Tigecycline Therapy for Infections Caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae in Critically Ill Patients

: We aimed to evaluate tigecycline on the clinical effectiveness in treating complicated skin and soft tissue infections (cSSTI), complicated intra-abdominal infections (cIAI), and pneumonia, caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, as data are limited. From three medical centers in Taiwan, we retrospectively studied the cSSTI, cIAI, and/or pneumonia caused by ESBL-producing Enterobacteriaceae. Among the 71 patients, including 39 patients infected with Klebsiella pneumoniae, 30 infected with Escherichia coli and others, the clinical success rate of tigecycline-based therapy was 80%–90% for pneumonia and cSSTI caused by E. coli and 50%–60% for cIAI caused by K. pneumoniae and E. coli. Microbiological and clinical outcome of pneumonia caused by carbapenem-resistant K. pneumoniae was poor. Univariate Cox analysis showed that dyspnea, SOFA score, septic shock, thrombocytopenia, prolonged prothrombin time, and lesser microbiological eradication were significant factors associated with 30-day mortality after the end of therapy. Cox regression proportional hazards model revealed dyspnea and a SOFA score > 8 to be independently associated with time to death. For ESBL producers, tigecycline showed good effects for cSSTI and pneumonia by E. coli, ordinary for cIAI, but ineffective for pneumonia by K. pneumoniae. Dyspnea and a high SOFA score predict a poor outcome.

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Clinical effectiveness of high dose versus standard dose of meropenem in ventilator-associated pneumonia caused by multidrug-resistant bacteria: a randomized single-blind clinical trial

Infectious Disorders - Drug Targets ◽

10.2174/1871526520666200227102013 ◽

2020 ◽

Vol 20 ◽

Author(s):

Mahila Monajati ◽

Shahram Ala ◽

Masoud Aliyali ◽

Roya Ghasemian ◽

Fatemeh Heidari ◽

...

Keyword(s):

Success Rate ◽

Sofa Score ◽

Dose Group ◽

Clinical Success ◽

Standard Dose ◽

Clinical Success Rate ◽

High Dose Group ◽

Resistant Bacteria ◽

High Dose ◽

Ventilator Associated Pneumonia

Background: Meropenem standard doses are based on the minimum inhibitory concentration of sensitive pathogens and the pharmacokinetic parameter of not critically ill patients. We compared the efficacy of high versus standard dose of meropenem in ventilator-associated pneumonia (VAP). Methods: 24 out of 34 eligible patients were randomized to receive meropenem 3 g q8h (high dose group, 11 patients) or 2 g q8h (standard dose group, 13 patients) as a 3h infusion. Primary outcome was considered as clinical success that was defined as stable hemodynamic, improved sequential organ failure assessment (SOFA) score, stable or improved PaO2/FiO2 after 7 days. A sputum culture was taken before intervention. Results: Clinical success rate was not significantly different between the high and standard dose group (54.5% vs. 38.5%, P= 0.431). There was a significant difference in reduction of clinical pulmonary infection score (CPIS) compared to high dose with standard group (P=0.038). SOFA score declined significantly in high dose group through the study (P=0.006). A shorter duration of VAP treatment was recorded in high dose group (P=0.061). We did not observe any significant adverse event related to meropenem. Acinetobacter spp. (34.8%), Klebsiella spp. (32.6%) and, Pseudomonas aeruginosa (19.5%) isolated more frequently from sputum cultures. Conclusion: Treatment with high dose of meropenem seems to be safe. However, it did not provide significantly higher clinical success rate in comparison with the standard dose, but could be considered as an appropriate empirical treatment in patients with severe infection due to reducing in SOFA and CPIS.

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1114. Oral β-lactams for the Treatment of Escherichia coli Bacteremia Secondary to Complicated Urinary Tract Infections Including Pyelonephritis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.978 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S396-S396

Author(s):

Nicole Harrington ◽

Megan Doran ◽

Stephen May ◽

Julianne Care ◽

Jillian Laude ◽

...

