bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacodynamic Optimization for the Treatment of Invasive Candida auris Infection
Authors: Lepak Alexander J , Zhao Miao , Berkow Elizabeth , Lockhart Shawn , Andes David R 
Published: October 2017

Abstract

Background
Candida auris is an emerging, nosocomial multidrug-resistant threat with high treatment failure rate and mortality. The optimal antifungal agent to use and susceptibility breakpoints are based on limited clinical data.

Methods
Nine clinical C. auris strains were used. MICs were determined by CLSI standards. Drug treatment studies consisted of: fluconazole (FLC) dose range 0.78–200 mg/kg/12 h, micafungin (MFG) dose range 0.3125–80 mg/kg/24 h, or amphotericin B deoxycholate (AMB) dose range 0.0.78–20 mg/kg/24 hours. Plasma PK was previously determined in the murine model for all three drugs. A 96 h neutropenic murine model of invasive candidiasis (IC) was used for all studies. The Emax Hill equation was used to model the dose–response data to PK/PD index AUC/MIC (FLC and MFG) and Cmax/MIC (AMB). The static and 1 log kill doses (when achieved) and the associated PK/PD targets (AUC/MIC or Cmax/MIC) were determined and compared with previous murine IC studies with C. albicans, C. glabrata, and C. parapsilosis.

Results
MIC range: FLC 2–256 mg/l, MFG 0.125–4 mg/l, and AMB 0.38–6 mg/l. Dose-dependent activity was observed with all three drugs. Net stasis was achieved against seven strains for FLC, eight strains for MFG, and eight strains for AMB. However, MFG performed significantly better than comparators for cidal endpoints. A 1 log kill endpoint was achieved in eight strains for MFG, whereas this endpoint was only achieved in one strain for FLC and three strains for AMB. PK/PD analyses demonstrated a strong relationship between AUC/MIC and treatment outcome for FLC (R2 0.61) and MFG (R2 0.77); and Cmax/MIC and treatment outcome for AMB (R2 0.64). The median static dose and 1 log kill dose (MFG only) and associated AUC/MIC or Cmax/MIC values are shown (Table).

Conclusion
MFG was the most potent drug over the dose range achieving up to 2 log kill against eight of nine strains. PK/PD targets for C. auris against FLC and AMB were similar to other Candida species; however, MFG targets were ≥20-fold lower than C. albicans, C. glabrata, and C. parapsilosis. Using the median stasis targets and human PK for each drug, resistance thresholds could be 16 mg/l for FLC, 2–4 mg/l for MFG, and 1–2 mg/l for AMB.

Disclosures
All authors: No reported disclosures.
Increasing Incidence of Blastomycosis Infection in Vermont
Authors: Kiatsimkul Porntip 
Published: October 2017

Abstract

Background
Blastomycosis is an invasive infection caused by the ubiquitous fungus Blastomyces. The clinical presentation ranges from limited cutanenous infections to pneumonia and disseminated disease. Endemic areas in the United States include: midwestern, south-central, and southeastern states; yearly incidence is &lt;0.3 cases per 100,000. Diagnosis is based on recovery of the organism on fungal culture. A urine antigen test is available for the detection of blastomycosis which has a sensitivity of 92.9% and specificity of 79.3%. Anecdotally, an increasing number of patients are presenting to the University of Vermont Medical Center (UVMMC) with disseminated blastomycosis – an area in which the fungus is rare. We hoped to determine the incidence of blastomycosis in Vermont over a 10-year period and examine the sensitivity of the urine antigen in our patient population.

Methods
After IRB approval, medical record numbers of all patients who had BD-glucan, blastomyces urine antigen, culture, or pathology positive for blastomyces during a 10-year period (2006–2016) were obtained. Chart review completed for all patients with diagnosis of blastomycosis. Data collected on demographic characteristics: zip code, comorbidities, site of infection, HIV, BD-glucan, blastomyces urine antigen, fungal culture, and treatment duration.

Results
Forty-one blastomycosis cases were found; 39 cases in Vermont residents. The incidence rate Vermont was 0.7 cases per 100,000. Mean age was 49 years, 60% of patients were male. Most patients had pulmonary (37%) or disseminated infection (37%). 17% of patients had localized cutaneous disease, bone and joint infection (7%) or CNS disease (2%). Urine antigen was positive in 78% overall, and in 90% with disseminated infection. Three deaths, none attributed to blastomycosis.

