bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary or Secondary Prophylaxis with Voriconazole Compared with Posaconazole for Prevention of Invasive Fungal Infections After Hematopoietic Stem Cell Transplantation
Authors: Jansen Jeffrey W , Pande Anupam , Romee Rizwan , Lawrence Steven J , Powderly William
Published: October 2017

Background

Invasive fungal infections (IFI) remain a serious complication in hematopoietic stem cell transplantation (HSCT) patients and are associated with increased costs, morbidity, and mortality. Posaconazole (PCZ) and voriconazole (VCZ) are frequently utilized as antifungal prophylaxis in this population. To date, no direct comparison between PCZ and VCZ exists for the prevention of IFI in adult HSCT patients.

Methods

A retrospective cohort analysis of HSCT patients aged ≥18 years who received ≥28 continuous days of primary (PPPx) or secondary (SPPx) antifungal prophylaxis with either VCZ or PCZ between February 26, 2003 and September 30, 2015 at Barnes-Jewish Hospital was conducted. Patients who received PPPx or SPPx with both VCZ and PCZ were analyzed following intention to treat of the initial agent received. Patients who received both PPPx and SPPx were included once for both PPPx and SPPx. The primary outcome of interest was development of possible, probable, or proven IFI as defined by EORTC/MSG guidelines. In the SPPx patients, development of IFI was confirmed as a distinct event from primary IFI based on manual chart review and radiographic evidence.

Results

Overall, there were 472 patients included; 402 in the VCZ group and 70 in the PCZ group. At baseline, patients in the PCZ group had more graft vs. host disease (GVHD) prior to prophylaxis (27.1% vs. 16.7%, P = 0.04) and were more likely to be on SPPx (60% vs. 41%, P < 0.01). There were 22 and 1 IFI events in the VCZ and PCZ groups, respectively, which corresponded to a crude incidence rate of 0.345 and 0.077 per 1000 person-days of prophylaxis. Figure 1 displays the Cox proportional hazard model which was completed in the backwards stepwise method accounting for gender, transplant type, GVHD prior to prophylaxis, disease remission, and PPPx or SPPX. The hazard ratio for development of IFI while on prophylaxis between VCZ and PCZ was 5.22 (95% CI: 0.69–39.4; P = 0.11) after controlling for PPPx or SPPx.

Conclusion

There was not a significant difference between rates of IFI in HSCT patients who received antifungal prophylaxis with VCZ compared with PCZ. Our data trends towards favoring PCZ but is limited by low rates of IFI. Larger, prospective analyses are necessary to confirm our findings.

Disclosures

W. Powderly, Merck: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Gilead: Scientific Advisor, Consulting fee. Astellas: Grant Investigator, Research grant
Posaconazole-Induced Hypertension and Hypokalemia: Mechanistic Evaluation
Authors: Thompson George R , Chang Diana , Wittenberg Rebecca , Mchardy Ian , Semrad Alison
Published: October 2017

Background

Recent studies have shown the new posaconazole delayed-release tablets have superior bioavailability compared with the liquid suspension formulation. As higher serum posaconazole concentrations have been associated with improved clinical responses, this formulation has been a welcome addition to available treatment options. However, higher serum and tissue levels are likely to reveal previously undescribed toxicity as adverse events attributed to “off-target” effects are observed.

Methods

We prospectively identified two patients with new onset hypertension, hypokalemia, and alkalosis after starting posaconazole tablets. Patient vital signs and laboratory values were within normal limits prior to starting posaconazole; however, following over 30 days of therapy both patients became newly hypertensive (mean systolic BP increase 59 mmHg). Serum posaconazole levels were 4.3–4.6 μg/ml. Complete suppression of renin and aldosterone, with increased 11-deoxycortisol, estradiol levels, and cortisol/cortisone ratios were observed in both patients. The TTKG in both patients was inappropriately elevated.

Results

Posaconazole-induced disruption of the steroid biosynthesis pathway in patients has not previously been described, but has been suggested by in vitro studies. Our patients’ laboratory results show clinically significant inhibition of 11β-hydroxysteroid dehydrogenase enzyme type 2 isoform (11β-HSD2) as evidenced by: the elevated 11-deoxycortisol (with subsequent suppression of renin and aldosterone), the highly elevated cortisol/cortisone ratio, and the inappropriately elevated TTKG in the setting of hypokalemia. The normal deoxycorticosterone confirms normal function of 11β-hydroxylase and the observed effects in our patients are thus downstream from this enzyme.

Conclusion

Our findings support in vitro predictions and highlight the clinical sequelae of posaconazole-mediated inhibition of 11β-HSD2. Additional studies are necessary to determine the frequency of posaconazole induced apparent mineralocorticoid excess syndrome and whether other azole antifungals can be associated with this phenomenon.

Disclosures

All authors: No reported disclosures.
Presentation and Outcome of Cryptococcal Infection Varies by Predisposing Illness
Authors: Raval Krunal , Powderly William , Spec Andrej
Published: October 2017

Background

Better treatment for HIV has led to the changing epidemiology of cryptococcosis. Important differences in outcomes have recently been demonstrated based on immune status. In this study, we describe the differences in presentation and outcome of cryptococcal infection by immune status in the post-HAART era.

Methods

We conducted a retrospective cohort study of patients diagnosed with cryptococcosis from 2002 through 2014 at our institution. Data included demographics, clinical features, diagnostics, and outcomes. Comparisons were made with χ 2 and one-way ANOVA. Survival analysis was performed with Cox regression with survival censored at 90 days.

