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

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.

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Relation between carotid vulnerable plaques and peripheral leukocyte: A case-control study of comparison utilizing multi-parametric CEUS

10.21203/rs.2.10587/v2 ◽

2019 ◽

Author(s):

Xianghong Luo ◽

Wanbin Li ◽

Yun Bai ◽

Lianfang Du ◽

Rong Wu ◽

...

Keyword(s):

Area Under The Curve ◽

Regression Tree ◽

Classification And Regression Tree ◽

Peripheral Leukocyte ◽

Regression Tree Analysis ◽

Vulnerable Plaques ◽

Asymptomatic Patients ◽

Contrast Enhanced ◽

The Relationship ◽

Control Study

Abstract Background: This study evaluates carotid vulnerable plaques using contrast-enhanced ultrasound (CEUS) and explores the relationship between vulnerable plaques and leukocytes.Methods: Sixty-two symptomatic and 54 asymptomatic patients underwent CEUS. The images were analyzed using time-intensity and fitting curves, and peak (PTIC), mean (MTIC), peak (PFC), sharpness (SFC), and area under the curve (AUCFC) were obtained. The relations between CEUS parameters and leukocytes were analyzed.Results: In the symptomatic group, total leukocytes and neutrophils were higher, while lymphocyte was decreased; PTIC, MTIC, PFC, SFC,, and AUCFC were significantly higher; MTIC and AUCFC were negatively correlated with lymphocytes, and MTIC was positively correlated with neutrophils. Classification and regression tree analysis showed that MTIC at a cutoff of 20.8 and AUCFC at a cutoff of 8.8 resulted in a predictive of acute cerebral infarction, accuracy of 84.3%, sensitivity of 87.1%, and specificity of 81.5%.Conclusions: The variation in the perivascular leucocyte is significantly related to intraplaque inflammatory activities, CEUS is a feasible monitor of intraplaque neovascularization, so CEUS combined with perivascular leucocyte could be helpful as a warning for vulnerable plaques.

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Pharmacokinetic/Pharmacodynamic Determinants of Vancomycin Efficacy in Enterococcal Bacteremia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01602-17 ◽

2017 ◽

Vol 62 (3) ◽

Cited By ~ 6

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.

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Multicenter Study of Clinical Features of Breakthrough Acinetobacter Bacteremia during Carbapenem Therapy

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00931-17 ◽

2017 ◽

Vol 61 (9) ◽

Cited By ~ 5

Author(s):

Yi-Tzu Lee ◽

Yung-Chih Wang ◽

Shu-Chen Kuo ◽

Chung-Ting Chen ◽

Chang-Pan Liu ◽

...

Keyword(s):

Survival Analysis ◽

Mortality Rate ◽

Cox Regression ◽

Severity Of Illness ◽

Carbapenem Resistance ◽

Resistance Rate ◽

Rank Test ◽

Bivariate Analysis ◽

Content Type ◽

Log Rank Test

ABSTRACT Breakthrough Acinetobacter bacteremia during carbapenem therapy is not uncommon, and it creates therapeutic dilemmas for clinicians. This study was conducted to evaluate the clinical and microbiological characteristics of breakthrough Acinetobacter bacteremia during carbapenem therapy and to assess the efficacy of various antimicrobial therapies. We analyzed 100 adults who developed breakthrough Acinetobacter bacteremia during carbapenem therapy at 4 medical centers over a 6-year period. Their 30-day mortality rate was 57.0%, and the carbapenem resistance rate of their isolates was 87.0%. Among patients with carbapenem-resistant Acinetobacter bacteremia, breakthrough bacteremia during carbapenem therapy was associated with a significantly higher 14-day mortality (51.7% versus 37.4%, respectively; P = 0.025 by bivariate analysis) and a higher 30-day mortality (P = 0.037 by log rank test of survival analysis) than in the nonbreakthrough group. For the treatment of breakthrough Acinetobacter bacteremia during carbapenem therapy, tigecycline-based therapy was associated with a significantly higher 30-day mortality (80.0%) than those with continued carbapenem therapy (52.5%) and colistin-based therapy (57.9%) by survival analysis (P = 0.047 and 0.045 by log rank test, respectively). Cox regression controlling for confounders, including severity of illness indices, demonstrated that treatment with tigecycline-based therapy for breakthrough Acinetobacter bacteremia was an independent predictor of 30-day mortality (hazard ratio, 3.659; 95% confidence interval, 1.794 to 7.465; P < 0.001). Patients with breakthrough Acinetobacter bacteremia during carbapenem therapy posed a high mortality rate. Tigecycline should be used cautiously for the treatment of breakthrough Acinetobacter bacteremia that develops during carbapenem therapy.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01463-13 ◽

2013 ◽

Vol 58 (3) ◽

pp. 1359-1364 ◽

Cited By ~ 41

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.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02571-19 ◽

2020 ◽

Vol 64 (8) ◽

Cited By ~ 1

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.

