Optimal sequencing of enzalutamide and abiraterone in men with metastatic castration-resistant prostate cancer (mCRPC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 308-308 ◽  
Author(s):  
Benjamin Louis Maughan ◽  
Daniel L. Suzman ◽  
Rosa Maria Nadal ◽  
Sunakshi Bassi ◽  
Emmanuel S. Antonarakis
Keyword(s):  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Small Sample Size ◽  
Cox Proportional Hazards ◽  
Small Sample ◽  
Castration Resistant Prostate Cancer ◽  
Optimal Sequencing ◽  
Opposite Sequence ◽  
Baseline Characteristics ◽  
Visceral Disease

308 Background: Both enzalutamide and abiraterone are approved for the treatment of mCRPC, each demonstrating improved overall survival (OS) versus placebo. However, it is unclear what the optimal sequencing of these two therapies should be to maximize clinical outcomes and survival. Here, we compare clinical outcomes among patients with mCRPC who received enzalutamide first followed immediately by abiraterone (enza-to-abi) or the opposite sequence (abi-to-enza). Methods: A retrospective review of consecutive mCRPC patients treated at Johns Hopkins with enza-to-abi or abi-to-enza was conducted. The combined PFS (PFS = PFS1 + PFS2) was the primary endpoint, measured from the start of the first therapy (i.e. enza or abi) until disease progression on the subsequent therapy (i.e.abi or enza). The OS from the start of the first therapy until death was the secondary endpoint. Cox proportional hazards multivariable regression analysis was performed to determine whether one sequence was better than the other after adjusting for baseline characteristics. Results: 71 patients were identified: 58 received abi-to-enza and 13 received enza-to-abi. Comparisons of baseline characteristics between groups identified differences in PSA levels (P = 0.007), hemoglobin (P < 0.001), and presence of visceral disease (P = 0.035). The abi-to-enza group had a longer combined PFS than the enza-to-abi group: median 16.3 vs 12.5 mo (HR 0.53, P = 0.04). There was also a numeric improvement in OS in the abi-to-enza group compared to the enza-to-abi group: median 29.0 vs 21.0 mo (HR 0.51, P < 0.10). In multivariable analyses incorporating PSA level, hemoglobin, visceral disease and prior docetaxel use, both combined PFS (HR 2.59, P = 0.03) and OS (HR 4.59, P < 0.01) demonstrated improved outcomes with the abi-to-enza sequence. Conclusions: This hypothesis-generating study potentially suggests superior PFS and OS in men with mCRPC receiving abiraterone then enzalutamide (compared to enzalutamide then abiraterone), although this could be due to baseline imbalances or the small sample size of this study. Prospective validation of this concept is ongoing (NCT02125357).

Plasma cell-free DNA (cfDNA) profiling of copy number variation (CNV) to identify poor prognostic biomarkers in metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 176-176
Author(s):  
Edmond Michael Kwan ◽  
Heidi Fettke ◽  
Patricia Bukczynska ◽  
Nicole Ng ◽  
Christine Hauser ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Castration Resistant Prostate Cancer ◽  
Pten Loss ◽  
Cox Proportional Hazards Models ◽  
Taxane Chemotherapy ◽  
Independent Cohort

176 Background: Multiple tumour tissue studies have demonstrated the prognostic utility of CNVs in mCRPC. However, accurate assessment of CNVs in plasma cfDNA remains challenging, and prognostic significance has not been well characterized. Using a large customized panel, we correlated plasma CNVs with clinical outcomes in a contemporary cohort of mCRPC patients. Methods: Deep targeted sequencing was performed using a 180-gene cfDNA panel (Predicine) in 56 patients commencing AR pathway inhibitors (enzalutamide or abiraterone; n = 34) or taxane chemotherapy (n = 22) at two Australian institutions. Kaplan-Meier estimates and Cox proportional-hazards models were used to correlate CNVs with progression-free survival (PFS) and overall survival (OS). Significant results were validated in an independent cohort (Mayo Clinic, n = 144). Results: Median follow-up was 19.4 months (mo; IQR 11.3-31.9). The most common CNVs in the Australian cohort are shown (Table). OS was significantly decreased in patients with PI3KCA gain (median 21.7 mo vs 6.6 mo, p < 0.0001), PTEN loss (24.8 mo vs 11.7 mo, p = 0.0019) and AR gain (21.7 mo vs 12.0 mo, p = 0.0083). Furthermore, all three alterations independently predicted for poor survival in multivariable analyses (MVA; Table). Findings in the independent cohort showed similar OS results in MVA: PIK3CA gain (HR 2.0, p = 0.07), PTEN loss (HR 1.7, p = 0.08) and AR gain (HR 1.7, p = 0.03). Conclusions: Sequencing of plasma cfDNA revealed that PTEN loss, and PIK3CA and AR gain are associated with inferior clinical outcomes in patients commencing contemporary systemic treatment. These data support therapeutic strategies co-targeting the PI3K and AR pathways in mCRPC.[Table: see text]