Keyword(s):

Urinary Tract ◽

Urinary Tract Infections ◽

Clinical Success ◽

Clinical Success Rate ◽

Bloodstream Infections ◽

E Coli ◽

Definitive Therapy ◽

Days Of Therapy ◽

Step Down ◽

Tract Infections

Abstract Background Complicated urinary tract infections (cUTI) including pyelonephritis may result in bacteremia, increasing the rate of morbidity and mortality. The Infectious Diseases Society of America recommends a fluoroquinolone as empiric therapy or trimethoprim/sulfamethoxazole as definitive therapy for acute pyelonephritis (AP). Oral β-lactams (BL) are considered sub-optimal based on historical efficacy data with aminopenicillins and variable bioavailability. Increasing resistance and toxicity with preferred agents, justifies further evaluation of oral BL for E. coli bacteremia secondary to urinary source. Methods This was a single-center, retrospective cohort study of patients with E. coli bacteremia secondary to AP or cUTI who received oral step-down therapy with a BL or non-BL. The primary outcome was the rate of clinical success defined by microbiological cure, clinical cure, and infection-related readmission. Secondary outcomes were time to oral step-down, total days of therapy, length of hospital stay, incidence of therapy escalation, 30-day readmissions, and antibiotic-associated adverse events. Results A total of 46 patients were included, with 23 patients in each group. The difference in clinical success between the BL and non-BL groups was not statistically significant (91.3% vs. 100%, P = 0.489). The most frequent oral step-down agents prescribed were cephalexin and ciprofloxacin. The median time to oral step-down was significantly lower in the non-BL group (4.39 vs. 3.41 days, P = 0.038), and the median duration of therapy in each group was 15 days. No patients required therapy escalation after oral step-down or had infection-related readmission within 30 days of discharge. Conclusion The observed clinical success rate of 91.3% remains consistent with previous studies evaluating oral BL as step-down therapy for Enterobacteriaceae bloodstream infections. The results of this study support the safety and efficacy of oral BL as step-down therapy for E. coli bacteremia due to cUTI, although larger studies may be beneficial. Disclosures All authors: No reported disclosures.

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NCOG-33. HEMATOLOGIC PREDICTORS OF OUTCOMES IN GLIOBLASTOMA TREATED WITH SURGERY AND CHEMORADIATION

Neuro-Oncology ◽

10.1093/neuonc/noaa215.571 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii136-ii136

Author(s):

Nicholas Damico ◽

Theresa Elder ◽

Michael Kharouta ◽

Anthony Sloan ◽

Amber Kerstetter-Fogle ◽

...

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Regression ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Continuous Variables ◽

Surgical Biopsy ◽

Platelet Counts ◽

Cell Counts ◽

Time Point

Abstract BACKGROUND There are conflicting reports regarding the prognostic value of platelet and other blood counts in glioblastoma. However, few series have looked at all hematologic parameters simultaneously. METHODS We performed a retrospective chart review of patients diagnosed with supratentorial glioblastoma from 2014-2019 who started conventional chemoradiation following initial surgical biopsy and/or resection. Hematologic parameters were collected at baseline, in the preoperative and postoperative periods and at the initiation and completion of chemoradiation. This included platelet counts, hemoglobin levels, white blood cell counts (WBC), neutrophil and lymphocyte counts with neutrophil:lymphocyte (NLR) and platelet:lymphocyte ratios (PLR) calculated at each time point. Cox regression was performed to assess the association between each hematologic parameter and both overall survival (OS) and progression free survival (PFS). A multivariate Cox proportional hazards model adjusted for all hematologic parameters, age, sex, race and KPS was generated for each time point. All hematologic parameters were modeled as continuous variables. RESULTS A total of 58 patients met inclusion criteria. 18 were female and 40 male. The median age was 59.5 (range 43-82). Median follow up for all patients was 15.3 months. A total of 52 patients completed radiation therapy and 18 completed 6 cycles of adjuvant chemotherapy. Hemoglobin and neutrophil counts at the conclusion of chemoradiation were associated with OS and PFS on univariate and multivariate analyses. The HR for OS were 0.74 (95% CI 0.5807-0.9313) and 1.28 (1.143-1.441) respectively. The HR for PFS were 0.70 (0.5531-0.8881) and 1.16 (1.05-1.271) respectively. Postoperative lymphocyte and platelet counts at initiation of chemoradiation were both associated with OS with unadjusted HR of 3.2 (1.037-9.960) and HR of 0.99 (0.9898-0.9999) respectively, which remained significant on multivariate analysis. However, neither were associated with PFS. CONCLUSION Several hematologic parameters are associated with glioblastoma outcomes in these initial analyses. Further analyses with additional patients are ongoing.

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508. Title Favipiravir for the Treatment of Coronavirus Disease 2019; A Propensity Score Matched Cohort Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.707 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S356-S356

Author(s):

Rand A Alattar ◽

Shiema A Ahmed ◽

Tasneem Abdallah ◽

Rashid Kazman ◽

Aseelah N Qadmour ◽

...

