scholarly journals 688: VANCOMYCIN AREA UNDER THE CURVE/MINIMUM INHIBITORY CONCENTRATION AND CORRESPONDING TROUGH IN AN ICU

2021 ◽  
Vol 50 (1) ◽  
pp. 338-338
Author(s):  
Sherif Ahmed ◽  
Michael Miller
2021 ◽  
Vol 7 (6) ◽  
pp. 425
Author(s):  
Brendan O’Kelly ◽  
Aia Mohamed ◽  
Colm Bergin ◽  
Fiona Lyons ◽  
Thomas R. Rogers ◽  
...  

We describe the successful use of isavuconazole for treatment of an HIV-positive patient with cryptococcal meningitis following induction therapy with liposomal amphotericin B and flucytosine. Because the Cryptococcus neoformans isolate from cerebrospinal fluid had a borderline minimum inhibitory concentration of 8 mg/L, initial consolidation therapy was given with a daily dose of fluconazole 1200 mg based on area under the curve to minimum inhibitory concentration modelling data. Toxicity, and the radiological emergence of a cryptococcoma in the setting of immune reconstitution inflammatory syndrome, prompted a therapeutic switch to isavuconazole. Subsequent imaging after 19 weeks of isavuconazole shows a significant reduction in cryptococcoma size from 11 mm to complete resolution. The patient remains well after 210 days of therapy with a view to completion of treatment after 1 year.


2019 ◽  
Vol 6 (10) ◽  
Author(s):  
Supavit Chesdachai ◽  
Radha Rajasingham ◽  
Melanie R Nicol ◽  
David B Meya ◽  
Felix Bongomin ◽  
...  

Abstract Background Fluconazole is lifesaving for treatment and prevention of cryptococcosis; however, optimal dosing is unknown. Initial fluconazole doses of 100 mg to 2000 mg/day have been used. Prevalence of fluconazole nonsusceptible Cryptococcus is increasing over time, risking the efficacy of long-established standard dosing. Based on current minimum inhibitory concentration (MIC) distribution, we modeled fluconazole concentrations and area under the curve (AUC) relative to MIC to propose a rational fluconazole dosing strategy. Method We conducted a systematic review using the MEDLINE database for reports of fluconazole MIC distribution against clinical Cryptococcus isolates. Then, we utilized fluconazole concentrations from 92 Ugandans who received fluconazole 800mg/day coupled with fluconazole’s known pharmacokinetics to predict plasma fluconazole concentrations for doses ranging from 100 mg to 2000 mg via linear regression. The fluconazole AUC above MIC ratio were calculated using Monte Carlo simulation and using the MIC distribution elucidated during the systemic review. Results We summarized 21 studies with 11 049 clinical Cryptococcus isolates. Minimum inihibitory concentrations were normally distributed with a geometric mean of 3.4 µg/mL, median (MIC50) of 4 µg/mL, and 90th percentile (MIC90) of 16 µg/mL. The median MIC50 trended upwards from 4 µg/mL in 2000–2012 to 8 µg/mL in 2014–2018. Predicted subtherapeutic fluconazole concentrations (below MIC) would occur in 40% with 100 mg, 21% with 200 mg, and 9% with 400 mg. The AUC:MIC ratio >100 would occur in 53% for 400 mg, 74% for 800 mg, 83% for 1200 mg, and 88% for 1600 mg. Conclusions Currently recommended fluconazole doses may be inadequate for cryptococcosis. Further clinical studies are needed for rational fluconazole dose selection.


2020 ◽  
Vol 27 (2) ◽  
pp. 201-208
Author(s):  
Ayda Esmaeili ◽  
Mohammadreza Salehi ◽  
Nava Makhdoomi ◽  
Yalda H. Ardakani ◽  
Mehdi Rajabi ◽  
...  