Results

We enrolled 243 patients with cryptococcosis: 91 (37.4%) with HIV, 24 (9%) with prior organ transplantation, and 128 (52.6%) with non-HIV non-transplant (NHNT). Age analysis showed HIV patients were younger (40 years) than transplant (53 years) and NHNT (60 years) (P < 0.001). Fevers and headache were more common in HIV (71 and 52%, P = 0.001) than in transplant (33 and 25%, P 0.001) and NHNT (51 and 39%, P 0.001), respectively. Meningitis (71%) was more common in HIV+ than in transplant recipients (45%) or NHNT (43%, P < 0.001). NHNT (37.5%) and transplant (45.8%) had more pulmonary cryptococcosis than HIV (10%, P < 0.001). Patients with NHNT had a higher risk of mortality (HR 2.642, 95% CI 1.481–4.713) as compared with HIV+. However, transplant recipients with cryptococcosis had risk of 90-day mortality (HR 0.99, 95% CI 0.33–2.99) similar to HIV+ patients.

Conclusion

Cryptococcosis in HIV+ and transplant recipients was less common than in NHNT in our institution and the presentation was different, with meningitis being less prominent. Cryptococcosis in NHNT was associated with higher risk of death than HIV+ patients or transplant recipients. NHNT patients comprise an important group that requires a high degree of clinical suspicion.

Survival curve of 243 patients with cryptococcosis by immune status: blue (NHNT), green (HIV), and red (any transplant). Patients in non-HIV non-transplant cohort had a higher mortality than those with HIV or transplant. Vertical dashes represent censored data (P < .001).

Disclosures

A. Spec, Astellas Pharma US, Inc.: Grant Investigator, Research grant
Erythema Sweetobullosum a Rare Presentation of Coccidioidomycosis
Authors: Heidari Arash , Abukamleh Hisham , Petersen Greti
Published: October 2017

Background

Erythema nodosum (EN) and erythema multiforme (EM) are known reactive cutaneous manifestations of acute infection with coccidioidomycosis. In endemic area, these findings could be diagnostic in the presence of proper clinical presentation. In our experience at Kern Medical similar to our colleagues in Arizona we have observed unique form of cutaneous manifestation of acute coccidioidiomycosis with blisters. This form of skin eruption was given different names such as toxic erythema in 1940 and recently sweet syndrome in 2005. The term erythema sweetobullosum (ESB) was suggested first by David J. Elbaum in 1998 in San Joaquin Valley California in a nine case series. This study showed in contrast to sweet syndrome in ESB histology appears to change based on when the patient is seen. Early on ESB shows lymphocytic dominance, later will be neutrophil rich and eventually histiocytic phase and even granulomatous.

Methods

Retrospective chart review.

Results

Six cases are identified. Upon presentation they were between 27 and 47 years old half male and other half female. In all cases, ESB lesions were present as multiple tense erythematous plaques base with central crusting and surrounding cluster of vesicular formation. ESB lesions were located on bilateral upper and lower arms in all cases (Figures 1–3). IgM immunodiffusion serology was positive in all cases. Chest X-ray was positive for infiltration or nodule or cavity in five cases. Eosinophilia was present in four cases (800–1600). All cases had EM and two cases had EN present. Histopathology in one case described as subepidermal vesicular dermatitis with lymphocytes and histocytes. No evidence of dissemination was found in all six cases. One case lost follow-up but rest had significant clinical, radiological and serological response to fluconazole therapy with complete resolution of all skin manifestations.

Conclusion

We are describing six cases of acute pulmonary coccidioidomycosis with unique reactive skin manifestation described as erythema sweetobullosum. The acknowledgment of skin findings assists in prompt clinical suspicious to make diagnosis and initiate treatment.

Disclosures

All authors: No reported disclosures.
Disseminated Coccidioidomycosis Among Children in Central California: A Retrospective Review
Authors: Naeem Fouzia , Mhaissen Mohammad Nael , McCarty James , Rongkavilit Chokechai
Published: October 2017

Background

The burden of coccidioidomycosis in central California is significant among children. Yet, the literature on such infection is limited, particularly on disseminated coccidioidomycosis (DC) in children.

Objectives

Review the natural history, treatment and outcomes of DC in a tertiary children’s hospital.

Methods

Retrospective review of patients ≤21 years old with DC seen at our facility during 1/1/07–12/31/16.

Results

Eighty cases were identified. Median age was 8.5 years (IQR 4.3–14.6); majority was hispanic (66%) and without comorbid conditions (85%). Pulmonary disease with other organ involvement occurred in 69%; 19% had meningitis. Overall, 82% had resolved and/or stable disease (RS), whereas 14% experienced relapse and/or progressive disease (RP). Meningitis more commonly seen in older age group (14.3 vs. 6.9 years, P = 0.04) and had low eosinophil’s (0.8 vs. 2.1%, P < 0.01). More organ involvement (64% vs. 35%, P = 0.03) and RP disease (22% vs. 5%, P = 0.04) commonly seen in children 10 years or older. Non-Hispanics also found to be older than Hispanics (12.2 vs. 7.4 years, P < .01); received multiple drug therapy (48% vs. 18%, P = 0.02). Although not significant, Non-Hispanics were more likely to have meningitis (30% vs. 13%, P = 0.07), coccidioidal complement fixation (CF) titers ≥ 32 (92% vs. 73%, P = 0.07), and RP disease (24% vs. 7%, P = 0.06) than Hispanics. No significant association was found between gender and age, CF titers, and/or outcomes. Higher CF titers were seen with >1 organ involvement (1:256 vs. 1;64, P < 0.01) and more antifungal therapy (1:256 vs. 1:32, P < 0.01). Coccidioides EIA antibody was positive in 50% of cases and 48% with negative/indeterminate results were positive by Immunodiffusion. On multivariate analysis, age remained independently associated with RP (OR = 1.2, 95% CI 1.0–1.5, P = 0.02); age (OR = 1.1, 95% CI 1.0–1.3, P = 0.01) and more antifungal therapy (OR = 3.7, 95% CI 1.4–9.5, P < 0.01) with non-Hispanics.

