Peak perihemorrhagic edema correlates with functional outcome in intracerebral hemorrhage

ObjectiveTo evaluate the association of perihemorrhagic edema (PHE) evolution and peak edema extent with day 90 functional outcome in patients with intracerebral hemorrhage (ICH) and identify pathophysiologic factors influencing edema evolution.MethodsThis retrospective cohort study included patients with spontaneous supratentorial ICH between January 2006 and January 2014. ICH and PHE volumes were studied using a validated semiautomatic volumetric algorithm. Multivariable logistic regression and propensity score matching (PSM) accounting for age, ICH volume, and location were used for assessing measures associated with functional outcome and PHE evolution. Clinical outcome on day 90 was assessed using the modified Rankin Scale (0–3 = favorable, 4–6 = poor).ResultsA total of 292 patients were included. Median age was 70 years (interquartile range [IQR] 62–78), median ICH volume on admission 17.7 mL (IQR 7.9–40.2). Besides established factors for functional outcome, i.e., ICH volume and location, age, intraventricular hemorrhage, and NIH Stroke Scale score on admission, multivariable logistic regression revealed peak PHE volume (odds ratio [OR] 0.984 [95% confidence interval (CI) 0.973–0.994]) as an independent predictor of day 90 outcome. Peak PHE volume was independently associated with initial PHE increase up to day 3 (OR 1.060 [95% CI 1.018–1.103]) and neutrophil to lymphocyte ratio on day 6 (OR 1.236 [95% CI 1.034–1.477; PSM cohort, n = 124]). Initial PHE increase (PSM cohort, n = 224) was independently related to hematoma expansion (OR 3.647 [95% CI 1.533–8.679]) and fever burden on days 2–3 (OR 1.456 [95% CI 1.103–1.920]).ConclusionOur findings suggest that peak PHE volume represents an independent predictor of functional outcome after ICH. Inflammatory processes and hematoma expansion seem to be involved in PHE evolution and may represent important treatment targets.

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Black Hole Sign Predicts Poor Outcome in Patients with Intracerebral Hemorrhage

Cerebrovascular Diseases ◽

10.1159/000486163 ◽

2018 ◽

Vol 45 (1-2) ◽

pp. 48-53 ◽

Cited By ~ 7

Author(s):

Qi Li ◽

Wen-Song Yang ◽

Sheng-Li Chen ◽

Fu-Rong Lv ◽

Fa-Jin Lv ◽

...

Keyword(s):

Black Hole ◽

Logistic Regression ◽

Intracerebral Hemorrhage ◽

Ct Scan ◽

Functional Outcome ◽

Multivariate Logistic Regression Analysis ◽

Hematoma Expansion ◽

Poor Functional Outcome ◽

Poor Outcome ◽

Prognostic Stratification

Background: In spontaneous intracerebral hemorrhage (ICH), black hole sign has been proposed as a promising imaging marker that predicts hematoma expansion in patients with ICH. The aim of our study was to investigate whether admission CT black hole sign predicts hematoma growth in patients with ICH. Methods: From July 2011 till February 2016, patients with spontaneous ICH who underwent baseline CT scan within 6 h of symptoms onset and follow-up CT scan were recruited into the study. The presence of black hole sign on admission non-enhanced CT was independently assessed by 2 readers. The functional outcome was assessed using the modified Rankin Scale (mRS) at 90 days. Univariate and multivariable logistic regression analyses were performed to assess the association between the presence of the black hole sign and functional outcome. Results: A total of 225 patients (67.6% male, mean age 60.3 years) were included in our study. Black hole sign was identified in 32 of 225 (14.2%) patients on admission CT scan. The multivariate logistic regression analysis demonstrated that age, intraventricular hemorrhage, baseline ICH volume, admission Glasgow Coma Scale score, and presence of black hole sign on baseline CT independently predict poor functional outcome at 90 days. There are significantly more patients with a poor functional outcome (defined as mRS ≥4) among patients with black hole sign than those without (84.4 vs. 32.1%, p < 0.001; OR 8.19, p = 0.001). Conclusions: The CT black hole sign independently predicts poor outcome in patients with ICH. Early identification of black hole sign is useful in prognostic stratification and may serve as a potential therapeutic target for anti-expansion clinical trials.