Background: The recent studies emphasized on the correlation of vancomycin antibacterial effect with pharmacokinetics properties such as the area under the curve/minimum inhibitory concentration (AUC24/MIC) ≥400 and serum trough level 15-20 mg /L in the patients with severe infection with methicillin-resistant Staphylococcus aureus (MRSA). The purpose is to assay the vancomycin pharmacokinetic properties in our population and evaluates the correlation between AUC24/MIC and trough serum level of vancomycin in given patients. Methods: The patients with a positive MRSA culture, treated with vancomycin, were enrolled in this cross-sectional study. Three plasma samples were obtained during the study including 30 min before fourth and the fifth dose as trough levels and 1 hour after the fourth dose as peak level to determine AUC24. E-TEST determined the MIC of vancomycin. Results: Thirty-eight patients with an average age of 48.33±16.44 were enrolled in this study. The mean ± SD of MIC was 0.99±0.30 mg/L. Thirty-four patients reached the adequate therapeutic range of AUC24/MIC ≥ 400 due to the standard vancomycin dosing method. In comparison, only 7 and 10 patients had the first and second trough levels in target intervals of 15-20 mg/L, respectively. Due to the receiver operating characteristic curve test (ROC test), the trough level after the fourth dose had a strong correlation with target AUC24/MIC with a sensitivity of 94.1%and specificity of 75.0%. Conclusion: This study concluded using only a trough level is not appropriate for therapeutic drug monitoring (TDM) of vancomycin. In our population, target AUC24/MIC (≥ 400) had a reasonably strong correlation with the trough level before the fifth dose which achieved with trough level ≥10.81 mg/L and MIC< 1 mg/L.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S717-S718
Author(s):  
Supavit Chesdachai ◽  
Radha Rajasingham ◽  
Melanie R Nicol ◽  
David Meya ◽  
Felix Bongomin ◽  
...  

Abstract Background Fluconazole is lifesaving for the treatment and prevention of cryptococcosis; however, optimal dosing is unknown. Initial fluconazole doses of 100 mg to 2000 mg/day have been used. Prevalence of fluconazole non-susceptible Cryptococcus is increasing over time, risking the efficacy of long-established standard dosing. Based on current minimum inhibitory concentration (MIC) distribution, we modeled fluconazole concentration and area under the curve (AUC) relative to MIC to propose a rational fluconazole dosing strategy. Methods First, we conducted a systematic review using the MEDLINE database for reports of fluconazole MIC distribution against clinical Cryptococcus isolates. Second, we utilized fluconazole concentrations from 92 Ugandans who received fluconazole 800 mg/day coupled with fluconazole’s known pharmacokinetics to predict plasma fluconazole concentrations for doses ranging from 100 mg to 2000 mg via linear regression. Third, the fluconazole AUC above MIC ratio were calculated using Monte Carlo simulation and using the MIC distribution elucidated during the systemic review. Results We summarized 21 studies with 11,094 clinical Cryptococcus isolates. MICs were normally distributed with geometric mean of 3.4 mg/mL, median (MIC50) of 4 mg/mL, and 90th percentile (MIC90) of 16 mg/mL. The median MIC50 trended upwards from 4 mg/mL in 2000–2012 to 8 mg/mL in 2014–2018. Predicted sub-therapeutic fluconazole concentrations (below MIC) would occur in 38% with 100 mg, 20% with 200 mg, and 8% with 400 mg. AUC/MIC ratio > 100 would occur in 53% for 400 mg, 74% for 800 mg, 84% for 1200 mg, and 88% for 1,600 mg. Conclusion Currently recommended fluconazole doses may be inadequate for cryptococcosis. Further clinical studies are needed for rational fluconazole dose selection. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 21 (11) ◽  
pp. 1129-1137 ◽  
Author(s):  
Somayeh Mirsadeghi ◽  
Masoumeh F. Koudehi ◽  
Hamid R. Rajabi ◽  
Seied M. Pourmortazavi

Background: Herein, we report the biosynthesis procedure to prepare silver nanoparticles as reduction and capping agents with the aqueous plant extract of Perovskia abrotanoides. Methods: The therapeutic application of silver nanoparticles entirely depends on the size and shape of the nanoparticles therefore, their control during the synthesis procedure is so important. The effects of synthesis factors, for example, silver ion concentration, the mass of plant extract, reaction time and extraction temperature, on the size of silver particles were considered and optimized. Several analytical methods were used for the characterization of silver NPs including FT-IR and UV–Vis spectrophotometer, XRD and SEM. Results: The results showed that the mean size of the silver particles was about 51 nm. Moreover, the antibacterial properties of biosynthesized silver NPs were investigated by the minimum inhibitory concentration, minimum bactericidal concentration, and Well-diffusion tests. The minimum inhibitory concentration/ minimum bactericidal concentration values of silver NPs and aqueous plant extract versus Gram-positive bacteria (Staphylococcus aureus and Bacillus cereus) and Gram-negative bacteria (E. coli) were 3.03/0.00, 1.20/0.01, 3.06/0.00, 0.98/1.04, 1.00/0.05 and 1.30/0.03 (mg/mL), respectively. Conclusion: The antimicrobial activity study displayed that the synthesized silver nanoparticles by plant extract have better antimicrobial properties compared to aqueous plant extract of Perovskia abrotanoides.


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