Conclusion

To our knowledge this is the largest series for pediatric DC. We identify older age group, non-Hispanics and higher CF titers as potential risk factors for DC, which require early intervention. Prospective studies are needed to identify predictors for adverse outcomes in pediatric DC.

Disclosures

All authors: No reported disclosures.
Real-World Use – Isavuconazole at a Large Academic Medical Center
Authors: Hassouna HabiBA , Brizendine Kyle , Athans Vasilios
Published: October 2017

Background

Invasive fungal infections cause significant mortality and morbidity. Isavuconazole (ISV) is a new triazole approved for treatment of mucormycosis and aspergillosis. Data on its effectiveness outside clinical trials and in patients receiving prior triazole prophylaxis are lacking.

Methods

We conducted a retrospective cohort study on all patients at the Cleveland Clinic 6/1/2015–1/31/2017 who received ISV to determine 6-week response in a population with varying underlying diseases, and previous triazole prophylaxis or treatment. Descriptive statistics and univariate associations were calculated.

Results

Thirty-three patients were identified including organ transplant recipients (5), hematopoietic cell transplant recipients (7), and acute leukemia (18). Twenty-five had lung involvement while 13 had rhino-orbital-cerebral disease. In 13 cases, a fungal pathogen was identified: Mucorales (7) and Aspergillus (6). Fifteen received triazole prophylaxis prior to initiating ISV. Twenty-four received antifungal therapy immediately prior to switching to ISV: amphotericin B (1), fluconazole (1), voriconazole (16), posaconazole (4), and micafungin (2). Switching was often to broaden empiric coverage (18). Six-week response according to subgroups is presented in Figure 1 patients had therapeutic drug monitoring (TDM). Median level (IQR) was 6.75 (5.6–7.0) g/ml. Patients given ISV following triazole prophylaxis, those undergoing TDM, and those with an identified fungal pathogen had increased odds of complete or partial response, but this did not reach statistical significance (Figure 2). At 6 weeks mortality was 36%; complete or partial response observed in 45%. No ISV-related adverse effects reported.

Conclusion

To our knowledge, this is the first study to assess a real-world setting and a heterogeneous population with previous triazole prophylaxis or treatment. Our 6-week response (45%) compares favorably to published trials (35% Aspergillus; 11% Mucorales). Mortality in our study (36%) is similarly comparable to trial results (19% Aspergillus; 35% Mucorales). No major safety signal was observed. Larger cohorts are needed to describe additional real-world ISV use and determine associations with patient outcomes.

Disclosures

All authors No reported disclosures.
Epidemiology and Clinical Features of Invasive Fungal Disease in a US Healthcare Network
Authors: Webb Brandon , Ferraro Jeffrey , Rea Susan , Kammerer Jennifer , Kaufusi Stephanie , Goodman Bruce , Martin Greta , Spalding James
Published: October 2017

Background

A better understanding of the epidemiology and clinical features of invasive fungal disease (IFD) is integral to improving outcomes. Here we aimed to describe the incidence, clinical features and outcomes of IFD in a large US healthcare network.

Methods

We developed a novel method of IFD cohort discovery to query all available records in the Intermountain Healthcare electronic data warehouse from 2006 to 2015 for clinical data associated with IFD (Figure 1). Resulting data were overlaid in 124 different combinations to identify high-probability IFD cases. The cohort was manually reviewed and exclusions applied. EORTC/MSG definitions were adapted to categorize IFD in a broad patient population. Linear regression was used to model variation in incidence over time.

Results

3,391 IFD episodes occurred in 3,171 patients. Mean incidence was 27.4 cases/100,000 patients per year (Figure 2). Estimated mean annual increase was 0.24 cases/100,000 patients (r2 = 0.09, P = 0.21). Candidiasis was most common (56%). Dimorphic fungi, primarily Coccidioides, comprised 24%, followed by aspergillosis (9%). Mean age was 50 years; pediatric cases accounted for 13%. 19.2% of patients had an active malignancy or primary immunodeficiency, 6.9% were transplant recipients, and 27.5% were on immunosuppression. Lymphopenia preceded IFD in 24.4% of patients. Hospital admission occurred in 75%; median length of stay was 12 days. All-cause mortality was 17% at 42 days and 28.6% at 1 year. 42-day mortality was highest in aspergillosis (27.5%), 20.5% for Candida, and lowest for dimorphic fungi (7.5%).

Conclusion

In this population, IFD was not uncommon, affected a broad spectrum of patients and had high observed mortality.