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Prediction of Hematoma Expansion in Patients With Intracerebral Hemorrhage Using Thromboelastography With Platelet Mapping: A Prospective Observational Study

Frontiers in Neurology ◽

10.3389/fneur.2021.746024 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qiuguang He ◽

You Zhou ◽

Chang Liu ◽

Zhongqiu Chen ◽

Rong Wen ◽

...

Keyword(s):

Logistic Regression ◽

Intracerebral Hemorrhage ◽

Functional Outcome ◽

Platelet Function ◽

Mediation Analysis ◽

Adenosine Diphosphate ◽

Hematoma Expansion ◽

Platelet Response ◽

Multivariate Logistic Regression ◽

Roc Curve Analysis

Background and Purpose: The purpose of the study was to evaluate the usefulness of thromboelastography with platelet mapping (TEG-PM) for predicting hematoma expansion (HE) and poor functional outcome in patients with intracerebral hemorrhage (ICH).Methods: Patients with primary ICH who underwent baseline computed tomography (CT) and TEG-PM within 6 h after symptom onset were enrolled in the observational cohort study. We performed univariate and multivariate logistic regression models to assess the association of admission platelet function with HE and functional outcome. In addition, a receiver operating characteristic (ROC) curve analysis investigated the accuracy of platelet function in predicting HE. A mediation analysis was undertaken to determine causal associations among platelet function, HE, and outcome.Results: Of 142 patients, 37 (26.1%) suffered HE. Multivariate logistic regression identified arachidonic acid (AA) and adenosine diphosphate (ADP) inhibition as significant independent predictors of HE. The area under the ROC curves was 0.727 for AA inhibition and 0.721 for ADP inhibition. Optimal threshold for AA inhibition was 41.75% (75.7% sensitivity; 67.6% specificity) and ADP inhibition was 65.8% (73.0% sensitivity; 66.7% specificity). AA and ADP inhibition were also associated with worse 3-month outcomes after adjusting for age, admission Glasgow Coma Scale score, intraventricular hemorrhage, baseline hematoma volume, and hemoglobin. The mediation analysis showed that the effect of higher platelet inhibition with poor outcomes was mediated through HE.Conclusions: These findings suggest that the reduced platelet response to ADP and AA independently predict HE and poor outcome in patients with ICH. Platelet function may represent a modifiable target of ICH treatment.

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Reported Antiplatelet Use Influences Long-Term Outcome Independently in Deep Intracerebral Hemorrhage

Neurosurgery ◽

10.1227/neu.0b013e3182311266 ◽

2011 ◽

Vol 70 (2) ◽

pp. 342-350 ◽

Cited By ~ 6

Author(s):

Joji B. Kuramatsu ◽

Christoph Mauer ◽

Ines-Christine Kiphuth ◽

Hannes Lücking ◽

Stephan P. Kloska ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Functional Outcome ◽

Independent Predictor ◽

Interquartile Range ◽

Hematoma Expansion ◽

Outcome Predictors ◽

Multivariate Models ◽

Term Outcome ◽

Long Term Outcome

Abstract BACKGROUND: Recent studies have focused on antiplatelet (AP) use in intracerebral hemorrhage (ICH) patients. Several outcome predictors have been debated, but influences on mortality and outcome still remain controversial, especially for different ICH locations. OBJECTIVE: To investigate the characteristics and functional outcome of ICH patients with reported regular AP use according to hemorrhage locations. METHODS: This retrospective analysis included 210 consecutive spontaneous ICH patients. Clinical data including the preadmission status, initial presentation, neuroradiological data, treatment, and outcome were evaluated. Analyses were calculated for AP use vs non-AP use according to hematoma locations, and multivariate models were calculated for hematoma expansion and unfavorable (modified Rankin Scale = 4–6) long-term functional outcome (at 1 year). RESULTS: For all AP users ICH volume was significantly larger, 27.7 mL (interquartile range 7.4-66.1) vs 16.8 mL (interquartile range 4.2-44.7); (P = .032). Analyses showed an increased mortality for AP users at 90 days and 1 year (P = .036; P = .008). Multivariately, for all ICH patients, prior AP use was independently associated with hematoma expansion (odds ratio [OR] 3.61; P = .026) and poorer functional outcome at 1 year (OR 3.82, P = .035). In deep ICH patients, AP use was an independent predictor of an unfavorable functional outcome at 1 year (OR 4.75, P = .048). CONCLUSION: Hematoma expansion and more frequent unfavorable long-term functional outcome were independently associated with prior AP use for all patients, and in deep ICH patients AP use was an independent predictor of an unfavorable long-term functional outcome.

