Falsely elevated vancomycin-concentration values from enzyme immunoassay leading to treatment failure

2019 ◽  
Author(s):  
Bridger Singer ◽  
Ryan W Stevens ◽  
Benjamin P Westley ◽  
David P Nicolau
Keyword(s):  
Protein Binding ◽  
Treatment Failure ◽  
Enzyme Immunoassay ◽  
High Performance ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Vancomycin Concentration ◽  
Alternative Agent ◽  
Percent Protein ◽  
Serum Vancomycin

Abstract Purpose A case of vancomycin enzyme immunoassay (EIA) interference confirmed by high-performance liquid chromatography (HPLC) is described. Summary Therapeutic drug monitoring is standard of practice in vancomycin dosing and monitoring in order to maximize the pharmacodynamic effects and minimize toxicity. After a 52-year-old woman received 5 doses of vancomycin, serum concentrations continued to rise for several days in the absence of ongoing vancomycin administration. Despite persistently elevated vancomycin concentrations, the patient clinically deteriorated and required treatment with an alternative agent. Subsequently, serum concentrations were processed via HPLC and analyzed for percent protein binding. Confirmatory analysis revealed substantially lower concentrations by HPLC than were obtained by EIA and an abnormal elevation in protein binding. After discharge from the index admission, the patient returned 11 months later and had a dectectable vancomycin concentration by EIA prior to receipt of vancomycin. HPLC analysis confirmed the true concentration was undetectable. Though the exact interfering substance was not identified, the above discrepancy in concentrations between the two assay methods indicates the presence of assay interference, and adds to the available literature suggesting similar occurrences. This case is particularly troubling given that the level of interference was not such that it would lead a clinician to immediately suspect interference, and the patient experienced treatment failure. Conclusion Falsely elevated values for serum vancomycin concentration, measured by EIA, contributed to treatment failure in a patient. The substance presumably responsible for EIA interferences was not identified.

Vancomycin Serum Protein Binding Determination by Ultrafiltration

1988 ◽  
Vol 22 (4) ◽  
pp. 300-303 ◽  
Author(s):  
Bruce H. Ackerman ◽  
E. Howard Taylor ◽  
Keith M. Olsen ◽  
Wedad Abdel-Malak ◽  
Alexandras A. Pappas
Keyword(s):  
Protein Binding ◽  
Correlation Coefficient ◽  
Pharmacokinetic Study ◽  
Room Temperature ◽  
Total Serum ◽  
Serum Protein Binding ◽  
Serum Concentrations ◽  
Orthogonal Regression ◽  
The Mean ◽  
Serum Vancomycin

Sixty-two serum concentrations were obtained from 12 infected patients enrolled in a vancomycin pharmacokinetic study. Both unbound and total serum vancomycin concentrations were measured using ultrafiltration and a commercial fluorescent polarization immunoassay. Ultrafiltrates were obtained by centrifugation at 1000 × g for ten minutes at room temperature and their assay indicated a range in protein binding from 7.9 to 71 percent. The mean protein binding (mean ±SD) was 41.95 ± 14.15 percent. No measurable adsorption of vancomycin onto the ultrafiltration membrane was noted. Orthogonal regression of unbound versus total vancomycin concentrations was described by the equation y=0.597x-0.362 with a correlation coefficient of 0.948.

scholarly journals Salivary Theophylline Concentrations in Neonates

1994 ◽  
Vol 31 (3) ◽  
pp. 277-280
Author(s):  
Susan J Thompson
Keyword(s):  
Enzyme Immunoassay ◽  
High Performance ◽  
High Performance Liquid Chromatographic ◽  
Serum Concentrations ◽  
Serum Theophylline ◽  
Chromatographic Procedure ◽  
Liquid Chromatographic ◽  
Free Serum ◽  
Homogeneous Enzyme Immunoassay

Salivary theophylline concentrations in neonates were measured by a homogeneous enzyme immunoassay and compared with serum concentrations. Free serum theophylline concentrations were also compared with salivary concentrations and the values obtained were almost identical. Results using the immunoassay agreed well with those obtained using a high-performance liquid chromatographic procedure (HPLC).

