30-day Recurrence Research Articles

The Impact of Concomitant Empiric Cefepime on Patient Outcomes of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections Treated With Vancomycin.

BackgroundData suggest that vancomycin + β-lactam combinations improve clearance of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs). However, it is unclear which specific β-lactams confer benefit. This analysis evaluates the impact of concomitant empiric cefepime on outcomes of MRSA BSIs treated with vancomycin.MethodsRetrospective cohort study of adults with MRSA BSI from 2006 to 2017. Vancomycin + cefepime therapy was defined as ≥24 hours of cefepime during the first 72 hours of vancomycin. The primary outcome was microbiologic failure, defined as BSI duration ≥7 days and/or 60-day recurrence. Multivariable logistic regression was used to evaluate the association between vancomycin + cefepime therapy and binary outcomes. Cause-specific and subdistribution hazard models were used to evaluate the association between vancomycin + cefepime and BSI clearance.ResultsThree hundred fifty-eight patients were included, 129 vancomycin and 229 vancomycin + cefepime. Vancomycin + cefepime therapy was independently associated with reduced microbiologic failure (adjusted odds ratio [aOR], 0.488; 95% confidence interval [CI], 0.271–0.741). This was driven by a reduction in the incidence of BSI durations ≥7 days (vancomycin + cefepime aOR, 0.354; 95% CI, 0.202–0.621). Vancomycin + cefepime had no association with 30-day mortality (aOR, 0.952; 95% CI, 0.435–2.425). Vancomycin + cefepime was associated with faster BSI clearance in both cause-specific (HR, 1.408; 95% CI, 1.125–1.762) and subdistribution hazard models (HR, 1.264; 95% CI, 1.040–1.536).ConclusionsConcomitant empiric cefepime improved MRSA BSI clearance and may be useful as the β-lactam component of synergistic vancomycin + β-lactam regimens when empiric or directed gram-negative coverage is desired.

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

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.

Use of non-carbapenem antibiotics to treat severe extended-spectrum β-lactamase-producing Enterobacteriaceae infections in intensive care unit patients

The aim of this study was to evaluate the use of non-carbapenem antibiotics to treat severe extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) infections in intensive care unit (ICU) patients. This retrospective observational study conducted in two ICUs compared the outcomes of patients with ESBL-E infections administered a carbapenem or a non-carbapenem antibiotic as their definitive treatment. The primary outcome was treatment failure within 30 days, a composite endpoint of ESBL-E infection recurrence and 30-day mortality. Secondary outcomes included 30-day and in-hospital mortality rates, ESBL-E infection recurrence and infection(s) due to other pathogen(s). Among 107 patients included in the study, 67 received a carbapenem and 40 received a non-carbapenem antibiotic as their definitive treatment. Clinical characteristics of the two groups were similar. Comparing patients given a non-carbapenem antibiotic with those administered a carbapenem, they had similar 30-day treatment failure (43% vs. 61%, respectively; P = 0.06) and ESBL-E infection recurrence rates (25% vs. 22%; P = 0.8), but the former had lower 30-day mortality (23% vs. 45%; P = 0.02) and in-hospital mortality rates (23% vs. 49%; P = 0.005). Secondary infection rates caused by other pathogen(s), including Clostridium difficile, were comparable. Outcomes were comparable regardless of whether or not patients received an empirical carbapenem. For ICU patients with severe ESBL-E infections, treatment with a non-carbapenem antibiotic was not associated with poorer outcomes compared with a carbapenem antibiotic.

Hypoalbuminemia as predictor of recurrence of Clostridium difficile infection.

SummaryBackgroundNovel drugs for Clostridium difficile (C. difficile) infections have been proven to reduce recurrent infections. Because of their high financial costs, identification of patients at high risk for recurrence is essential to provide optimal treatment. The ATLAS score’s ability to predict 90-day recurrence, disease complications and 1‑year all-cause mortality was evaluated.Methods144 consecutive symptomatic patients with positive stool test for C. difficile were enrolled. The ATLAS score (consisting of the variables age, temperature, leukocyte count, albumin, systemic antibiotics, serum creatinine) was calculated and patients were stratified into 4 subgroups according to their scores. A Cox regression model was used to estimate the extent to which ATLAS was associated with 90-day recurrence. Furthermore, the score was correlated with disease complications and one-year all-cause mortality.ResultsATLAS was unable to predict 90-day recurrence (p = 0.064, HR 1.134 [0.993;1.295]), but performed well for disease complications (D = 0.382, p < 0.001, HR 1.547 [1.266;1.889]) and mortality (p < 0.001, HR 1.374 [1.194;1.583]). Serum albumin was the only parameter able to predict 90-day recurrence (p = 0.016, HR 0.958 [0.926;0.992]) and was also a predictor of disease complications (p < 0.001, HR 0.865[0.809;0.924]) and one-year all-cause mortality (p < 0.001, HR 0.923 [0.896;0.950]). A threshold of 33.1g/L (sensitivity = 56%, specificity = 80%, AUC 0.683) and 29.2g/L (sensitivity = 75%, specificity = 70%, AUC 0.763) of serum albumin could be identified to be predictive for 90-day recurrence and one-year all-cause mortality, respectively.ConclusionsSerum albumin and ATLAS are predictors of disease complications and mortality, while only serum albumin is significantly associated with 90-day disease recurrence.

