A guide to therapeutic drug monitoring of β‐lactam antibiotics

Fratoni, A.; Nicolau, David P.; Kuti, Joseph L.

doi:10.1002/phar.2505

Cited by 73 publications

(63 citation statements)

References 102 publications

(198 reference statements)

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“…While Bayesian methods can estimate more accurate PK profiles for individual patients, the use of first order equations is a reasonable and practical alternative to determining target attainment. 32 Our sampling times were all during the post-distribution phase, samples were collected at steady-state, and the precise timing of sampling was recorded, minimizing bias of this approach. Further, to our knowledge, no currently available Bayesian dosing software programs incorporate pediatric PK models for FEP.…”

Section: Discussionmentioning

confidence: 99%

Urinary Biomarkers and Attainment of Cefepime Therapeutic Targets in Critically Ill Children

Downes

Sharova

Gianchetti

et al. 2022

Preprint

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INTRODUCTION: The recommended therapeutic target for cefepime (FEP) is the time above MIC (fT>MIC). The frequency of target attainment and risk factor for sub-therapeutic concentrations in children have not been extensively studied. METHODS: We performed a prospective observational pilot study in children in our PICU receiving standard dosing of FEP for suspected sepsis (≥2 SIRS criteria). Three FEP concentrations were measured per subject and a urine sample was collected prior to PK sampling for measurement of urinary biomarkers. We used log linear regression to calculate the fT>MIC for each subject across a range of MIC values (1-16 µg/mL). We compared clinical factors/biomarkers between patients who did and did not achieve 100% fT>MIC for 8 µg/mL (cut-point for Pseudomonas) and tested the correlation between covariates and FEP troughs. RESULTS: 21 subjects were enrolled (median SIRS criteria: 3). PK sampling occurred after a median of 5 doses (range: 3-9). 43% of subjects achieved 100% fT>MIC for an MIC of 8 µg/mL. Younger age (p=.005), higher estimated GFR (p=.03), and lower urinary NGAL (p=.006) and KIM-1 (.03) were associated with failure to attain 100% fT>8 µg/mL. Age (r = 0.53), eGFR (r = -0.58), urinary NGAL (r = 0.42) and KIM-1 (r = 0.50) were significantly correlated with FEP troughs. CONCLUSIONS: A significant proportion of critically ill children failed to attain target concentrations for treatment of Pseudomonas aeruginosa with FEP. Younger patients and those with good kidney function (high GFR, low urinary biomarkers) may be at highest risk for subtherapeutic FEP concentrations.

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Section: Discussionmentioning

confidence: 99%

Urinary Biomarkers and Attainment of Cefepime Therapeutic Targets in Critically Ill Children

Downes

Sharova

Gianchetti

et al. 2022

Preprint

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“…As the β-lactam antibiotics are time-dependent antimicrobial agents, the duration that the free (protein unbound) antibiotic concentration is greater than the minimal inhibitory concentration (MIC) (f T >MIC ) determines microbicidal efficacy [38]. For critically ill patients, the recommended pharmacodynamic (PD) target for the β-lactams is at least 100% f T >MIC for the given pathogen [39].…”

Section: Discussionmentioning

confidence: 99%

Rapid Detection of Multiple Classes of β-Lactam Antibiotics in Blood Using an NDM-1 Biosensing Assay

