scholarly journals Impact of Nonlinear Interactions of Pharmacokinetics and MICs on Sputum Bacillary Kill Rates as a Marker of Sterilizing Effect in Tuberculosis

2014 ◽  
Vol 59 (1) ◽  
pp. 38-45 ◽  
Author(s):  
Emmanuel Chigutsa ◽  
Jotam G. Pasipanodya ◽  
Marianne E. Visser ◽  
Paul D. van Helden ◽  
Peter J. Smith ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Sputum Sample ◽  
Bactericidal Effect ◽  
Multivariate Adaptive Regression Splines ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Content Type ◽  
Drug Concentrations ◽  
Adaptive Regression ◽  
Rate Of Decline

ABSTRACTThe relationships between antituberculosis drug exposure and treatment effects on humans receiving multidrug therapy are complex and nonlinear. In patients on treatment, an analysis of the rate of decline in the sputum bacillary burden reveals two slopes. The first is the α-slope, which is thought to reflect bactericidal effect, followed by a β-slope, which is thought to reflect sterilizing activity. We sought to characterize the effects of standard first-line treatment on sterilizing activity. Fifty-four patients receiving combination therapy for pulmonary tuberculosis in a clinical trial had drug concentrations measured andMycobacterium tuberculosisisolates available for MIC identification. Sputum sample cultures were performed at baseline and weekly for 8 weeks. A time-to-event model based on the days to positivity in the liquid cultures was used to estimate the β-slope. The pharmacokinetic parameters of rifampin, isoniazid, ethambutol, and pyrazinamide were determined for each patient. Multivariate adaptive regression splines analyses, which simultaneously perform linear and nonlinear analyses, were used to identify the relationships between the predictors and the β-slope. The potential predictors examined included HIV status, lung cavitation, 24-h area under the concentration-time curve (AUC), peak drug concentration (Cmax), AUC/MIC ratio,Cmax/MIC ratio, and the time that that concentration persisted above MIC. A rifampinCmaxof >8.2 mg/liter and a pyrazinamide AUC/MIC of >11.3 were key predictors of the β-slope and interacted positively to increase the β-slope. In patients with a rifampin AUC of <35.4 mg · h/liter, an increase in the pyrazinamide AUC/MIC and/or ethambutolCmax/MIC increased the β-slope, while increasing isoniazidCmaxdecreased it, suggesting isoniazid antagonism. Antibiotic concentrations and MICs interact in a nonlinear fashion as the main drivers of a sterilizing effect. The results suggest that faster speeds of sterilizing effect might be achieved by omitting isoniazid and by increasing rifampin, pyrazinamide, and ethambutol exposures. However, isoniazid and ethambutol exposures may only be of importance when rifampin exposure is low. These findings need confirmation in larger studies. (This study has been registered atcontrolled-trials.comunder registration no. ISRCTN80852505.)

Pharmacokinetics and Monte Carlo Simulations of Doripenem in Patients with Febrile Neutropenia

2012 ◽  
Vol 46 (10) ◽  
pp. 1281-1286 ◽  
Author(s):  
Gary E Stein ◽  
Grace Kulhanek ◽  
Curtis L Smith ◽  
Joseph L Kuti ◽  
David P Nicolau ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Febrile Neutropenia ◽  
Drug Exposure ◽  
Elimination Rate ◽  
Pharmacokinetic Parameters ◽  
Gram Negative Bacteria ◽  
Time Curve ◽  
Gram Negative ◽  
Probability Estimates ◽  
Drug Concentrations