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

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. 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. 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]). 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.

The Impact of Diabetes on Outcomes After Acute Ischemic Stroke: A Prospective Observational Study

Background: Stroke in diabetics may delay recovery and increases the risk of early recurrence of stroke. We compared the outcomes of patients (with and without diabetes) admitted with an acute ischemic stroke (AIS) in the state of Qatar. Patients and methods: We prospectively compared the clinical presentation, complications, discharge outcome, and stroke recurrence at 90 days in patients with and without diabetes. Results: Five thousand two hundred twenty-eight stroke patients were admitted between January 2014 and December 2017. Two thousand nine hundred sixty-one had confirmed AIS, 1695 (57.2%) had diabetes, 429 (14.5%) had prediabetes and 873 (29.5%) had no diabetes. Comparing diabetic patients to prediabetic and nondiabetics, they were significantly older (58.5 ± 11.9 versus 54.0 ± 12.9 versus 49.5 ± 13.8, P = .0001), had higher rates of hypertension (80.8% versus 67.4% versus 59.2%), previous stroke (18.0% versus 5.4% versus 6.2%), and coronary artery disease (12.9% versus 5.6% versus 5.0%; P = .001 for all). The percentage of patients with modified Rankin scale 3-6 at discharge (39.7% versus 32.6% versus 30.2%; P = .0001) and 90 days (26.7% versus 18.8% versus 21.4%, P = .001); 90-day mortality (6.2% versus 2.2% versus 5.2%; P = .03) and stroke recurrence (4.2% versus .7% versus 2.2%; P = .005) was significantly higher in diabetic patients. Conclusions: Patients with diabetes and AIS have more in-hospital complications, worse discharge outcomes, higher mortality and stroke recurrence at 90 days, compared to prediabetes and no diabetes.

1110. A multicenter Evaluation of Outcomes Associated With Oral Vancomycin Dose in Patients With Clostridium difficile Infection

Background Clostridium difficile infection (CDI) is a significant cause of morbidity and mortality. IDSA guidelines recommend oral vancomycin (VAN) for the treatment of CDI, although doses used in practice vary substantially. The purpose of this study was to determine differences in outcomes between patients treated with high dose (HD; ≥250 mg four times daily [QID]) vs. standard dose (SD; 125 mg QID) VAN for CDI.MethodsThis multicenter study evaluated patients at two hospitals in Albany, NY diagnosed with CDI and treated with oral VAN between January 2013 and August 2017. Hospitalized patients were included if: age ≥18 years, positive C. difficile toxin polymerase chain reaction (PCR), symptomatic infection (e.g., new onset or increased frequency of loose stools), and received ≥48 hours of VAN QID. Patients were excluded if: received ≥48 hours of metronidazole prior to VAN initiation, VAN per rectum, required surgical intervention ≤48 hours from PCR, had a history of fecal microbiota transplant, received ≥1 dose of fidaxomicin or tigecycline prior to or within 48 hours from PCR, or died ≤48 hours from PCR. The primary outcome was 90-day CDI recurrence; secondary outcomes included 30-day all-cause mortality and 90-day readmission. Variables with a P-value <0.2 in univariate analysis were evaluated in multivariate (MV) analyses.ResultsFour hundred fifty-eight patients were included (site 1: 270; site 2: 188). Two hundred twenty-four patients received SD VAN (48.9%); 234 received HD VAN [250 mg QID: 199 (43.5%); 500 mg QID: 35 (7.6%)]. Baseline demographics were similar between groups. Patients treated with HD were more likely to present with colitis (19.2 vs. 29.5%, P = 0.01) and have higher infection severity based on IDSA (P < 0.01), Zar (P < 0.01), and American College of Gastroenterology (P < 0.02) criteria. Modified APACHE II scores were similar between SD and HD groups (median: 12.2 vs. 12.9, P = 0.17). MV analysis identified no difference in 90-day recurrence with HD (OR 1.65, P = 0.13) after controlling for solid tumor cancers, immunosuppression, and IDSA severity. Similarly, no significant differences between SD and HD were observed for 30-day mortality and 90-day readmission.ConclusionNo differences in recurrence, mortality, or readmission were identified between SD and HD oral VAN for the treatment of CDI, though HD VAN patients primarily received 250 mg QID.Disclosures All authors: No reported disclosures.