Conclusion
Vermont appears to have a higher incidence than what has been reported in the US overall. This increase may have to do with better reporting and testing rather than a true increase in disease. Most common disease presentation was localized pulmonary or disseminated disease. Urine antigen sensitivity ranged from 78% (overall) to 90% (disseminated disease). This appears consistent with what has been reported in other studies, but is lower than the overall reported sensitivity.

Disclosures
All authors: No reported disclosures.
Clinical Characteristics and Outcomes in Hospitalized Patients with Proven and Probable Coccidioidomycosis at the National Institute of Respiratory Diseases in Mexico City
Authors: Martinez-Orozco Jose Arturo , Contreras-Cortez Angelina , Morales-Villareal Fernando , Vargas Eduardo Becerril 
Published: October 2017

Abstract

Background
Coccidioides spp. an endemic dimorphic fungi is present in the north and south of Mexico. The Ministry of Health report in Mexico between 1988 and 1994 0.5 to 1.3 cases per 100,000 habitants. The clinical picture ranges from asymptomatic to disseminated disease. They should be classified according to the EORTC/MSG criteria in proven and probable disease, in Mexico there is no study about clinical characteristics and outcomes in hospitalized patients according to this classification.

Objective
Evaluate the clinical characteristics and outcomes in hospitalized patients with proven and probable coccidioidomycosis according to EORTC/MSG criteria.

Methods
The National Institute of Respiratory Diseases in Mexico City is the national referral center for complicated pulmonary infectious diseases. This retrospective cohort from 2010 to 2016 included proven and probable Coccidioidomycosis hospitalized patients classified according to EORTC/MSG 2008 criteria. We collected data about clinical characteristics on admission and outcomes.

Results
Fifty-seven patients were evaluated, 26 proven and 31 probable, mean age was 43 years. The proven group was associated with DM2 OR 2.8 (IC95% 1.1–7, P = 0.014) and hemoptysis OR 3.2 (IC95% 1.1–9, P = 0.013), the probable group with dyspnea OR 3.5 (IC 95% 1.08–11, P = 0.024), high respiratory rate 27.2 ± 13 vs. 22 ± 3.3 (P = 0.05), and low O2 saturation 83.97% ± 11.1 vs. 91.8% ± 4.31 (P &lt; 0.001). In the proven group, multiple cavities in CT scan were more frequent. The probable had association with severe ARDS (P 0.011), use of invasive mechanical ventilation (P 0.025), and increase in mortality 14% vs. 1.8% OR 1.2 (IC95% 1.03–1.6 P = 0.025) with lower survival in Kaplan–Meier (P &lt; 0.02). In the proven group, there was more disseminated disease (P &lt;0.001), HIV was associated with lower survival (P &lt;0.001) and they received more days of antifungal treatment 109.5 ± 127 vs. 59.8 ± 93 days. Amphotericin B was the most prescribed in both groups.

Conclusion
At present, we do not use the EORTC/MSG criteria due to lack of tests in our country, in this study the probable group referred usually from community centers had worse outcome and clinical characteristics, that is why we cannot underestimate this group of patients. We need to have better diagnostic tests in order to identify promptly these patients and avoid a late disease presentation.

Disclosures
All authors: No reported disclosures.
Review of Treatment Regimens for Mucormycosis in a Las Vegas County Hospital Between 2013 and 2017
Authors: Villamagna Angela , Frani Ian Adrian , Leuthner Kimberly D , Asad Shadaba 
Published: October 2017

Abstract

Background
Mucormycosis (MC) is a group of invasive fungal infections with a mortality rate approaching 100% in disseminated disease. The incidence of MC is low, with one study estimating 500 cases/year in the United States, making optimal treatment difficult to identify. Liposomal amphotericin B (L-ampho), along with aggressive surgical intervention, is the first-line treatment for MC. Isavuconazole (ISA) and posaconazole (POSA) are newer azoles used as salvage therapy in patients not improving with L-ampho. Limited data are available about the use of L-ampho in combination with ISA or POSA as an initial treatment regimen, but aggressive treatment empirically may increase favorable outcomes.

Methods
We performed a retrospective review of patients diagnosed with MC from 2013 to2017 at University Medical Center of Southern Nevada in Las Vegas, Nevada. Data collected included patient demographics, comorbidities, and predisposing risk factors as well as treatment regimens. Patients were evaluated for outcome after treatment therapy with monotherapy (L-ampho, POSA or ISA) or combination therapy (L-ampho with ISA).