Keyword(s):

Clinical Improvement ◽

Propensity Scores ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Regression ◽

Supplemental Oxygen ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Ordinal Scale ◽

All Cause Mortality

Abstract Background We investigated clinical outcomes of favipiravir in patients with COVID-19 pneumonia. Methods Patients who between 23 May 2020 and 18 July 2020 received ≥24 hours of favipiravir were assigned to the favipiravir group, while those who did not formed the non-favipiravir group. The primary outcome was 28-day clinical improvement, defined as two-category improvement from baseline on an 8-point ordinal scale. Propensity scores (PS) for favipiravir therapy were used for 1:1 matching. Cox regression was used to examine associations with the primary endpoint. Results The unmatched cohort included 1,493 patients, of which 51.7% were in the favipiravir group, and 48.3% were not receiving supplemental oxygen at baseline (table 1). Favipiravir was started within a median of 5 days from symptoms onset. Significant baseline differences between the two unmatched groups existed, but not between the PSmatched groups (N = 774) (table 1). After PS-matching, there were no significant differences between the two groups in the proportion with 28-day clinical improvement (93.3% versus 92.8%, P 0.780), or 28-day all-cause mortality (2.1% versus 3.1%, P 0.360) (Table 2). Favipiravir was associated with more viral clearance by day 28 (79.8% versus 64.1%, P < 0.001) (table 2). In the adjusted Cox proportional hazards model, favipiravir therapy was not associated 28-day clinical improvement (adjusted hazard ratio 0.978, 95% confidence interval 0.862 –1.109, P 0.726) (Table 3). Conclusion Favipiravir therapy for COVID-19 pneumonia is well tolerated but is not associated with an increased likelihood of clinical improvement or reduced all-cause mortality by 28 days. Disclosures All Authors: No reported disclosures

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Stem-like markers in the circulating tumor cells assessment in ovarian cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e17542 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e17542-e17542

Author(s):

Snezhanna Gening ◽

Tatyana Abakumova ◽

Inna Antoneeva ◽

Tatyana Gening

Keyword(s):

Ovarian Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Regression ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Ca 125 ◽

Blood Samples

e17542 Background: Circulating tumor cells (CTCs) are a potential source of dissemination and relapse in ovarian cancer (OC). Stem cell properties can provide a survival advantage for CTCs. The clinical significance of stem-like CTCs in OC remains to be studied. We aimed to assess the quantities of the stem, epithelial, mesenchymal CTCs and their relationships with the clinical parameters in the OC. Methods: Peripheral blood samples (7.5 ml) were obtained from patients with primary epithelial OC before treatment. CTCs were isolated by flow cytometry (Cytoflex S (Beckman Coulter, USA)) using antibodies to CD45 (BioLegend, USA); CD44 (BioLegend, USA), CD133 (Miltenyi biotec, Germany), ALDH (Stemcell, Canada) to detect the stem markers; EpCAM (BioLegend, USA), cytokeratins 8, 18 (Abcam plc., UK), vimentin (BioLegend, USA) for epithelial and mesenchymal markers. Blood samples from patients with benign ovarian tumors served as a control. Informed voluntary consent was obtained from all the women. Statistical processing included Mann-Whitney U-test, linear regression, Cox proportional hazards model for progression-free survival (PFS) (Statistica 13.0 (TIBCO, USA)). Results: The study included 30 patients, median age 64 (34-76) years. 15 patients had a FIGO stage IV, 12 - stage III, 1 – stage II and 1 – stage I. The content of CTCs populations is presented in the table. The CTCs counts did not differ depending on age, platelet count, and stage 3 or 4. The amount of CD45-CK+Vim- was higher in the presence of ascites (p = 0.035). We found a regression relationship between the serum CA-125 and the number of CD45-CD44+CD133+ (R2= 0.220, p = 0.016); the leukocyte count in blood and CD45-CD44+ALDHhigh (R2= 0.234, p = 0.017); the number of CD45-Vim+ and CD45-CD44+CD133+ALDH+ (R2= 0.305, p = 0.014); CD45-CK-Vim+ and CD45-EpCAM+CK+ (R2= 0.717, p < 0.001). The Cox regression model for PFS included the number of CD45-CD44+CD133+ALDH+ (HR 1.51 95% CI 1.01-2.24 p = 0.043) and the cytoreductive surgery performance (HR 0.09 95% CI 0.01-0.89 p = 0.039) during the first line of treatment. Conclusions: Various populations of circulating tumor cells coexist in ovarian cancer patients. The use of a combination of stem markers in the CTCs detection can increase their prognostic value in OC. This work was supported by the RFBR grant No. 19-315-90011.[Table: see text]

