scholarly journals 1259. Carbapenems Versus Non-carbapenem Beta-Lactams for the Treatment of Ceftriaxone-Susceptible and Piperacillin-Tazobactam-Nonsusceptible Enterobacterales Isolates

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S718-S718
Author(s):  
Nadeem Baalbaki ◽  
Sharon Blum ◽  
Michael Bosco ◽  
Meredith Akerman ◽  
Lana Zaki ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Day Treatment ◽  
Univariate Analysis ◽  
Clinical Failure ◽  
Sequencing Data ◽  
Beta Lactam ◽  
Increased Risk ◽  
Definitive Therapy ◽  
Significant Difference ◽  
Esbl Producers

Abstract Background Ceftriaxone-susceptible (CRO-S) and piperacillin-tazobactam-non susceptible (TZP-NS) Enterobacterales isolates have become a frequently isolated phenotype emerging in practice. The genotypic profile is still not clearly elucidated, although prior genotypic sequencing data of these isolates with this phenotypic profile suggests that they are not extended-spectrum beta-lactamase (ESBL) producers. Due to the unfamiliarity with this phenotype and the potential for overuse of broad-spectrum antibiotics, we investigated the clinical outcomes of CRO-S/TZP-NS isolates with carbapenem versus non-carbapenem beta-lactam (NCBL) therapy. Methods This was a retrospective chart review of patients with a diagnosed infection caused by a CRO-S/TZP-NS Enterobacterales isolate admitted to any of the three NYU hospitals: Long Island, Tisch, or Brooklyn campuses, treated with a beta-lactam (BL) antibiotic from October 2015 to October 2020. The primary outcome was treatment failure defined as an escalation of antibiotics due to clinical worsening, 30-day all-cause mortality, or relapse of infection with the same genus and species. Patients who received ≥ 72 consecutive hours of BL antibiotics were considered to be on definitive therapy. Results A total of 111 patients were included in this study, 9 in the carbapenem group and 102 in the NCBL group. There was no statistically significant difference in the clinical failure rate between the two groups (0% vs 10.8% respectively, P=0.56). A univariate analysis assessed the association of clinical failure with TZP, CRO, cefpodoxime, cefepime, and 1st-3rd generation cephalosporins grouped. There were no statistically significant increases in 30-day treatment failure in any of the individual categories. Conclusion There were no statistically significant differences in 30-day failure with the use of carbapenem vs NCBL antibiotics. No individual BLs or classes were associated with an increased risk of clinical failure. This study suggests that there is a role for NCBL antibiotics for Enterobacterales isolates with this phenotypic presentation and supports prior data that they are less likely to be ESBL producers. Prospective studies are warranted to confirm these findings. Disclosures All Authors: No reported disclosures

scholarly journals 301. Penicillin Versus Cefazolin or Anti-staphylococcal Penicillins for Penicillin-Susceptible Staphylococcus aureus Bacteremia

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S149-S149
Author(s):  
Mohammed Aldhaeefi ◽  
Jeffrey Pearson ◽  
Sanjat Kanjilal ◽  
Brandon Dionne
Keyword(s):  
Staphylococcus Aureus ◽  
Blood Culture ◽  
Positive Blood Culture ◽  
Medical Center ◽  
Academic Medical Center ◽  
Similar Distribution ◽  
Clinical Failure ◽  
Staphylococcus Aureus Bacteremia ◽  
Definitive Therapy ◽  
Significant Difference