scholarly journals The effect of the body mass index and creatinine clearance on serum trough concentration of vancomycin in adult patients

2019 ◽  
Author(s):  
Yuyan Pan ◽  
Xiaomei He ◽  
Xinyu Yao ◽  
Fengjiao Wang ◽  
Xinyuan Ding ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Creatinine Clearance ◽  
Body Mass ◽  
Trough Concentration ◽  
The Body ◽  
Adult Patients ◽  
Therapeutic Drug ◽  
Optimal Dosage ◽  
Vancomycin Concentration ◽  
Serum Vancomycin

Abstract Background: The aim of this study was to evaluate the influence of patient body mass index (BMI) and estimated creatinine clearance (CrCl) on serum vancomycin concentrations in order to define a possible optimal dosage regimen in overweight patients from data obtained during therapeutic drug monitoring.Methods: This retrospective study used data collected from January 2017 to January 2019. Adult patients (n=204) receiving vancomycin treatment at a dose of 1000 mg in every 12 h and undergoing serum monitoring. Data collected included patient gender, age, height and weight, vancomycin regimens and concentrations, and serum creatinine. In this study, statistical comparisons were made on the results from patients according to serum vancomycin concentration.Results: Serum vancomycin concentration was significantly related to BMI (P < 0.001) and CrCl (P < 0.05) in adult patients. Further, the trough serum vancomycin concentration showed a logarithmic correlation with BMI (R = -0.5108, 95 % CI: -0.6082 to -0.3982, P < 0.001) and CrCl (R = -0.5739, 95 % CI: -0.6616 to -0.4707, P < 0.001). In addition, the CrCl was significantly related to BMI (P < 0.01). Besides, some of the patients with higher BMI (≥ 24 kg/m2) met the goal trough concentration after an adjustment from 1000 mg every 12 h to 1000 mg every 8 h.Conclusions: Serum vancomycin concentration decreases progressively with increasing BMI due to the augment in CrCl in adult patients. Therefore, dose adjustment should be based on BMI and CrCl for safe and effective use of vancomycin in adult patients (BMI ≥ 24 kg/m2).

Vancomycin Therapeutic Drug Monitoring: Is it Necessary?

1993 ◽  
Vol 27 (5) ◽  
pp. 594-598 ◽  
Author(s):  
Dennis F. Thompson ◽  
Marsha A. Raebel ◽  
Collin D. Freeman ◽  
Richard Quintiliani ◽  
Charles H. Nightingale
Keyword(s):  
Clinical Setting ◽  
Data Extraction ◽  
English Literature ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Medline Search ◽  
Lack Of Information ◽  
Drug Concentrations ◽  
Serum Vancomycin

OBJECTIVE: To review the literature and assess the validity of obtaining vancomycin serum drug concentrations in patients. DATA SOURCES: A MEDLINE search of the English literature and a bibliographic review of articles pertaining to vancomycin serum concentrations, their use, and the rationale of cited therapeutic ranges. STUDY SELECTION AND DATA EXTRACTION: Studies pertaining to the use of vancomycin concentrations in the clinical setting, methods for predicting these concentrations, and studies that reported efficacy or toxicity associated with vancomycin use and possible correlation of serum concentrations. DATA SYNTHESIS: The usefulness of vancomycin serum concentrations, the determination of a therapeutic range of values, and their correlation to antibacterial efficacy and drug toxicity in the clinical setting are controversial. Old reports of toxicities need to be critically examined due to lack of information and the actual frequency of toxic reactions. The efficacy of vancomycin's antibacterial effect and its correlation with reported therapeutic ranges may advocate obtaining a vancomycin trough concentration in certain groups of patients. CONCLUSIONS: Determination of serum vancomycin concentrations in the clinical setting and their usefulness in patient care is questionable and unnecessary in the majority of patients.

scholarly journals Vancomycin monitoring in term newborns: comparison of peak and trough serum concentrations determined by high performance liquid chromatography and fluorescence polarization immunoassay