Abstract TP252: Extended Window TPA is Safe at Community Emergency Departments via Telestroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Jerome A Jeevarajan ◽  
Alicia M Zha ◽  
Liang Zhu ◽  
Christy M Ankrom ◽  
Alyssa D Trevino ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Small Sample Size ◽  
Small Sample ◽  
Acute Ischemia ◽  
Advanced Imaging ◽  
Severe Stroke ◽  
Off Label ◽  
Imaging Capability ◽  
Baseline Characteristics ◽  
Ct Brain

Introduction: Recent studies support tPA for acute ischemic stroke (AIS) patients presenting beyond 4.5 hours from last known well (LKW), if established infarct is not evident on advanced imaging. Many community hospitals, where AIS patients may be managed via telestroke (TS), lack advanced imaging capability and hesitate to administer off-label tPA. In our TS network, physicians adhere to an extended window tPA (EW) protocol also used in the hub emergency room; eligibility includes NIHSS≤25, <1/3 MCA territory hypodensity on CT brain, and off-label tPA consent. Here, we characterize patients receiving EW via TS and investigate safety. Methods: We identified 1,150 AIS patients who received tPA via TS (9/2015-12/2018). We compared baseline characteristics between patients who received EW (arrival >4.5 hrs) and those who received standard window tPA (SW, arrival ≤4.5 hrs). We explored clinical outcomes and describe incidence of adverse effects from tPA. Results: Forty patients received EW, with median ASPECTS of 9 (Q1-Q3: 9-10). Median LKW to arrival time was 491 mins with EW and 66 mins with SW (p<0.0001, Table 1). EW led to few tPA complications; symptomatic intracranial hemorrhage incidence was 2%. EW was given for more severe stroke than SW (median NIHSS 10 vs 7, p=0.011). Both groups had comparable baseline characteristics, except a higher rate of tobacco use with EW. EW patients had longer length of stay (median 5 vs 3, p=0.023) and were more likely to be discharged to rehab than home (OR: 2.05 (1.01 4.15), p=0.046), however a small number of EW patients precludes in-depth comparative outcomes analysis. Conclusions: Our data suggest that EW is safe via TS for select patients with favorable CT, in settings that may lack advanced imaging capability. A specified mismatch between NIHSS and acute ischemia on plain CT is not part of our EW protocol, however EW is more likely given for severe stroke in our TS network. Small sample size warrants further study on clinical outcomes.

PETCO2 gradient: a novel prognostic parameter in cardiopulmonary exercise testing

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I.D Poveda Pinedo ◽  
I Marco Clement ◽  
O Gonzalez ◽  
I Ponz ◽  
A.M Iniesta ◽  
...  
Keyword(s):  
Exercise Testing ◽  
Proportional Hazards ◽  
Cardiopulmonary Exercise Testing ◽  
Cox Proportional Hazards ◽  
Prognostic Parameter ◽  
Cardiopulmonary Exercise ◽  
Proportional Hazards Regression ◽  
Kaplan Meier ◽  
Baseline Characteristics ◽  
The Difference

