scholarly journals Inflammation Is Associated with Voriconazole Trough Concentrations

2014 ◽  
Vol 58 (12) ◽  
pp. 7098-7101 ◽  
Author(s):  
Marjolijn J. P. van Wanrooy ◽  
Lambert F. R. Span ◽  
Michael G. G. Rodgers ◽  
Edwin R. van den Heuvel ◽  
Donald R. A. Uges ◽  
...  

ABSTRACTVoriconazole concentrations display a large variability, which cannot completely be explained by known factors. Inflammation may be a contributing factor, as inflammatory stimuli can change the activities and expression levels of cytochrome P450 isoenzymes. We explored the correlation between inflammation, reflected by C-reactive protein (CRP) concentrations, and voriconazole trough concentrations. A retrospective chart review of patients with at least one steady-state voriconazole trough concentration and a CRP concentration measured on the same day was performed. A total of 128 patients were included. A significantly (P< 0.001) higher voriconazole trough concentration was observed in patients with severe inflammation (6.2 mg/liter; interquartile range [IQR], 3.4 to 8.7 mg/liter;n= 20) than in patients with moderate inflammation (3.4 mg/liter; IQR, 1.6 to 5.4 mg/liter;n= 60) and in patients with no to mild inflammation (1.6 mg/liter; IQR, 0.8 to 3.0 mg/liter;n= 48). The patients in all three groups received similar voriconazole doses based on mg/kg body weight (P= 0.368). Linear regression analyses, both unadjusted and adjusted for covariates of gender, age, dose, route of administration, liver enzymes, and interacting coadministered medications, showed a significant association between voriconazole and CRP concentration (P< 0.001). For every 1-mg/liter increase in the CRP concentration, the voriconazole trough concentration increased by 0.015 mg/liter (unadjusted 95% confidence interval [CI], 0.011 to 0.020 mg/liter; adjusted 95% CI, 0.011 to 0.019 mg/liter). Inflammation, reflected by the C-reactive protein concentration, is associated with voriconazole trough concentrations. Further research is necessary to assess if taking the inflammatory status of a patient into account is helpful in therapeutic drug monitoring of voriconazole to maintain concentrations in the therapeutic window, thereby possibly preventing suboptimal treatment or adverse events.

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Bonny Rockette-Wagner ◽  
Claudia Holzman ◽  
Bertha L Bullen ◽  
Andrew D Althouse ◽  
Janet M Catov

Introduction: Elevated serum C-reactive protein (CRP) can be a marker of disease activity involving inflammation, such as pregnancy complications and cardiovascular disease (CVD). Systemically high levels of CRP in women, including during pregnancy, may indicate higher risk for CVD. It is unknown if CRP measured during the pro-inflammatory state of pregnancy correlates with concentrations assessed 7-13 years after delivery. Hypothesis: Concentrations of CRP assessed during pregnancy will be related to CRP measured several years after pregnancy, independent of weight gain. Methods: We studied the first 252 women enrolled in the follow-up of the Pregnancy Outcomes and Community Health Study (POUCHmoms 2011-2013) with complete CRP data for the pregnancy (mean gestational age: 22.36 [2.22] weeks) and POUCHmoms visits (mean follow-up: 10.76 [1.38] years). The relative risk for high hsCRP (≥ 3.39 μg/ml) at the follow-up visit, related to quartiles of CRP during pregnancy, was examined using stepwise regression models. Results: Median (IQR) levels of pregnancy CRP and hsCRP at the follow-up visit were 5.68 [3.08, 9.76] and 3.39 [0.69, 9.73] μg/ml, respectively. Although absolute values of hsCRP at follow-up were generally lower than pregnancy CRP, 56% of women in the top and bottom quartiles of pregnancy CRP (71 of 126) were in the same quartile for hsCRP at follow-up (figure). The relative risk of having high hsCRP (≥ 3.39 μg/ml) at follow-up ranged from 2.7-5.2 for the 2 nd - 4 th quartiles of pregnancy CRP (vs. the 1st quartile). Controlling for pre-pregnancy BMI and follow-up weight change, the relative risk of having high hsCRP at follow-up was significantly higher for the 2 nd (1.15 [1.02-1.30]),3 rd (1.19 [1.05-1.35), and 4 th (1.22 [1.05-1.41]) quartiles of pregnancy CRP. Conclusions: Pregnancy CRP levels are related to hsCRP levels several years later in this cohort of women, even after adjusting for pre-pregnancy BMI and follow-up weight change. CRP assessed in pregnancy may reflect inflammatory status later in life.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Manzoor Parry ◽  
Hamad Jeelani