Abstract Background Staphylococcus aureus bacteremia is a significant cause of mortality. Penicillin (PCN) may have a role in the treatment of penicillin-susceptible Staphylococcus aureus (PSSA) bacteremia as it has a narrower spectrum of activity than cefazolin and is better tolerated than antistaphylococcal penicillins (ASPs). The aim of this study is to evaluate the safety and effectiveness of PCN versus cefazolin or ASPs in the treatment of PSSA bacteremia. Methods This is a single-center, retrospective study at a tertiary academic medical center. All patients with a PSSA blood culture from January 1, 2012 to September 1, 2019 were screened. Patients were excluded if they were treated with a definitive antibiotic (defined as antimicrobial therapy received 72 hours after positive blood culture) other than the study comparators, or if they received combination antibiotic therapy >72 hours from the initial positive blood culture result. The primary outcome was 60-day clinical failure, which was a composite endpoint of change in antibiotic after 72 hours of definitive therapy, recurrence of PSSA bacteremia, infection-related readmission, or all-cause mortality. Results Of 277 patients with PSSA bacteremia, 101 patients were included in the study; 62 (61%) were male and 11 (11%) had a β-lactam allergy. At baseline, 40 patients (40%) had hardware, 25 (25%) had an intravenous line, 6 (6%) were on dialysis, and 4 (4%) had active IV drug use, with similar distribution across antibiotic groups. Penicillin was the most common antibiotic used (Table 1). There was a significant difference among groups with respect to the 60-day clinical failure (log-rank p=0.019). In terms of unadjusted 60-day clinical failure, penicillin had similar outcomes to cefazolin (95% CI -0.29 to 0.104, p=0.376), however, it had statistically significant better outcomes in comparison to the ASPs, nafcillin or oxacillin (95% CI 0.023 to 0.482, p=0.031) (Table 1). Table 1. 60-day outcomes of PSSA bacteremia Conclusion Penicillin is effective and safe in the treatment of PSSA bacteremia and may be preferable to antistaphylococcal penicillins Disclosures All Authors: No reported disclosures

Does the Beta-Lactam Matter? Nafcillin versus Cefazolin for Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections

Chemotherapy ◽  
2018 ◽  
Vol 63 (6) ◽  
pp. 345-351 ◽  
Author(s):  
Corey C. Burrelli ◽  
Eleanor K. Broadbent ◽  
Alice Margulis ◽  
Graham M. Snyder ◽  
Howard S. Gold ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Adverse Effects ◽  
Treatment Failure ◽  
Kidney Injury ◽  
Bloodstream Infections ◽  
Composite Endpoint ◽  
Acute Interstitial Nephritis ◽  
Beta Lactam ◽  
Significant Difference

Background: Antistaphylococcal penicillins have historically been regarded as the drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI). However, recent outcomes data compared to cefazolin treatment are conflicting. Objective: This study compared treatment failure and adverse effects associated with nafcillin and cefazolin for MSSA BSI. Methods: Adult inpatients with MSSA BSI between January 1, 2009 and August 31, 2015 were included in this retrospective cohort study if they received ≥72 h of nafcillin or cefazolin as directed therapy after no more than 72 h of any empiric therapy. The primary composite endpoint was treatment failure defined by clinician documentation, 30-day recurrence of infection, all-cause 30-day in-hospital mortality, or loss to follow-up. Secondary outcomes included antibiotic-related acute kidney injury (AKI), acute interstitial nephritis (AIN), hepatotoxicity, and rash. Results: Among 157 patients, 116 (73.9%) received nafcillin and 41 (26.1%) received cefazolin. The baseline characteristics were similar except cefazolin-treated patients had higher APACHE II scores and more frequent renal dysfunction. No difference in the composite treatment failure outcome (28.4 vs. 31.7%; p = 0.69) was detected between the nafcillin and cefazolin groups, respectively. In a sensitivity analysis excluding patients without known follow-up, there was no significant difference of treatment failure. AKI, AIN, hepatotoxicity, and rash were all numerically more frequent among nafcillin-treated patients. Conclusions: Among nafcillin- or cefazolin-treated patients with MSSA BSI, there was no significant difference in treatment failure. Observing more frequent presumptive adverse effects associated with nafcillin receipt, future prospective studies evaluating cefazolin appear warranted.