Background: Doripenem is a group 2 carbapenem with enhanced in vitro activity against gram-negative bacteria including Pseudomonas aeruginosa. There is a paucity of pharmacokinetic/pharmacodynamic data on doripenem in patients with febrile neutropenia. Objective: To conduct a pharmacokinetic evaluation of 2 doses of doripenem in patients with febrile neutropenia and provide probability estimates of attaining effective drug exposure against common gram-negative pathogens. Methods: We obtained multiple blood samples from 12 adults with febrile neutropenia who were receiving either 500 mg or 1000 mg of intravenous doripenem over 4 hours every B hours. Following at least 2 doses, serum concentrations were measured in each subject at 1, 4, 6, and 8 hours after initiation of a dose by a validated high-performance liquid chromatography assay. The derived pharmacokinetic parameters from these serum levels were used to perform a 5000-patient Monte Carlo simulation against bacteria with minimal inhibitory concentrations (MICs) of 0.008-64 mg/L to determine probability estimates of the time in which unbound drug concentrations remain above the MIC (fT>MIC). Results: The mean pharmacokinetic parameters in these patients were a volume of distribution of 43.9 L, an elimination rate constant of 0.37 h-1, a total clearance of 14.4 L/h, and an area under the concentration-time curve of 57.6 mg·h/L. An optimal probability of target attainment (40% fT>MIC) of 90% was obtained against bacteria with MICs ≤2 mg/L and ≤4 mg/L with 500-mg and 1000-mg doses, respectively. Adverse events associated with doripenem were not observed. Conclusions: The findings from this analysis of doripenem suggest that higher doses, as well as prolonged infusions, may be necessary to optimally treat selected gram-negative bacteria (eg, P. aeruginosa) in patients with febrile neutropenia.

scholarly journals Pharmacokinetic/Pharmacodynamic Evaluation of a Novel Aminomethylcycline Antibiotic, KBP-7072, in the Neutropenic Murine Pneumonia Model against Staphylococcus aureus and Streptococcus pneumoniae

2018 ◽  
Vol 63 (3) ◽  
Author(s):  
Alexander J. Lepak ◽  
Miao Zhao ◽  
Qingmei Liu ◽  
Ping Wang ◽  
Yanli Wang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Rational Design ◽  
Dose Range ◽  
Free Drug ◽  
Pharmacokinetic Parameters ◽  
Infection Model ◽  
Time Curve ◽  
Content Type ◽  
Drug Concentrations

ABSTRACT KBP-7072 is a novel aminomethylcycline antibiotic in clinical development for community-acquired pneumonia. The goal of present studies was to determine which pharmacokinetic/pharmacodynamic (PK/PD) parameter magnitude correlated with efficacy in the murine pneumonia infection model against Staphylococcus aureus and Streptococcus pneumoniae. KBP-7072 pharmacokinetic measurements were performed in plasma and epithelial lining fluid (ELF) at 4-fold-increasing doses from 1 to 256 mg/kg of body weight subcutaneously. Pharmacokinetic parameters were calculated using a noncompartmental model and were linear over the dose range. Penetration into ELF ranged from 82% to 238% comparing ELF drug concentrations to plasma free drug concentrations. Twenty-four-hour dose-ranging efficacy studies were then performed in the neutropenic murine pneumonia model against 5 S. aureus (3 methicillin-resistant and 2 methicillin-susceptible) and 6 S. pneumoniae (2 Tetr and 2 Penr) strains. KBP-7072 demonstrated potent in vivo activity resulting in a 3- to 5-log10 kill in CFU burden compared to the start of therapy for all strains. The PK/PD index area under the concentration-time curve (AUC)/MIC corelated well with efficacy (R2, 0.80 to 0.89). Net stasis was achieved at plasma 24-h free drug AUC/MIC values of 1.13 and 1.41 (24-h ELF AUC/MIC values of 2.01 and 2.50) for S. aureus and S. pneumoniae, respectively. A 1-log10 kill was achieved at 24-h plasma AUC/MIC values of 2.59 and 5.67 (24-h ELF AUC/MIC values of 4.22 and 10.08) for S. aureus and S. pneumoniae, respectively. A 2-log10 kill was achieved at 24-h plasma AUC/MIC values of 7.16 and 31.14 (24-h ELF AUC/MIC values of 8.37 and 42.92) for S. aureus and S. pneumoniae, respectively. The results of these experiments will aid in the rational design of dose-finding studies for KBP-7072 in patients with community-acquired bacterial pneumonia (CAP).

scholarly journals Population Pharmacokinetics and Dosing of Ethionamide in Children with Tuberculosis

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Henrik Bjugård Nyberg ◽  
Heather R. Draper ◽  
Anthony J. Garcia-Prats ◽  
Stephanie Thee ◽  
Adrie Bekker ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Multidrug Resistant ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Limited Information ◽  
Once Daily ◽  
Content Type ◽  
Mixed Effects Modeling ◽  
Hiv Coinfection ◽  
Antituberculosis Treatment