2001 ◽  
Vol 56 (5) ◽  
pp. 149-152 ◽  
Author(s):  
Rubens Feferbaum ◽  
José Kleber Kobol Machado ◽  
Edna Maria de Albuquerque Diniz ◽  
Thelma S. Okay ◽  
Silvia R. C. J. Santos ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Newborn Infants ◽  
Correlation Coefficients ◽  
Serum Concentrations ◽  
Serum Samples ◽  
Random Fashion ◽  
Trough Serum ◽  
Serum Vancomycin

INTRODUCTION: Peak and trough serum concentrations of vancomycin were determined in term newborn infants with confirmed or suspected Staphylococcus sp sepsis by high performance liquid chromatography and flourescence polarization immunoassay. OBJECTIVE: To statistically compare the results of the high performance liquid chromatography and flourescence polarization immunoassay techniques for measuring serum vancomycin concentrations. METHODS: Eighteen peak and 20 trough serum samples were assayed for vancomycin concentrations using high performance liquid chromatography and flourescence polarization immunoassay from October 1995 to October 1997. RESULTS: The linear correlation coefficients for high performance liquid chromatography and flourescence polarization immunoassay were 0.27 (peak, P = 0.110) and 0.26 (trough, P = 0.1045) respectively, which were not statistically significant. CONCLUSION: There was wide variation in serum vancomycin concentrations determined by high performance liquid chromatography as compared with those determined by flourescence polarization immunoassay. There was no recognizable pattern in the variability; in an apparently random fashion, the high performance liquid chromatography measurement was sometimes substantially higher than the flourescence polarization immunoassay measurement, and at other times it was substantially lower.

scholarly journals Effects of the combination of second-generation antipsychotics on serum concentrations of aripiprazole and dehydroaripiprazole in Chinese patients with schizophrenia

2021 ◽  
Vol 34 (2) ◽  
pp. e100423
Author(s):  
Ping Jiang ◽  
Xiujia Sun ◽  
Juanjuan Ren ◽  
Hongmei Liu ◽  
Zhiguang Lin ◽  
...  
Keyword(s):  
Clinical Significance ◽  
High Performance ◽  
Second Generation ◽  
Statistical Significance ◽  
Linear Regression Analysis ◽  
Multiple Linear Regression Analysis ◽  
Chinese Patients ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Second Generation Antipsychotics

BackgroundAripiprazole (ARI) is often prescribed alone or in combination with other second-generation antipsychotics (SGAs) to treat patients with schizophrenia. However, this may increase the potential clinical significance of drug–drug interactions. Therapeutic drug monitoring (TDM) is an important and fundamental tool both when administering ARI alone and in combination with other SGAs to monitor ARI pharmacokinetics, adjust the dosage and thereby achieve more effective and safer treatment.AimsThis study retrospectively investigated the effects of four SGA comedications (clozapine, risperidone, quetiapine (QTP) and olanzapine) and other potential factors (sex, age and ARI dose) on the serum concentrations of ARI and dehydroaripiprazole (DARI) in Chinese patients with schizophrenia using TDM data.MethodsHigh-performance liquid chromatography was used to test the serum concentrations of ARI, DARI and ARI+DARI. In addition, steady-state dose-adjusted serum concentrations (ie, concentration-to-dose ratios, C:D ratios) of ARI, DARI and ARI+DARI; sex; age; ARI dose and SGA comedication dose between 299 inpatients with schizophrenia who received ARI or SGA comedication were all collected and analysed. Spearman’s correlation and multiple linear regression analysis were used to evaluate bivariate associations between ARI dose and serum ARI and DARI concentrations and describe the effect of independent variables on serum ARI and DARI concentrations, respectively.ResultsThere were significant differences in the C:D ratios of ARI (χ2=−3.21, p=0.001) and ARI+DARI (χ2=−2.50, p=0.01) between the ARI and SGA groups, as well as in the C:D ratios of ARI (χ2=−3.59, p<0.001) and ARI+DARI (χ2=−3.10, p=0.002) between the female patients in the two groups. Of the four SGAs, only QTP had significant effects on the C:D ratios of ARI (Z=−4.12, p<0.001) and ARI+DARI (Z=−3.62, p<0.001) when compared with the ARI group in the whole sample and on the C:D ratios of ARI, DARI and ARI+DARI (Z=−3.96, p<0.001; Z=−2.22, p=0.03; Z=−3.75, p<0.001, respectively) in women when compared with their counterparts in the ARI group.ConclusionComedication with SGAs resulted in lower C:D ratios of ARI and ARI+DARI compared with ARI monotherapy, and comedication with QTP resulted in lower C:D ratios of ARI and ARI+DARI than ARI monotherapy. Despite this statistical significance of our findings, whether the presently observed effect has clinical significance requires exploration by further research. TDM and dosage regulation of ARI should be performed in Chinese inpatients with schizophrenia who are receiving SGA comedication (especially QTP) to maintain a safe and effective dose-adjusted serum concentration of ARI and DARI.