Obesity Does Not Preclude Safe and Effective Myeloablative Hematopoietic Cell Transplantation (HCT) for Acute Myeloid Leukemia (AML) in Adults

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 51-51
Author(s):  
Willis H. Navarro ◽  
Manza-A Agovi ◽  
Brent Logan ◽  
Andrea Bacigalupo ◽  
Karen K Ballen ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Normal Weight ◽  
Overweight And Obesity ◽  
Weight Group ◽  
Risk Of Death ◽  
Increased Risk ◽  
Significant Difference ◽  
Underweight Patients ◽  
Autologous Hct ◽  
Weight Groups

Abstract INTRODUCTION: Obesity is increasingly common in the US and is frequently associated with co-morbid medical conditions that may increase the risk of HCT, often the optimal treatment for AML. HCT risk and outcomes for AML on the basis of body mass index (BMI) have not been well-characterized. Using data from the Center for International Blood and Marrow Transplant Research (CIBMTR), we have previously shown no significant difference in outcomes for autologous HCT for lymphoma among normal weight, overweight, and obese patients (pts) but worse outcomes for underweight pts (Navarro et al, BBMT 2006, 12(5): 541–51). Here, we compare outcomes by weight groups for AML patients who underwent autologous, related, or unrelated HCT. METHODS: Our final population included patients age ≥ 18 who underwent myeloablative unpurged autologous or allogeneic HCT for AML in 1st or 2nd complete remission, primary induction failure, or 1st relapse reported to the CIBMTR from 1995 to 2004. Cord blood HCTs were excluded. Four weight groups were defined based on BMI (BMI=weight (kg)/ height (m2)): underweight <18; normal=18–25; overweight >25–30; and obese >30. Treatment-related mortality (TRM), relapse, leukemia-free survival (LFS), and overall survival (OS) were compared using multivariable proportional hazards regression analysis accounting for patient, disease and HCT-related variables. RESULTS: We included 373 autologous, 2041 related, and 1801 unrelated transplant recipients. Patient-, disease-, and transplant characteristics were well-matched across weight groups and transplant types. Multivariable analysis examining risks (95% confidence intervals) relative to the normal weight group are: HCT Type Normal Underweight Overweight Obese -- =not done due to insufficient number of pts; NS=not significant; treatment failure = death or recurrence of disease. Autologous n=164 n=5 n=112 n=81 Death -- NS NS Treatment failure -- NS NS Relapse -- NS NS TRM -- NS NS Related Allogeneic n=1161 n=31 n=543 n=268 Death 1.86 (1.24–2.78) NS 1.23 (1.04–1.47) Treatment failure 2.08 (1.37–3.15) NS 1.19 (1.00–1.42) Relapse 2.02 (1.18–3.47) NS NS TRM 2.22 (1.17–4.22) NS 1.32 (1.02–1.70) Unrelated Allogeneic n=846 n=31 n=523 n=368 Death NS NS NS Treatment failure NS NS NS Relapse NS 0.82 (0.68–0.99) 0.76 (0.60–0.96) TRM NS NS NS CONCLUSIONS: There were no significant differences in risk of TRM, LFS, relapse or OS for normal weight, overweight or obese patient groups who received autologous HCT. Obese recipients of related HCT for AML had increased risk of death, treatment failure, and TRM, though the magnitude was small, an effect was not seen in the unrelated HCT group. Underweight patients who received a related, but not unrelated HCT, fared substantially worse than normal weight patients for all outcomes. It may be that the higher risk of the unrelated HCT procedure masks important but less obvious risks associated with being underweight whereas in the related donor HCT setting, such risks become manifest. Small numbers of patients limit the ability to better characterize this finding in underweight patients. Disproportionately, fewer transplants have been reported in underweight patients which suggest they experience disease and patient-related factors that preclude transplantation. No differences were observed for incidence of acute or chronic GVHD for any weight group. Overweight and obesity should not be a barrier to HCT; however, caution should be exercised in selecting underweight patients for HCT.