2439. Outcomes of Minocycline Use on Gram-Negative Infections and Implications of MIC

BackgroundMinocycline (MINO) is a treatment option for Acinetobacter baumannii and Stenotrophomonas maltophilia infections due to high in vitro susceptibility. Literature suggests it may also be an option for carbapenamase-producing enterobacteriaceae. MINO minimum inhibitory concentrations (MICs) vary by organism and dosing varies by center. Additional data are needed to assess MINO effectiveness in Gram-negative infections and determine if a relationship exists between MIC and treatment outcomes.MethodsRetrospective study evaluating MINO use in adults at NewYork-Presbyterian Hospital from 2012 to 2017. Patients included received MINO ≥2 days for a culture-positive Gram-negative infection (CDC/NHSN criteria) susceptible to MINO. Patients with MINO started >5 days after positive culture or with untreated polymicrobial infections were excluded. The primary outcome was clinical failure at the end of therapy. Secondary outcomes included 30-day mortality, development of resistance or recurrence within 90 days.Results114 patients were included: majority were male (51%) with median age 57 years. Median duration was 12 days with 8 patients receiving high-dose MINO (≥150 mg q12H). S. maltophilia was the most prevalent pathogen (72%) followed by Klebsiella pneumoniae (16%) with a median MINO MIC of 1 mg/L. 68% of patients received combination therapy. Treatment success was observed in 71 patients (63%). Patients with treatment failure had higher median Charlson Comorbidity Index (5 vs. 3; P = 0.026), SOFA score (7 vs. 5; P = 0.028), and were more likely to have underlying leukemia or lymphoma (39% vs. 7%; P < 0.001). No differences were seen in primary or secondary outcomes between combination and monotherapy regimens. MICs had no impact on failure outcome, 30-day mortality or 90-day recurrence (all P > 0.05); however, MICs ≤ 2 mg/L were associated with increased development of resistance (34% vs. 12%; P = 0.021). In a multivariable analysis, vasopressor use (OR 2.79; 95% CI 1.05,7.41; P = 0.04) and underlying leukemia/lymphoma (OR 4.49; 95% CI 1.26,15.95; P = 0.02) were associated with increased risk of treatment failure.ConclusionMINO MIC impacted resistance, but did not correlate with treatment failure, mortality or recurrence. Severity of illness and comorbidities but not choice of MINO may be associated with clinical failures.Disclosures All authors: No reported disclosures.

2379. Multicenter Evaluation of Ceftazidime–Avibactam for Multidrug-Resistant Gram-Negative Bacterial Infections

BackgroundThe increasing prevalence of multidrug-resistant (MDR) Gram-negative bacteria (GNB) represents an urgent public health threat. Ceftazidime–avibactam (CZA) is a novel cephalosporin/β-lactamase inhibitor with activity against MDR GNB including carbapenem-resistant Enterobacteriaceae (CRE). Real-world experience with CZA in the treatment of MDR GNB is accumulating but remains limited by the small number of patients thus far described. We sought to build upon prior reports by describing the clinical characteristics and outcomes of a diverse cohort of patients with MDR GNB infections treated with CZA.MethodsRetrospective, multicenter, cohort study of patients treated with CZA (≥72 h) for suspected or confirmed MDR GNB (resistant to ≥1 antibiotic in ≥3 classes) infections between 2015 and 2018. The primary outcome was clinical failure defined as a composite of 30-day mortality, 30-day recurrence, or worsening signs and symptoms while on CZA. Independent predictors of clinical failure were sought through multivariable logistic regression analysis.ResultsA total of 114 patients were included. The median (IQR) age was 65 (53, 74), the median Charlson Comorbidity Index was 4 (2, 6), and the median APACHE II score was 20 (14, 28). CRE and MDR Pseudomonas aeruginosa were isolated in 74 (66%) and 31 (28%) of cases, respectively. The predominant sources were respiratory (40%) and urinary tract (20%). Blood cultures were positive in 10% of cases. Combination therapy (≥48 h) was used in 40%. Among carbapenem-resistant Klebsiella pneumoniae (n = 34), 97% were susceptible to CZA. The resistant isolate was positive for NDM and OXA. Clinical failure, 30-day mortality, and recurrence were 28%, 13% and 5%, respectively. Independent predictors of clinical failure were immune compromise (aOR 6.25, 95% CI 1.30, 30.11), Glasgow Coma scale ≤ 12 (aOR 3.76, 95% CI 1.30, 10.88), primary bacteremia or respiratory source (aOR 2.96, 1.07–8.17) and age less than 65 (aOR 2.87, 95% CI 1.09, 7.61).ConclusionThe use of CZA was associated with a clinical failure rate of 28% which compares favorably with historical controls of MDR GNB infections. Future investigations evaluating long-term outcomes and comparative studies are needed to more precisely define the role of CZA in MDR GNB infections.Disclosures S. L. Davis, Achaogen: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. Melinta: Scientific Advisor, Consulting fee. Nabriva: Scientific Advisor, Consulting fee. Zavante: Scientific Advisor, Consulting fee. M. J. Rybak, Allergan: Consultant, Grant Investigator and Speaker’s Bureau, Research grant and Research support. Achaogen: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Bayer: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Melinta: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Merck: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Theravance: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Sunovian: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Zavante: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. NIAID: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support.

