scholarly journals Pharmacokinetic/Pharmacodynamic Determinants of Vancomycin Efficacy in Enterococcal Bacteremia

2017 ◽  
Vol 62 (3) ◽  
Author(s):  
Muhammed Taufiq Bin Jumah ◽  
Shawn Vasoo ◽  
Sanjay R. Menon ◽  
Partha Pratim De ◽  
Michael Neely ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Regression Tree ◽  
Classification And Regression Tree ◽  
Vancomycin Therapy ◽  
Content Type ◽  
Regression Tree Analysis ◽  
Gradient Diffusion ◽  
All Cause Mortality ◽  
Mic Value ◽  
Enterococcal Bacteremia

ABSTRACTWhile pharmacokinetic-pharmacodynamic targets for vancomycin therapy are recognized for invasive methicillin-resistantStaphylococcus aureusinfections, scant data are available to guide therapy for other Gram-positive infections. A retrospective single-center cohort of patients withEnterococcusbacteremia hospitalized between 1 January 2009 and 31 May 2015 were studied. The average vancomycin AUC0–24was computed using a Bayesian approach. The MIC was determined by gradient diffusion (Etest; bioMérieux), and the average AUC0–24/MIC value over the initial 72 h of therapy was calculated. We assessed 30-day all-cause mortality as the primary outcome. Classification and regression tree analysis (CART) was used to identify the vancomycin AUC0–24/MIC value associated with 30-day mortality. Fifty-seven patients with enterococcal bacteremia (32E. faecium, 21E. faecalis, and 4 otherEnterococcusspp.) were studied. The median vancomycin MIC was 0.75 mg/liter (range, 0.38 to 3 mg/liter). All-cause 30-day mortality occurred in 10 of 57 patients (17.5%). A CART-derived vancomycin AUC/MICEtestvalue of ≥389 was associated with reduced mortality (P= 0.017); failure to achieve this independently predicted 30-day mortality (odds ratio, 6.83 [95% confidence interval = 1.51 to 30.84];P= 0.01). We found that a vancomycin AUC/MICEtestvalue of ≥389 achieved within 72 h was associated with reduced mortality. Larger, prospective studies are warranted to verify the vancomycin pharmacodynamic targets associated with maximal clinical outcomes and acceptable safety.

scholarly journals Pharmacodynamic Analysis of Daptomycin-treated Enterococcal Bacteremia: It Is Time to Change the Breakpoint

2018 ◽  
Vol 68 (10) ◽  
pp. 1650-1657 ◽  
Author(s):  
Lindsay M Avery ◽  
Joseph L Kuti ◽  
Maja Weisser ◽  
Adrian Egli ◽  
Michael J Rybak ◽  
...  
Keyword(s):  
Regression Tree ◽  
Classification And Regression Tree ◽  
Population Pharmacokinetic ◽  
Time Curve ◽  
Regression Tree Analysis ◽  
Lactam Antibiotic ◽  
Infection Source ◽  
High Doses ◽  
Susceptibility Breakpoint ◽  
Enterococcal Bacteremia

Abstract Background Currently, there is debate over whether the daptomycin susceptibility breakpoint for enterococci (ie, minimum inhibitory concentration [MIC] ≤4 mg/L) is appropriate. In bacteremia, observational data support prescription of high doses (>8 mg/kg). However, pharmacodynamic targets associated with positive patient outcomes are undefined. Methods Data were pooled from observational studies that assessed outcomes in daptomycin-treated enterococcal bacteremia. Patients who received an additional antienterococcal antibiotic and/or a β-lactam antibiotic at any time during treatment were excluded. Daptomycin exposures were calculated using a published population pharmacokinetic model. The free drug area under the concentration-time curve to MIC ratio (fAUC/MIC) threshold predictive of survival at 30 days was identified by classification and regression tree analysis and confirmed with multivariable logistic regression. Monte Carlo simulations determined the probability of target attainment (PTA) at clinically relevant MICs. Results Of 114 patients who received daptomycin monotherapy, 67 (58.8%) were alive at 30 days. A fAUC/MIC >27.43 was associated with survival in low-acuity (n = 77) patients (68.9 vs 37.5%, P = .006), which remained significant after adjusting for infection source and immunosuppression (P = .026). The PTA for a 6-mg/kg/day (every 24 hours) dose was 1.5%–5.5% when the MIC was 4 mg/L (ie, daptomycin-susceptible) and 91.0%–97.9% when the MIC was 1 mg/L. Conclusions For enterococcal bacteremia, a daptomycin fAUC/MIC >27.43 was associated with 30-day survival among low-acuity patients. As pharmacodynamics for the approved dose are optimized only when MIC ≤1 mg/L, these data continue to stress the importance of reevaluation of the susceptibility breakpoint.

