bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Candida auris Response to Antifungal Drugs Using Time–Kill Assays and an Animal Model
Authors: Ben-Ami Ronen , Ashkenazi Liat , Berman Judith , Korolker Nuphar , Novikov Anna 
Published: October 2017

Abstract

Background
Candida auris is an emerging nosocomial pathogen that is resistant to Fluconazole and variably susceptible to other systemic drug classes. Treatment with echinocandins has been recommended based on MICs in the susceptible range, but supporting in vivo data is lacking.

Methods
We tested the MIC of C. auris strains (n = 12) to fluconazole, voriconazole, posaconazole. anidulafungin, amphotericin B and flucytosine. Representative C. auris strains from Israel and South Africa, and a reference C. albicans strain were analysed using time–kill curve assays. Fungicidal activity was defined as reduction of ≥3 log from baseline CFU/ml. Response to caspofungin treatment was assessed in BALB/c mice immunosuppressed with cyclophosphamide and inoculated with 7 × 107C. auris cells by tail vein injection. Mice were treated from day +1 to day +7 with caspofungin (IP) at doses of 1 or 5 mg/kg and compared with sham-treated controls. Survival was assessed daily. Kaplan-Meier survival analyses were performed and treatment arms were compared using the log-rank test.

Results
Drug susceptibility results (MIC50 and MIC90) were: fluconazole, 64 and 128 mg/l; voriconazole, 0.5 and 24 mg/l; posaconazole, 0.5 and 27 mg/l; anidulafungin, 0.03 and 0.06 mg/l; amphotericin B, 2 and 8 mg/l; flucytosine, 0.3 and 1 mg/l. Time–kill curve analyses showed log reduction from baseline CFU concentration of −3.0 to −2.8 for fluconazole (MIC ×1), 5.6–6.1 for amphotericin B (MIC ×4) and −0.4 to −0.9 for caspofungin (MIC ×16), consistent with fungicidal activity of amphotericin B and weak fungistatic activity of caspofungin. In the mouse model, survival rate was similar with sham treatment (33%) and treatment with caspofungin 1 mg/kg/day (44%) and 5 mg/kg/day (22%), P = 0.7.

Conclusion
Despite generally low MIC, caspofungin has only mild fungistatic activity on C. auris and no effect on survival in a mouse infection model. Amphotericin B has fungicidal activity against C. auris.

Disclosures
All authors: No reported disclosures.
Risk Factors and Mortality Associated with Candida krusei Bloodstream Infections
Authors: Kronen Ryan , Lin Charlotte , Hsueh Kevin , Powderly William , Spec Andrej 
Published: October 2017

Abstract

Background
Candida krusei (CK) candidemia is associated with high mortality, but whether this is due to underlying comorbidities in affected patients or the organism itself is unknown. We analyzed factors associated with C. krusei candidemia and its outcomes.

Methods
A retrospective analysis of hospitalized patients with candidemia was conducted at our institution between 2002 and 2015. Data were collected on demographics, comorbidities, medications, procedures, central lines, vital signs, and labs. Univariable logistic and Cox regression were used to identify potential risk factors associated with CK and mortality, respectively. Multivariable analyses were then constructed parsimoniously from these variables.

Results
Of 1,873 candidemia events, 59 were due to CK. In multivariable analysis, CK candidemia was predicted by hematologic malignancy (OR 8.9, 95% CI [4.1, 19.7]), stomach cancer (OR 14.6, 95% CI [2.9, 72.5]), absolute neutrophil count (OR 2.4, 95% CI [1.2, 4.8]), and the use of prophylactic azole antifungals (OR 2.2, 95% CI [1.1, 4.3]), monoclonal antibodies (OR 5.7, 95% CI [2.0, 15.8]), and penicillin β-lactamase inhibitors (OR 2.5, 95% CI [1.3, 4.8]). The C-statistic was 0.86 (95% CI [0.81, 0.91]). The crude mortality rates were 86.4% for CK candidemia and 63.6% for non-CK candidemia. Although CK was associated with higher mortality in univariable Cox regression (Figure 1, HR 1.8, 95% CI [1.3, 2.4]), this relationship was no longer significant (HR 1.2, 95% CI [0.8, 1.7]) with the addition of the following confounders: hematologic malignancy (HR 0.9, 95% CI [0.7, 1.1]), absolute neutrophil count (HR 1.7, 95% CI [1.4, 2.2]), stomach cancer (HR 1.0, 95% CI [0.5, 1.9]), coagulopathy (HR 1.0, 95% CI [0.9, 1.2], and prophylactic corticosteroids (HR 1.4, 95% CI [1.2, 1.7] (Figure 2).