Disclosures

B. Webb, Astellas Pharma Global Development, Inc.: Grant Investigator, Research grant. J. Ferraro, Astellas Pharma Global Development, Inc.: Grant Investigator, Research support. S. Rea, Astellas Pharma Global Development, Inc.: Grant Investigator, Research support. J. Kammerer, Astellas Pharma Global Development, Inc..: Employee, Salary. S. Kaufusi, Astellas Pharma Global Development, Inc.: Grant Investigator, Research support. B. Goodman, Astellas Pharma Global Development, Inc.: Grant Investigator, Research support. G. Martin, Astellas Pharma Global Development, Inc.: Grant Investigator, Research support. J. Spalding, Astellas Pharma Global Development, Inc.: Employee, Salary
Blastomyces helicus, an Emerging Dimorphic Fungal Pathogen Causing Fatal Pulmonary and Disseminated Disease in Humans and Animals in Western Canada and United States
Authors: Schwartz Ilan S , Wiederhold Nathan P , Patterson Thomas F , Sigler Lynne
Published: October 2017

Background

Blastomyces helicus (formerly Emmonsia helica) is a recently described dimorphic fungus first isolated from a man who died of encephalitis in Alberta, Canada. The geographic range, epidemiology and clinical features are unknown.

Methods

We reviewed clinical and veterinary isolates of Blastomyces and Emmonsia at the University of Alberta Microfungus Collection and Herbarium and the UT Health San Antonio Fungus Testing Laboratory. Isolates were selected based on low B. dermatitidis DNA probe values and/or atypical morphology. DNA sequence analysis was performed. Epidemiological and clinical data were analyzed.

Results

Isolates of B. helicus were identified from eight human (Table 1) and five veterinary cases (Table 2). Mycelial and yeast-like phases of typical clinical isolates are shown in Figures 1 and 2, respectively. Isolates were referred from provinces and states shown in Figure 3.

Conclusion

Blastomyces helicus caused pulmonary and fatal disseminated disease, mainly in immunocompromised persons, and lung disease in companion animals in western Canada and US. Epidemiological investigations are needed to establish the burden of disease and geographic range of this pathogen.

Disclosures

All authors: No reported disclosures.
Ocular Candidiasis in Patients with Candidemia at a Large Tertiary Care Center
Authors: Lee Bonny , Breskin Lydia , Reddy Laya , Iliceto Alessandro , Ashcraft Deborah , Pankey George , Nussdorf Jonathan , Garcia-Diaz Julia
Published: October 2017

Background

Bloodstream infections (BSI) caused by Candida sp. have a high mortality rate and have been increasing in recent years. Ocular candidiasis (OC) is one systemic manifestation of Candida infection; either chorioretinitis or endophthalmitis, and may lead to vision loss. Therefore, IDSA recommends an ophthalmology exam for all patients with Candida BSI. However, reported incidence of OC varies from 1 to 25%, questioning routine eye exams in these patients. The purpose of this study was to evaluate the number of patients who undergo ophthalmological exams and those diagnosed with OC at Ochsner Medical Center, New Orleans (OMC-NO).

Methods

One hundred and forty-four patients were identified from January 2013 to December 2015 with at least one positive blood culture for Candida sp. (only albicans, glabrata, and parapsilosis were included). Records were reviewed through the EPIC system.

Results

Of the 144 patients, 65 were females and 79 males; average age 58 years old. Seventy-six (52.8%) had an ophthalmological exam at Ochsner; excluding one patient who refused an exam, one patient who was excessively combative, and one patient in whom exam was deferred due to medical condition. Three patients (3.9%) showed Candida chorioretinitis; none endophthalmitis.

Conclusion

OC can have devastating consequences if left untreated and early diagnosis is imperative. Our analysis reveals that OC is present in 3.9% of ophthalmology exams, but this may be biased towards patients who are cooperative and can tolerate a dilated eye exam. Critical patients with multiple co-morbidities may be at higher risk for OC. A weakness of our study is that it is limited to ophthalmology records at Ochsner, and there may be records at outside facilities. Further data is required to make recommendations in patients with Candida BSI.

Disclosures

All authors: No reported disclosures.
Antifungal Resistance and Predictors of Response in Patients with Hematologic Malignancy
Authors: Wey Shiuan (Shannon) , Kriengkauykiat Jane , Chan Ayla , Tegtmeier Bernard , Ito James , Dadwal Sanjeet
Published: October 2017

Background

Invasive aspergillosis (IA) causes significant morbidity and mortality in patients with hematologic malignancies (HM). Azole resistance has emerged as a therapeutic challenge in managing IA. The aim of this study was to investigate Aspergillus susceptibility to antifungals over the past decade among HM patients, and correlate susceptibility to clinical outcomes.

Methods

All Aspergillusisolates banked from 2002 to 2014 isolated from HM patients with probable/proven IA were tested for antifungal susceptibility. Patients with hematopoietic cell transplant, duplicate and non-viable isolates were excluded. Data were collected on demographics and clinical factors that could affect the treatment response, antifungal susceptibility (MICs/MECs), and treatment response at 14, 30, and 90 days.

Results

Forty patients were identified. MICs for amphotericin B slightly increased over the past decade (R = 0.32, P = 0.09), but were stable for voriconazole (R = −0.08, P = 0.61). The MIC50 during the first 3 years (2002–2004) and last 3 years (2012–2014) for amphotericin B were 0.5 and 1 mg/l, and for voriconazole 0.5 and 1. Mean age 56 years, 48% male, 82% had active HM and 45% had received chemotherapy within 14 days of IA. 50% were neutropenic and 30% had circulating blasts. Forty percent were on antifungal prophylaxis. Seventy-five percent of isolates were A. fumigatus. Fourteen responded to treatment (TR) and 26 were non-responders (NTR), and they did not differ in baseline characteristics. However, neutropenia (14% TR vs. 58%, NTR, P < 0.017) and circulating blasts (0% TR vs. 35% NTR, P < 0.02) at 14 days differed. The MIC50 for voriconazole was 0.5 mg/l in both groups, and for amphotericin B was 0.25 in TR vs. 1 mg/l in NTR. Fourteen-day response correlated with 90-day response (R = 0.74, P < 0.01) which validated the use of 14-day response for clinical outcome. All responders on amphotericin B at 14, 30, and 90 days had isolates with MIC < 1, whereas no apparent MIC-response correlation was found for voriconazole.