scholarly journals Multicenter Study of the Relationship between Carbapenem MIC Values and Clinical Outcome of Patients with Acinetobacter Bacteremia

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Ya-Sung Yang ◽  
Yung-Chih Wang ◽  
Shu-Chen Kuo ◽  
Chung-Ting Chen ◽  
Chang-Pan Liu ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Regression Tree ◽  
Classification And Regression Tree ◽  
Rank Test ◽  
Bivariate Analysis ◽  
Content Type ◽  
Medical Centers ◽  
Regression Tree Analysis ◽  
Log Rank Test ◽  
The Relationship

ABSTRACT The Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) offer different recommendations for carbapenem MIC susceptibility breakpoints for Acinetobacter species. In addition, the clinical efficacy of the intermediate category remains uncertain. This study was designed to determine the optimal predictive breakpoints based on the survival of patients with Acinetobacter bacteremia treated with a carbapenem. We analyzed the 30-day mortality rates of 224 adults who received initial carbapenem monotherapy for the treatment of Acinetobacter bacteremia at 4 medical centers over a 5-year period, according to the carbapenem MICs of the initial isolates. The 30-day mortality was about 2-fold greater in patients whose isolates had carbapenem MICs of ≥8 mg/liter than in those with isolates with MICs of ≤4 mg/liter. The differences were significant by bivariate analysis (53.1% [60/113] versus 25.2% [28/111], respectively; P < 0.001) and on survival analysis by the log rank test (P < 0.001). Classification and regression tree analysis revealed a split between MICs of 4 and 8 mg/liter and predicted the same difference in mortality, with a P value of <0.001. Carbapenem treatment for Acinetobacter bacteremia caused by isolates with carbapenem MICs of ≥8 mg/liter was an independent predictor of 30-day mortality (odds ratio, 4.218; 95% confidence interval, 2.213 to 8.039; P < 0.001). This study revealed that patients with Acinetobacter bacteremia treated with a carbapenem had a more favorable outcome when the carbapenem MICs of their isolates were ≤4 mg/liter than those with MICs of ≥8 mg/liter.

scholarly journals Clinical Pharmacodynamics of Antipseudomonal Cephalosporins in Patients with Ventilator-Associated Pneumonia

2013 ◽  
Vol 58 (3) ◽  
pp. 1359-1364 ◽  
Author(s):  
Shawn H. MacVane ◽  
Joseph L. Kuti ◽  
David P. Nicolau
Keyword(s):  
Confidence Interval ◽  
Regression Tree ◽  
Classification And Regression Tree ◽  
Population Pharmacokinetic ◽  
Ventilator Associated Pneumonia ◽  
Gram Negative ◽  
Content Type ◽  
Regression Tree Analysis ◽  
Dosing Regimens ◽  
Predictor Of Success

ABSTRACTAdvanced-generation cephalosporins are frequently used for empirical coverage of ventilator-associated pneumonia (VAP) due to their activity against a broad spectrum of Gram-positive and Gram-negative aerobic bacteria, includingPseudomonas aeruginosaandEnterobacteriaceae. Providing optimal antibiotic exposure is essential to achieving successful response in patients with VAP. We evaluated exposures of two antipseudomonal cephalosporins, ceftazidime and cefepime, in patients with VAP due to Gram-negative bacilli to identify the pharmacodynamic parameter predictive of microbiological success. Population pharmacokinetic models were used to estimate individual free drug exposures. Pharmacodynamic indices were determined for each patient using the baseline Gram-negative bacilli with the highest drug MIC. Classification and regression tree analysis was utilized to partition exposure breakpoints, and multivariate logistic regression was conducted to identify predictors of microbiological success. A total of 73 patients (18 receiving ceftazidime therapy and 55 receiving cefepime therapy) were included. MICs ranged widely from 0.047 to 96 μg/ml. The microbiological success rate was 58.9%. Predictive breakpoints were identified for all pharmacodynamic parameters, including a serumfT > MIC greater than 53% (P= 0.02). When controlling for APACHE II (odds ratio [OR], 1.01; 95% confidence interval, 0.93 to 1.09;P= 0.85) and combination therapy (OR, 0.74; 95% confidence interval, 0.25 to 2.19;P= 0.59), achieving a greater than 53%fT > MIC remained a significant predictor of success (OR, 10.3; 95% confidence interval, 1.1 to 92.3;P= 0.04). In patients with VAP due to Gram-negative bacilli, serum exposure of greater than 53%fT > MIC was found to be a significant predictor of favorable microbiological response for antipseudomonal cephalosporins. These data are useful when determining dosing regimens for cephalosporin agents under development for pneumonia.