Factors affecting time to treatment in hepatocellular cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19088-e19088 ◽  
Author(s):  
Karan Seegobin ◽  
Umair Majeed ◽  
Ashton Ritter ◽  
Natasha Wylie ◽  
Jason Scott Starr ◽  
...  
Keyword(s):  
Socioeconomic Factors ◽  
Low Income ◽  
Treatment Initiation ◽  
Univariate Analysis ◽  
Published Data ◽  
Time To Treatment ◽  
Risk Of Death ◽  
Increased Risk ◽  
Significant Difference ◽  
Time To Treatment Initiation

e19088 Background: Significant disparities in the stage at diagnosis and survival outcomes exist between various groups diagnosed with hepatocellular carcinoma (HCC) based on sex, race, insurance coverage, and marital status. Previously published data shows disparities more in patients who are African-American, Asian and low income. Little data has been published on factors that influence timeliness to treatment initiation in patients diagnosed with HCC. Methods: Retrospective analysis was performed on 96,586 patients diagnosed with HCC from 2004-2014 using data in the National Cancer Database (NCDB). Time to treatment was divided into two categories: ≤40 days (early, n = 66322) and > 40 days (late, n = 30264). We carried out univariate and multivariate analyses to compare demographic, clinical, treatment, and facility-related factors influencing the timeliness of treatment initiation in HCC. Results: Univariate analysis revealed a significant difference in time to treatment initiation based on age, race, income, insurance status, type of area, geographic region, type of facility, and cancer stage (P < 0.001). Multivariate analysis showed that household income < $30,000/year, Pacific region, urban area of residence, black race, age 70-79 years old or ≥80 years old, academic centers, stage II disease and medicaid insurance were all factors with longer time to treatment initiation. Discussion: HCC is the sixth most common cancer and the second leading cause of cancer mortality worldwide. The 5-year relative survival for localized, regional, and distant stages are 32.6%, 10.8% and 2.4% respectively. In our results we noted significant disparities in time to treatment with respect to various socioeconomic factors. These results are comparable to that reported in other cancer types. Further subgroup analysis of our data shows 2581 patients who received their first treatment after 200 days. In a similar study done in Taiwan, those treated more than 181 days and 61–180 days after diagnosis had a 1.68 and a 1.39 increased risk of death respectively, which were statistically significant. Many factors contribute to delayed treatment, some of which are difficult to circumvent, however where possible efforts should be made to overcome these. Conclusions: Various socioeconomic factors were found to affect the time to treatment initiation in HCC patients. The next step would be to strategically implement policies and practices to address these factors.

MLL-Rearranged Acute Myeloid Leukemias Drive Expression Of Mir-9, a Critical Oncogene In Leukemogenesis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3740-3740
Author(s):  
Colles Price ◽  
Ping Chen ◽  
Zejuan Li ◽  
Yuanyuan Li ◽  
Anissa Wiley ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Cancer Biology ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
The United States ◽  
The Cancer Genome Atlas ◽  
Leukemic Cells ◽  
Sequencing Data ◽  
Significant Difference ◽  
Acute Myeloid