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Hematoma Hounsfield units and expansion of intracerebral hemorrhage: A potential marker of hemostatic clot contraction

International Journal of Stroke ◽

10.1177/1747493019895703 ◽

2020 ◽

pp. 174749301989570 ◽

Cited By ~ 1

Author(s):

Han-Gil Jeong ◽

Jae Seung Bang ◽

Beom Joon Kim ◽

Hee-Joon Bae ◽

Moon-Ku Han

Keyword(s):

Computed Tomography ◽

Logistic Regression ◽

Intracerebral Hemorrhage ◽

Hematoma Expansion ◽

P Value ◽

Discrimination Power ◽

Multivariable Logistic Regression ◽

C Statistic ◽

Potential Marker ◽

Clot Contraction

Background Clot contraction reinforces hemostasis by providing an impermeable barrier and contractile force. Since computed tomography attenuation of intracerebral hemorrhage is largely determined by the density of red blood cells, clot contraction can be reflected in an increase of Hounsfield unit (HU) of hematoma. Aims We hypothesized that hematoma expansion is inversely associated with mean HU of intracerebral hemorrhage at presentation. Methods Eighty-nine consecutive spontaneous intracerebral hemorrhage patients with onset to first computed tomography within 24 h were included. Hematomas were segmented using semiautomated planimetry to measure the volume and mean HU. Hematoma expansion was defined as an increase in hematoma volume by over 33% or 6 mL. Multivariable logistic regression was performed for hematoma expansion. The discrimination power of mean HU for hematoma expansion was assessed using C-statistic. Results The computed tomography attenuation of hematoma at presentation was 57.5 ± 3.3 HU and the volume was 16.9 ± 23.2 mL. Hematoma expansion occurred in 37.1% of patients. The computed tomography attenuation of hematoma was lower in patients with hematoma expansion than with no expansion (55.7 ± 2.9 HU vs. 58.6 ± 3.1 HU, p-value < 0.01). Multivariable logistic regression revealed that the mean HU of hematoma was inversely associated with hematoma expansion (adjusted odds ratio, 0.64; 95% confidence interval, 0.51–0.80). The C-statistic of the model with four known predictors increased from 0.66 to 0.84 after incorporating mean HU (p-value < 0.01). Conclusions Intracerebral hemorrhage with lower mean HU of hematoma at presentation is more likely to undergo hematoma expansion. This finding suggests the potential presence of clot contraction process that reinforces hemostasis in intracerebral hemorrhage.

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Abstract W P322: Prediction of Intracerebral Hemorrhage Expansion With Clinical, Laboratory, Pharmacologic, and Noncontrast Radiographic Variables

Stroke ◽

10.1161/str.46.suppl_1.wp322 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Sheila Chan ◽

Vivek A Rao ◽

Alexander C Flint

Keyword(s):

Logistic Regression ◽

Intracerebral Hemorrhage ◽

Goodness Of Fit ◽

Clinical Laboratory ◽

Healthcare Delivery ◽

Hematoma Expansion ◽

Contrast Extravasation ◽

Head Ct ◽

Multivariable Logistic Regression ◽

D Model

Introduction: Hematoma expansion (HE) is a cause of excess mortality in intracerebral hemorrhage (ICH), and HE is potentially preventable if at-risk patients can be identified. Contrast extravasation on initial computed tomographic angiography (CTA) strongly predicts HE, yet most centers do not integrate CTA into early ICH management. We therefore asked whether other variables available at presentation might be used to predict HE. Methods: We searched the electronic medical records of a large integrated healthcare delivery system to identify patients with a hospitalization discharge diagnosis of ICH during a three year period (2008-2010). HE was defined as ICH volume increase by 1/3 or by 12.5mL, as determined by ABC/2 estimation, within 48 hours of presentation. Pre-specified patient variables including age, gender, medical comorbidities, medication use, and in-hospital vital signs were extracted. Stepwise multivariable logistic regression was performed to model HE in patients with at least two head CT scans (HE group), and HE or death by 48 hours among patients with only one head CT (HE+D group). The area under the receiver operating characteristic curve (AUROC) and pseudo r-squared (pseudo-r2) statistics were used to assess model goodness-of-fit. Results: For the 2 study cohorts, 91/257 (35%) had HE and 163/343 (48%) had HE+D. In stepwise multivariable logistic regression, antithrombotic use (OR = 1.9, P=0.04) and initial mNIHSS (OR = 1.06, P=0.001) were significant predictors in the HE model (AUROC = 0.6712, pseudo-R2 = 0.0641). In the HE+D model, age (OR = 1.02, P=0.02), initial mNIHSS (OR = 1.07, P<0.001), and initial hematoma volume (OR = 1.01, P=0.03) were significant predictors (AUROC = 0.7579, pseudo-R2 = 0.1722). Conclusion: Our model predicting HE+D was better fitted than the HE model. The resemblance to known predictors of ICH mortality in the HE+D model suggests that the improved fit may be driven by mortality rather than HE. CTA contrast extravasation remains the strongest predictor of HE and merits consideration as a standard in early ICH care.