scholarly journals Time above the MIC of Piperacillin-Tazobactam as a Predictor of Outcome in Pseudomonas aeruginosa Bacteremia

2020 ◽  
Vol 64 (8) ◽  
Author(s):  
Elias Tannous ◽  
Shelly Lipman ◽  
Antonella Tonna ◽  
Emma Hector ◽  
Ziad Hussein ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Regression Tree ◽  
Free Fraction ◽  
Classification And Regression Tree ◽  
Bacterial Killing ◽  
Tree Analysis ◽  
Content Type ◽  
Regression Tree Analysis ◽  
Classification And Regression

ABSTRACT Pseudomonas aeruginosa bacteremia is an infection associated with a high mortality rate. Piperacillin-tazobactam is a β-lactam–β-lactamase inhibitor combination that is frequently used for the management of Pseudomonas aeruginosa infections. The pharmacokinetic-pharmacodynamic index associated with in vitro maximal bacterial killing for piperacillin-tazobactam is the percentage of the time between doses at which the free fraction concentration remains above the MIC (%fT>MIC). However, the precise %fT>MIC target associated with improved clinical outcomes is unknown. The aim of this study was to investigate the correlation between the survival of patients with Pseudomonas aeruginosa bacteremia and the threshold of the piperacillin-tazobactam %fT>MIC. This retrospective study included all adult patients hospitalized over an 82-month period with Pseudomonas aeruginosa bacteremia and treated with piperacillin-tazobactam. Patients with a polymicrobial infection or those who died within 72 h of the time of collection of a sample for culture were excluded. The %fT>MIC of piperacillin-tazobactam associated with in-hospital survival was derived using classification and regression tree analysis. After screening 270 patients, 78 were eligible for inclusion in the study; 18% died during hospitalization. Classification and regression tree analysis identified a %fT>MIC of >60.68% to be associated with improved survival, and this remained statistically significant after controlling for clinical covariates (odds ratio = 7.74, 95% confidence interval = 1.32 to 45.2). In conclusion, the findings recommend dosing of piperacillin-tazobactam with the aim of achieving a pharmacodynamic target %fT>MIC of at least 60% in these patients.

Structuring subjectivity in Asian Englishes

2017 ◽  
Vol 10 (1) ◽  
pp. 132-164 ◽  
Author(s):  
Sandra C. Deshors
Keyword(s):  
Developmental Process ◽  
Multiple Correspondence Analysis ◽  
Regression Tree ◽  
Classification And Regression Tree ◽  
Multivariate Techniques ◽  
Content Type ◽  
Language Varieties ◽  
Regression Tree Analysis ◽  
Usage Patterns ◽  
Varietal Variation

This study investigates the usage patterns of four near-synonymous mental predicates (believe, guess, suppose and think) across three Asian ESL (English as a Second Language) varieties as well as British and American Englishes. Using two multivariate techniques, multiple correspondence analysis and classification and regression tree analysis, the study shows the benefits of exploring cross-varietal variation through the lens of lexicalization patterns. The study also demonstrates that to make sense of semantic patterns it is crucial to account for extra-linguistic factors such as genre, as different ESL writers structure the meaning of believe, guess, suppose and think differently depending on their type of writing. Ultimately, in the broader context of the emancipation of ESL varieties, the results raise important questions about the developmental process of Asian Englishes and the place that semantic structure holds in this endeavor.

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