Conclusion
A similar set of patient characteristics is associated with both CK infection and increased mortality, suggesting that patients with CK candidemia are at higher risk of mortality due to underlying illness rather than organism-specific mechanisms.

Disclosures
W. Powderly, Merck: Grant Investigator and Scientific Advisor, Consulting fee and Research grant Gilead: Scientific Advisor, Consulting fee Astellas: Grant Investigator, Research grant A. Spec, Astellas Pharma US, Inc.: Grant Investigator, Research grant
Risk Factors for Candidemia as Compared with Patients with Negative Blood Cultures Placed on Empiric Micafungin
Authors: Carr Amy , Berhe Mezgebe 
Published: October 2017

Abstract

Background
Numerous risk factors have been linked to invasive candidiasis; however, they are nonspecific and often trigger empiric antifungal therapy in a large number of patients. Identification of more precise predictors could promote judicious use of empiric echinocandins. Ultimately, this could decrease antifungal exposure, development of resistance, and associated costs.

Methods
This was a retrospective review of patients admitted to Baylor University Medical Center from 10/1/14 to 10/25/16. Patients with positive blood cultures for Candida spp. were compared with a randomly selected cohort of patients on empiric micafungin for 3 or more days and with blood cultures negative for Candida spp. This study excluded patients on prophylactic antifungals and patients with positive abscess cultures but negative blood cultures for Candida spp. Data was analyzed using the χ 2 test, t-test comparing means, and logistic regression as applicable.

Results
There were 127 patients with candidemia and 134 patients without candidemia on empiric micafungin. Factors associated with candidemia included positive 1,3-β-d-glucan assay (86.4% vs. 33.3%, P &lt; 0.001), total parenteral nutrition (TPN) (26.0% vs. 15.7%, P = 0.040), and multifocal Candida colonization (35.3% vs. 4.5%, P &lt; 0.001). Patients without candidemia on empiric micafungin were more likely to receive antibiotic therapy in the previous 10 days (55.9% vs. 79.9%, P &lt; 0.001) and more likely to be taking immunosuppressive medications (11.0% vs. 30.6%, P &lt; 0.001). There was no difference in mean length of stay (25.5 days vs. 27.3 days, P = 0.631) or 30-day all-cause mortality (32.3% vs. 23.9%, P = 0.131) between patients with candidemia and patients on empiric micafungin, respectively.

Conclusion
A negative 1,3-β-d-glucan assay in patients without multifocal Candida colonization or receiving TPN was inversely correlated with invasive candidiasis, as defined by candidemia. Therefore, the absence of these factors may be used to deescalate empiric micafungin therapy. Risk factors for candidemia identified in this study are consistent with previously published literature. These findings highlight an opportunity to improve empiric micafungin prescribing patterns at our institution.

Disclosures
All authors: No reported disclosures.
Breakthrough Invasive Candidiasis in Children
Authors: Dong Sara , Antonara Stella , Stanek Joseph , Ardura Monica I 
Published: October 2017

Abstract

Background
Breakthrough invasive candidiasis (bIC) has been described in adults, but the epidemiology and outcomes in children are unknown.