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Hematoma Ventricle Distance on Computed Tomography Predicts Poor Outcome in Intracerebral Hemorrhage

Frontiers in Neuroscience ◽

10.3389/fnins.2020.589050 ◽

2020 ◽

Vol 14 ◽

Author(s):

Lan Deng ◽

Yun-Dong Zhang ◽

Jian-Wen Ji ◽

Wen-Song Yang ◽

Xiao Wei ◽

...

Keyword(s):

Computed Tomography ◽

Logistic Regression ◽

Intracerebral Hemorrhage ◽

Functional Outcome ◽

Final Analysis ◽

Hematoma Expansion ◽

Youden Index ◽

Multivariable Logistic Regression Analysis ◽

Poor Outcome

ObjectiveTo investigate the relationship between hematoma ventricle distance (HVD) and clinical outcome in patients with intracerebral hemorrhage (ICH).MethodsWe prospectively enrolled consecutive patients with ICH in a tertiary academic hospital between July 2011 and April 2018. We retrospectively reviewed images for all patients receiving a computed tomography (CT) within 6 h after onset of symptoms and at least one follow-up CT scan within 36 h. The minimum distance of hematoma border to nearest ventricle was measured as HVD. Youden index was used to evaluate the cutoff of HVD predicting functional outcome. Logistic regression model was used to assess the HVD data and clinical poor outcome (modified Rankin Scale 4–6) at 90 days.ResultsA total of 325 patients were included in our final analysis. The median HVD was 2.4 mm (interquartile range, 0–5.7 mm), and 119 (36.6%) patients had poor functional outcome at 3 months. After adjusting for age, admission Glasgow coma scale, intraventricular hemorrhage, baseline ICH volume, admission systolic blood pressure, blood glucose, hematoma expansion, withdrawal of care, and hypertension, HVD ≤ 2.5 mm was associated with increased odds of clinical poor outcome [odd ratio, 3.59, (95%CI = 1.72–7.50); p = 0.001] in multivariable logistic regression analysis.ConclusionHematoma ventricle distance allows physicians to quickly select and stratify patients in clinical trials and thereby serve as a novel and useful addition to predict ICH prognosis.

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Machine Learning-Based Approaches for Prediction of Patients’ Functional Outcome and Mortality after Spontaneous Intracerebral Hemorrhage

Journal of Personalized Medicine ◽

10.3390/jpm12010112 ◽

2022 ◽

Vol 12 (1) ◽

pp. 112

Author(s):

Rui Guo ◽

Renjie Zhang ◽

Ran Liu ◽

Yi Liu ◽

Hao Li ◽

...

Keyword(s):