1001. Evaluation of the Clinical Efficacy and Safety of Oral Antibiotic Therapy for Streptococcus spp. Bloodstream Infections

BackgroundDespite the severity and frequency of bloodstream infections (BSI), the effectiveness of oral definitive therapy remains unknown. The objective of this study was to evaluate the efficacy and safety of step down oral antibiotics for the treatment of Streptococcus spp. BSI.MethodsThis was a retrospective cohort study of adult, hospitalized patients with Streptococcus spp. BSI between June 2015 and June 2017. Patients were excluded if received <48 hours of antibiotic therapy or therapy was started >48 hours from first positive culture. Patients were grouped by receipt of step down oral antibiotic therapy (PO group) vs. full course IV therapy (IV group) and compared for demographics, clinical course, and outcomes. The primary outcome was 30-day mortality and hospital length of stay (LOS). The secondary outcomes included 30-day recurrence of BSI and adverse events (AEs).ResultsOne hundred ninety-five patients met inclusion criteria; median age was 51 year old, 68% were male, 57% were Hispanic, and 71% had community-onset BSI. Sixty-four (33%) were treated with step down oral therapy. The most common source of bacteremia was pneumonia (21%); 8% had endocarditis. Comorbidities were similar between the groups, with diabetes being most common (IV 22% vs. PO 19%, P = 0.29). Severity of illness measured by need for ICU admission, initial lactate level, and SOFA score was similar between the two groups. S. viridans was the most frequent pathogen isolated (IV 28% vs. PO 27%, P = 0.87). Ceftriaxone (39%) for the IV group and levofloxacin (30%) for the PO group were the most common definitive therapy prescribed. PO group received 4 days of IV therapy prior to transition to orals. The IV group had significantly higher mortality rate (11% vs. 2%, P = 0.02) and longer LOS (median 9 days [IQR 5–18] vs. 5 days [4–7.75], P ≤ 0.01) compared with the PO group. 30-day recurrence (IV 2% vs. PO 5%, P = 0.40) and AEs (IV 2% vs. PO 3%, P = 0.60) were similar between the two groups.ConclusionIn Streptococcus spp. BSI, step down oral antibiotic therapy was associated with a significantly shorter LOS compared with IV only therapy without compromise of clinical outcomes. Larger prospective trials evaluating step down oral therapy are warranted to confirm our results.Disclosures All authors: No reported disclosures.

288. Expediting Discharge in Acute Bacterial Skin and Skin Structure Infections: A Clinical and Economic Comparison Between Vancomycin and Oritavancin

BackgroundAcute bacterial skin and skin structure infections (ABSSSI) have a high economic burden secondary to prolonged hospitalizations and high rates of recurrent infections. Utilizing oritavancin rather than vancomycin, select inpatients may be discharged earlier in their hospitalization with anticipated decreased infection recurrences and cost avoidance.MethodsAll inpatients administered oritavancin to expedite discharge and/or vancomycin for the treatment of ABSSSI between May 2017 and January 2018 were included in this retrospective evaluation. The primary endpoint was to determine the 30-day ABSSSI recurrence rate between treatment arms. The secondary endpoints were to evaluate financial expenditures associated with utilization of oritavancin when compared with vancomycin, and to assess for potential risk factors associated with poor outcomes. A financial analysis was performed for patients based on their DRG (diagnosis-related group) applying hospital-specific expenditures provided by the finance department. Data were analyzed using Fisher’s exact test, χ2 test, or t-test as appropriate.ResultsA total of 51 patients receiving oritavancin and 50 patients receiving vancomycin were identified as meeting inclusion criteria. Nine of 50 patients (18%) returned for recurrent infections in the vancomycin arm while only 2 of 51 (4%) returned in the oritavancin arm (P = 0.0279). Out of the 11 patients with recurrent infections, 6 were current intravenous drug users (55%), 3 left against medical advice at their initial visit (27%) and 7 had an emergency department visit in the prior 30 days for the same infection (64%). Overall, there were 111.7 hospitalization days avoided in 51 patients receiving oritavancin, resulting in an estimated cost avoidance of $217,206 compared with conventional treatment with vancomycin.ConclusionUtilizing oritavancin to expedite discharge in hospitalized patients appears to be an effective and financially beneficial treatment for ABSSSI.Disclosures All authors: No reported disclosures.