Abstract A critical area of cancer biology is the study of the deregulation of noncoding RNAs called microRNAs (miRNAs). Acute leukemia represents one of the most deadly cancers in the United States. One subset of leukemia with a poor to intermediate clinical outcome are chromosomal translocations involving Mixed Lineage Leukemia (MLL). As MLL-translocations are sufficient to drive leukemogenesis, and few additional mutations are observed in patients, it is imperative to understand the biology driving leukemogenesis. Previously, we and others have shown that several miRNAs are deregulated in MLL-rearranged Acute Myeloid Leukemia (AML). To identify miRNAs that are driving leukemogenesis we performed messenger RNA and miRNA expression profiling on primary patient samples and identified microRNA-9 (miR-9) as specifically overexpressed in MLL-rearranged AML. We further confirmed this observation using publically available microRNA sequencing data from the Cancer Genome Atlas (TCGA) and several AML cell lines. After showing that MLL directly binds and regulates miR-9 we show that depletion of MLL-fusion expression leads to the loss of miR-9 expression. Using publically available Illumina 450K methylation data from TCGA, we show that there is no significant difference in modified cytosine between miR-9 high and miR-9-low patients, suggesting that expression of miR-9 is likely not be regulated by DNA methylation machinery in AML patients. We show that miR-9 in the presence of MLL-AF9 (a common MLL-fusion) promotes colony growth over multiple passages while blocking miR-9 using a miR-9 sponge remarkably inhibits MLL-fusion-mediated cell transformation. Furthermore, we show that miR-9 increases proliferation and reduces apoptosis of human MLL-rearranged leukemic cells in vitro using MTT and Caspase 3/7 assays. We then show that co-transfection of miR-9 with MLL-AF9 in a bone marrow transplantation assay results in a higher leukemia burden in vivo compared to MLL-AF9 alone and promotes an immature cellular phenotype. Using microarray data we found several putative miR-9 targets by identifying genes that had an inverse correlation to miR-9. Next, we verified several genes were being inhibited by miR-9 such as Ras homology gene family member H (RHOH) and Ring1- and YY1-binding protein (RYBP). To understand the role of miR-9 in context with other miRNAs we did an association analysis of the top 300 differentially expressed miRNAs in the TCGA dataset. We found interestingly, that two of the miR-9 genes, miR-9-1 and miR-9-2, are highly correlated with each other across all the patients although they are located on distinct chromosomes. We also found that several other miRs were either negatively (e.g., miR-130a and miR-221) or positively (e.g., miR-191 and miR-642) associated with miR-9 expression, suggesting that these miRs might be operating either cooperatively or antagonistically in a complex circuitry. To support this hypothesis we found in univariate analysis that miR-9 itself was not a good predictor of patient survival but was a better predictor when combined with other miRs including the miR-181 family. Together this suggests that miR-9 is an important and critical regulator of MLL-rearranged AML and is a very good candidate for potential therapeutic targeting. Disclosures: No relevant conflicts of interest to declare.

scholarly journals 1010. Effectiveness of Oral Antibiotics for Definitive Therapy of Gram-Positive Bloodstream Infections

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S300-S301
Author(s):  
Danya Roshdy ◽  
Nick Quinn ◽  
Jamie Sebaaly ◽  
Megan Templin ◽  
David Weinrib
Keyword(s):  
Medical Center ◽  
Academic Medical Center ◽  
Bloodstream Infections ◽  
Definitive Treatment ◽  
Common Source ◽  
Clinical Failure ◽  
Gram Positive ◽  
Definitive Therapy ◽  
Significant Difference ◽  
Antibiotic Group

Abstract Background Transition from intravenous (IV) to oral (PO) antibiotics is common practice in patients with Gram-positive bloodstream infections (GP-BSI); however, clinical data evaluating IV to PO switch options are lacking. The objective of this study was to examine effectiveness of PO antibiotics for definitive treatment GP-BSI, with a focus on bioavailability (BA). Methods This was a single-center, retrospective cohort study of adult inpatients admitted to an 874-bed academic medical center in Charlotte, NC between September 1, 2014 and August 31, 2017. Patients with a GP-BSI who received appropriate antibiotic therapy with at least one third of their total course administered PO were included. Patients with GP-BSI caused by staphylococcal species were excluded. The primary endpoint was clinical failure in patients receiving high (≥90%) vs. low (&lt;90%) BA agents. Secondary endpoints included clinical failure stratified by antibiotic group, bactericidal vs. bacteriostatic agents, and organism. Chi-square and Fisher’s exact tests were used to examine clinical failure. Results One hundred three patients were included, 26 in the high BA group, and 77 in the low BA group. The median age was 58, 51% were women, 74.8% of patients had streptococcal bacteremia (26.2% S. pneumoniae), with pulmonary being the most common source (30.1%). There were no major differences in baseline demographic and clinical characteristics between groups. The median treatment duration with IV antibiotics was 4 and 5 days in the high and low BA groups, respectively (P = 0.12). There was no statistically significant difference in clinical failure in the high vs. low BA groups (19% vs. 23%, P = 0.66, respectively). Clinical failure stratified by antibiotic group, bacteriostatic vs. bactericidal agent (OR 1.43, CI 0.26–7.90), and organism also did not yield statistically significant differences. Conclusion These data demonstrate similar rates of clinical failure among patients definitively treated with high or low BA agents for GP-BSI. High BA agents such as fluoroquinolones may not be needed for all patients with GP-BSI, where more targeted β-lactam therapies may be appropriate. Additional prospective studies with larger sample sizes are needed to further validate these conclusions. Disclosures All authors: No reported disclosures.