scholarly journals 1303. Characterization of Isavuconazole Serum Concentrations with Various Administration Routes in a Hospitalized Cohort

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S665-S666
Author(s):  
Justin Spivey ◽  
Rebekah Wrenn ◽  
Beiyu Liu ◽  
Eileen K Maziarz ◽  
Eileen K Maziarz ◽  
...  
Keyword(s):  
High Performance ◽  
Fungal Infections ◽  
Cohort Analysis ◽  
Package Insert ◽  
Hospitalized Patients ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Post Transplant ◽  
Administration Routes

Abstract Background Patients with invasive fungal infections are often critically ill and immunosuppressed with multiple comorbidities that may impact drug absorption and exposure. This study sought to characterize isavuconazole serum concentrations (ISCs) in a cohort of real-world hospitalized patients when administered by intravenous solution (IV), enteral as intact capsules, or tube as opened capsule contents. Methods This retrospective cohort analysis included all hospitalized patients who received isavuconazole as prophylaxis or treatment between September 2017 and September 2018 and had therapeutic drug monitoring performed. For patients receiving isavuconazole by tube, the capsules were opened and contents were diluted with 10-30 mL of sterile water. Administration was per package insert for intact capsules and IV solution. ISCs were obtained as part of routine care and were quantified by high-performance liquid chromatography. An appropriate trough was defined as within 4 hours of the next scheduled dose. Currently, there is a lack of correlation between isavuconazole exposure and efficacy or toxicity; thus, ISCs were compared between administration routes. Results 93 ISCs were obtained during 65 encounters from 55 unique patients. The majority of patients were post-transplant (69.1%) and death occurred during 12 (18.5%) encounters. ISCs based on different characteristics of the cohort are shown in Table 1. All ISC assessments were detectable, median 2.3 mg/dL (Q1: 1.5 mg/dL, Q3: 3.3 mg/dL). Administration via tube achieved similar ISCs compared with IV therapy (1.6 mg/dL vs. 1.9 mg/dL, respectively). However, administration of intact capsules resulted in higher median ISCs, 3 mg/dL (Q1: 1.9 mg/dL, Q3: 4.1 mg/dL). All 14 patients with administration via tube were post-transplant, which was not shown to have a significant impact on ISCs (median, transplant 2.2 mg/dL vs. non-transplant 2.7 mg/dL). Table 1. Characterization of Isavuconazole Concentrations Conclusion ISCs were detectable in all patients regardless of transplant status or location at the time of assessment. Administration of isavuconazole via an enteral feeding tube achieved comparable serum concentrations compared with FDA-approved routes of administration and may represent an important alternative for select patients. Disclosures All Authors: No reported disclosures

scholarly journals Determination of carbamazepine in serum and saliva samples by high performance liquid chromatography with ultraviolet detection

2009 ◽  
Vol 66 (5) ◽  
pp. 347-352 ◽  
Author(s):  
Snezana Djordjevic ◽  
Vesna Kilibarda ◽  
Tomislav Stojanovic
Keyword(s):  
Antiepileptic Drug ◽  
High Performance ◽  
Biological Fluids ◽  
Ultra Violet ◽  
Therapeutic Index ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Ultraviolet Detection ◽  
Spiked Serum