Methods
Retrospective cohort analysis of children diagnosed with IC from 9/1/09 to 1/30/17. bIC was defined as isolation of Candida spp. from sterile site despite receiving ≥3 doses of antifungal (AF) to which isolate is susceptible. Clinical and microbiological data, management, and outcomes were collected. Non-parametric and logistic regression statistics were applied.

Results
There were 92 patients with IC, 23 of which were bIC (Table 1). Underlying conditions included GI (n = 26), hem/onc (n = 17), prematurity (n = 16), cardiac (n = 15), HCT (n = 4), SOT (n = 5), and other (n = 9). Patients received an azole (n = 17), micafungin (n = 5), or amphotericin B (n = 1) for median of 20 days [3–522] before bIC as: prophylaxis (n = 8), targeted therapy (n = 5), or empiric fever driven therapy (n = 10). bIC was caused by non-albicans Candida in 16/23 (70%) cases. Compared with IC controls, children with bIC had increased ICU admission, vasopressor use, mechanical ventilation, and renal failure (all with P &lt; 0.01). In multivariate analysis, immunosuppression was an independent risk factor for bIC (OR 39.4, 95% CI 7.5–205). Death attributable to IC occurred in bIC group (n = 3, P = 0.04).

Conclusion
bIC in our cohort was caused most frequently by non-albicans Candida spp. and associated with significantly worse outcomes, including mortality.

Disclosures
All authors: No reported disclosures.
QTc Prolongation in Patients Receiving Triazoles and Amiodarone
Authors: Cook Katherine , Sraubol Thitinan , Campbell Kristen Bova , Mourad Ahmad , Stiber Jonathan , Perfect John R , Johnson Melissa 
Published: October 2017

Abstract

Background
Prolonged QT interval may lead to ventricular arrhythmias, torsade de pointes and sudden death. Triazole antifungals are often administered to inpatients with cardiac disease and with other QT prolonging drugs. Amiodarone is a commonly used antiarrhythmic that can prolong QT and be proarrhythmic but safety of co-administering these agents in the clinical setting is not known.

Methods
We conducted a retrospective, observational cohort study of adult inpatients at Duke University Medical Center who received concomitant systemic azoles and amiodarone from 2007 to 2013. Included subjects had ≥1 electrocardiogram (EKG) performed while receiving either agent alone within 1 month of starting concomitant therapy (baseline, BL) and ≥1 follow-up (FU) EKG after ≥2 days of concomitant therapy. A paired t-test was used to assess the maximum change in corrected QT interval (QTc, Bazett’s correction) from BL to FU. Logistic regression was used to evaluate predictors of FU QTc ≥500 ms (age, race, gender, and BL QTc ≥500 ms). Patient discharge diagnoses of ventricular arrhythmias or other cardiac events were reviewed to assess clinical outcome.

Results
Of 816 subjects identified, 252 had EKG results eligible for analysis. Azoles received were fluconazole (86.5%), voriconazole (11.5%), posaconazole (1.6%) or itraconazole (0.4%). Subjects were a median of 65 (IQR 25–88) years of age, 64.3% male and 78.6% Caucasian. Median duration of concomitant therapy was 7 days (IQR 4–11 days). Mean maximal change in QTc was +32 ms from BL (95% CI 26.2–38.6, P &lt; 0.0001). 25.4 and 48.8% of subjects had a BL and FU QTc ≥500 ms, respectively. BL QTc ≥500 ms but not age, race, or gender was associated with FU QTc ≥500 ms (OR 6.32 95% CI 3.21–12.43). Thirty-day all-cause mortality was 26.2%. No cardiac events were apparent in relation to concomitant azole-amiodarone therapy.

Conclusion
Prolongation of the QTc interval was frequently observed in this cohort of patients receiving azoles and amiodarone. Clinical impact is challenging to assess in this critically ill, complex patient population but appears to be limited. Additional analyses are needed to further evaluate safety of azoles in the setting of other QTc prolonging agents.

