.5 g/24 h if eGFR ≥ 20 mL/min). Target plasma concentration was four times the minimal inhibitory (range ± 20%) underlying pathogen, respectively, Pseudomonas aeruginosa empiric situation. Primary outcome mean total Sequential Organ Failure Assessment (SOFA) score up day 10. Among 249 evaluable (66.3 13.7 years; female, 30.9%), there no significant difference SOFA between (7.9 points; 95% CI 7.1–8.7) and without (8.2 7.5–9.0) (p 0.39). Patients TDM-guided showed lower 28-day mortality (21.6% vs. 25.8%, RR 0.8, 0.5–1.3, p 0.44) higher rate clinical (OR 1.9; 0.5–6.2, 0.30) microbiological cure 2.4; 0.7–7.4, 0.12), but these differences did not reach statistical significance. Attainment target more common (37.3% 14.6%, OR 4.5, 95%, 2.9–6.9, < 0.001). beneficial effect regard score. Larger studies strategies ensure optimization are needed definitively answer question.

Language: Английский

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Management of sepsis and septic shock in the emergency department

Internal and Emergency Medicine, Journal Year: 2021, Volume and Issue: 16(6), P. 1649 - 1661

Published: April 22, 2021

Abstract Early management of sepsis and septic shock is crucial for patients’ prognosis. As the Emergency Department (ED) place where first medical contact patients likely to occur, emergency physicians play an essential role in early phases patient management, which consists accurate initial diagnosis, resuscitation, antibiotic treatment. Since issuing Surviving Sepsis Campaign guidelines 2016, several studies have been published on different aspects adding a substantial amount new information pathophysiology treatment shock. In light this emerging evidence, present narrative review provides comprehensive account recent advances ED.

Language: Английский

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Pharmacokinetic Alterations Associated with Critical Illness

Clinical Pharmacokinetics, Journal Year: 2023, Volume and Issue: 62(2), P. 209 - 220

Published: Feb. 1, 2023

Language: Английский

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Guidelines for the diagnosis, treatment, prevention and control of infections caused by carbapenem-resistant gram-negative bacilli

Journal of Microbiology Immunology and Infection, Journal Year: 2023, Volume and Issue: 56(4), P. 653 - 671

Published: Feb. 18, 2023

The dissemination of carbapenem-resistant Gram-negative bacilli (CRGNB) is a global public health issue. CRGNB isolates are usually extensively drug-resistant or pandrug-resistant, resulting in limited antimicrobial treatment options and high mortality. A multidisciplinary guideline development group covering clinical infectious diseases, microbiology, pharmacology, infection control, methodology experts jointly developed the present practice guidelines based on best available scientific evidence to address issues regarding laboratory testing, therapy, prevention infections. This focuses Enterobacteriales (CRE), Acinetobacter baumannii (CRAB), Pseudomonas aeruginosa (CRPA). Sixteen questions were proposed from perspective current translated into research using PICO (population, intervention, comparator, outcomes) format collect synthesize relevant inform corresponding recommendations. grading recommendations, assessment, evaluation (GRADE) approach was used evaluate quality evidence, benefit risk profile interventions formulate recommendations suggestions. Evidence extracted systematic reviews randomized controlled trials (RCTs) considered preferentially for treatment-related questions. Observational studies, non-controlled expert opinions as supplementary absence RCTs. strength classified strong conditional (weak). informing derives studies worldwide, while implementation suggestions combined Chinese experience. target audience this clinician related professionals involved management diseases.

Language: Английский

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Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis

JAMA, Journal Year: 2023, Volume and Issue: 330(2), P. 141 - 141

Published: June 16, 2023

Meropenem is a widely prescribed β-lactam antibiotic. exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, administration of meropenem may improve clinical outcomes.To determine whether reduces composite mortality and emergence pandrug-resistant or extensively drug-resistant bacteria compared in critically ill patients sepsis.A double-blind, randomized trial enrolling sepsis septic shock who had been their treating clinicians at 31 intensive care units 26 hospitals 4 countries (Croatia, Italy, Kazakhstan, Russia). Patients were enrolled between June 5, 2018, August 9, 2022, final 90-day follow-up was completed November 2022.Patients receive an equal dose antibiotic either (n = 303) 304).The primary outcome all-cause day 28. There secondary outcomes, including days alive free from antibiotics 28, unit 90. Seizures, allergic reactions, recorded as adverse events.All 607 (mean age, 64 [SD, 15] years; 203 women [33%]) included measurement 28-day follow-up. The majority (369 patients, 61%) shock. median time hospital admission randomization 9 (IQR, 3-17 days) duration therapy 11 6-17 days). Only 1 crossover event recorded. occurred 142 (47%) group 149 (49%) (relative risk, 0.96 [95% CI, 0.81-1.13], P .60). Of none statistically significant. No events seizures reactions related study reported. At 90 days, 42% both (127 303 patients) 304 patients).In sepsis, did not 28.ClinicalTrials.gov Identifier: NCT03452839.