scholarly journals 1380. Effect of Absolute Body Weight on Clinical Outcomes of Obese Patients Treated with Cefepime

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S423-S423
Author(s):  
Jamie L Wagner ◽  
Austin R Morrison ◽  
J Taylor Loper ◽  
Katie E Barber ◽  
Kayla R Stover
Keyword(s):  
Treatment Failure ◽  
Clinical Outcomes ◽  
Treatment Initiation ◽  
Package Insert ◽  
Source Control ◽  
Clinical Failure ◽  
Single Temperature ◽  
Definitive Therapy ◽  
All Cause Mortality ◽  
Clinical Worsening

Abstract Background Differences in pharmacokinetic and pharmacodynamic parameters for obese (OB) patients compared with nonobese (NOB) patients are well known, but drug safety and efficacy when using package insert dosing remain unclear. The purpose of this study was to evaluate the clinical outcomes of cefepime (FEP) for OB patients vs. NOB patients. Methods This retrospective cohort included inpatient adults ≥18 years treated with FEP monotherapy for ≥72 hours between July 2015 and July 2017. Exclusion criteria were source control not achieved within 72 hours and polymicrobial infections requiring &gt; 1 antibiotic for definitive therapy. Additional data collected were demographics, comorbid conditions, laboratory markers, site of infection, and microbiology. The primary endpoint was clinical treatment failure, defined as change in definitive therapy at &gt;72 hours due to clinical worsening, leukocytosis (WBC &gt; 10 × 109/L) for &gt;72 hours after treatment initiation, fever (single temperature &gt;100.9°F) after &gt;72 hours of treatment initiation, or readmission within 30 days due to re-infection. Secondary outcomes were 30-day inpatient all-cause mortality and 30-day readmission. Results One hundred fourteen subjects were included (58 OB; 56 NOB). Median (IQR) age 58[46–66] years; 66(58%) males. Median [IQR] weight 107[95–124] kg OB patients; 75[63–84] kg NOB patients. Median Charlson score was 3[2–5] (P = 0.478). Sixty-two percent OB patients vs. 46% NOB patients experienced a respiratory infection (P = 0.094); 28% OB patients vs. 39% NOB patients experienced a urinary tract infection (P = 0.185). 62% OB patients and 59% NOB patients received FEP 1g q8h (P = 0.732). Most common minimum inhibitory concentration (MIC) in both groups was 1 mg/L (74% OB vs. 83% NOB; P = 0.289). Clinical failure occurred in 52% (67% OB vs. 36% NOB; P = 0.001). OB patients more likely to need a second antibiotic (31% vs. 14%; P = 0.033) and have persistent leukocytosis (50% vs. 30%; P = 0.033). Inpatient all-cause mortality occurred in 17% (22% OB vs. 12% NOB; P = 0.164). 72% of patients were not readmitted within 30 days of discharge. Conclusion OB patients experienced higher treatment failure than NOB patients. Further examination is needed to assess impact of FEP dose and organism MIC on clinical failure in OB patients. Disclosures All authors: No reported disclosures.