Disclosures
All authors: No reported disclosures.
Epidemiology and Risk Factors for Antifungal Resistance in Patients with Candidemia
Authors: Aldardeer Namareq , Albar Hadeil , Alattas Majda , Qutub Mohammed , Alraddadi Basem 
Published: October 2017

Abstract

Background
Candida is a common nosocomial blood pathogen associated with high mortality. Data on antifungal resistance from Saudi Arabia is scarce. The objective of this study is to examine epidemiology, risk factors for antifungal resistance, and outcome among patients with candidemia.

Methods
A retrospective study conducted at King Faisal Specialist Hospital and Research Center-Jeddah branch (KFSHRC-J) The study included all patients 18 years and older with positive blood culture for candida over a 5-year period (2012–2016).

Results
We identified 92 cases of candidemia. The mean age was 59 years SD (18). Candida galabrata was the most prominent species 33 (36%) followed by Candida parapsilosis 22 (24%), Candida albican 20 (22%), Candida tropicalis 13 (14%), Candida krusei 2 (2%), and others 2 (2%).
Resistance to fluconazole was identified in 14 (15%) cases, four of them were also resistance to voriconazole. Among cases resistance to fluconazole, seven (50%) cases were C. parapsilosis, two (14%) of each C. galabrata, C.krusei, and C. Albicans and one (7%) was C. tropicalis. In univariate analysis, previous exposure to echanicancdin and mechanical ventilation within 3 months were associated with fluconazole resistance candidemia (12(15%) vs 7(50%), (P = 0.007), 28(36%) vs 10(71%), (P = 0.014), respectively). Patients with fluconazole resistance candida had a longer length of intensive care unit stay (median 26 days (IQR 6–40) days and 12 days (IQR 7–36)), respectively. Length of hospital stay was longer in patients with fluconazole resistance compared with nonresistance (median 83 days (IQR 29–199 days) and (31 days (IQR 17–75), respectively. Thirty-day mortality of patients fluconazole resistance compared with non-resistance cases was not significant 43 and 55%, respectively (P = 0.28).

Conclusion
In our cohort, Candida galabrata is the most common species causing candidemia. Increasing fluconazole resistance candida parapsilosis is alarming. More regional epidemiological antifungal resistance studies are required to confirm this finding.

Disclosures
All authors: No reported disclosures.
Assessment of Musculoskeletal Infection Society (MSIS) Diagnostic Criteria as Predictors of Treatment Success in Hip Arthroplasty Infections Treated with Two-Stage Exchange
Authors: Henry Michael , Russell Celeste , Nocon Allina , Westrich Geoffrey , Miller Andy 
Published: October 2017

Abstract

Background
Prosthetic joint infection (PJI) is a grave complication of total hip arthroplasty (THA). Predicting outcome is difficult. Musculoskeletal Infection Society (MSIS) criteria are sensitive and specific for the diagnosis of PJI. In prior work, we systematically studied the value of each MSIS criterion as a prognostic marker among a large cohort of patients with infected hip and knee arthroplasty treated with debridement, antibiotics, and implant retention (DAIR) at our specialized orthopedic hospital. We found that sinus tract drainage and culture positivity predicted explantation within 2 years of DAIR; the minor MSIS criteria were not predictive. Here, we sought to evaluate the utility of MSIS criteria in predicting outcomes of infected THR PJI treated with two-stage exchange arthroplasty. We sought to evaluate whether MSIS criteria can predict outcome of infected THR PJI treated with two-stage exchange arthroplasty.

Methods
A retrospective cohort of PJI from 2007 to 2014 treated with two-stage exchange was identified via an administrative database. Two-year implant retention was the primary outcome. Collected data included demographics and comorbidities, duration of symptoms, implant age, and pathogen. Continuous variables were assessed using the Mann–Whitney U-tests and categorical variables using the χ 2 test and Fisher’s exact test when appropriate.

