Method Based on the<i>β</i>-Lactamase PenPC Fluorescent Labeled for<i>β</i>-Lactam Antibiotic Quantification in Human Plasma

Andresen, Max; Wong, Kam Yuet; Leung, Yun Chung; Wong, Wai Ting; Chan, P.H.; Andresen-Vasquez, Max; Alegría, Leyla; Silva, Camila; Tapía, Pablo; Downey, Patricio; Soto, Dagoberto

doi:10.1155/2016/4307987

Cited by 6 publications

(14 citation statements)

References 8 publications

(9 reference statements)

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“…The time-course of fluorescence measurements have been previously described [ 24 ]. Briefly, 10 μL of standard or conveniently diluted samples were placed into the wells of a black-walled 96-wells microplate.…”

Section: Methodsmentioning

confidence: 99%

“…This disparity was solved by using the area under the curve (AUC) of the plotted fluorescence level against time induced by the different antibiotic concentrations. In this way, all the curves obtained were fitted to a 4PL or boltzman curve, independently of the antibiotic and its sensitivity to catalytic activity of the biosensor [ 24 ]. Thus, in this study the antibiotic concentration on each sample was interpolated into the AUC curve obtained from the standard curve ( Figure S1 in Supplementary Materials ).…”

Section: Methodsmentioning

confidence: 99%

“…This dynamic range is at or below the MIC of the pathogens targeted by meropenem, making the biosensor a useful tool to determine clinically relevant information such as pharmacokinetics (PK) of the drug at the bedside. Indeed PenP has been shown to be useful for PK testing in animals and healthy humans [ 23 , 24 ]. Despite these promising results, the usefulness of this biosensor in situations of high complexity such as those observed in critically ill patients, has not yet been proven.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Meropenem Pharmacokinetics in an Experimental Acute Respiratory Distress Syndrome (ARDS) Model during Extracorporeal Membrane Oxygenation (ECMO) by Using a PenP β-Lactamase Biosensor

Andresen

Araos

Wong

et al. 2018

Sensors

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Introduction: The use of antibiotics is mandatory in patients during extracorporeal membrane oxygenation (ECMO) support. Clinical studies have shown high variability in the antibiotic concentrations, as well as sequestration of them by the ECMO circuit, suggesting that the doses and/or interval administration used during ECMO may not be adequate. Thus, a fast response sensor to estimate antibiotic concentrations in this setting would contribute to improve dose adjustments. The biosensor PenP has been shown to have a dynamic range, sensitivity and specificity useful for pharmacokinetic (PK) tests in healthy subjects. However, the use of this biosensor in the context of a complex critical condition, such as ECMO during acute respiratory distress syndrome (ARDS), has not been tested. Objectives: To describe, by using PenP Biosensor, the pharmacokinetic of meropenem in a 24-h animal ARDS/ECMO model. Methods: The PK of meropenem was evaluated in a swine model before and during ECMO. Results: The PK parameters such as maximum concentration (Cmax), elimination rate constant (Ke), and cleareance (Cl), were not significantly altered during ECMO support. Conclusions: (a) ECMO does not affect the PK of meropenem, at least during the first 24 h; and (b) PenP has the potential to become an effective tool for making medical decisions associated with the dose model of antibiotics in a critical patient context.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of Meropenem Pharmacokinetics in an Experimental Acute Respiratory Distress Syndrome (ARDS) Model during Extracorporeal Membrane Oxygenation (ECMO) by Using a PenP β-Lactamase Biosensor

Andresen

Araos

Wong

et al. 2018

Sensors

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“…This can reduce the health hazard of antibiotic allergy and antibiotic resistance by minimizing the exposure of the antibiotics to the hypersensitive individuals and the environment [ 23 ]. Second, it offers a pharmacokinetics monitoring of the medically prescribed β-lactam antibiotics [ 24 , 25 ]. This surveillance provides valuable information for optimizing the antibiotic dosage, which prevents the overuse of β-lactam antibiotics.…”