ABSTRACT Ethionamide has proven efficacy against both drug-susceptible and some drug-resistant strains of Mycobacterium tuberculosis. Limited information on its pharmacokinetics in children is available, and current doses are extrapolated from weight-based adult doses. Pediatric doses based on more robust evidence are expected to improve antituberculosis treatment, especially in small children. In this analysis, ethionamide concentrations in children from 2 observational clinical studies conducted in Cape Town, South Africa, were pooled. All children received ethionamide once daily at a weight-based dose of approximately 20 mg/kg of body weight (range, 10.4 to 25.3 mg/kg) in combination with other first- or second-line antituberculosis medications and with antiretroviral therapy in cases of HIV coinfection. Pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling. The MDR-PK1 study contributed data for 110 children on treatment for multidrug-resistant tuberculosis, while the DATiC study contributed data for 9 children treated for drug-susceptible tuberculosis. The median age of the children in the studies combined was 2.6 years (range, 0.23 to 15 years), and the median weight was 12.5 kg (range, 2.5 to 66 kg). A one-compartment, transit absorption model with first-order elimination best described ethionamide pharmacokinetics in children. Allometric scaling of clearance (typical value, 8.88 liters/h), the volume of distribution (typical value, 21.4 liters), and maturation of clearance and absorption improved the model fit. HIV coinfection decreased the ethionamide bioavailability by 22%, rifampin coadministration increased clearance by 16%, and ethionamide administration by use of a nasogastric tube increased the rate, but the not extent, of absorption. The developed model was used to predict pediatric doses achieving the same drug exposure achieved in 50- to 70-kg adults receiving 750-mg once-daily dosing. Based on model predictions, we recommend a weight-banded pediatric dosing scheme using scored 125-mg tablets.

scholarly journals Paritaprevir and Ritonavir Liver Concentrations in Rats as Assessed by Different Liver Sampling Techniques

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Charles S. Venuto ◽  
Marianthi Markatou ◽  
Yvonne Woolwine-Cunningham ◽  
Rosemary Furlage ◽  
Andrew J. Ocque ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Needle Aspiration ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Time Curve ◽  
Tissue Samples ◽  
Drug Concentrations ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass

ABSTRACT The liver is crucial to pharmacology, yet substantial knowledge gaps exist in the understanding of its basic pharmacologic processes. An improved understanding for humans requires reliable and reproducible liver sampling methods. We compared liver concentrations of paritaprevir and ritonavir in rats by using samples collected by fine-needle aspiration (FNA), core needle biopsy (CNB), and surgical resection. Thirteen Sprague-Dawley rats were evaluated, nine of which received paritaprevir/ritonavir at 30/20 mg/kg of body weight by oral gavage daily for 4 or 5 days. Drug concentrations were measured using liquid chromatography-tandem mass spectrometry on samples collected via FNA (21G needle) with 1, 3, or 5 passes (FNA1, FNA3, and FNA5); via CNB (16G needle); and via surgical resection. Drug concentrations in plasma were also assessed. Analyses included noncompartmental pharmacokinetic analysis and use of Bland-Altman techniques. All liver tissue samples had higher paritaprevir and ritonavir concentrations than those in plasma. Resected samples, considered the benchmark measure, resulted in estimations of the highest values for the pharmacokinetic parameters of exposure (maximum concentration of drug in serum [C max] and area under the concentration-time curve from 0 to 24 h [AUC0–24]) for paritaprevir and ritonavir. Bland-Altman analyses showed that the best agreement occurred between tissue resection and CNB, with 15% bias, followed by FNA3 and FNA5, with 18% bias, and FNA1 and FNA3, with a 22% bias for paritaprevir. Paritaprevir and ritonavir are highly concentrated in rat liver. Further research is needed to validate FNA sampling for humans, with the possible derivation and application of correction factors for drug concentration measurements.

scholarly journals Apotransferrin in Combination with Ciprofloxacin Slows Bacterial Replication, Prevents Resistance Amplification, and Increases Antimicrobial Regimen Effect