scholarly journals Comparison of therapy with β-lactam/β-lactamase inhibitor combinations or carbapenems for bacteraemia of nonurinary source caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Hong Luo ◽  
Yanping Xiao ◽  
Yaping Hang ◽  
Yanhui Chen ◽  
Hongying Zhu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Escherichia Coli ◽  
Multivariate Analysis ◽  
Propensity Score ◽  
Klebsiella Pneumoniae ◽  
Treatment Failure ◽  
Day Treatment ◽  
Univariate Analysis ◽  
Treatment Failure Rate ◽  
Lactamase Inhibitor

Abstract Background Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae has become a public health concern. This study aimed to compare the clinical outcomes of patients with nonurinary source bacteraemia caused by ESBL-producing Escherichia coli (E. coli) or Klebsiella pneumoniae (ESBL-producing EK) receiving β-lactam/β-lactamase inhibitor combinations (BLICs) versus carbapenem treatment and assess the risk factors of mortality with these two drugs. Methods We conducted a retrospective single-centre study of adult hospitalised patients with ESBL-producing EK bloodstream infection (BSI) from nonurinary source at our centre over a 4-year period. One hundred and eighty patients who received BLICs or carbapenems were included in the analysis. The outcome variables were 14-day treatment failure and 30-day mortality. For more reliable results, propensity score analysis was performed to compare the efficacy of the two drugs and analyse their risk factors for 30-day mortality. Results Out of 180 patients, 114 received BLICs, and 66 received carbapenem therapy. Compared to carbapenem-treated patients, those treated with BLICs were older and had higher age-adjusted Charlson comorbidity index, but they had shorter stay in the hospital. Additionally, their Pitt bacteraemia score, SOFA score, rate of leukaemia, and immune compromise were lower. After propensity score matching (PSM), the baseline characteristics of patients in the two treatment groups were balanced. BLICs were associated with a higher 14-day treatment failure rate (20.6%, 13/63) than carbapenems (16.3%, 7/43), although the difference was not significant in either univariate analysis (P = 0.429) or multivariate analysis (P = 0.122). And the 30-day mortality rate in BTG (11.1%, 7/63) and CTG (11.6%, 5/43) did not significantly differ (univariate analysis, P = 0.926; multivariate analysis, P = 0.420). In the multivariate analysis, after PSM, leukaemia was the only independent predictor of mortality in both BTG and CTG. Conclusions Our study showed that BLICs had higher 14-day treatment failure rate compared with carbapenems, although there were no statistically significant differences because of the small number of patients, therefore, further evaluation of the efficacy of BLICs is needed.

Androgen deprivation therapy (ADT) and cardiovascular mortality (CVD) in men with early-stage prostate cancer (PC) receiving curative radiation therapy (RT).

2018 ◽  
Vol 36 (7_suppl) ◽  
pp. 127-127
Author(s):  
Ashley Hanlon ◽  
Steven Fleming ◽  
Ann S Hamilton ◽  
Michaela Ann Dinan ◽  
Chiara Melloni ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Early Stage ◽  
Univariate Analysis ◽  
Cancer Registries ◽  
Population Based ◽  
Vital Statistics ◽  
Increased Risk ◽  
Definitive Therapy ◽  
Breast And Prostate Cancer ◽  
Artery Disease