Conclusion

Although not statistically significant, a trend of increasing Aspergillus amphotericin B MICs was observed over the past decade. Neutropenia and persistent disease correlated with treatment failure. Clinical response was not affected by the azole or polyene MICs.

Disclosures

J. Ito, Astellas: Speaker’s Bureau, Speaker honorarium. S. Dadwal, Merck: Investigator, Research support. GlaxoSmithKline: Investigator, Research support. Ansun Biopharma: Investigator, Research support. Oxford Immunotec: Investigator, Research support. Gilead Sciences: Investigator, Research support
Candida parapsilosis Candidemia Resistance Patterns and Treatment Outcomes: An Opportunity for Antifungal Stewardship
Authors: Fong Gary , Ngo Kim , Russo Hannah , Beyda Nicholas
Published: October 2017

Background

Candida parapsilosis has emerged as an important fungal pathogen with mortality rates up to 30%. Recent studies show no difference in treatment outcomes for patients treated both empirically and definitively with either echinocandins or fluconazole. However, the impact of antifungal susceptibility testing and opportunities for antifungal stewardship are less clear in this patient population. The purpose of this study was to assess antifungal susceptibility rates, treatment patterns, and outcomes among patients with C. parapsilosis candidemia.

Methods

This was a single-center, retrospective cohort review of adult patients with a positive blood culture for C. parapsilosis hospitalized at Baylor St. Luke’s Medical Center, between 2006 and 2016. Patients with mixed or breakthrough candidemia were excluded as well as patients who expired within 3 days of candidemia onset.

Results

Eighty patients with C. parapsilosis candidemia were identified of which 48 met inclusion criteria. Nine patients had infections caused by fluconazole non-susceptible isolates (19%). The most common empiric treatment choice was an echinocandin (33/48, 69%), followed by fluconazole (9/48, 19%), and combination therapy (6/48, 13%). Of the 39 patients with fluconazole susceptible isolates, only 17 were treated with fluconazole definitively (44%). Among patients who received empiric echinocandin vs. fluconazole therapy, there was no difference in 14-day mortality (9% vs. 11%, P = 1.00) or in-hospital mortality (12% vs. 11%, P = 1.00). Empiric combination therapy was the only independent risk factor for treatment failure (OR, 13.8; 95% CI, 1.4–138.3; P = 0.03).

Conclusion

Treatment outcomes for patients receiving echinocandins were similar for those receiving fluconazole. At our institution, the increased incidence of fluconazole non-susceptible isolates warrants the use of echinocandins empirically. Patients were more likely to remain on echinocandin therapy even when fluconazole susceptible isolates were identified. This study reinforces the guideline suggestion that neither echinocandins nor fluconazole treatment leads to superior outcomes, but also identifies a cohort of patients in need of antifungal stewardship.

Disclosures

N. Beyda, Astellas: Grant Investigator and Scientific Advisor, Research grant
Epidemiology of Invasive Fungal Disease by Aspergillus in a University Hospital in Santiago – Chile, During the Period 2005–2015
Authors: Valenzuela Pablo , Rabagliati Ricardo , Legarraga Paulette
Published: October 2017

Background

In Chile, there is little information on invasive fungal disease (IFD) due to filamentous fungi. A study of our institution showed 41 episodes in hemato oncological patients between the years 2004 and 2008, being the main cause Aspergillus, but the epidemiological characteristics of this infection in Chilean patients are not currently known. The objective describes the epidemiology of IFD by Aspergillusin our center.

Methods

Retrospective study in adults patients hospitalized in our center, diagnosed with IFD by Aspergillus between 2005 and 2015. Medical records of identified cases were review, incidence were calculated with the discharges numbers and total numbers of IFD. The study was approved by the Institutional Ethics Committee.

Results

Sixty-seven cases were identified, with an incidence of 2.53 per 10,000 discharges between 2005 and 2015, with 35 cases of IFD in the period 2005–2010 and 32 cases in the period 2011–2015. The etiologies were A. fumigatus 42%, A. flavus 7%, A. terreus 7%, A. niger 3%, and Aspergillus spp. 40%. According EORTC/MSG criteria, 39% were proven, 52% probable, and 9% possible. The 55% of patients were male, the mean ± SD age was 51 ± 18 years, 57% had hematological conditions, mainly acute leukemias, rheumatological conditions in 15% and solid organ transplant in 13%, neutropenia under 500/mm3 in 37% and serum galactomannan test >0.5 in 67%. The clinical focus was 73% pulmonary and 17% rhinosinusal. The treatment was 81% monotherapy, 73% with voriconazole, 15% with liposomal amphotericin B and 6% with caspofungin. The 30 days mortality was 39%.

Conclusion

The epidemiology of IFD by Aspergillus is similar to that described in developed countries, in highly vulnerable patients with a mortality close to 40%. More epidemiological information from other hospitals is necessary to complete the epidemiology of Aspergillus infections in our country.