Results
One hundred and thirty patients who underwent two-stage exchange for THA PJI meeting MSIS criteria were identified. Ninety percent remained infection free after 2 years of observation. Neither of the major criteria [the presence of sinus drainage[(P = 0.5416), and &gt;1 positive culture (P = 0.1052)], nor any of the minor criteria, reached statistically significant association with treatment outcome.

Conclusion
Individual MSIS diagnostic criteria, which do have prognostic utility in hip and knee PJI treated with DAIR, may not be powerful predictors of outcome of hip PJI after two-stage exchange, likely in part because of the high success rate of this procedure.

Disclosures
All authors: No reported disclosures.
Assessment of a Modified Antibiotic Prophylaxis Open Fracture Protocol
Authors: Hill Brandon , Sanasi-Bhola Kamla , Okoye Stella , Madera Margaret , Ferren Janie , Justo Julie Ann , Bookstaver P Brandon 
Published: October 2017

Abstract

Background
National guidelines support antibiotic prophylaxis for open fracture with cefazolin +/− aminoglycoside based on fracture grade and contamination. The purpose of this study was to assess a modified adult antibiotic prophylaxis open fracture protocol (AOFP) which recommended weight-based cefazolin for low-grade fractures or ciprofloxacin plus vancomycin for high-grade fractures.

Methods
Adult patients with open fractures admitted to Palmetto Health Richland between January 2012 and December 2016 were screened for study inclusion. Exclusion criteria were receipt of antibiotics for reasons other than open fracture, death prior to wound closure, and local admission time &gt;48 hours after time of injury. Compliance to all elements of AOFP was assessed. Clinical endpoints including open fracture infection rates, epidemiology, and drug-related adverse events were compared between pre-implementation (January 2012 – December 2012) and post-implementation period (November 2015 – December 2016). χ 2 and t-tests as appropriate were used to compare outcomes between groups.

Results
Following exclusions 189 patients were included in the analysis (90 pre- vs. 99 post-AOFP, respectively). Post-AOFP, a 17% (16/93) adherence rate to all AOFP elements was found. Appropriate agents were selected in 82.8% (77/93). The most common reasons for non-adherence were incorrect dosing and prolonged antibiotic duration. Fracture site infection rates were 23.3% (21/90) and 7.1% (7/99) in pre- and post-AOFP groups, respectively (P = 0.001). Infections primary caused by Gram-negative pathogens in pre-AOFP and Gram-negative organisms comprised 62 and 40% of open fracture site infections in pre- and post-AOFP groups, respectively. Incidence of acute kidney injury, Clostridium difficile-associated diarrhea, and other antibiotic-associated AEs were rare and comparable between groups. Change in median days to infection (55.6 days vs. 56.55 days, P = 0.71) and median duration of antibiotics in hours (48.0 vs. 54.7, P = 0.59) was not significantly different post implementation.

Conclusion
Local adherence to all elements of the modified AOFP was low, yet the appropriate agent(s) was used in majority of cases. The modified AOFP was associated with a numerical decrease in infection rates post-open fracture and comparable AEs.

Disclosures
P. B. Bookstaver, Rock Pointe: Content Developer, Consulting fee
Clinical Features and Treatment Outcomes of Bone-Joint Infection Between Bacteria and Mycobacterium Tuberculosis
Authors: Chumsaengsri Chumsaeng , Salee Parichat , Louthrenoo Worawit 
Published: October 2017

Abstract

Background
Bone-joint infection is an emergency condition that requires immediate management. Delayed in treatment or improper management can lead to a significant morbidity and mortality.

Methods
The medical records of patients with bone-joint infection seen at Maharaj Nakorn Chiang Mai Hospital between 1 November 2010 and 30 September 2015 were reviewed. The diagnosis of bone-joint infection was confirmed by pathogen identification or pathohistological report. Only those with adequate clinical features and treatment outcomes were included for analysis.