1952. Evaluation of Relapse and Reinfection Using Whole-Genome Sequencing of Clostridium difficile Isolates From Elderly Patients With C. difficile Infection (CDI) in the EXTEND Randomized, Controlled, Comparative Study of Extended-Pulsed Fidaxomicin and Vancomycin for the Treatment of CDI

BackgroundThe EXTEND study demonstrated reduced 90-day recurrence rates for an extended-pulsed regimen of fidaxomicin (EPFX) vs. standard vancomycin (SV) in the treatment of Clostridium difficile infection (CDI): treatment difference −13%, P = 0.00073.1 Whole-genome sequencing (WGS) is used to differentiate between same-strain relapse and new-strain reinfection of CDI. We used WGS of paired C. difficile samples from patients with CDI recurrence in the EXTEND study to assess EPFX and SV in relation to relapse and reinfection.MethodsPatients aged ≥60 years with CDI were randomized (1:1) to receive either EPFX (fidaxomicin 200 mg tablets, twice daily on Days 1–5 and once daily on alternate days on Days 7–25) or SV (125 mg capsules, four times daily on Days 1–10). Paired stool samples were collected from all patients at screening and from patients with recurrence after test-of-cure (TOC). Recurrence was defined as diarrhoea occurring to a greater extent than the frequency recorded at TOC, and confirmed positive for C. difficile toxin A/B and requiring further CDI therapy. C. difficile isolates from paired samples underwent WGS and single nucleotide variant (SNV) difference analysis. Paired samples with ≤2 SNV differences were considered relapses, paired samples with >10 SNV differences were considered reinfection, and those with >2 but ≤10 SNV differences (or without WGS) were considered indeterminate.ResultsAt Day 90, 11/177 (6%) patients in the EPFX arm and 34/179 (19%) patients in the SV arm had CDI recurrence. Of these, samples from 7/11 EPFX- and 19/34 SV-treated patients were available for paired WGS analysis. SNV analysis showed that most CDI recurrences were new-strain reinfections (table). ConclusionMost recurrences were reinfections, but small sample sizes limited definitive conclusions.Reference1. Guery et al. (2017). Lancet Inf Dis 18:296–307.Disclosures M. Wilcox, Astellas Pharma: Consultant and Grant Investigator, Consulting fee, Research grant, Speaker honorarium and This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas. O. A. Cornely, Astellas Pharma: Grant Investigator, Lecture speaker and Scientific Advisor, Research grant, Speaker honorarium and This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas. B. Guery, Astellas Pharma: Consultant, Consulting fee and This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas. C. Longshaw, Astellas Pharma: CL was a full-time employee of Astellas Pharma, Inc., during the study conduct and is now an employee of Shionogi Europe Ltd.; he also has a patent WO2015169451 A1 pending. and Employee, Medical writing support was provided by Cello Health MedErgy and funded by Astellas and Salary. A. Georgopali, Astellas Pharma: Employee, Medical writing support was provided by Cello Health MedErgy and funded by Astellas. and Salary. A. Karas, Astellas Pharma: AK has patents WO2015169451 A1 and EP17167541.6 pending. and Employee, Medical writing support was provided by Cello Health MedErgy and funded by Astellas. and Salary. G. Kazeem, Astellas Pharma: Independent Contractor, Medical writing support was provided by Cello Health MedErgy and funded by Astellas. and Salary. J. A. Palacios-Fabrega, Astellas Pharma: AP-F has a patent EP17167541.6 pending. and Employee, Medical writing support was provided by Cello Health MedErgy and funded by Astellas. and Salary. M. J. G. T. Vehreschild, Astellas Pharma: Consultant and Grant Investigator, Consulting fee, Grant recipient and This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas.

Clinical outcomes of fidaxomicin vs oral vancomycin in recurrent Clostridium difficile infection

Recurrent Clostridium difficile infection (CDI) occurs after initial treatment in approximately 20%-30% of patients, regardless of therapy chosen. The objective of this study was to assess clinical outcomes of recurrent CDI treated with fidaxomicin or oral vancomycin. This study was a retrospective, propensity score-matched nationwide analysis of adult patients with first or second CDI recurrence prescribed fidaxomicin or oral vancomycin from any Veterans Affairs Medical Center between June 2011 and December 2015. The primary outcome was evidence of clinical failure or 90-day recurrence. Univariate variables associated with failure or recurrence were identified among 65 fidaxomicin-treated episodes and 1065 vancomycin-treated episodes and placed into a multivariable logistic regression model. Propensity scores were calculated from this model; 195 vancomycin-treated episodes were matched by the next-nearest propensity score to 65 fidaxomicin-treated episodes. CDI failure or recurrence was similar between the two groups (18 of 65 [27.7%] fidaxomicin-treated episodes vs 42 of 195 [21.5%] vancomycin-treated episodes [P=0.31]). Multivariate analysis demonstrated only baseline second recurrence episode, not choice of drug, as independently associated with failure or recurrence. There was no difference in the combined outcome of clinical failure or 90-day recurrence between fidaxomicin and oral vancomycin in the treatment of first or second recurrent CDI.