Disclosures

All authors: No reported disclosures.
Improved Survival of Candida CLABSI by Adherence to Standard of Care and Involvement of Infectious Diseases Consultant: A 5-Year Experience in a Single Academic Center
Authors: John Blessy , Malinis Maricar , Fairweather Iyanna , Aniskiewicz Michael , Rivera-Vinas Jose , Baltimore Robert , Martinello Richard
Published: October 2017

Background

Candidemia is the fourth most common nosocomial blood stream infection with significant morbidity and mortality. Central lines have been considered a risk factor for invasive fungal infection. We evaluated the epidemiology, management, and outcomes of Candida CLABSI in an academic medical center.

Methods

We conducted a retrospective cohort study in a single academic center from January 1, 2011 to December 31, 2016 of patients who had positive blood cultures for Candida sp. and met CDC criteria for CLABSI. Outcomes measured were 30-day mortality and relapse or recurrence. Descriptive statistics were used to compare the outcomes of patients who had infectious diseases consult and managed per standard of care (SOC) as defined by IDSA guidelines and those without.

Results

Of 722 CLABSI cases, 82 (11%) were due to Candida sp. Candida species isolated were as follows: C. glabrata (40%), C. albicans (32%), C. parapsilosis (9%), and others (19%). Median age of pediatric patients was 2.25 years (range 0.5–6) and median age of adults was 59 years (19–92). Most common comorbidities were malignancy (35%) and end-stage renal disease (21%). Non-tunneled catheters were present in 58% of cases. Median time from line placement to candidemia was 15 days (IQR 8–29). Sepsis was present in 34 (42%) cases. Seventy-four (90%) cases were initiated on antifungal therapy (AFT) when culture turned positive. After Candida speciation, AFT was adjusted appropriately for 82 (100%) cases. IDC was present in 56 (68%), of which 41 (73%) followed SOC, whereas 15 (27%) did not. Two of 26 patients (8%) without IDC received SOC. Complications occurred in 11/82 (13%) (three endocarditis, two osteomyelitis, three endophthalmitis, and four septic thrombophlebitis). Cure was achieved in 26/82 (32%). Relapse or recurrence occurred in 15/82 (18%). The 30-day mortality for the cohort was 50%. Patients with IDC who received SOC had lower mortality compared with those who did not (35% vs. 67%, respectively; P = 0.03).

Conclusion

Candida CLABSI was infrequent but had significant mortality in our cohort. Our results suggest that adherence to SOC per IDSA guidelines and involvement of IDC may improve survival of patients with Candida CLABSI. Future studies are needed to validate these findings.

Disclosures

All authors: No reported disclosures.
Septic Arthritis of Native Joints: Are Outcomes Better with Medical or Surgical Management?
Authors: McConnell Ian , Baghban Adam , Holleck Jurgen , Gupta Shaili
Published: October 2017

Background

There is limited evidence to support medical vs. surgical management of native joint septic arthritis (SA) with no established guidelines for care. Advantages of medical (antibiotics with or without serial needle aspiration) and surgical (arthroscopic or arthrotomic drainage) treatments are unknown.

Methods

We conducted a single-center retrospective chart review of veterans diagnosed with SA over 10 years at the West Haven VA Hospital. Demographic, clinical, laboratory, imaging, and outcome data were extracted. Cases meeting inclusion criteria (positive culture or synovial fluid WBC >50,000) were stratified by surgical vs. medical management. Evaluated outcomes included joint recovery, time to recovery, sterilization of synovial fluid, duration of antibiotics, length of stay, recurrence of SA, and mortality. Odds ratios were calculated by multivariate analyses for correlation of outcomes to risk factors and to management approach taken.

Results

Sixty-one cases of SA met inclusion criteria. Average age was 67, 95% of patients were men, 89% White, 11% Black, 43% diabetic, and 43% had preexisting joint disease. 69% (41/61) of cases were managed surgically. Average length of stay for surgical group was 20 days compared with 14 days for medical group (P = 0.28). Duration of antibiotics was longer in surgical group (60.3) than medical group (35.4), (P = 0.09). S. aureus was the most common pathogen isolated (56%), followed by Streptococcus (11%) and gram-negative organisms (8%). Six (10%) patients had culture-negative SA. Mortality rate at 1 year was 3.2%. Full recovery of joint function at 1 year was achieved equally in both groups (P = 1.0), by 15/20 medically managed (75%) and 31/41 surgically managed (76%), with no significant differences by pathogen. Full recovery at 3 months was noted in 10/20 (50%) medically managed vs. 8/41 (19.5%) surgically managed (P = 0.02). Poor outcomes were not associated with joint location, pathogen, type of joint drainage, number of days to OR, or duration of antibiotics. Blacks had increased odds of poor outcome (OR 9.5; 95% CI 1.3–65.4).

Conclusion

We detected no statistically significant difference in outcomes at 12 months between patients managed medically vs. surgically for native joint septic arthritis. Full recovery at 3 months was significantly higher among the medical group.

Disclosures

All authors: No reported disclosures.
Time-to-Report of the Bone Culture and Microbiologic Adequacy of Empiric Antibiotics in Patient’s with Diabetic Foot Osteomyelitis
Authors: Kim Hyun Kyung , Vasylyeva Olga
Published: October 2017

Background

Bone cultures in diabetic foot infection is the most accurate method to identify causative pathogen, while there is only 30% concordance between superficial wound swab and bone biopsy cultures. Diabetic foot infection is commonly polymicrobial, therefore report on the bone biopsy culture may come with several updates before it is finalized. Our study is aimed to describe how often additional pathogens were identified after patients’ discharge on antibiotics therapy for diabetic foot osteomyelitis, and evaluate microbiological appropriateness of antibiotic regimen upon discharge based on the final result of the bone culture.