Abstract Background Previous parameters such as peak VO2, VE/VCO2 slope and OUES have been described to be prognostic in heart failure (HF). The aim of this study was to identify further prognostic factors of cardiopulmonary exercise testing (CPET) in HF patients. Methods A retrospective analysis of HF patients who underwent CPET from January to November 2019 in a single centre was performed. PETCO2 gradient was defined by the difference between final PETCO2 and baseline PETCO2. HF events were defined as decompensated HF requiring hospital admission or IV diuretics, or decompensated HF resulting in death. Results A total of 64 HF patients were assessed by CPET, HF events occurred in 8 (12.5%) patients. Baseline characteristics are shown in table 1. Patients having HF events had a negative PETCO2 gradient while patients not having events showed a positive PETCO2 gradient (−1.5 [IQR −4.8, 2.3] vs 3 [IQR 1, 5] mmHg; p=0.004). A multivariate Cox proportional-hazards regression analysis revealed that PETCO2 gradient was an independent predictor of HF events (HR 0.74, 95% CI [0.61–0.89]; p=0.002). Kaplan-Meier curves showed a significantly higher incidence of HF events in patients having negative gradients, p=0.002 (figure 1). Conclusion PETCO2 gradient was demonstrated to be a prognostic parameter of CPET in HF patients in our study. Patients having negative gradients had worse outcomes by having more HF events. Time to first event, decompensated heart Funding Acknowledgement Type of funding source: None

scholarly journals 1611. Evaluating Clinical Outcomes and Efficacy of Daptomycin in Combination with a Beta-Lactam for the Treatment of Vancomycin-Resistant Enterococcus (VRE) Bacteremia

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S799-S800
Author(s):  
Nerea Irusta ◽  
Ana Vega ◽  
Yoichiro Natori ◽  
Lilian M Abbo ◽  
Lilian M Abbo ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Primary Outcome ◽  
Small Sample Size ◽  
Univariate Analysis ◽  
Small Sample ◽  
Significant Difference ◽  
Vancomycin Resistant ◽  
Secondary Outcomes ◽  
Related Mortality

Abstract Background In-vitro studies have shown synergistic bactericidal activity with daptomycin (DAP) plus β-lactam antimicrobials against vancomycin resistant enterococci (VRE). There is a paucity of data regarding clinical outcomes with this combination in VRE bloodstream infections (BSI). The purpose of this study was to assess the efficacy of DAP plus a β-lactam with in-vitro activity vs. other therapies for treatment of VRE BSI. Methods IRB-approved, single-center, retrospective study of patients with VRE BSI from 01/2018-09/2019. Patients were excluded if &lt; 18 years old, pregnant, or incarcerated. The primary outcome was time-to-microbiological clearance. Secondary outcomes included infection-related mortality, 30-day all-cause mortality, and incidence of recurrent BSI within 30 days of index culture. Targeted DAP doses were ≥ 8mg/kg and based on MIC. Factors associated with significance for outcomes, via univariate analysis, were evaluated with multivariable logistic regression (MLR), removed in a backward-step approach. Results A total of 85 patients were included, 23 of which received DAP plus a β-lactam. The comparator arm included linezolid or DAP monotherapy. Patients with combination therapy had significantly higher Charlson Comorbidity Index (CCI) (p=0.013) and numerically higher Pitt Bacteremia scores (PBS) (p=0.087) (Table 1). There was no difference seen in the primary outcome (Table 2). Secondary outcomes are provided in Table 2. The presence of polymicrobial infection and higher PBS were significantly associated with infection-related mortality (p=0.008 and p=0.005, respectively) by MLR. A Mann Whitney U test indicated that presence of infection-related mortality was greater for patients with higher MICS (U=20.5, p=0.06). The presence of an underlying source may be related to recurrence of BSI (p=0.075). Table 1: Patient Characteristics Table 2. Primary and Secondary Outcomes Conclusion We did not find a significant difference in time-to-microbiological clearance, although patients treated with DAP and a β-lactam had higher CCI and PBS. These results are limited by retrospective design, small sample size, and potential selection bias. Prospective randomized studies are needed to further validate these findings. Disclosures All Authors: No reported disclosures

scholarly journals Impact of Pathological Stratification on the Clinical Outcomes of Advanced Well-Differentiated/Dedifferentiated Liposarcoma Treated with Trabectedin

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1453
Author(s):  
Chiara Fabbroni ◽  
Giovanni Fucà ◽  
Francesca Ligorio ◽  
Elena Fumagalli ◽  
Marta Barisella ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Case Series ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Low Grade ◽  
High Grade ◽  
Retrospective Case ◽  
Well Differentiated ◽  
The Impact