Section: Introductionmentioning

confidence: 99%

BADAN-conjugated β-lactamases as biosensors for β-lactam antibiotic detection

Au¹,

Tsang²,

Chen³

et al. 2020

PLoS ONE

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β-Lactam antibiotic detection has significant implications in food safety control, environmental monitoring and pharmacokinetics study. Here, we report the development of two BADAN-conjugated β-lactamases, E166Cb and E166Cb/N170Q, as sensitive biosensors for β-lactam antibiotic detection. These biosensors were constructed by coupling an environment-sensitive BADAN probe onto location 166 at the active site of the PenP β-lactamase E166C and E166C/N170Q mutants. They gave fluorescence turn-on signals in response to β-lactam antibiotics. Molecular dynamics simulation of E166Cb suggested that the turn-on signal might be attributed to a polarity change of the microenvironment of BADAN and the removal of the fluorescence quenching effect on BADAN exerted by a nearby Tyr-105 upon the antibiotic binding. In the detection of four β-lactams (penicillin G, penicillin V, cefotaxime and moxalactam), both E166Cb and E166Cb/N170Q delivered signal outputs in an antibiotic-concentration dependent manner with a dynamic range spanning from 10 nM to 1 μM. Compared to E166Cb, E166Cb/N170Q generally exhibited more stable signals owing to its higher deficiency in hydrolyzing the antibiotic analyte. The overall biosensor performance of E166Cb and E166Cb/N170Q was comparable to that of their respective fluorescein-modified counterparts, E166Cf and E166Cf/N170Q. But comparatively, the BADAN-conjugated enzymes showed a higher sensitivity, displayed a faster response in detecting moxalactam and a more stable fluorescence signals towards penicillin G. This study illustrates the potential of BADAN-conjugated β-lactamases as biosensing devices for β-lactam antibiotics.

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“…Our group has been working on antimicrobial concentration, and we have developed a biosensor functionally characterized by exhibiting a variation in its intrinsic fluorescence during interaction with β -lactam antibiotics. It has highly selective capacity for fluorescence turn-on response after exposure to β -lactam antibiotics [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Plasma and Renal Cortex Meropenem Concentrations in Patients Undergoing Percutaneous Renal Biopsy

Sepúlveda

Downey

Soto

et al. 2019

BioMed Research International

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Background Urinary tract infection (UTI) is the most common bacterial infection in the world. Some cases can have serious complication as death by septic shock. With the increasing spread of multidrug-resistant bacteria, the therapeutic possibilities against the complicated UTI are exhausted, forcing the use of broad-spectrum antibiotics such as meropenem. Objectives To evaluate the penetrating ability of meropenem to renal tissue using an enzymatic biosensor in samples of renal cortex and its correlation with plasma levels. Method We conducted a descriptive study in humans with indication of kidney biopsy. Meropenem was administered 1 hour before performing the biopsy, and the concentrations of meropenem in a series of samples of plasma and renal biopsy were determined. Results Renal biopsy and plasma samples of 14 patients, 64% women with body mass index of 26.3 kg/m2 (SD ± 2.9) and estimated glomerular filtration rate of 57.5 mL/min/1.73 m2 (SD ± 44.1), were examined. Renal biopsy was done at 68.9 minutes (SD ± 20.3), and the second plasma sample was obtained at 82.1 minutes (SD ± 21.2) and the third at 149.6 minutes (SD ± 31.5). The mean kidney meropenem concentration was 3.1 μg/mL (SD ± 1.9). For each patient, a decay curve of plasma meropenem concentration was constructed. The proportion of meropenem concentrations in renal tissue and plasma at biopsy moment was 14% (SD ± 10) with an interquartile range of 5.5–20.3%. With normal renal function, meropenem can achieve a bactericidal effect towards bacteria with MIC-90 < 0.76 μg/mL in the renal parenchyma. Conclusions Meropenem is effective to treat the most frequent uropathogens with the bactericidal effect. Nevertheless, for resistant bacteria, it is necessary to adjust the dose to achieve adequate parenchymal concentration.

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Method Based on theβ-Lactamase PenPC Fluorescent Labeled forβ-Lactam Antibiotic Quantification in Human Plasma

Cited by 6 publications

References 8 publications

Evaluation of Meropenem Pharmacokinetics in an Experimental Acute Respiratory Distress Syndrome (ARDS) Model during Extracorporeal Membrane Oxygenation (ECMO) by Using a PenP β-Lactamase Biosensor

Evaluation of Meropenem Pharmacokinetics in an Experimental Acute Respiratory Distress Syndrome (ARDS) Model during Extracorporeal Membrane Oxygenation (ECMO) by Using a PenP β-Lactamase Biosensor

BADAN-conjugated β-lactamases as biosensors for β-lactam antibiotic detection

Plasma and Renal Cortex Meropenem Concentrations in Patients Undergoing Percutaneous Renal Biopsy

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