et al. 2021

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Currently, assays for rapid therapeutic drug monitoring (TDM) of β-lactam antibiotics in blood, which might be of benefit in optimizing doses for treatment of critically ill patients, remain challenging. Previously, we developed an assay for determining the penicillin-class antibiotics in blood using a thermometric penicillinase biosensor. The assay eliminates sample pretreatment, which makes it possible to perform semicontinuous penicillin determinations in blood. However, penicillinase has a narrow substrate specificity, which makes it unsuitable for detecting other classes of β-lactam antibiotics, such as cephalosporins and carbapenems. In order to assay these classes of clinically useful antibiotics, a novel biosensor was developed using New Delhi metallo-β-lactamase-1 (NDM-1) as the biological recognition layer. NDM-1 has a broad specificity range and is capable of hydrolyzing all classes of β-lactam antibiotics in high efficacy with the exception of monobactams. In this study, we demonstrated that the NDM-1 biosensor was able to quantify multiple classes of β-lactam antibiotics in blood plasma at concentrations ranging from 6.25 mg/L or 12.5 mg/L to 200 mg/L, which covered the therapeutic concentration windows of the tested antibiotics used to treat critically ill patients. The detection of ceftazidime and meropenem was not affected by the presence of the β-lactamase inhibitors avibactam and vaborbactam, respectively. Furthermore, both free and protein-bound β-lactams present in the antibiotic-spiked plasma samples were detected by the NDM-1 biosensor. These results indicated that the NDM-1 biosensor is a promising technique for rapid TDM of total β-lactam antibiotics present in the blood of critically ill patients.

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“…Vancomycin and β-lactams are the antibiotics most frequently used and measured in plasma in the intensive care unit (ICU) setting, because of their antimicrobial spectrum and their PK/PD characteristics [7,8]. Vancomycin TDM and its use in continuous or prolonged infusion (PI) could have a beneficial effect in reaching PK targets and reducing nephrotoxicity and renal replacement therapy [9,10].…”

Section: Introductionmentioning

confidence: 99%

“…With reference to β-lactam's TDM literature status, studies have shown positive results in terms of clinical cure rates (the reduction of procalcitonin in patients with TDM follow-up), a shorter mean duration of invasive ventilation, the achievement of PK parameters and an easier dose guidance process, particularly in critically ill patients or patients undergoing renal replacement therapy [7,[11][12][13][14][15][16]. More clinical studies should be developed to demonstrate the conclusive benefits of this practice.…”

Section: Introductionmentioning

confidence: 99%

“…Clinical practice guidelines recommend the use of extended or continuous infusions and the use of TDM with early obtainment of plasma concentration results between 24−48 h after the start of treatment with vancomycin or β-lactams [7,10,[18][19][20]. The literature recommends the use of specialized software, as well as the reporting of the minimum inhibitory concentration (MIC) of the isolated microorganism, to generate adequate PK modeling [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

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Administration and Therapeutic Drug Monitoring of β-lactams and Vancomycin in Critical Care Units in Colombia: The ANTIBIOCOL Study

et al. 2021

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Therapeutic drug monitoring (TDM) and continuous infusion strategies are effective interventions in clinical practice, but these practices are still largely unknown in Colombia, especially in the critical care setting. This study aims to describe the practices involved in the administration and TDM of β-lactams and vancomycin reported by specialists in critical care in Colombia and to explore the factors that are related to the use of extended infusion. An online nationwide survey was applied to 153 specialists, who were selected randomly. A descriptive, bivariate analysis and a logistic regression model were undertaken. In total, 88.9% of the specialists reported TDM availability and 21.57% reported access to results within 6 h. TDM was available mainly for vancomycin. We found that 85.62% of the intensivists had some type of institutional protocol; however, only 39.22% had a complete and socialized protocol. The odds of preferring extended infusions among those who did not have institutional protocols were 80% lower than those with complete protocols, OR 0.2 (95% CI: 0.06−0.61). The most important perceived barriers to performing continuous infusions and TDM were the lack of training and technologies. This pioneering study in Colombia could impact the quality of care and outcomes of critically ill patients in relation to the threat of antimicrobial resistance.

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A guide to therapeutic drug monitoring of β‐lactam antibiotics

Cited by 73 publications

References 102 publications

Urinary Biomarkers and Attainment of Cefepime Therapeutic Targets in Critically Ill Children

Urinary Biomarkers and Attainment of Cefepime Therapeutic Targets in Critically Ill Children

Rapid Detection of Multiple Classes of β-Lactam Antibiotics in Blood Using an NDM-1 Biosensing Assay

Administration and Therapeutic Drug Monitoring of β-lactams and Vancomycin in Critical Care Units in Colombia: The ANTIBIOCOL Study

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