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Paul G. Ambrose ◽  
Brian D. VanScoy ◽  
Brian M. Luna ◽  
Jun Yan ◽  
Amber Ulhaq ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Bactericidal Effect ◽  
Bacterial Density ◽  
Infection Model ◽  
Time Curve ◽  
Content Type ◽  
Wide Range ◽  
Bacterial Replication ◽  
The Impact

ABSTRACT There has been renewed interest in combining traditional small-molecule antimicrobial agents with nontraditional therapies to potentiate antimicrobial effects. Apotransferrin, which decreases iron availability to microbes, is one such approach. We conducted a 48-h one-compartment in vitro infection model to explore the impact of apotransferrin on the bactericidal activity of ciprofloxacin. The challenge panel included four Klebsiella pneumoniae isolates with ciprofloxacin MIC values ranging from 0.08 to 32 mg/liter. Each challenge isolate was subjected to an ineffective ciprofloxacin monotherapy exposure (free-drug area under the concentration-time curve over 24 h divided by the MIC [AUC/MIC ratio] ranging from 0.19 to 96.6) with and without apotransferrin. As expected, the no-treatment and apotransferrin control arms showed unaltered prototypical logarithmic bacterial growth. We identified relationships between exposure and change in bacterial density for ciprofloxacin alone (R2 = 0.64) and ciprofloxacin in combination with apotransferrin (R2 = 0.84). Addition of apotransferrin to ciprofloxacin enabled a remarkable reduction in bacterial density across a wide range of ciprofloxacin exposures. For instance, at a ciprofloxacin AUC/MIC ratio of 20, ciprofloxacin monotherapy resulted in nearly 2 log10 CFU increase in bacterial density, while the combination of apotransferrin and ciprofloxacin resulted in 2 log10 CFU reduction in bacterial density. Furthermore, addition of apotransferrin significantly reduced the emergence of ciprofloxacin-resistant subpopulations compared to monotherapy. These data demonstrate that decreasing the rate of bacterial replication with apotransferrin in combination with antimicrobial therapy represents an opportunity to increase the magnitude of the bactericidal effect and to suppress the growth rate of drug-resistant subpopulations.

scholarly journals Bactericidal Effect and Pharmacodynamics of Cethromycin (ABT-773) in a Murine Pneumococcal Pneumonia Model

2002 ◽  
Vol 46 (10) ◽  
pp. 3185-3192 ◽  
Author(s):  
Myo-Kyoung Kim ◽  
Wen Zhou ◽  
Pamela R. Tessier ◽  
Dawei Xuan ◽  
Min Ye ◽  
...  
Keyword(s):  
Goodness Of Fit ◽  
Drug Exposure ◽  
Bactericidal Effect ◽  
Free Drug ◽  
Bacterial Density ◽  
Maximum Effect ◽  
Time Curve ◽  
Initiation Of Therapy

ABSTRACT Cethromycin (ABT-773), a new ketolide, possesses potent in vitro activity against Streptococcus pneumoniae. The objective of this study was to investigate the in vivo bactericidal activity of cethromycin against macrolide-susceptible and -resistant S. pneumoniae in a murine pneumonia model and to describe the pharmacodynamic (PD) profile of cethromycin. Eight (two macrolide susceptible, six macrolide resistant) clinical isolates of S. pneumoniae were investigated. Cyclophosphamide administration rendered ICR mice transiently neutropenic prior to intratracheal inoculation with 0.05 ml of an S. pneumoniae suspension containing 107 to 108 CFU/ml. Oral cethromycin was initiated 12 to 14 h postinoculation over a dosage range of 0.1 to 800 mg/kg of body weight/day. Lungs from seven to eight mice per treatment and control groups were collected at 0 and 24 h posttherapy to assess bacterial density. The cumulative mortality (n = 12 to 13) was assessed at 120 h (end of therapy) and at 192 h (3 days posttherapy). Recovery of pneumococci from the lungs of infected animals prior to the initiation of therapy ranged from 4.6 to 7.2 log10 CFU. Growth in untreated control animals over a 24-h study period increased 0.3 to 2.7 log10 CFU. Cethromycin demonstrated a substantial bactericidal effect, regardless of macrolide susceptibility. Correlation between changes in bacterial density (24 h) and survival over both 120 and 192 h were statistically significant. All three PD parameters demonstrated a significant correlation with changes in log10 CFU/lung (Spearman's correlation coefficient, P < 0.001); however, the goodness of fit as assessed with the maximum effect (E max) model revealed that the maximum concentration of free drug in serum (C max free)/MIC and the area under the free drug concentration-time curve (AUCfree)/MIC best explained the relationship between drug exposure and reductions in viable bacterial counts. These data reveal that an approximate cethromycin AUCfree/MIC of 50 or C max free/MIC of 1 results in bacteriostatic effects, while higher values (twofold) maximize survival.