Background. We previously showed that grading can prognosticate the outcome of retroperitoneal liposarcoma (LPS). In the present study, we aimed to explore the impact of pathological stratification using grading on the clinical outcomes of patients with advanced well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) treated with trabectedin. Patients: We included patients with advanced WDLPS and DDLPS treated with trabectedin at the Fondazione IRCCS Istituto Nazionale dei Tumori between April 2003 and November 2019. Tumors were categorized in WDLPS, low-grade DDLPS, and high-grade DDLPS according to the 2020 WHO classification. Patients were divided in two cohorts: Low-grade (WDLPS/low-grade DDLPS) and high-grade (high-grade DDLPS). Results: A total of 49 patients were included: 17 (35%) in the low-grade cohort and 32 (65%) in the high-grade cohort. Response rate was 47% in the low-grade cohort versus 9.4% in the high-grade cohort (logistic regression p = 0.006). Median progression-free survival (PFS) was 13.7 months in the low-grade cohort and 3.2 months in the high-grade cohort. Grading was confirmed as an independent predictor of PFS in the Cox proportional-hazards regression multivariable model (adjusted hazard ratio low-grade vs. high-grade: 0.45, 95% confidence interval: 0.22–0.94; adjusted p = 0.035). Conclusions: In this retrospective case series, sensitivity to trabectedin was higher in WDLPS/low-grade DDLPS than in high-grade DDLPS. If confirmed in larger series, grading could represent an effective tool to personalize the treatment with trabectedin in patients with advanced LPS.

Fibroblast growth factor receptor alteration (FGFRa) status and progression outcomes of patients with advanced or metastatic urothelial cancer (mUC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4530-4530
Author(s):  
Sarah Fleming ◽  
Dina Gifkins ◽  
Waleed Shalaby ◽  
Jianjun Gao ◽  
Philip Rosenberg ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
The United States ◽  
Cox Proportional Hazards ◽  
Small Sample ◽  
Prognostic Impact ◽  
Patient Records ◽  
Front Line ◽  
Convenience Sample ◽  
Adjusted Risk ◽  
Metastatic Urothelial Cancer

4530 Background: FGFRa appear in approximately 15% of cases of mUC. Data on whether FGFRa in mUC have a prognostic impact or predictive benefit for particular treatments have been limited by small sample sizes. The objective of this study was to evaluate the association between tumor FGFRa and clinical outcomes of patients with advanced UC or mUC regardless of therapy type and status. Methods: A convenience sample of oncologists and urologists across the United States provided patient level data on 400 patients with stage IIIb or IV UC via a standardized questionnaire over a 1-month period (August 17, 2020 – September 20, 2020). Study design enriched for FGFRa by requiring physicians to provide ≥1 FGFRa patient record. The questionnaire included physician characteristics, patient demographic information, FGFR status, therapy given, response, and clinical and radiographic measures of progression. Patient records were eligible for inclusion if they were identified and treated during July 1, 2017, to June 30, 2019. Cox proportional hazards models were used to estimate adjusted risk of disease progression by FGFR status. Results: A total of 104 physicians (58.7% medical oncologists, 31.7% hematologic oncologists, and 9.6% urologic oncologists) contributed 414 patient records Overall, 73.9% of the patients were male and the average age was 64.5 years (SD ±10.6). Median follow-up was 15 months. Of the 414 patients, 218 (52.7%) had FGFRa and 196 (47.3%) had FGFR wild-type ( FGFRwt) mUC . Of the 218 patients with FGFRa, 47.2% were treated with front-line chemo, 27.5% with a programmed death-ligand 1 inhibitor (PD-L1), 11.5% with chemo + PD-L1, and 13.8% with other treatments. Of the 196 FGFRwt patients, 63.2% were treated with front-line chemo, 21.9% with PD-L1, 12.2% with chemo + PD-L1, and 2.6% with other treatments. There was no difference in response or progression status for those receiving front-line chemo (HR, 1.15; 95% CI, 0.86-1.55). Among 97 patients (55 FGFRa and 42 FGFRwt) who received PD-L1 alone as front-line therapy, those who had FGFRa had an adjusted risk of progression 2 times higher than their FGFRwt counterparts (HR, 2.12; 95% CI, 1.13-4.00). Conclusions: Patients with FGFRa mUC progressed earlier than FGFRwt patients treated with front-line PDL-1 inhibitors; however, there was no difference in progression in patients treated with chemo based upon FGFR status. This real-world study using a survey design efficiently generated a relatively large FGFRa dataset, mitigating a core limitation of other studies assessing the patient population with FGFRa. Further work is warranted to validate these results and determine the optimal strategy for treating the patient with FGFRa mUC. Gene expression profiling of FGFRa mUC samples from clinical trials will help determine the potential impact of subtype or other features that may associate with benefit from therapy.