Methods

Medical records of the patients 18 years old or older, who had inpatient bone biopsy, deep tissue debridement or amputation for diabetic foot infection, were reviewed from January 2014 through Dec 2015 in Rochester Regional Health System. Antibiotic regimens for the patients discharged before final culture result were evaluated for microbiological appropriateness by two reviewers trained in infectious diseases.

Results

In total, 198 procedures were screened, 158 procedures met inclusion criteria, out of which 74 patients with 80 procedures (51%) were discharged before the final culture result was available. Average time from procedure to the final culture report was 6 days, and from discharge to the final culture was 3.7 days. In most of the cases (70%, 56 out of 80) the patients were discharged on empiric regimen discordant with final culture result. Predominant organisms were Gram-positive bacteria 74%, with Gram negatives 24%, and yeast 2%. Most infections were polymicrobial (81%), mixed with anaerobic bacteria in 37%. The most frequent isolates were Staphylococcus aureus (15%), Corynebacterium (14%), anaerobic Gram-positive cocci (12%), and Staphylococcus epidermidis (8%). All negative Gram stains (31%, 25 out of 80) had positive growth on culture.

Conclusion

Half of the patients with diabetic foot osteomyelitis, who underwent bone biopsy, were discharged before final culture results were available. Most of them were discharged on empiric regimen discordant with final culture. This data suggests that careful outpatient follow-up on the final culture would likely result in modification of antibiotics therapy to target newly reported pathogen.

Disclosures

All authors: No reported disclosures.
Microbiological Epidemiology Depending on Time to Occurrence of Prosthetic Joint Infection (PJI): Impact on the Empirical Antimicrobial Strategies
Authors: Ferry Tristan , Triffault-Fillit Claire , Laurent Frederic , Dupieux Céline , Lustig Sébastien , Fessy Michel-Henri , Chidiac Christian , Valour Florent
Published: October 2017

Background

Empirical antimicrobial therapy of prosthetic-joint infection (PJI) is a major clinical challenge and current guidelines recommend the combination of vancomycin plus a broad-spectrum β-lactamin. As Gram-negative bacilli (GNB) are probably less represented in late infections, we evaluate the microbiological epidemiology in patients with PJI according to the chronology of infection.

Methods

All patients managed in a reference center for complex bone and joint infections in France (2011 and 2016) were included in a prospective cohort study. Microbiological data at the time of diagnosis were collected and analyzed according to the chronology of infection.

Results

We included 567 PJI (284 males, 50.1%; median age 70.3 years). The median occurrence time was 23.4 weeks after prosthesis implantation (285 hip and 255 knee PJI, which were revision prosthesis in 216 [40.3%] cases). Microbiological bone samples found 164 [28.9%] S. aureus (including 26 [16.3%] MRSA), 162 [28.6%] coagulase-negative Staphylococci (CoNS, including 80 [58.8%] methicillin-resistant CoNS), 80 (14.1%) Enterobacteriaceae, 74 (13.1%) Streptococci, and 85 (15.0%) anaerobes (including 60 [10.6%] Propionibacterium). Infection was plurimicrobial in 10 [18.2%] cases. Among the 183 patients (32%) with late PJI (occurring >1 year), obtained after exclusion of the 59 patients (10.4%) with hematogenous origins, Enterobacteriacecae  (n = 8; 4.4%; P < 10–3) were much less represented than in patients with early PJI occurring <1 year. No difference was observed regarding the the presence of non-fermenting GNB, with a prevalence of 4.6 and 2.7% in early and late PJI, respectively. Taken together, these data suggest that a broad-spectrum β-lactam antibiotic might be useful in only 12 (6.6%) patients with late PJI, compared with 66 (20.3%) patients with early PJI (P < 10–3). Of note, there were statistically more anaerobes (n = 40; 21.9%) in late PJI, including 32 Propionibacterium (17.5%; P < 10–3).

Conclusion

Considering the minority amount of GNB in late post-operative PJI and the overrepresentation of anaerobes including P. acnes, the empirical treatment should be reconsidered, especially when a two-stage exchange is planned. In those situations, another acceptable option could be the vancomycin+clindamycin combination.

Disclosures

T. Ferry, HERAEUS: Consultant, Speaker honorarium. S. Lustig, Heraeus: Consultant, Consulting fee.
Oral vs. Intravenous Antibiotics for the Treatment of Acute Bacterial Osteomyelitis in the Veteran Population
Authors: Turnbull Caitlin , Young Lisa , Lowery Sheryl
Published: October 2017

Background

The optimal route for administration of antibiotics in the treatment of acute bacterial osteomyelitis (ABOM) has not been clearly defined. Based on pharmacokinetic data and expert opinion, intravenous (IV) antibiotics are considered the standard of care. Studies demonstrate reasonable oral (PO) absorption and bone penetration of certain antibiotics, supporting the potential efficacy of their use in the treatment of ABOM. The purpose of this study was to determine whether a difference exists in treatment outcomes in Veterans with ABOM treated with PO vs. IV antibiotics.