scholarly journals Comparative Study on Pharmacokinetics of Four Long-Acting Injectable Formulations of Enrofloxacin in Pigs

2021 ◽  
Vol 7 ◽  
Author(s):  
Salah Uddin Ahmad ◽  
Jichao Sun ◽  
Fusheng Cheng ◽  
Bing Li ◽  
Safia Arbab ◽  
...  
Keyword(s):  
Comparative Study ◽  
High Performance ◽  
Pasteurella Multocida ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Reference Formulation ◽  
Time Curve ◽  
Drug Concentrations ◽  
Long Acting

A comparative study on pharmacokinetics of four long-acting enrofloxacin injectable formulations was investigated in 36 healthy pigs after intramuscular injection according to the recommended single dose @ 2.5 mg/kg body weight. The drug concentrations in the plasma were computed using high-performance liquid chromatography (HPLC) with fluorescence detection. WinNonLin5.2.1 software was used to analyze the experimental data and compared it under one-way ANOVA using SPSS software with a 95% confidence interval (CI). The main pharmacokinetic parameters, that is, the maximum plasma concentrations (Cmax), the time to maximum concentration (Tmax), area under the time curve concentration (AUCall) and Terminal half-life (T1/2) were 733.84 ± 129.87, 917.00 ± 240.13, 694.84 ± 163.49, 621.98 ± 227.25 ng/ml, 2.19 ± 0.0.66, 1.50 ± 0.37, 2.89 ± 0.24, 0.34 ± 0.13 h, 7754.43 ± 2887.16, 8084.11 ± 1543.98, 7369.42 ± 2334.99, 4194.10 ± 1186.62 ng h/ml, 10.48 ± 2.72, 10.37 ± 2.38, 10.20 ± 2.81, and 10.61 ± 0.86 h for 10% enrofloxacin (Alkali), 20% enrofloxacin (Acidic), Yangkang and control drug Nuokang® respectively. There were significant differences among Cmax, Tmax, and AUCall of three formulations compare with that of the reference formulation. No significant differences were observed among the T1/2 for tested formulations compare with the reference formulation. The pharmacokinetic parameters showed that the tested formulations were somewhat better compared to the reference one. The calculated PK/PD indices were effective for bacteria such as Actinobacillus pleuropneumoniae and Pasteurella multocida with values higher than the cut-off points (Cmax/MIC90≥10–12 and AUC/MIC90 ≥ 125). However, they were not effective against bacteria like Haemophilus parasuis, Streptococcus suis, E. coli, and Bordetella bronchiseptica where lower values were obtained.

scholarly journals Kinetic Driver of Antibacterial Drugs against Plasmodium falciparum and Implications for Clinical Dosing

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Emily Caton ◽  
Elizabeth Nenortas ◽  
Rahul P. Bakshi ◽  
Theresa A. Shapiro
Keyword(s):  
Plasmodium Falciparum ◽  
Response Characteristic ◽  
Microtiter Plate ◽  
Fiber System ◽  
Time Curve ◽  
Antibacterial Drugs ◽  
Content Type ◽  
Drug Concentrations ◽  
Static Conditions