Overall survival (OS) and metastasis-free survival (MFS) by depth of prostate-specific antigen (PSA) decline in the phase III PROSPER trial of men with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with enzalutamide (ENZA).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 94-94
Author(s):  
Maha H. A. Hussain ◽  
Cora N. Sternberg ◽  
Eleni Efstathiou ◽  
Karim Fizazi ◽  
Qi Shen ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Reference Group ◽  
Specific Antigen ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Analysis Model ◽  
Increased Risk ◽  
Psa Nadir ◽  
Post Hoc

94 Background: The PROSPER trial demonstrated prolonged MFS and OS for men with nmCRPC and rapidly rising PSA treated with ENZA vs placebo, both in combination with androgen deprivation therapy (ADT). The final survival analysis of PROSPER (Sternberg et al. NEJM 2020) recently reported a median OS of 67.0 months (95% CI, 64.0 to not reached) with ENZA and 56.3 months (95% CI, 54.4 to 63.0) with placebo (hazard ratio [HR] for death, 0.73; 95% CI, 0.61 to 0.89; P = .001). Post hoc analyses of PROSPER evaluating PSA dynamics have demonstrated longer MFS with greater PSA decline (Hussain et al. ESMO Sept 19-21, 2020. Poster 685P) and increased risk of metastases in patients with even modest PSA progression vs those without (Saad et al. Eur Urol 2020). Here we further explored the relationship between PSA dynamics and outcomes in PROSPER using uniquely defined PSA subgroups of decline. Methods: Eligible men in PROSPER had nmCRPC, a PSA level ≥ 2 ng/mL at baseline, and a PSA doubling time ≤ 10 months. Men continued ADT, were randomized 2:1 to ENZA 160 mg once daily vs placebo, and had PSA evaluation at week 17 and every 16 weeks thereafter. This post hoc analysis evaluated OS and MFS for 4 mutually exclusive subgroups defined by PSA nadir using men with PSA reduction < 50% as the reference group. The HR is based on an unstratified Cox proportional hazards analysis model. Results: 1401 men were enrolled in PROSPER; 933 were treated with ENZA and PSA data were available for 905. Measured at nadir, 38% of these men achieved PSA reduction ≥ 90% (actual nadir < 0.2 ng/mL), and another 27% achieved PSA reduction ≥ 90% (actual nadir ≥ 0.2 ng/mL). Among men in the placebo arm of PROSPER only 3/457 reported PSA reduction ≥ 90%. Median OS and MFS increased with increasing depth of PSA decline (Table). Conclusions: In men with nmCRPC and rapidly rising PSA treated with ADT plus ENZA, there was a close relationship between the degree of PSA decline and survival outcomes. Defining PSA by both percent decline and actual decline below 0.2 ng/mL revealed a previously under-appreciated relationship between these PSA metrics and highlights the importance of PSA nadir as an intermediate biomarker in nmCRPC. Clinical trial information: NCT02003924. [Table: see text]

Abstract 15467: Impact of Thrombocytopenia on Clinical Outcomes in Atrial Fibrillation Patients With Anemia: The Fushimi Af Registry

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kenjiro Ishigami ◽  
Syuhei Ikeda ◽  
KOSUKE DOI ◽  
Yasuhiro Hamatani ◽  
Akiko Fujino ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Outcomes ◽  
Major Bleeding ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Antithrombotic Drugs ◽  
Prospective Survey ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Independent Determinant