Methods

This is a retrospective, electronic chart review of patients diagnosed with ABOM between October 1, 2008, and September 30, 2013. Subjects were evaluated and placed into two groups: (1) IV antibiotics for at least 4 weeks or (2) PO antibiotics for at least 4 weeks. The primary endpoint was treatment failure within one year of diagnosis. Treatment failure was defined as recurrence of infection, amputation of the infected bone, or if they were lost to follow-up.

Results

In total, 83 patients, accounting for 89 episodes of ABOM were included in this study; 41 in the IV group and 48 in the PO group. Treatment failure occurred in 14 patients in the IV group (34.15%) and 17 patients in the PO group (35.42%), P = 0.90. Subgroup analysis of subjects with diabetes mellitus, peripheral vascular disease, body mass index ≥ 30 kg/m2, and those ≥ 65 years also found no difference between groups. After at least 4 weeks of antibiotic therapy, 10 patients in the IV group and five patients in the PO group had an amputation of the infected bone, P = 0.14. Mean length of hospital stay was significantly longer in the IV group at 8.55 days as compared with the PO group at 2.23 days, P < 0.0001.

Conclusion

Treatment of ABOM with PO antibiotics may serve as a reasonable alternative to IV antibiotics, showing similar efficacy and reduced hospital stay.

Disclosures

All authors: No reported disclosures.
Clinical Outcomes of Antipseudomonal vs. Non-Antipseudomonal Therapy in Patients with Osteomyelitis
Authors: Jansen Jeffrey W , Moenster Ryan P
Published: October 2017

Background

Osteomyelitis (OM) in diabetics is frequently a polymicrobial infection that rarely involves Pseudomonas (4–5% of cases). Bone cultures have a low-positive yield of 34–50% and, as a result, many patients receive antimicrobial regimens which include antipseudomonal (AP) therapy.

Methods

A retrospective cohort analysis of adult Veterans with OM treated with AP compared with non-antipseudomonal (NAP) therapy was conducted. Patients managed by the VA St. Louis outpatient parenteral antimicrobial therapy (OPAT) service from 1/1/2009 to 7/31/2015 were identified and screened for inclusion. Patients with culture negative (CN) or non-pseudomonal superficial swab cultures (SCx) were included. Figure 1 presents the study profile and exclusion criteria. The primary outcome was clinical failure, defined as a composite of: (1) extension of antibiotics beyond 1 week of the planned duration, (2) recurrence of OM at the same anatomical site within 12 months, or (3) any unplanned surgery or amputation at the anatomical site within 12 months of ABx completion.

Results

Overall, 104 patients with 109 OM encounters were included; there were 29 CN encounters and 80 SCx encounters. Table 1 presents baseline demographics. The overall failure rate was 55/109 (50.5%). The results of the analysis are shown in Table 2. While not included in the primary analysis, Pseudomonas was isolated from 8/88 (9.1%) swab cultures and 5/33 (15%) deep cultures.

Conclusion

Empiric AP therapy did not improve clinical outcomes in patients with either CN or SCx OM.

Disclosures

All authors: No reported disclosures.
Microbiological Epidemiology in Patients Experiencing Microbiological or Clinical Failure Following Reimplantation After a Two-Stage Exchange Strategy for Hip or Knee Prosthetic Joint Infection (PJI)
Authors: Ferry Tristan , Serrier Hassan , Laurent Frederic , Mabrut Eugenie , Fessy Michel-Henri , Chidiac Christian , Huot Laure , Lustig Sébastien , Valour Florent
Published: October 2017

Background

Patients with late PJI are at risk for superinfection at the time of reimplantation. Different commercially available antibiotic-loaded cements (gentamicin, vancomycin, gentamicin+clindamycin [G+C], gentamicin+vancomycin [G+V]) could be used for the fixation of the new prosthesis and could be effective to treat or prevent superinfection. We aim to determine the microbiological epidemiology in patients experiencing failure following reimplantation to establish, based on the drug susceptibilities, which cement could be the most active.

Methods

Prospective cohort study including all patients with a two-stage exchange in 2013–2015. Microbiological failure was defined by positive culture at the time of reimplantation. Clinical failure was defined by patients with clinical signs of infection requiring a new surgery.

Results

We included 117 patients (median age 70 years). Fourteen patients (12%) experienced a failure: seven patients with microbiological failure (four CoNS, one P. acnes, one corynebacterium, and three Candida albicans); seven patients with a clinical relapse requiring a new surgery (three Enterobacteriaceae, two P. aeruginosa, one streptococcus spp., one CoNS, one P. acnes, one E. faecalis). Considering the use of a vancomycin-loaded cement, this antibiotic was inactive on Candida (n = 3) and Gram-negative isolates (n = 5). Considering the use of gentamicin, this antibiotic was inactive on Candida (n = 3) and five bacterial isolates. These five letter isolates were also not susceptible to Clindamycin. Considering the use of G+V, this combination was inactive on Candida (n = 3) and only one bacterial isolate (a gentamicin-resistant K. pneumonia). Consequently, the vancomycin-, gentamicin- and G+C-loaded cements may effectively treat or prevent 42.9% of superinfections, only. Conversely, the G+V-loaded cement may effectively treat or prevent 71.4% of them.

Conclusion

Considering the commercially available antibiotic loaded: none of the Candida albicans superinfection could be locally treated, and the G+V-loaded cement could treat or prevent most bacterial superinfections.

Disclosures

T. Ferry, HERAEUS: Consultant, Speaker honorarium. S. Lustig, Heraeus: Consultant, Consulting fee