Impact of the use of local fidaxomicin treatment algorithms for managing Clostridium difficile infection in hospitalized patients in southeastern United States

BackgroundClostridium difficile-associated diarrhea (CDAD) is a major public health threat that results in increased length of stay, hospital readmissions, deaths, and economic burden. CDAD treatment is often guided by severity of disease. Although various tools exist to determine CDAD severity, real-world data evaluating the use of such tools in treatment algorithms are sparse.MethodsA local CDAD treatment pathway was developed independently to guide fidaxomicin prescribing at wellStar Health System (WellStar) and at Lee Health (LH) and Sarasota Memorial Hospital (SMH). Each algorithm was designed locally by the stewardship pharmacist and was utilized to identify patients at high risk for C. difficile recurrence. Patient and clinical data was retrospectively gathered to evaluate the utility and outcomes of the treatment pathway.ResultsThere were 262 patients that received fidaxomicin at these three hospitals during the study time period. Only 30% at WellStar and 20% at LH or SMH met the study criteria and adhered to the pathway requirements. After completion of fidaxomicin, 30-day recurrence rates at WellStar was 0 and at LH and SMH 7%. Clinical cure rates were 83% in WellStar and 93% in LH and SMH.ConclusionsThe results from these two pathways show positive outcomes for the use of fidaxomicin in patients at high risk for CDAD recurrence. This data supports the potential utility of fidaxomicin against CDAD.

Impact of antimicrobial treatment duration on outcome of Staphylococcus aureus bacteraemia: a cohort study

ObjectivesTo assess the outcome of Staphylococcus aureus bacteraemia (SAB) according to factors associated with necessity for longer treatment in conjunction with the duration of treatment. MethodsWe prospectively collected the data of patients with SAB consecutively during 12 to 39 months from 11 hospitals. If multiple episodes of SAB occurred in one patient, only the first episode was enrolled. Factors associated with necessity for longer treatment were defined as follows: persistent bacteraemia, metastatic infection, prosthesis and endocarditis. If any of the factors were present, then the case was defined as longer antibiotic treatment warranted (LW) group; those without any factors were defined as shorter antibiotic treatment sufficient (SS) group. Poor outcome was defined as a composite of 90-day mortality or 30-day recurrence. Duration of antibiotic administration was classified as <14 or ≥14 days in the SS group and <28 or ≥28 days in the LW group. ResultsAmong 2098 cases, the outcome was analysed in 1866 cases, of which 591 showed poor outcome. The SS group accounted for 964 cases and the LW group for 852. On multivariate analysis, age over 65 years, pneumonia, higher Sequential Organ Failure Assessment (SOFA) score and chronic liver diseases were risk factors for poor outcome. Administration of antibiotics less than the recommendation was associated with poor outcome, but this significance was observed only in the LW group (adjusted odds ratio = 1.68; 95% confidence interval, 1.00–2.83; p 0.05). ConclusionsInappropriately short antibiotic treatment was associated with poor outcome in the LW group. Vigilant evaluation for risk factors to determine the duration of treatment may improve the outcome among patients with SAB.

PROGNOSTIC FACTORS OF 30-DAY MORTALITY AND RECURRENCE OF MALIGNANT PLEURAL EFFUSION IN HIGH-RISK TUMORS ACCORDING TO THE LENT SCORE STUDY