Results
From 2013 to 2017, seven cases of MC were identified – five rhinocerebral (RC), one cutaneous (CT), and 1onepulmonary (PM). The most common risk factor was uncontrolled diabetes (5/7), followed by HIV (2/7) and non-Hodgkin lymphoma (1/7). Fifty-seven percent of patients received monotherapy and 43% received combination therapy (L-ampho/ISA). All the patients receiving combination therapy had RC. Seventy-one percent of patients survived to discharge regardless of treatment regimen. One hundred percent of combination therapy patients survived to discharge, whereas 50% of monotherapy patients survived to discharge. The two mortalities were patients with PM and CT MC.

Conclusion
MC is a rare infection with high mortality. For this reason, we are using ISA in combination with L-ampho as initial treatment to improve clinical outcomes. With our limited experience, combination therapy showed better rates of survival to discharge, without increasing adverse events. Our data suggest the use of combination therapy may improve outcomes in MC, but a larger sample of patients treated with initial combination therapy is required to strengthen conclusions about patient outcomes.

Disclosures
All authors: No reported disclosures.
Treatment Bundle Improves Outcomes in the Management of Candidemia at Large Urban Academic Medical Center
Authors: Cook Gregory , Advani Shreena , Rab Saira , Kandiah Sheetal , Patel Manish , Wong Jordan 
Published: October 2017

Abstract

Background
A candidemia treatment bundle (CTB) may increase adherence to guideline recommended candidemia management and improve patient outcomes. The purpose of this study was to evaluate the impact of a best practice alert (BPA) and order-set on optimizing compliance with all CTB components and patient outcomes.

Methods
A single center, pre-/post-intervention study was completed at Grady Health System from August 2015 to August 2017. Post-CTB intervention began August 2016. The CTB included a BPA that fires for blood cultures positive for any Candida species to treatment clinicians upon opening the patient’s electronic health record. The BPA included a linked order-set based on treatment recommendations including: infectious diseases (ID) and ophthalmology consultation, repeat blood cultures, empiric echinocandin therapy, early source control, antifungal de-escalation, intravenous to oral (IV to PO) switch, and duration of therapy. The primary outcome of the study was total adherence to the CTB. The secondary outcomes include adherence with the individual components of the CTB, 30-day mortality, and infection-related length of stay (LOS).

Results
Forty-five patients in the pre-group and 24 patients in the CTB group with candidemia were identified. Twenty-seven patients in the pre-group and 19 patients in the CTB group met inclusion criteria. Total adherence with the CTB occurred in one patient in the pre-group and threepatients in the CTB group (4% vs. 16%, P = 0.29). ID was consulted in 15 patients in the pre-group and 17 patients in the CTB group (56% vs. 89%, P = 0.02). Source control occurred in three and 11 patients, respectively (11% vs. 58% P &lt; 0.01). The bundle components of empiric echinocandin use (81% vs. 100%, P = 0.07), ophthalmology consultation (81% vs. 95%, P = 0.37), and IV to PO switch (22% vs. 32%, P = 0.5) also improved in the CTB group. Repeat cultures and antifungal de-escalation were similar among groups. Thirty-day mortality decreased in the CTB group by 10% (26% vs. 16%, P = 0.48). Median iLOS decreased from 30 days in the pre-group to 17 days in the CTB group (P = 0.05).

Conclusion
The CTB, with a BPA and linked order-set, improved guideline recommended management of candidemia specifically increasing the rates of ID consultation and early source control. There were quantitative improvements in mortality and iLOS.

Disclosures
All authors: No reported disclosures.
Searching for Bacterial Pathogens in Pediatric Patients with Chronic Recurrent Multifocal Osteomyelitis Using 16S rRNA Quantitative Real-Time PCR
Authors: Searns Justin 
Published: October 2017

Abstract

Background
Chronic recurrent multifocal osteomyelitis (CRMO) is a rare auto-inflammatory disease in children that causes relapsing episodes of pain. Patients are treated with anti-inflammatory medications or immune-modulating agents. Increasing evidence suggests that CRMO is mediated by dysregulation of the interleukin-1 pathway, not a bacterial source. However, CRMO is often a diagnosis of exclusion, and patients occasionally receive antimicrobials for possible culture negative infectious osteomyelitis. Few prior studies have utilized molecular diagnostic techniques to identify bacterial pathogens in CRMO bone biopsies.