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The Overlooked Immune State in Candidemia: A Risk Factor for Mortality

Journal of Clinical Medicine ◽

10.3390/jcm8101512 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1512 ◽

Cited By ~ 1

Author(s):

Ortega-Loubon ◽

Cano-Hernández ◽

Poves-Alvarez ◽

Muñoz-Moreno ◽

Román-García ◽

...

Keyword(s):

Lymphocyte Count ◽

Independent Predictor ◽

Area Under The Curve ◽

Regression Tree ◽

Classification And Regression Tree ◽

Multivariable Logistic Regression Analysis ◽

Poor Outcome ◽

Regression Tree Analysis ◽

The Impact ◽

The Relationship

Lymphopenia has been related to increased mortality in septic patients. Nonetheless, the impact of lymphocyte count on candidemia mortality and prognosis has not been addressed. We conducted a retrospective study, including all admitted patients with candidemia from 2007 to 2016. We examined lymphocyte counts during the first 5 days following the diagnosis of candidemia. Multivariable logistic regression analysis was performed to determine the relationship between lymphocyte count and mortality. Classification and Regression Tree analysis was used to identify the best cut-off of lymphocyte count for mortality associated with candidemia. From 296 cases of candidemia, 115 died, (39.8% 30-day mortality). Low lymphocyte count was related to mortality and poor outcome (p < 0.001). Lymphocyte counts < 0.703 × 109 cells/L at diagnosis (area under the curve (AUC)-ROC, 0.783 ± 0.042; 95% confidence interval (CI), 0.700–0.867, p < 0.001), and lymphocyte count < 1.272 × 109 cells/L five days later (AUC-ROC, 0.791 ± 0.038; 95%CI, 0.716–0.866, p < 0.001) increased the odds of mortality five-fold (odds ratio (OR), 5.01; 95%CI, 2.39–10.93) at time of diagnosis, and three-fold (OR, 3.27; 95%CI, 1.24–8.62) by day 5, respectively. Low lymphocyte count is an independent predictor of mortality in patients with candidemia and might serve as a biomarker for predicting candidemia-associated mortality and poor outcome.

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Relation between carotid vulnerable plaques and peripheral leukocyte: A case-control study of comparison utilizing multi-parametric CEUS

10.21203/rs.2.10587/v1 ◽

2019 ◽

Author(s):

Xianghong Luo ◽

Wanbin Li ◽

Yun Bai ◽

Lianfang Du ◽

Rong Wu ◽

...

Keyword(s):

Area Under The Curve ◽

Regression Tree ◽

Classification And Regression Tree ◽

Peripheral Leukocyte ◽

Regression Tree Analysis ◽

Vulnerable Plaques ◽

Asymptomatic Patients ◽

Contrast Enhanced ◽

The Relationship ◽

Control Study

Abstract Background This study evaluates carotid vulnerable plaques using contrast-enhanced ultrasound (CEUS) and explores the relationship between vulnerable plaques and leukocytes. Methods Sixty-two symptomatic and 54 asymptomatic patients underwent CEUS. The images were analyzed using time-intensity and fitting curves, and peak (PTIC), mean (MTIC), peak (PFC), sharpness (SFC), and area under the curve (AUCFC) were obtained. The relations between CEUS parameters and leukocytes were analyzed. Results In the symptomatic group, total leukocytes and neutrophils were higher, while lymphocyte was decreased; PTIC, MTIC, PFC, SFC and AUCFC were significantly higher; MTIC and AUCFC were negatively correlated with lymphocytes, and MTIC was positively correlated with neutrophils. Classification and regression tree analysis showed that MTIC at a cutoff of 20.8 and AUCFC at a cutoff of 8.8 resulted in a predictive of acute cerebral infarction, accuracy of 84.3%, sensitivity of 87.1%, and specificity of 81.5%. Conclusions CEUS is a feasible predictor of vulnerable plaques, and related to leukocytes.

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Structuring subjectivity in Asian Englishes

English Text Construction ◽

10.1075/etc.10.1.07des ◽

2017 ◽

Vol 10 (1) ◽

pp. 132-164 ◽

Cited By ~ 4

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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