SESSION TITLE: Advances in the Diagnosis of Lung Cancer SESSION TYPE: Original Investigations PRESENTED ON: 10/09/2018 02:30 PM - 03:30 PM PURPOSE: The aim of this study was to identify predictors of 30-day mortality and recurrence after palliative pleural procedures in patients with malignant pleural effusion (MPE) and high-risk tumors according to the LENT Score Study. METHODS: Data was collected from our database between January 2013 and December of 2015 of patients high-risk tumors according to the LENT Score and MPE. MPE was characterized as circumstances with malignant cells in pleural fluid, those with pleural infiltration recognized in the pathological evaluation or in patients with metastatic cancer at other locations validated by the pathological analyze and pleural effusion with no additional diagnosed causes after the review by the clinical team. Recurrence was defined as the need for a new pleural procedureAll patients were followed-up at least 30 days after the pleural procedure. We studied radiological aspects, biochemical and hematimetric parameters beyond clinical features. To analyze 30-day mortality, patients were divided into two groups. The first group included patients who had died up to 30 days after the palliative procedure, and the second group included patients who survived for more than 30 days after the palliative procedure. Prognostic factors for pleural recurrence and 30-day mortality were identified by univariate analysis, using Fisher's exact. Subsequently, the significant variables were entered into a multivariate logistic regression analysis (p < 0.05). RESULTS: A total of 134 patients were included in the analysis. Median follow-up time for surviving patients was 56 (range 2 to 623) days. High-risk primary tumors included lung 66,4%, gastrointestinal 24,6% , sarcoma 3,7%, urologicals 3,7% and others 1,5%. There were 44 patients in Group II and overall 22 patients had recurrence. Factors affecting 30-day mortality in univariate analysis were: procedure, Eastern Cooperative Oncology Group (ECOG), albumin, leukocytes, neutrophil to lymphocyte ratio (NRL) e hemoglobin in peripheral blood. Factors affecting recurrence were: procedures, systemic treatment, albumin and platelets. At the multivariate analysis, the type of procedure (therapeutic pleural aspiration – TPA) (p = 0.011), ECOG 3 e 4 (p = 0.004), NLR > 5 (p = 0.037) and leukocytes > 8000 (p = 0.042) were identified as independents predictors of 30-day mortality. About recurrence, only systemic treatment further than first line (p = 0.042) was identified as independent predictor. CONCLUSIONS: Patients with MPE who underwent TPA, ECOG 3 and 4, with leukocytes > 8000, NLR > 5 were significantly associated with 30-day mortality, and systemic treatment greater than first line was associated with recurrence. CLINICAL IMPLICATIONS: Recurrence and early mortality of patients with MPE varies greatly and given the invasive nature of the treatment options available, The identification of those prognostic factors may assist the choice of the optimal palliative technique. DISCLOSURES: No relevant relationships by Fernando Abrao, source=Web Response No relevant relationships by Antonio Flávio Bina Biazzotto, source=Web Response No relevant relationships by Mariana Campello de Oliveira, source=Web Response No relevant relationships by Igor Renato Louro Bruno de Abreu, source=Web Response No relevant relationships by Geisa Viana, source=Web Response

Surgical treatment of cholangiocarcinoma at a single institution over 2 decades

Introduction: Bile duct adenocarcinoma develops at various regions and surgical treatment of cholangiocarcinoma (CCA) includes pancreaticoduodenectomy (PD), liver resection (LR), extrahepatic bile duct resection (EHBDrxn), LR+EHBDrxn, and orthotopic liver transplantation (OLT). This study reviews the surgical treatment of CCA including surgical outcomes, recurrence, and overall survival at a single institution over a 22-year time period. Methods: 170 patients undergoing surgical resection of CCA from 1995 to 2016 were reviewed. Patients with gallbladder or mixed hepatocellular variant malignancies were excluded. 90-day complications, recurrence, and survival were compared between types of CCA and surgical interventions for CCA. Results: Extrahepatic, hilar, and intrahepatic CCA was noted in 31 (18.2%), 75 (44.1%), and 64 (37.6%) respectively. The mean age and BMI was 61.7 years and 27.2 respectively and were predominately male (121, 71.2%). Surgical treatment included PD, LR, EHBDrxn, LR+EHBDrxn and OLT in 31 (18.2%), 40 (23.5%), 6 (3.5%), 37(21.8%) and 56 (32.9%) respectively. Mean operative time and blood transfusions given was 334 minutes and 4 units respectively. Average length of stay was 11.5 days and overall major complications occurred in 59 (34.7%) including reoperation in 13 (7.6%) and mortality in 6 (3.5%). Mean tumor size was 4.2 cm and 39 (22.9%) patients had node positive disease. Recurrence was noted in 74 (43.5%) at a mean of 23 months. Overall survival was found in 61 (35.9%) at a mean of 39.7 months. Conclusion: Surgical treatment of CCA is optimal. OLT for hilar and incidental intrahepatic CCA results in the best survival.