Machine Learning ◽

Logistic Regression ◽

Intracerebral Hemorrhage ◽

Functional Outcome ◽

Laboratory Data ◽

Predictive Performance ◽

High Morbidity ◽

Spontaneous Intracerebral Hemorrhage ◽

Receiver Operating Characteristic Curves ◽

Ich Score

Spontaneous intracerebral hemorrhage (SICH) has been common in China with high morbidity and mortality rates. This study aims to develop a machine learning (ML)-based predictive model for the 90-day evaluation after SICH. We retrospectively reviewed 751 patients with SICH diagnosis and analyzed clinical, radiographic, and laboratory data. A modified Rankin scale (mRS) of 0–2 was defined as a favorable functional outcome, while an mRS of 3–6 was defined as an unfavorable functional outcome. We evaluated 90-day functional outcome and mortality to develop six ML-based predictive models and compared their efficacy with a traditional risk stratification scale, the intracerebral hemorrhage (ICH) score. The predictive performance was evaluated by the areas under the receiver operating characteristic curves (AUC). A total of 553 patients (73.6%) reached the functional outcome at the 3rd month, with the 90-day mortality rate of 10.2%. Logistic regression (LR) and logistic regression CV (LRCV) showed the best predictive performance for functional outcome (AUC = 0.890 and 0.887, respectively), and category boosting presented the best predictive performance for the mortality (AUC = 0.841). Therefore, ML might be of potential assistance in the prediction of the prognosis of SICH.

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Outcome of intracerebral hemorrhage associated with different oral anticoagulants

Neurology ◽

10.1212/wnl.0000000000003886 ◽

2017 ◽

Vol 88 (18) ◽

pp. 1693-1700 ◽

Cited By ~ 77

Author(s):

Duncan Wilson ◽

David J. Seiffge ◽

Christopher Traenka ◽

Ghazala Basir ◽

Jan C. Purrucker ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Functional Outcome ◽

Scale Score ◽

Vitamin K ◽

Pooled Analysis ◽

Vitamin K Antagonist ◽

Cox Proportional Hazards Model ◽

Hematoma Expansion ◽

All Cause Mortality ◽

International Collaborative

Objective:In an international collaborative multicenter pooled analysis, we compared mortality, functional outcome, intracerebral hemorrhage (ICH) volume, and hematoma expansion (HE) between non–vitamin K antagonist oral anticoagulation–related ICH (NOAC-ICH) and vitamin K antagonist–associated ICH (VKA-ICH).Methods:We compared all-cause mortality within 90 days for NOAC-ICH and VKA-ICH using a Cox proportional hazards model adjusted for age; sex; baseline Glasgow Coma Scale score, ICH location, and log volume; intraventricular hemorrhage volume; and intracranial surgery. We addressed heterogeneity using a shared frailty term. Good functional outcome was defined as discharge modified Rankin Scale score ≤2 and investigated in multivariable logistic regression. ICH volume was measured by ABC/2 or a semiautomated planimetric method. HE was defined as an ICH volume increase >33% or >6 mL from baseline within 72 hours.Results:We included 500 patients (97 NOAC-ICH and 403 VKA-ICH). Median baseline ICH volume was 14.4 mL (interquartile range [IQR] 3.6–38.4) for NOAC-ICH vs 10.6 mL (IQR 4.0–27.9) for VKA-ICH (p = 0.78). We did not find any difference between NOAC-ICH and VKA-ICH for all-cause mortality within 90 days (33% for NOAC-ICH vs 31% for VKA-ICH [p = 0.64]; adjusted Cox hazard ratio (for NOAC-ICH vs VKA-ICH) 0.93 [95% confidence interval (CI) 0.52–1.64] [p = 0.79]), the rate of HE (NOAC-ICH n = 29/48 [40%] vs VKA-ICH n = 93/140 [34%] [p = 0.45]), or functional outcome at hospital discharge (NOAC-ICH vs VKA-ICH odds ratio 0.47; 95% CI 0.18–1.19 [p = 0.11]).Conclusions:In our international collaborative multicenter pooled analysis, baseline ICH volume, hematoma expansion, 90-day mortality, and functional outcome were similar following NOAC-ICH and VKA-ICH.

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Liver fibrosis indices associated with substantial hematoma expansion in Chinese patients with primary intracerebral hemorrhage

BMC Neurology ◽

10.1186/s12883-021-02494-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Huan Wang ◽

Jiongxing Wu ◽

Xue Yang ◽

Junfeng Liu ◽

Wendan Tao ◽

...