Abstract Background and Aims The prevalence of chronic kidney disease (CKD) in India varies from 0.16–0.78%. The reported incidence of malnutrition in CKD patients is 37–84%. There is a paucity of data on the quantification of malnutrition and inflammation in undialyzed patients of CKD from north east of India. This study analyzed the prevalence and causes of malnutrition and inflammation in patients with CKD before the initiation of dialysis treatment. Method This study was conducted from May 2017 to May 2019 in the department of nephrology Guahati medical college hospital. Assessment of nutritional and inflammatory status was carried out in patients with CKD before initiation of dialysis. Serum albumin; body mass index (BMI); triceps skin fold thickness (TST); mid-arm muscle circumference (MAMC); and subjective global assessment (SGA) scoring were used for assessment of nutritional parameters. Serum C-reactive protein; serum albumin and serum ferritin level were used to assess the inflammatory status in these patients. Results A total of 528 (male:female= 359:169) patients with CKD participated in this study. Diabetic Nephropathy (35%) was the most common; followed by; hypertension (23%) and chronic glomerulonephritis (20 %). The evidence of malnutrition was noted in 344 (65%). The mean age of patients with malnutrition was 52.8±12.45 years with a male predominance (68%). On the basis of SGA score; malnutrition was noted in 344 patients (mild moderate [36%]; severe; [30%]); remaining (34%) were well nourished. Thus; evidence of Malnutrition was noted in 65% of patients with CKD.). Serum total protein & albumin were higher in the non-malnourished patients in comparison to malnourished (5.83±1.0 vs 5.31±1.12 p&lt;0.05; 3.65±0.7 vs 2.62±0.74) The inflammatory markers (serum ferritin & C reactive protein) were elevated significantly in patients with malnutrition in comparison to those without malnutrition (308.15±60.18 mg/dL vs. 251.64±63.14 mg/dL; p &lt; 0.001; 77% vs. 50%; p &lt; 0.01). Conclusion Malnutrition and inflammation are common in patients with CKD before the commencement of dialysis. This indicates that an emphasis should be placed on the assessment and prevention or correction of malnutrition and inflammatory burden in these patients with CKD.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Christina M Parrinello ◽  
Pamela L Lutsey ◽  
Christie M Ballantyne ◽  
Aaron R Folsom ◽  
James S Pankow ◽  
...  

Background: High levels of C-reactive protein (CRP) are associated with cardiovascular disease, diabetes and mortality. It is unclear whether changes in CRP or persistently high CRP are associated with these outcomes beyond the baseline measure. Methods: We conducted a prospective cohort analysis of 10,229 participants from the ARIC Study with two measurements of CRP six years apart (at visits 2 and 4, 1990-92 and 1996-98, respectively). CRP was categorized into two groups using a standard cut-point for defining high levels (≥3 vs. <3 mg/L). Six-year change in CRP was categorized as: persistently not high (<3 mg/L), decreasing (≥3 to <3 mg/L), increasing (<3 to ≥3 mg/L), and persistently high (≥3 mg/L). Cox proportional hazards models were used to assess the association between visit 2 CRP, visit 4 CRP and six-year change in CRP and each of the following outcomes from visit 4 through 2010: diabetes, coronary heart disease, ischemic stroke, heart failure and all-cause mortality. Models were adjusted for traditional risk factors at visit 2. Sensitivity analyses additionally adjusted for visit 4 covariates. Results: Persons with CRP ≥3 mg/L at visit 2 or 4 had higher risk of each outcome compared to those with CRP <3 mg/L ( Table ). We observed higher risk of all outcomes in persons with persistently high CRP, and of all outcomes except stroke in persons with increasing CRP, compared to those with CRP <3 mg/L at both visits ( Table ). Persons whose CRP decreased from high to <3 mg/L did not have significantly increased risk of cardiovascular outcomes or diabetes compared to those with CRP persistently <3 mg/L. Results were similar after adjusting for visit 4 covariates. Conclusions: Persons with sustained high levels of CRP or whose CRP increased to high levels had higher risk of diabetes, cardiovascular disease, and death, while those whose levels decreased from high to moderate or low were at lower risk. Multiple measures of CRP may better characterize inflammatory status and provide more comprehensive information regarding long-term risk.