Possibility of Poor Outcomes after Treatment Using Teicoplanin at the Minimum Inhibitory Concentration of &gt;2 μg/mL in Methicillin-resistant &lt;i&gt;Staphylococcus aureus&lt;/i&gt; Bacteremia

Only minimal information exists regarding the treatment outcomes of patients suffering from methicillin-resistant Staphylococcus aureus (MRSA) bacteremia treated with teicoplanin (TEIC) when the TEIC minimum inhibitory concentration (MIC) is close to the upper limit of the "susceptibility range" according to the Clinical Laboratory Standards Institute (CLSI). We investigated the outcome of TEIC-treated patients in MRSA bacteremia, focusing on TEIC MIC against MRSA. A retrospective cohort study was conducted on patients with MRSA bacteremia. TEIC treatment failure was defined as any of the following: (1) all-cause 60-day mortality, (2) persistent bacteremia until the end of TEIC treatment, or (3) 30-day recurrence of MRSA bacteremia. Nineteen patients were enrolled, of whom 15 exhibited TEIC MICs ≤2 μg/mL and the remaining 4 exhibited >2 μg/mL. The rate of treatment failure and all-cause 60-day mortality in patients with MIC >2 μg/mL were significantly higher than those in patients with MIC ≤2 μg/mL [4 patients (100%) versus 4 patients (26.7%) (p=0.018) and 4 patients (100%) versus 2 patients (13.3%) (p=0.004), respectively]. Three of four patients (75%) with MIC >2 μg/mL had persistent bacteremia, which was quantitatively higher than in patients with MIC ≤2 μg/mL (1 of 7 patients, 14.3%). Our finding suggests that TEIC MIC >2 μg/mL may be related to poor treatment outcome in MRSA bacteremia, and that TEIC should not be used in this case.

Fidaxomicin for the treatment of Clostridium difficile infection (CDI) in at-risk patients with inflammatory bowel disease, fulminant CDI, renal impairment or hepatic impairment: a retrospective study of routine clinical use (ANEMONE)

Information is limited or lacking on fidaxomicin treatment of Clostridium difficile infection (CDI) in patients with inflammatory bowel disease, fulminant or life-threatening CDI, severe renal impairment, moderate-to-severe hepatic impairment and pregnancy. The ANEMONE study investigated fidaxomicin use in a routine clinical setting, focusing on these medical conditions of specific interest (MCSIs). This retrospective, post-authorisation study reviewed hospital records from Austria, Germany, Spain and the UK (June 2012–June 2015), collecting data from hospital admission to 30 days after last fidaxomicin dose. The primary objective was to identify the proportion of fidaxomicin-treated patients with MCSIs. Secondary objectives were to describe 30-day mortality, changes in ECG and laboratory parameters, fidaxomicin exposure and CDI response (resolution of diarrhoea; 30-day recurrence). 45.3% (261/576) of patients had ≥ 1 MCSI. Thirty-day mortality (post-first dose) was 17.0% (98/576) in the total population and slightly higher (24.6–27.6%) in patients with fulminant CDI or severe renal impairment. 29.6% (24/81) deaths of known cause were attributable to CDI. Of changes in laboratory parameters or ECG findings, only a decrease in leucocyte counts appeared associated with fidaxomicin, consistent with a positive treatment response. Diarrhoea resolved in 78.0% (404/518) of treatment episodes; diarrhoea resolution was lowest in patients with fulminant CDI (investigator-defined, 67.5%, 56/88) and severe renal impairment (68.0%, 68/100). Thirty-day recurrence (18.8%, 79/420) was similar across MCSI subgroups. Although almost half of fidaxomicin-treated patients had ≥ 1 MCSI, the majority of patients in all subgroups had positive responses to treatment, and no particular safety concerns were identified.

Center volume and the outcomes of percutaneous transluminal angioplasty and stenting in patients with symptomatic intracranial vertebrobasilar stenoses: A meta-analysis.

BackgroundEvidence for the preventative effects of percutaneous transluminal angioplasty and stenting (PTAS) on the recurrence of stroke in patients with severe intracranial vertebrobasilar stenoses (IVBS) varies, and the influence of study characteristics on the study outcomes have not been determined.MethodsA study level based meta-analysis was performed to investigate the influence of baseline characteristics on the 30-day and follow-up stroke recurrence or death in symptomatic IVBS patients receiving PTAS. Relevant single center studies were retrieved by searching PubMed and Embase. A random effect model was applied to synthesize the outcomes. Meta-regression and subgroup analyses were performed to evaluate the potential influence of study characteristics on outcomes.ResultsFifteen cohort studies comprising 554 symptomatic IVBS patients were included. PTAS was associated with an 8% incidence of stroke recurrence or death (95% CI: 5% to 12%) in IVBS patients within 30 days, and 8 per 100 person-years (95% CI: 5 to 11 per 100 person-years) of cumulative stroke recurrence or death during follow-up. Meta-regression indicated that the center volume, as defined by the numbers of cases per year, was negatively correlated with 30-day (regression coefficient = -0.09, p = 0.02) and follow-up (regression coefficient = -0.60, p = 0.01) stroke recurrence or death. Age, gender, or comorbidities have no significant effect on the outcomes.ConclusionsCenters of higher procedural volume may be associated with better clinical outcomes for symptomatic IVBS patients receiving PTAS.