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Genetic and nongenetic factors for contralateral progression of unilateral moyamoya disease: the first report from the SUPRA Japan Study Group

Journal of Neurosurgery ◽

10.3171/2021.3.jns203913 ◽

2021 ◽

pp. 1-10

Author(s):

Yohei Mineharu ◽

Yasushi Takagi ◽

Akio Koizumi ◽

Takaaki Morimoto ◽

Takeshi Funaki ◽

...

Keyword(s):

Risk Factors ◽

Moyamoya Disease ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Regression ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Multicenter Cohort Study ◽

Cox Regression Analysis ◽

Unilateral Moyamoya Disease

OBJECTIVE Although many studies have analyzed risk factors for contralateral progression in unilateral moyamoya disease, they have not been fully elucidated. The aim of this study was to examine whether genetic factors as well as nongenetic factors are involved in the contralateral progression. METHODS The authors performed a multicenter cohort study in which 93 cases with unilateral moyamoya disease were retrospectively reviewed. The demographic features, RNF213 R4810K mutation, lifestyle factors such as smoking and drinking, past medical history, and angiographic findings were analyzed. A Cox proportional hazards model was used to find risk factors for contralateral progression. RESULTS Contralateral progression was observed in 24.7% of cases during a mean follow-up period of 72.2 months. Clinical characteristics were not significantly different between 63 patients with the R4810K mutation and those without it. Cox regression analysis showed that the R4810K mutation (hazard ratio [HR] 4.64, p = 0.044), childhood onset (HR 7.21, p < 0.001), male sex (HR 2.85, p = 0.023), and daily alcohol drinking (HR 4.25, p = 0.034) were independent risk factors for contralateral progression. CONCLUSIONS These results indicate that both genetic and nongenetic factors are associated with contralateral progression of unilateral moyamoya disease. The findings would serve to help us better understand the pathophysiology of moyamoya disease and to manage patients more appropriately.

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Abstract 15644: Proinflammatory Diet Independently Predicts Shorter Event-free Survival in Patients With Heart Failure

Circulation ◽

10.1161/circ.142.suppl_3.15644 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Junghee Kang ◽

Debra K Moser ◽

Martha J Biddle ◽

Terry A Lennie

Keyword(s):

Heart Failure ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Regression ◽

Enzyme Inhibitor ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Event Free Survival ◽

Free Survival ◽

Phone Calls

Introduction: Inflammation is a common biological process accompanying chronic conditions, such as heart failure (HF) that can be moderated by diet. The association between foods thought to promote inflammation and event-free survival in patients with HF has not been investigated. Hypothesis: The inflammatory potential of individuals’ diets, measured using the dietary inflammatory index (DII), will be associated with event-free survival in patients with HF. Methods: The DII scores were calculated from 4-day food diaries recorded at baseline by 213 patients with HF (age 61±12years, 35% female, 43% NYHA III/IV). Patients were followed for a median of 365 days by monthly phone calls, medical record review, and death records to determine time to all cause-hospitalization or death. The DII scores were dichotomized using median value for the Cox regression model. Hierarchical multivariate Cox proportional hazards model was used to determine whether DII scores predicted event-free survival after controlling for age, gender, body mass index, prescribed angiotensin-converting-enzyme inhibitor, beta-blocker, cholesterol lowering agent, antiinflammatory agent, N-terminal pro B-type natriuretic peptide, comorbidity, depressive symptoms, and the New York Heart Association functional classification. Results: The DII scores independently predicted event-free survival in the model constant ( p = 0.012). Higher DII scores were associated with more than double the risk of an event compared to lower DII scores (HR: 2.28, 95% Confidence Interval =1.21-4.36). Conclusions: Greater intake of foods considered to promote inflammation was associated with shorter event-free survival in patients with HF. These results provide further evidence of the importance of diet to HF outcomes.