Keyword(s):

Logistic Regression ◽

Liver Fibrosis ◽

Intracerebral Hemorrhage ◽

Chinese Population ◽

Binary Logistic Regression ◽

Chinese Patients ◽

Hematoma Expansion ◽

West China Hospital ◽

West China ◽

Increased Risk

Abstract Background Whether liver fibrosis is associated with increased risk for substantial hematoma expansion (HE) after intracerebral hemorrhage (ICH) is still uncertain. We evaluated the association between various liver fibrosis indices and substantial HE in a Chinese population with primary ICH. Methods Primary ICH patients admitted to West China Hospital within 24 h of onset between January 2015 and June 2018 were consecutively enrolled. Six liver fibrosis indices were calculated, including aspartate aminotransferase (AST)-platelet ratio index (APRI), AST/alanine aminotransferase ratio-platelet ratio index (AARPRI), fibrosis-4 (FIB-4), modified fibrosis-4 (mFIB-4), fibrosis quotient (FibroQ) and Forns index. Substantial HE was defined as an increase of more than 33% or 6 mL from baseline ICH volume. The association of each fibrosis index with substantial HE was analyzed using binary logistic regression. Results Of 436 patients enrolled, about 85% showed largely normal results on standard hepatic assays and coagulation parameters. Substantial HE occurred in 115 (26.4%) patients. After adjustment, AARPRI (OR 1.26, 95% CI 1.00-1.57) and FIB-4 (OR 1.15, 95% CI 1.02-1.30) were independently associated with substantial HE in ICH patients within 24 h of onset, respectively. In ICH patients within 6 h of onset, each of the following indices was independently associated with substantial HE: APRI (OR 2.64, 95% CI 1.30-5,36), AARPRI (OR 1.55, 95% CI 1.09-2.21), FIB-4 (OR 1.35, 95% CI 1.08-1.68), mFIB-4 (OR 1.09, 95% CI 1.01-1.18), FibroQ (OR 1.08, 95% CI 1.00-1.16) and Forns index (OR 1.37, 95% CI 1.10-1.69). Conclusions Liver fibrosis indices are independently associated with higher risk of substantial HE in Chinese patients with primary ICH, which suggesting that subclinical liver fibrosis could be routinely assessed in such patients to identify those at high risk of substantial HE.

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Clinical Impact of the Revised 2019 CLSI Levofloxacin Breakpoints in Patients with Enterobacterales Bacteremia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00074-21 ◽

2021 ◽

Author(s):

Ho-Yin Huang ◽

Chu-Feng Wang ◽

Po-Liang Lu ◽

Sung-Pin Tseng ◽

Ya-Ling Wang ◽

...

Keyword(s):

Logistic Regression ◽

Retrospective Cohort ◽

Primary Outcome ◽

Clinical Evidence ◽

Inhibitory Concentration ◽

Clinical Impact ◽

Secondary Outcome ◽

Lower Survival Rate ◽

Multivariable Logistic Regression ◽

Kaplan Meier

Background The Clinical and Laboratory Standards Institute (CLSI) revised the fluoroquinolone minimal inhibitory concentration (MIC) breakpoints for Enterobacterales in 2019, based on pharmacokinetic/pharmacodynamic analyses. However, clinical evidence supporting these breakpoints revision is limited. Methods A retrospective cohort was conducted at 3 hospitals in Taiwan between January 2017 and March 2019. Patients treated with levofloxacin for Enterobacterales bacteremia with high-MIC (1 or 2 μg/mL; levofloxacin-susceptible by pre-2019 CLSI breakpoints) were compared with those with low-MIC (≤0.5 μg/mL; levofloxacin-susceptible by 2019 CLSI breakpoints) to assess therapeutic effectiveness in multivariable logistic regression. The primary outcome was 30-day mortality and the secondary outcome was the emergence of levofloxacin-resistant isolates within 90 days after levofloxacin initiation. Results A total of 308 patients were eligible in the study. Kaplan-Meier analysis showed that patients infected with high-MIC isolates (n=63) had a significantly lower survival rate compared with those infected with low-MIC isolates (n=245) (p=0.001). Multivariable logistic regression revealed high levofloxacin MIC was a predictor of 30-day mortality [odds ratio (OR) 6.05, 95% confidence interval (CI) 1.51-24.18, p=0.011]. We consistently found similar result in propensity-score matched cohort (OR 5.38, 95%CI 1.06-27.39, p=0.043). The emergence of levofloxacin-resistant isolates was likely more common in the high-MIC group compared to the low-MIC group (7.5% vs. 25.0%, p=0.065). An estimated AUC/MIC ratio≥ 87 was significantly associated with better survival (p=0.002). Conclusions Patients with high levofloxacin MICs within the pre-2019 CLSI susceptible range of 1 or 2 μg/mL were associated with higher mortality compared to those with MICs ≤0.5 μg/mL.

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