Methods
Musculoskeletal specimens sent for culture during routine clinical care were banked from patients admitted to Children’s Hospital Colorado from 6/2012 to 10/2016. On retrospective chart review, 28 specimens were collected from 16 patients ultimately diagnosed with CRMO. Specimens were processed and extracted prior to molecular testing. All samples underwent quantitative real-time PCR (qPCR) testing using bacterial load assays targeting the bacterial 16S rRNA gene.

Results
Mean age at time of sample collection was 9.2 years. CRMO diagnosis was made by clinical, pathologic, and radiographic findings. All patients had pathology findings consistent with CRMO including lymphoplasmacytic infiltrate, focal necrosis, and/or marrow fibrosis. All patients had MRI findings consistent with CRMO. No patient had bacteria identified on Gram stain; 2/28 samples (7%) had bacterial growth on culture (both were coagulase-negative staphylococcus, felt to be contaminant). None of the 28 specimens met the threshold of bacterial load on qPCR testing to necessitate bacterial sequencing. None of the 16 patients were treated with antimicrobials and there were no readmissions for clinical worsening.

Conclusion
CRMO patients did not have bacteria identified on universal bacterial 16S rRNA testing. This finding further supports that CRMO patients do not require antimicrobial therapy. Future steps to exclude infectious pathogens in CRMO could include next-generation DNA sequencing.

Disclosures
All authors: No reported disclosures.
Clinical Outcomes of Prosthetic Knee Joint Infection in a United States Tertiary Healthcare Center
Authors: Ayoade Folusakin , Todd John 
Published: October 2017

Abstract

Background
The 2013 IDSA prosthetic joint infection (PJI) guidelines identified some research gaps, some of which include what factors may predict PJI outcome. We therefore conducted a retrospective single-center study with the goal of addressing some of these gaps.

Objectives
1. Describe the incidence, pathogens, role of inflammatory markers, and treatment outcomes of knee PJI. 2. Identify correlations between joint aspiration (JA) and intraoperative (IO) cultures.

Methods
We retrospectively analyzed all adult knee PJI that were diagnosed and managed at our institution between 1/1/2005 and 12/31/2015. Statistical analysis was done using the paired t-test, Fisher exact and McNemar χ 2 tests as applicable.

Results
Forty-six subjects met the inclusion criteria and were analyzed. See table below.
The incidence rate of PJI for the study period was 5.4%.. Staph. aureus was the commonest pathogen accounting for 11(65%) JA and 13(40%) of IO cultures. Low virulence organisms [Staph. epidermidis n = 8 (25%) and Corynebacterium spp. n =1 (3%)] were only recovered from IO cultures. Gram-negative bacilli accounted for 5(30%) JA and 7(28%) IO cultures.. JA correlates well with IO cultures using paired sample correlations (t-test); (correlation 0.61, P = 0.027).. 97% of subjects had elevated ESR while 96% had elevated CRP.. Concerning outcome, there was no statistically significant difference between groups based on implant duration (P = 0.98), symptom onset (P = 0.23), pathogen type (P = 0.83), and treatment options (P = 0.39).

Conclusion
1. JA culture is a good predictor of IO culture in knee PJI. 2. Yield of low virulence organisms from JA culture is poor. 3. Elevated ESR and CRP can support diagnosis of knee PJI. 4. Implant duration, pathogen type, duration of symptoms and treatment type do not appear to affect outcome.

Disclosures
All authors: No reported disclosures.
Clinical and Epidemiological Aspects Related to Infection of Orthopedic Prostheses in Argentinean Children. A 10-Year Period Study
Authors: Vergara Lobo Carlos Mauricio , Ferolla Fausto M , Contreras Elen , Carballo Carolina , Yfran Walter , Pannunzio Eugenia , Anteliz Eliana , Reviriego Juan , Escalada Maria , Rositto Gabriel , Legarreta Carlos , Cazes Claudia I , Contrini María M , Lopez Eduardo L 
Published: October 2017

Abstract

Background
Management of orthopedic prostheses infections (PI) in children is a main challenge, not only for the complexity of the disease but also for the scarce of evidence in this field.

Objectives
To describe the burden of PI and to analyze clinical and epidemiological aspects in pediatric patients.