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Long-term frailty modeling using a non-proportional hazards model: Application with a melanoma dataset

Statistical Methods in Medical Research ◽

10.1177/0962280219883905 ◽

2019 ◽

Vol 29 (8) ◽

pp. 2100-2118 ◽

Cited By ~ 1

Author(s):

Vinicius F Calsavara ◽

Eder A Milani ◽

Eduardo Bertolli ◽

Vera Tomazella

Keyword(s):

Survival Data ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Regression ◽

Population Based ◽

Likelihood Method ◽

Cure Rate Models ◽

Power Variance ◽

Incident Cases

The semiparametric Cox regression model is often fitted in the modeling of survival data. One of its main advantages is the ease of interpretation, as long as the hazards rates for two individuals do not vary over time. In practice the proportionality assumption of the hazards may not be true in some situations. In addition, in several survival data is common a proportion of units not susceptible to the event of interest, even if, accompanied by a sufficiently large time, which is so-called immune, “cured,” or not susceptible to the event of interest. In this context, several cure rate models are available to deal with in the long term. Here, we consider the generalized time-dependent logistic (GTDL) model with a power variance function (PVF) frailty term introduced in the hazard function to control for unobservable heterogeneity in patient populations. It allows for non-proportional hazards, as well as survival data with long-term survivors. Parameter estimation was performed using the maximum likelihood method, and Monte Carlo simulation was conducted to evaluate the performance of the models. Its practice relevance is illustrated in a real medical dataset from a population-based study of incident cases of melanoma diagnosed in the state of São Paulo, Brazil.

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Simulation Extrapolation Method for Cox Regression Model with a Mixture of Berkson and Classical Errors in the Covariates using Calibration Data

The International Journal of Biostatistics ◽

10.1515/ijb-2018-0028 ◽

2019 ◽

Vol 15 (2) ◽

Author(s):

Jean de Dieu Tapsoba ◽

Edward C. Chao ◽

Ching-Yun Wang

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Regression ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Classical Type ◽

Calibration Data ◽

Finite Sample ◽

Cox Regression Analysis ◽

Simulation Extrapolation

Abstract Many biomedical or epidemiological studies often aim to assess the association between the time to an event of interest and some covariates under the Cox proportional hazards model. However, a problem is that the covariate data routinely involve measurement error, which may be of classical type, Berkson type or a combination of both types. The issue of Cox regression with error-prone covariates has been well-discussed in the statistical literature, which has focused mainly on classical error so far. This paper considers Cox regression analysis when some covariates are possibly contaminated with a mixture of Berkson and classical errors. We propose a simulation extrapolation-based method to address this problem when two replicates of the mismeasured covariates are available along with calibration data for some subjects in a subsample only. The proposed method places no assumption on the mixture percentage. Its finite-sample performance is assessed through a simulation study. It is applied to the analysis of data from an AIDS clinical trial study.

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Impacto do Escore de Desnutrição-Inflamação na sobrevida de pacientes em hemodiálise

Abr-Jun - Braspen Journal ◽

10.37111/braspenj.2020353011 ◽

2020 ◽

Vol 35 (3) ◽

pp. 264-269

Author(s):

Melissa Nihi Sato ◽

Caroline Finger Sostisso ◽

Mayara Olikszechen ◽

Scheila Karam ◽

Miriam de Aguiar Souza Cruz Oliveira ◽

...

Keyword(s):

Vascular Access ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Regression ◽

Clinical Laboratory ◽

Protein Energy Malnutrition ◽

Nutritional Risk ◽

Chi Square ◽

Integrated Method ◽

Kaplan Meier

Introduction: The protein-energy malnutrition is found in a large proportion in dialysis patients. The malnutrition-inflammation score (MIS) seems to be the most appropriate integrated method for assessing the nutritional status or nutritional risk of these patients. The aim of the study is to evaluate the MIS, in the diagnostic accuracy for the assessment of malnutrition, and its correlation with the survival time of patients in hemodialysis (HD). Methods: Study carried out in HD units in the city of Curitiba, Brazil, from January 2013 to December 2015. Clinical, laboratory and anthropometric data were evaluated. The data comparison between patients was made according to the t-test and the chi-square. The Kaplan-Meier curve was constructed to assess the influence of MIS on patient survival and log rank tests were used to verify the equality of survival distributions in these groups. Results: 113 HD patients were evaluated, 74% male. From the multivariable proportional hazards model (Cox regression), the MIS> 5 was a predictor of mortality, as well as creatinine <7 mg/dl and vascular access via HD catheter. In Kaplan-Meier survival analysis, patients with MIS <5 had a significantly higher survival rate. It was also possible to confirm a significant association between creatinine <7 mg/dl and catheter vascular access, and mortality. Conclusion: MIS is an independent predictor of mortality in HD patients. The cutoff 5 was able to predict mortality

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