Results
Of 125 bone-joint infected patients seen during the study period, 92 patients were caused by bacterial infection and 33 from tuberculous infection. Their mean ± standard deviation age was 55.3 ± 17.7 years, and had total disease duration of 7.1 ± 8.2 months. Sixty-four percent were men. Of 33 TB cases, 24 (72.7%) had spinal involvement. Among 92 cases with bacterial infection, 52 (56.5%) had non-spinal joint involvement, and 38 (41.3%) had non-spinal bone involvement. Regarding clinical features, TB cases had mean duration of symptom of 5.3 ± 6.1 months. Multivariate logistic regression analyses showed that neurological manifestations (adjusted OR = 314.1, 95% CI 14.4–6831, P &lt; 0.001), pulmonary symptoms (AOR = 222.1, 95% CI 3.0–16,560, P = 0.014), symptom duration over 1 month (AOR = 67.4, 95% CI 4.2–1070, P = 0.003), afebrile illness (AOR = 24.1, 95%CI 1.2–493.7, P = 0.039), ESR &lt;70 mm/hour (AOR = 4.7, 95% CI 1.1–19.9, P = 0.039), and CRP &lt;30 mg/l (AOR = 7.0, 95% CI 1.6–31.2, P = 0.010) were risk factor of TB bone-joint infection. There were 120 (96.0%) patients with clinical improvement, and five (4.0%) died patients. There were no significant differences among the clinical improvement, recurrent infection, and mortality between the two groups.

Conclusion
Distinguish of bone-joint infection between bacteria and mycobacterium tuberculosis is difficult. However, patients with TB bone-joint infections significantly had more symptom duration over 1 month, the presence of paraplegia, the presence of pulmonary symptoms, and the presence of afebrile illness than those with bacterial infection. There were no significant differences among treatment outcomes and mortality between the two groups.

Disclosures
All authors: No reported disclosures.
Optimizing Envitonmental Hygiene to Successfully Decrease Clostridiun Difficile Transmission
Authors: Carling Philip , Scott Mary 
Published: October 2017

Abstract

Background
In light of the challenges involved in reducing healthcare onset colstridium Difficile infection (HO-CDI), we implemented a multifaceted hospital wide intervention program to optimize environmental hygiene in our 197 bed regional referral hospital.

Methods
Following an 18 month period during which HO-CDI rates were monitored, we simultaneously replaced routine quartinary ammodium cleaning of patient rooms with an environmentally non-damaging sporicidal peroxyacetic acid/hydrogen peroxide disinfectant, implemented an educational program for environmental services staff which included ongoing objective monitoring of the thoroughness of disinfection cleaning (TDC). We also evaluated cleaned environmental surface bioburden elimination. terminal room cleaning efficiency and HO-CDI rates.

Results
During the 33 month intervention period, TDC rapidly improved from 81% to 92% and remained greater than 88% during the remainder of the study (P = . 01)(Figure 1.) Bioburden elimination of cleaned surfaces improved from 24% to 84% (P = .03) with sporacide use. Efficiency of terminal room cleaning improved by 33% (36minutes to 27 minutes)(P = .02). HO-CDI rates fell significantly during the intervention period from an average of 8.9 to 3.2 /10,000 patient-days (P =.0001, 95% CI 3.48 to 7.81)(Figure 2.) as did months without documented CDI cases (P .02). No changes in potential confounders including antibiotic use patterns, intensive care unit days, prevalence density of CDI at the time of admission, hand hygiene compliance rates, isolation practices and over all patient-days were identified.

Conclusion
In the context of a single site, quasi-experimental study design, this 44 month study documented a significant impact (P = .0001) of an objectively monitored hospital-wide sporicidal disinfection cleaning program on endemic HO-CDI. The program was also associated with significantly improved efficiency of cleaning and post cleaning bioburden elimination of cleaned patient zone surfaces. Assuming a continued incidence of HO-CDI without intervention, the program resulted in an average non-reimbursed cost savings of approximately $ 10,000./month during the intervention period.

Disclosures
P. Carling, Ecolab: Consultant, Royalty; M. Scott, Ecolab, Inc.: Research Contractor, Research support