Methods
Retrospective study in a tertiary pediatric hospital. Clinical charts of patients &lt;18 years who underwent surgery for bone and/or joint implantation at “R. Gutierrez” Children’s Hospital in Buenos Aires from January 2007 to December 2016 were reviewed, and all PI cases were analyzed. PI was defined as early (E) when presentation was within 3 months of prothesis implantation, delayed (D) when presenting between 3–24 months and late (L) if presenting beyond 2 years.

Results
811 surgeries performed; 89 PI detected: E(n = 63); D(n = 9), L(n = 17); 58% male; median(m) age: 13 years (range[r] 4–20); m hospital stay 30 days (r 6–180). Annual incidence: 11% (CI95%: 8.9–13.1) (Figure 1). Underlying conditions: scoliosis (58.4%), malignancy (16.8%). Clinical features are detailed in Figure 2. Bacterial isolation in 63 (70.8%) cases, 51(57.3%) with a single microorganism (Figure 3). Gram(+) bacteria were isolated in 58% of E PI, 86% of D PI and 49% of L PI. Gram(−) pathogens in 49% of E PI and in 38% of L PI. Three febrile PI (3,4%) had Gram(+) bacteremia, two of them L PI. No differences were seen in white blood cell count (WBC) and C-reactive protein(CRP) levels on admission in children with and without bacteremia, nor among the different types of PI; m WBC 9000/mm3 (r 3200–25550), m CRP 37 mg/l (r 1–270). WBC on admission in MRSA PI was significantly higher, P &lt; 0,01. Duration of EV treatment was different according to type of microorganism (P 0.03), higher in PI by Gram(−). Forty-eight (53.9%) cases continued with trimethoprim-sulfamoxazole orally, without side effects requiring its discontinuation. Total treatment duration (m): 189 days (r 28–756). Eighty-two children (92.1%) underwent surgical toilette, 37 (45.1%) required more than one. Six (6.7%) presented relapse and eight (9%) reinfection.

Conclusion
· PI in children is a considerable burden, with high morbidity. · Incidence of bacteremia was low. · Results of the study could help to delineate preventive strategies and improve decision making in PI in children.

Disclosures
All authors No reported disclosures.
A data-driven approach to predict daily risk of Clostridium difficile infection at two large academic health centers
Authors: Makar Maggie , Oh Jeeheh , Fusco Christopher , Marchesani Joseph , McCaffrey Robert , Rao Krishna , Ryan Erin E , Washer Laraine , West Lauren R , Young Vincent B , Guttag John , Hooper David C , Shenoy Erica S , Wiens Jenna 
Published: October 2017

Abstract

Background
An estimated 293,300 healthcare-associated cases of Clostridium difficile infection (CDI) occur annually in the United States. Prior research on risk-prediction models for CDI have focused on a small number of risk factors with the goal of developing a model that works well across hospitals. We hypothesize that risk factors are, in part, hospital-specific. We applied a generalizable machine learning approach to discovering, or “learning”, hospital-specific risk-stratification models using electronic health record (EHR) data collected during the course of patient care from the Massachusetts General Hospital (MGH) and the University of Michigan Health System (UM).

Methods
We utilized EHR data from 115,958 adult inpatient admissions from 2012–2014 (MGH) and 258,050 adult inpatient admissions from 2010–2016 (UM) (Fig 1). We extracted patient demographics, admission details, patient history, and daily hospitalization details, resulting in 2,964 and 4,739 features in the MGH and UM models, respectively. We used L2 regularized logistic regression to learn the models and measured the discriminative performance of the models on a year of held-out data from each hospital.

Results
The MGH and UM models achieved AUROCs of 0.74 (CI: 0.73–0.75) and 0.77 (CI: 0.75–0.80), respectively. The relative importance of risk factors varied significantly across hospitals. In particular, in-hospital locations appeared in the set of top risk factors at one hospital and in the set of protective factors at the other. On average, both models were able to predict CDI five days in advance of clinical diagnosis (Fig 2).

Conclusion
We used EHR data to generate a daily estimate of the risk of CDI for each inpatient hospitalization. We applied a generalizable data-driven approach to existing data from two large institutions with different patient populations and different data formats and content. In contrast to approaches that focus on learning models that apply generally across hospitals, our proposed approach yields risk stratification models tailored to an institution’s EHR system and patient population. In turn, these hospital-specific models could allow for earlier and more accurate identification of high-risk patients.

Disclosures
All authors: No reported disclosures.