127 Background: Combined with RT, ADT is a highly effective and utilized treatment for men with localized PC, but some studies suggest that use of ADT leads to increased CVD. We explored the association between ADT and CVD in men receiving RT for localized PC in the National Program for Cancer Registry’s (NPCR) Breast and Prostate Cancer Patterns of Care (POC) study. Methods: From 7 population-based cancer registries, we constructed a sample of men with localized PC treated with definitive RT, stratified by race/ethnicity. Cases diagnosed in 2004 were followed through 2009. Comorbidity, at or before diagnosis, was quantified using the Adult Comorbidity Evaluation 27; subcategories were combined into CV disease (CVD = myocardial infarction, coronary artery disease, congestive heart failure, arrhythmia), CVD-equivalents (CVE = peripheral artery disease and stroke) and CV-risk factors (CVRF = hypertension, diabetes, obesity). Cause of death was determined from the National Death Index data and linkage with vital statistics data. Rates of CV death, in those receiving RT alone versus RT+ADT, were compared in univariate and multivariable analyses. Results: The sample included 2,413 men with mean age 67.7 years (range 39-94), 54.5% white non-Hispanic, 997 received RT alone and 1,416 received RT+ADT. Five-year CVD was 2.3% with RT alone and 3.4% with RT+ADT. In univariate analysis, the following predicted higher CVD with ADT: age < 60 (OR 1.42, p = 0.04), white (OR 2.06, p = 0.001), divorced/separated/widowed (OR 1.29, p = 0.02), insured by Medicare (OR 1.64, p = 0.04), living in mixed urban-rural area (OR 1.87, p = 0.03), higher education level (OR 1.56, p = 0.05), high socioeconomic status (OR 1.70, p = 0.03), no or mild comorbidity level (OR 2.14, p = 0.05 and OR 1.66, p = 0.02, respectively), low PSA (OR 5.44, p = 0,02), and Gleason score 3 (OR 2.12, p = 0.02). In multivariate analysis, use of ADT did not significantly predict hazard of death from heart disease (HR 1.21, p = 0.28) or PC (HR 0.76, p = 0.34). Conclusions: After controlling for confounding variables, use of ADT was not associated with increased risk of CVD in men receiving radiation as definitive therapy for localized PC.

Effects of Extended-Release Niacin on Quartile Lp-PLA2 Levels and Clinical Outcomes in Statin-treated Patients with Established Cardiovascular Disease and Low Baseline Levels of HDL-Cholesterol: Post Hoc Analysis of the AIM HIGH Trial

2019 ◽  
Vol 24 (6) ◽  
pp. 534-541
Author(s):  
Radmila Lyubarova ◽  
John J. Albers ◽  
Santica M. Marcovina ◽  
Yao Yao ◽  
Ruth McBride ◽  
...  
Keyword(s):  
Placebo Group ◽  
Clinical Outcomes ◽  
Extended Release ◽  
Univariate Analysis ◽  
Post Hoc Analysis ◽  
Increased Risk ◽  
Significant Difference ◽  
Baseline Levels ◽  
Cv Disease ◽  
Post Hoc

Background: Lipoprotein-associated phospholipase A2 (LpPLA2) is an inflammatory marker that has been associated with the presence of vulnerable plaque and increased risk of cardiovascular (CV) events. Objective: To assess the effect of extended-release niacin (ERN) on Lp-PLA2 activity and clinical outcomes. Methods: We performed a post hoc analysis in 3196 AIM-HIGH patients with established CV disease and low baseline levels of high-density lipoprotein cholesterol (HDL-C) who were randomized to ERN versus placebo on a background of simvastatin therapy (with or without ezetimibe) to assess the association between baseline Lp-PLA2 activity and the rate of the composite primary end point (CV death, myocardial infarction, stroke, hospitalization for unstable angina, and symptom-driven revascularization). Results: Participants randomized to ERN, but not those randomized to placebo, experienced a significant 8.9% decrease in LpPLA2. In univariate analysis, the highest quartile of LpPLA2 activity (>208 nmol/min/mL, Q4) was associated with higher event rates compared to the lower quartiles in the placebo group (log rank P = .032), but not in the ERN treated participants (log rank P = .718). However, in multivariate analysis, adjusting for sex, diabetes, baseline LDL-C, HDL-C, and triglycerides, there was no significant difference in outcomes between the highest Lp-PLA2 activity quartile versus the lower quartiles in both the placebo and the ERN groups. Conclusion: Among participants with stable CV disease on optimal medical therapy, elevated Lp-PLA2 was associated with higher CV events; however, addition of ERN mitigates this effect. This association in the placebo group was attenuated after multivariable adjustment, which suggests that Lp-PLA2 does not improve risk assessment beyond traditional risk factors.

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