Introduction: Anemia has been reported to be associated with poor prognosis in patients with atrial fibrillation (AF). Concomitant thrombocytopenia (TP) may or may not affect the prescription of antithrombotic drugs and clinical outcomes in these patients. Methods: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto. We defined TP as platelet counts less than 150,000/μL and anemia as hemoglobin less than 11 g/dL. Among 666 patients with anemia, we compared the clinical backgrounds and outcomes of those with TP (n=183) and those without (n=483). Results: Compared with patients without TP, patients with TP were more likely to have chronic kidney disease (75.4% vs. 61.8%, p=0.001), and less likely to have hypertension (58.5% vs. 67.0%, p=0.0393), and less likely to have dyslipidemia (27.3% vs. 38.3%, p=0.0079). Age, sex, body weight, CHADS 2 score, CHA 2 DS 2 -VASc score, HAS-BLED score, and previous major bleeding were comparable between the groups. Furthermore, prescription of anti-thrombotic drugs was comparable (Figure A). On Kaplan-Meier analysis, the incidence of all-cause death was higher in TP group (hazard ratio [HR] 1.52; 95% confidence interval [CI] 1.20-1.91, p<0.05) (Figure B-1). There was no significant difference in other adverse events between patients with and without TP (major bleeding: HR 1.11; 95% CI 0.41-3.31, p=0.8, hospitalization for heart failure: HR 1.11; 95% CI 0.74-1.61, p= 0.61 and stroke or systemic embolism: HR 0.91; 95% CI 0.43-1.78, p=0.80) (Figure B-2, 3, 4). Multivariate Cox proportional hazards regression analysis adjusting for potential confounders revealed that TP was an independent determinant of all-cause death (adjusted HR: 1.41, 95% CI; 1.11-1.78, p=0.006). Conclusions: Concomitant TP in AF patients with anemia did not affect the prescription of antithrombotic drugs, and was independently associated with all-cause death in the Fushimi AF Registry.

scholarly journals What Is the Role for Metronidazole in the Treatment of Clostridium difficile Infection? Results From a National Cohort Study of Veterans With Initial Mild Disease

2018 ◽  
Vol 69 (8) ◽  
pp. 1288-1295 ◽  
Author(s):  
Haley J Appaneal ◽  
Aisling R Caffrey ◽  
Kerry L LaPlante
Keyword(s):  
Clostridium Difficile ◽  
Clinical Outcomes ◽  
Clostridium Difficile Infection ◽  
Proportional Hazards ◽  
Therapeutic Option ◽  
Cox Proportional Hazards ◽  
First Episode ◽  
Mild Disease ◽  
All Cause Mortality ◽  
National Cohort

Abstract Background Metronidazole may still be an appropriate therapeutic option for mild Clostridium difficile infection (CDI) in select patients, but data are limited to guide clinicians in identifying these patients. Methods Our 2-stage study included a national cohort of Veterans with a first episode of mild CDI (2010–2014). First, among those treated with metronidazole, we identified predictors of success, defined as absence of all-cause mortality or recurrence 30 days posttreatment, using multivariable unconditional logistic regression. Second, among a subgroup of patients with characteristics predictive of success identified in the first stage, we compared clinical outcomes among those treated with metronidazole compared with vancomycin, using Cox proportional hazards models for time to 30-day all-cause mortality, CDI recurrence, and failure. Results Among 3656 patients treated with metronidazole, we identified 3282 patients with success and 374 patients without success (failure). Younger age was the only independent predictor of success. Age ≤65 years was associated with an odds of success 1.63 times higher (95% confidence interval [CI], 1.29–2.06) than age >65 years. Among 115 propensity score–matched pairs ≤65 years of age, no significant differences were observed between metronidazole and vancomycin (reference) for all-cause mortality (hazard ratio [HR], 0.29 [95% CI, .06–1.38]), CDI recurrence (HR, 0.62 [95% CI, .26–1.49]), or failure (HR, 0.50 [95% CI, .23–1.07]). Conclusions Among patients ≤65 years of age with initial mild CDI, clinical outcomes were similar with metronidazole and vancomycin. These data suggest that metronidazole may be considered for the treatment of initial mild CDI among patients 65 years of age or younger.

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