bluuebunny/crossref_metadata_2025 huggingface dataset:
Coccidioidomycosis After Solid Organ Transplantation: A Population-Based Study
Authors: George Ige , Santos Carlos
Published: October 2017

Background

Coccidioidomycosis is an invasive fungal infection in solid organ transplantation (SOT) recipients with an incidence of 1.4–6.9% in endemic regions. There are no population-level data describing the incidence and outcomes of coccidioidomycosis in SOT recipients.

Methods

We assembled a large cohort of adult SOT recipients using ICD-9-CM billing data from the California State Inpatient Databases from 2004 to 2011. Demographics, comorbidities, coccidioidomycosis coded during hospitalization and inpatient death were identified. We used Cox proportional hazard multivariate analyses to identify risk factors for coccidioidomycosis and death.

Results

20,602 SOT recipients were identified during the study period (median follow-up time = 1507 days). Eighty-seven patients (0.42%) with coccidioidomycosis were identified of whom 17 (20%) were coded with progressive/disseminated disease. Median time to diagnosis was 164 days (IQR 16–844) from transplantation. Fifty-one of 87 (58%) of these infections were diagnosed within the first year posttransplant and 29/87 (33.3%) were identified within the first month. Twenty-one of 87 (24%) of patients with coccidioidomycosis died compared with 1928/18587 (9.4%) of patients without coccidioidomycosis (P < 0.001). Coccidioidomycosis was independently associated with death (HR, 3.1; 95% CI, 2.0–4.4), after adjusting for age, type of transplantation, transplant failure/rejection, and other comorbidities (Table) (Figure).

Conclusion

Coccidioidomycosis resulting in hospitalization is rare in an endemic region in the current era of screening and prophylactic antifungal therapy. Preventing infection in solid organ transplant recipients is imperative because overall mortality remains high.

Disclosures

All authors: No reported disclosures.
Detection of (1,3)-β-d-Glucan in Cerebrospinal Fluid in Histoplasma Meningitis
Authors: Myint Thein , Bloch Karen , Raymond-Guillen Luke , Wheat L Joseph
Published: October 2017

Background

Central nervous system (CNS) histoplasmosis is a life-threatening condition, and represents a diagnostic and therapeutic challenge. Although CSF (1,3)-β-d-glucan (CSF BDG) is available as a biologic marker for diagnosis of fungal meningitis, there are limited data on its use for diagnosis of Histoplasma meningitis. We evaluated CSF BDG detection using the Fungitell assay in patients with CNS histoplasmosis and controls.

Methods

Patients were classified as cases if there was CNS inflammation (CSF WBC ≥ 5 mm3/ml) plus laboratory confirmation of H. capsulatumin CNS samples or from extra-CNS sites with no alternative etiology for CSF pleocytosis. Controls were patients with histoplasmosis but no evidence of CNS involvement, an alternative diagnosis, or other fungal meningitis.

Results

In total, 47 cases and 153 controls were evaluated (Table 1). Forty-nine percent of patients with CNS histoplasmosis and 43.8% of controls were immunocompromised. CSF BDG was positive in 25 (53.2%) cases using a level of ≥80 pg/ml, the median CSF BDG level was 140.5 pg/ml (range from <31 to 500 pg/ml). The detection of CSF BDG level ≥80 pg/ml was not associated with positive CSF Histoplasma antigen (P = 0.28) or positive CSF Histoplasma culture (P = 0.56). The sensitivity for detection of CSF BDG was 53.2% and the specificity was 87.3%, compared with 78.7%  (P = 0.009) and 96.4% (P = 0.003), respectively, for detection of antigen. CSF BDG was positive in 20 of 153 (13.1%) patients in the control group. Seven of 11 (63.6%) other CNS fungal meningitis cases (five Cryptococcus, two Aspergillus, two Blastomyces, one Candida, and one suspected fungal meningitis) had CSF BDG ≥80 pg/ml.

Conclusion

A positive CSF BDG supports the diagnosis of fungal meningitis but cannot distinguish among the different etiologies. The sensitivity and specificity of detection of CSF BDG was lower than that of antigen detection.

Disclosures

L. J. Wheat, MiraVista: President and owner, equity and Salary
Natural History of Non-CNS Disseminated Coccidioidomycosis
Authors: Bays Derek , Thompson George R , Reef Susan , Snyder Linda , Huppert Milton , Salkin David , Galgiani John
Published: October 2017

Background

The number of patients with coccidioidomycosis continues to increase yearly. Patients with CNS disease require lifelong antifungal therapy due to the high morbidity and mortality of this disease. However, the morbidity and mortality in non-CNS disseminated disease has not been well characterized.

Methods

We conducted a retrospective study of 373 VA-armed forces coccidioidomycosis patients diagnosed between 1955 and 1958 and followed to 1966. Groups were identified as non-disseminated disease, non-CNS disseminated disease with and without multisite dissemination, and disseminated disease to the CNS with and without multisite dissemination. Clinical variables including demographic information, duration and severity of symptoms, coccidioidal serologies, type of infection and complications, time to disseminated disease, and mortality were abstracted from patient charts.