ABSTRACT Antibacterial drugs are an important component of malaria therapy. We studied the interactions of clindamycin, tetracycline, chloramphenicol, and ciprofloxacin against Plasmodium falciparum under static and dynamic conditions. In microtiter plate assays (static conditions), and as expected, parasites displayed the delayed death response characteristic for apicoplast-targeting drugs. However, rescue by isopentenyl pyrophosphate was variable, ranging from 2,700-fold for clindamycin to just 1.7-fold for ciprofloxacin, suggesting that ciprofloxacin has targets other than the apicoplast. We also examined the pharmacokinetic-pharmacodynamic relationships of these antibacterials in an in vitro glass hollow-fiber system that exposes parasites to dynamically changing drug concentrations. The same total dose and area under the concentration-time curve (AUC) of the drug was deployed either as a single short-lived high peak (bolus) or as a constant low concentration (infusion). All four antibacterials were unambiguously time-driven against malaria parasites: infusions had twice the efficacy of bolus regimens, for the same AUC. The time-dependent efficacy of ciprofloxacin against malaria is in contrast to its concentration-driven action against bacteria. In silico simulations of clinical dosing regimens and resulting pharmacokinetics revealed that current regimens do not maximize time above the MICs of these drugs. Our findings suggest that simple and rational changes to dosing may improve the efficacy of antibacterials against falciparum malaria.

scholarly journals Pharmacokinetics of Miltefosine in Children and Adults with Cutaneous Leishmaniasis

2016 ◽  
Vol 61 (3) ◽  
Author(s):  
María del Mar Castro ◽  
Maria Adelaida Gomez ◽  
Anke E. Kip ◽  
Alexandra Cossio ◽  
Eduardo Ortiz ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Drug Exposure ◽  
Mononuclear Cells ◽  
Open Label ◽  
Time Curve ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Liquid Chromatography Tandem Mass ◽  
Intracellular Compartments

ABSTRACT An open-label pharmacokinetics (PK) clinical trial was conducted to comparatively assess the PK and explore the pharmacodynamics (PD) of miltefosine in children and adults with cutaneous leishmaniasis (CL) in Colombia. Sixty patients, 30 children aged 2 to 12 years and 30 adults aged 18 to 60 years, were enrolled. Participants received miltefosine (Impavido) at a nominal dose of 2.5 mg/kg/day for 28 days. Miltefosine concentrations were measured in plasma and peripheral blood mononuclear cells by liquid chromatography-tandem mass spectrometry of samples obtained during treatment and up to 6 months following completion of treatment, when therapeutic outcome was determined. Fifty-two patients were cured, 5 pediatric patients failed treatment, and 3 participants were lost to follow-up. Leishmania (Viannia) panamensis predominated among the strains isolated (42/46; 91%). Noncompartmental analysis demonstrated that plasma and intracellular miltefosine concentrations were, overall, lower in children than in adults. Exposure to miltefosine, estimated by area under the concentration-time curve and maximum concentration, was significantly lower in children in both the central and intracellular compartments (P < 0.01). Leishmania persistence was detected in 43% of study participants at the end of treatment and in 27% at 90 days after initiation of treatment. Clinical response was not dependent on parasite elimination. In vitro miltefosine susceptibility was similar for Leishmania strains from adults and children. Our results document PK differences for miltefosine in children and adults with cutaneous leishmaniasis that affect drug exposure and could influence the outcome of treatment, and they provide bases for optimizing therapeutic regimens for CL in pediatric populations. (This study has been registered at ClinicalTrials.gov under identifier NCT01462500.)

scholarly journals Failure of Posaconazole Therapy in a Renal Transplant Patient with Invasive Aspergillosis Due to Aspergillus fumigatus with Attenuated Susceptibility to Posaconazole

2011 ◽  
Vol 55 (7) ◽  
pp. 3564-3566 ◽  
Author(s):  
Saskia Kuipers ◽  
Roger J. M. Brüggemann ◽  
Ruud G. L. de Sévaux ◽  
John P. F. A. Heesakkers ◽  
Willem J. G. Melchers ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Drug Exposure ◽  
Renal Transplant Patient ◽  
Transplant Patient ◽  
Kidney Transplant Recipient ◽  
Time Curve ◽  
Content Type ◽  
Concentration Time

ABSTRACTWe report the case of a kidney transplant recipient with invasive aspergillosis due toAspergillus fumigatusresistant to voriconazole and intermediately susceptible to posaconazole who failed posaconazole therapy. Plasma posaconazole concentrations indicated an unfavorable ratio of the area under the concentration-time curve over the MIC. Posaconazole should be used with caution for invasive aspergillosis caused by strains with attenuated posaconazole susceptibility, as drug exposure may be inadequate, resulting in therapeutic failure.

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