2017 ◽  
Vol 42 (1) ◽  
pp. 01-07
Author(s):  
Sufia Jannat ◽  
MD Abdul Kader Akanda ◽  
Md Khalequzzaman ◽  
Mohammad Ullah ◽  
Md Monirujjaman ◽  
...  

Emerging evidence links an elevated baseline inflammatory status to adverse outcome among patients undergoing percutaneous coronary intervention (PCI). Baseline inflammation measured by high sensitivity C-reactive protein hsCRP may prove useful for identification of high risk patients requiring adjunctive therapies. This prospective study was carried out in the department of cardiology, National Institute of Cardiovascular Diseases, Dhaka, during October 2012 to September 2013.Two hundred consecutive patients with CSA and UA undergoing PCI were included in the study. Study patients were divided into two groups on the basis of hsCRP levels. In Group I hsCRP levels were elevated, that is ?3 mg/L and in Group II hsCRP levels were normal, that is < 3 mg/L, with 100 patients in each group. Fol-lowing the procedure in-hospital outcome of study patients were observed. Increased inci-dence (44%) of adverse in-hospital outcome was found in Group I (44% Vs. 11%). Higher incidence of post procedural angina (17%), peri-procedural myocardial infarction (6%) and peri-procedural myocardial injury (10%) was observed in this group. Nonsignificant rate of acute myocardial infarction, significant arrhythmia, acute LVF, cardiogenic shock and death were found in elevated hsCRP Group. Overall Major Adverse Cardiac Events (6% Vs. 0%) were found in pre-procedural elevated hsCRP group. High sensitivity C-reactive protein remained independently predictive of adverse in-hospital outcome, with 95% CI of RR 1.4 – 4.4 and p<001. The present study concludes that the hsCRP is an important and independent predictor of adverse in hospital outcome.


1990 ◽  
Vol 266 (1) ◽  
pp. 283-290 ◽  
Author(s):  
A S Whitehead ◽  
K Zahedi ◽  
M Rits ◽  
R F Mortensen ◽  
J M Lelias

A full-length C-reactive protein (CRP) cDNA clone has been isolated from a CBA/J-strain-mouse acute-phase liver library. The 1614-nucleotide cDNA specifies mRNA 5′ and 3′ untranslated regions of 81 and 858 bases respectively that flank 675 bases encoding mouse pre-CRP. The derived amino acid sequence predicts a 19-residue leader peptide followed by a 206-residue mature mouse CRP that shows considerable sequence identity with both human and rabbit CRP. Northern-blot analysis of mouse liver CRP mRNA concentrations after inflammatory stimuli and comparison with hepatic induction of mRNA for the major mouse acute-phase protein serum amyloid P component established that CRP, a major acute-phase reactant in human and rabbit, is a minor acute-phase reactant in mouse. The size and organization of the mouse CRP mRNA 5′ and 3′ untranslated regions are significantly different from those of human and rabbit CRP mRNA and may have implications for its anomalous minimal induction during acute inflammation.


2018 ◽  
Vol 62 (4) ◽  
pp. e01647-17 ◽  
Author(s):  
Sheng-Hsuan Tseng ◽  
Chuan Poh Lim ◽  
Qi Chen ◽  
Cheng Cai Tang ◽  
Sing Teang Kong ◽  
...  