Language: Английский

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The spectrum of sepsis-associated encephalopathy: a clinical perspective

Critical Care, Journal Year: 2023, Volume and Issue: 27(1)

Published: Oct. 5, 2023

Abstract Sepsis-associated encephalopathy is a severe neurologic syndrome characterized by diffuse dysfunction of the brain caused sepsis. This review provides concise overview diagnostic tools and management strategies for SAE at acute phase in long term. Early recognition diagnosis are crucial effective management. Because evaluation can be confounded several factors intensive care unit setting, multimodal approach warranted Diagnostic commonly employed include clinical evaluation, metabolic tests, electroencephalography, neuroimaging selected cases. The usefulness blood biomarkers injury remains limited. Clinical involves assessing patient's mental status, motor responses, brainstem reflexes, presence abnormal movements. Electroencephalography rule out non-convulsive seizures help detect patterns various severity such as generalized slowing, epileptiform discharges, triphasic waves. In patients with encephalopathy, value non-contrast computed tomography septic persistent seizures, and/or focal signs, magnetic resonance imaging detects more than 50% cases, mainly cerebrovascular complications, white matter changes. Timely identification treatment underlying infection paramount, along control systemic that may contribute to secondary injury. Upon admission ICU, maintaining appropriate levels oxygenation, pressure, balance crucial. Throughout ICU stay, it important mindful potential neurotoxic effects associated specific medications like midazolam cefepime, closely monitor seizures. efficacy targeted neurocritical during optimizing patient outcomes deserves further investigated. lead permanent sequelae. Seizures occurring increase susceptibility long-term epilepsy. Extended stays sepsis-associated linked functional disability neuropsychological sequelae, underscoring necessity surveillance comprehensive patients.

Language: Английский

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Aminoglycosides for the Treatment of Severe Infection Due to Resistant Gram-Negative Pathogens

Antibiotics, Journal Year: 2023, Volume and Issue: 12(5), P. 860 - 860

Published: May 6, 2023

Aminoglycosides are a family of rapidly bactericidal antibiotics that often remain active against resistant Gram-negative bacterial infections. Over the past decade, their use in critically ill patients has been refined; however, due to renal and cochleovestibular toxicity, indications treatment sepsis septic shock have gradually reduced. This article reviews spectrum activity, mode action, methods for optimizing efficacy aminoglycosides. We discuss current aminoglycosides, with an emphasis on multidrug-resistant bacteria, such as extended-spectrum β-lactamase-producing Enterobacterales, carbapenemase-producing Pseudomonas aeruginosa, carbapenem-resistant Acinetobacter baumannii. Additionally, we review evidence nebulized

Language: Английский

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Recent Development of Implantable Chemical Sensors Utilizing Flexible and Biodegradable Materials for Biomedical Applications

ACS Nano, Journal Year: 2024, Volume and Issue: 18(5), P. 3969 - 3995

Published: Jan. 25, 2024

Implantable chemical sensors built with flexible and biodegradable materials exhibit immense potential for seamless integration biological systems by matching the mechanical properties of soft tissues eliminating device retraction procedures. Compared conventional hospital-based blood tests, implantable have capability to achieve real-time monitoring high accuracy important biomarkers such as metabolites, neurotransmitters, proteins, offering valuable insights clinical applications. These innovative could provide essential information preventive diagnosis effective intervention. To date, despite extensive research on bioresorbable electronics, development has faced several challenges related design, resulting in only a limited number successful accomplishments. This review highlights recent advancements based materials, encompassing their sensing strategies, geometric configurations. The following discussions focus demonstrated detection various objects including ions, small molecules, few examples macromolecules using and/or sensors. Finally, we will present current explore future directions.

Language: Английский

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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

Critical Care, Journal Year: 2024, Volume and Issue: 28(1)

Published: April 16, 2024

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

Language: Английский

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