Background/Aim. Carbamazepine is antiepileptic drug widely used for the treatment of epilepsy. Due to low therapeutic index of carbamazepine there is a need for routine measuring its concentrations in biological fluids. The aim of the study was to describe a method for concomitant determination of carbamazepine in the serum and saliva. Methods. Separation of the drug from matrix is achieved by reversedphase chromatography on a C18 column, with a mobile phase of methanol-water-acetic acid (65:34:1) at a flow-rate of 1.0 ml/min. Detection was effected by ultra-violet absorption at 285 nm. The total run time was 5 min. Samples were prepared by alkaline extraction (pH 10) using chlorophorm. Results. Calibration curves were in the range 0.1-5 ?g/mL for serum and saliva samples. Mean recoveries of spiked serum and saliva were 97.59 and 92.30%, respectively. Limits of detection (LOD) of carbamazepine in serum and saliva were 0.166 and 0.178 ?g/mL, respectively. Limits of quantification (LOQ) in the serum and saliva were 0.237 and 0.226 ?g/mL, respectively. The method precision was carried out with coefficient of variation of 2.10% and 4.03% for the serum and saliva, respectively. The obtained data showed that there was a strong correlation between saliva and serum concentrations (r = 0.9481, p < 0.001). Conclusion. The method described here is rapid, precise, accurate and simple, and can be used for quantitative determination of carbamazepine in human serum and saliva after therapy applying. Saliva samples could be used as an alternative matrix for therapeutic drug monitoring of this antiepileptic drug.

scholarly journals Effect of Obesity on Clinical Failure of Patients Treated with Beta-Lactams

2021 ◽  
Author(s):  
Nathan A Pinner ◽  
Natalie G Tapley ◽  
Katie E Barber ◽  
Kayla R Stover ◽  
Jamie L Wagner
Keyword(s):  
Treatment Failure ◽  
Clinical Outcomes ◽  
Hospital Length Of Stay ◽  
Source Control ◽  
Definitive Treatment ◽  
Therapeutic Drug ◽  
Obese Patients ◽  
Definitive Therapy ◽  
All Cause Mortality ◽  
The Impact

Abstract Background Altered pharmacokinetics in obese patients raise concerns over worse clinical outcomes. This study assessed whether obese patients receiving a beta-lactam (BL) have worse clinical outcomes compared to non-obese patients and to identify if therapeutic drug monitoring (TDM) may be beneficial. Methods This multi-center, retrospective cohort included hospitalized adults admitted from July 2015-July 2017 treated with a BL as definitive monotherapy against a Gram-negative bacilli for ≥72 hours. Patients were excluded if there was lack of source control or if polymicrobial infections required &gt;1 antibiotic for definitive therapy. Patients were classified based on body mass index (BMI): non-obese (BMI ≤29.9 kg/m 2) and obese (BMI ≥30.0 kg/m 2). The primary outcome was clinical treatment failure, and secondary were hospital length of stay (LOS), inpatient all-cause mortality, and 30-day all-cause readmission. Results There were 257 (43.6%) obese patients and 332 (56.4%) non-obese patients included. The most common infections were urinary (50.9%) and respiratory (31.4%). Definitive treatment was driven by 3 rd generation cephalosporins (46.9%) and cefepime (44.7%). Treatment failure occurred in 131 (51%) obese patients and 109 (32.8%) non-obese patients (p&lt;0.001). Obesity and respiratory source were independently associated with increased likelihood of treatment failure. Obese patients were hospitalized longer than non-obese patients (p=0.002), but no differences were found for all-cause mortality (p=0.117) or infection-related readmission (0=0.112). Conclusions Obese patients treated with BLs have higher rates of treatment failure and longer hospitalization periods than non-obese patients. Future studies are needed to assess the impact of TDM and specific dosing recommendations for targeted infection types.

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