ABSTRACT Bacterial sepsis is a major cause of morbidity and mortality in neonates, especially those involving methicillin-resistant Staphylococcus aureus (MRSA). Guidelines by the Infectious Diseases Society of America recommend the vancomycin 24-h area under the concentration-time curve to MIC ratio (AUC24/MIC) of >400 as the best predictor of successful treatment against MRSA infections when the MIC is ≤1 mg/liter. The relationship between steady-state vancomycin trough concentrations and AUC24 values (mg·h/liter) has not been studied in an Asian neonatal population. We conducted a retrospective chart review in Singapore hospitals and collected patient characteristics and therapeutic drug monitoring data from neonates on vancomycin therapy over a 5-year period. A one-compartment population pharmacokinetic model was built from the collected data, internally validated, and then used to assess the relationship between steady-state trough concentrations and AUC24. A Monte Carlo simulation sensitivity analysis was also conducted. A total of 76 neonates with 429 vancomycin concentrations were included for analysis. Median (interquartile range) was 30 weeks (28 to 36 weeks) for postmenstrual age (PMA) and 1,043 g (811 to 1,919 g) for weight at the initiation of treatment. Vancomycin clearance was predicted by weight, PMA, and serum creatinine. For MRSA isolates with a vancomycin MIC of ≤1, our major finding was that the minimum steady-state trough concentration range predictive of achieving an AUC24/MIC of >400 was 8 to 8.9 mg/liter. Steady-state troughs within 15 to 20 mg/liter are unlikely to be necessary to achieve an AUC24/MIC of >400, whereas troughs within 10 to 14.9 mg/liter may be more appropriate.


1991 ◽  
Vol 72 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Andreas Nussler ◽  
Sylvianne Pied ◽  
Michel Pontet ◽  
Francois Miltgen ◽  
Laurent Renia ◽  
...  

2007 ◽  
Vol 22 (suppl 1) ◽  
pp. 40-45 ◽  
Author(s):  
Mardem Machado de Souza ◽  
José Eduardo de Aguilar-Nascimento ◽  
Diana Borges Dock-Nascimento

PURPOSE: The aim of this study was to investigate the effect of enemas containing probiotics and budesonide on the systemic inflammatory response in experimental colitis. METHODS: Fifty male Wistar rats with experimental colitis induced by 10% acetic acid enema were randomized to five groups (10 rats each) according to the treatment: group 1 - saline solution, group 2 - budesonide (0.75 mg/kg/day), group 3 - probiotics (1mg/day), group 4 - probiotics plus budesonide, and group 5 - control, with not-treated rats. The following variables were studied: body weight, serum levels of albumin, C-reactive protein and interleucine-6 (IL-6). RESULTS: All animals lost weight between the beginning and the end of the experiment (280+ 16 mg versus 249+21 mg, p< 0.001). There was a significant decrease in the serum albumin between the normal pre-induction level (3.45 + 0.49mg/dL) and the 1st day after colitis induction (1.61+051mg/dL, p< 0.001) in all treated groups when compared to the control group. C- reactive protein increased after induction and diminished on the 7th day in all groups. In the control group there was an increase in the IL-6 after colitis induction. None of the treated groups significantly differed from IL-6 pre-colitis status (p>0.05). Only probiotic rats presented a significant decrease of IL-6 than controls (0,30±0,08 mg/dL vs. 0,19±0,03 mg/dL; p<0.01). CONCLUSION: Probiotic associated with budesonida Probiotics are effective to diminished inflammatory status mediated by IL-6 in experimental colitis.


Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1130
Author(s):  
Yichang Zhao ◽  
Jingjing Hou ◽  
Yiwen Xiao ◽  
Feng Wang ◽  
Bikui Zhang ◽  
...  

This prospective observational study aimed to clinically describe voriconazole administrations and trough concentrations in patients with Child–Pugh class C and to investigate the variability of trough concentration. A total of 144 voriconazole trough concentrations from 43 Child–Pugh class C patients were analyzed. The majority of patients (62.8%) received adjustments. The repeated measured trough concentration was higher than the first and final ones generally (median, 4.33 vs. 2.99, 3.90 mg/L). Eight patients with ideal initial concentrations later got supratherapeutic with no adjusted daily dose, implying accumulation. There was a significant difference in concentrations among the six groups by daily dose (p = 0.006). The bivariate correlation analysis showed that sex, CYP2C19 genotyping, daily dose, prothrombin time activity, international normalized ratio, platelet, and Model for end-stage liver disease score were significant factors for concentration. Subsequently, the first four factors mentioned above entered into a stepwise multiple linear regression model (variance inflation factor <5), implying that CYP2C19 testing makes sense for precision medicine of Child–Pugh class C cirrhosis patients. The equation fits well and explains the 34.8% variety of concentrations (R2 = 0.348). In conclusion, it needs more cautious administration clinically due to no recommendation for Child–Pugh class C patients in the medication label. The adjustment of the administration regimen should be mainly based on the results of repeated therapeutic drug monitoring.


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