Results

Mortality attributed to coccidioidomycosis in the non-disseminated group was 0.3% (1/297) compared with the non-CNS disseminated group of 8.5% (4/47, median survival 12 months, range 12–24 months, P = 0.0002). Mortality in the CNS disseminated group was 86% (19/22, median survival of 12 months, range 12–156 months, P < 0.0001 compared with non-CNS disseminated). The single site non-CNS disseminated group had a mortality of 4.1% (1/24, survival of 12months) compared with the multiple site non-CNS disseminated group of 13% (3/23, median survival of 18 months, range of 12–24 months, P = 0.57).

Conclusion

This retrospective cohort study demonstrates significant mortality differences between different forms of disseminated coccidioidomycosis. CNS dissemination exhibited the highest mortality rate; however, non-CNS dissemination also exhibited an unacceptably high mortality rate. There was no significant difference in mortality between single site non-CNS disseminated disease and multiple site non-CNS disseminated disease.

Disclosures

All authors: No reported disclosures.
Invasive Mold Infections (IMIs) of the Central Nervous System (CNS) in Patients with Hematologic Cancer (HC) (2000–2016): Uncommon but Deadly
Authors: Economides Minas Platon , Ballester Leomar , Kumar VInc.e , Jiang Ying , Tarrand Jeffrey J , Prieto Victor , Torres Harrys , Kontoyiannis Dimitrios P
Published: October 2017

Background

There is paucity of data regarding IMIs of the CNS in patients with HC or stem cell transplantation (SCT).

Methods

Review of the records of patients with HC and/or SCT recipients who were diagnosed with CNS IMIs at MD Anderson Cancer Center (1/1/2000–5/31/2016). IMIs were classified as proven or probable (EORTC/MSG criteria). We excluded patients with mixed CNS infections. Risk factors for survival at day 42 post diagnosis (dx) were assessed. A multivariate logistic regression analysis was performed to identify independent predictors of mortality.

Results

We identified 40 patients (16 proven; 40%). Most patients were white (29; 73%) and male (33; 83%). Median age was 58 years. The most common HC was acute leukemia (23; 58%). Seventeen patients (43%) were SCT recipients; 13 (76%) had GVHD. Most patients had active HC and neutropenia at dx (38; 95% and 21; 53%, respectively). Twenty-seven patients (68%) were in the ICU at dx. Aspergillus sp. (13; 33%) and Mucorales (8; 20%) accounted for >50% of cases. CNS IMIs were deemed to be secondary to direct extension or hematogenous spread in 9 (23%) and 31 (77%) patients, respectively. In the latter group, 28/31 (90%) had fungal pneumonia. Of the 27 and 9 patients who had Aspergillus galactomannan antigen tested from serum and CSF, respectively, 18 had positivity in serum (66%) and 3 in CSF (33%). Most patients (30; 75%) had exposure to mold-active agents within 30d of dx. Most patients (34; 85%) received lipid AMB and were treated with combination therapy (33; 83%). Most CNS lesions presented as ring-enhancing abscesses radiographically (26; 65%). Absence of giant cells and granulomas in the pathologic examination of the brain lesions were associated with increased 42 days mortality (0% vs. 70%, P = 0.01 and 0% vs. 60% in those who survived, P = 0.03, respectively). In multivariate analysis, co-infection at the time of dx was associated with increased mortality (OR: 16.5, 95% CI: 1.4–198.3, P = 0.03) while steroid tapering was associated with decreased mortality (OR: 0.06, 95% CI: 0.01–0.53, P = 0.01). There was a trend towards protective role of surgical drainage (ORn = 0.18, 95% CI = 0.03–1.14, P = 0.07).

Conclusion

CNS IMIs occur in ill patients with active HC who are often pre-exposed to antifungals. Immune response in pathology, steroid tapering and possibly surgical drainage are associated with improved outcome.

Disclosures

D. P. Kontoyiannis, Pfizer: Research Contractor, Research support and Speaker honorarium. Astellas: Research Contractor, Research support and Speaker honorarium. Merck: Honorarium, Speaker honorarium. Cidara: Honorarium, Speaker honorarium. Amplyx: Honorarium, Speaker honorarium. F2G: Honorarium, Speaker honorarium
Comparing Diagnostic-Driven Approaches to Empiric Therapy in the Treatment of Invasive Aspergillosis in Patients with Hematologic Malignancy
Authors: Dib Rita Wilson , Chaftari Anne-Marie , Ghaly Fady , Jiang Ying , Hachem Ray Y , Raad Issam
Published: October 2017

Background

Early antifungal therapy of invasive aspergillosis (IA) has been shown to be associated with improved outcome. Given the difficulty to establish the diagnosis of IA based on conventional methods, early initiation of empiric antifungal therapy has been used in patients with clinically suspected IA. Diagnostic-driven approach (DDA) relies on using novel diagnostic methods (e.g., early galactomannan testing). In this current study, we compared the outcomes of hematological malignancy (HM) patients with IA who were treated with Voriconazole using the DDA (DDA-Vori) vs. empiric therapy with a non-Voriconazole containing regimen (EMP-non-Vori) or empiric therapy with Voriconazole (EMP-Vori).

Methods

We retrospectively reviewed the medical records of 604 HM patients with documented, proven or probable IA (according to EORTC/MSG criteria) diagnosed between July, 1993 and February, 2016 at our center. We included 346 patients with underlying host factors, a suggestive CT findings of IA, and positive biopsy, fungal culture or galactomannan indicative of IA, and who received at least 7 days of DDA-Vori, EMP-Vori, or EMP-non-Vori. Outcome assessment included response to therapy (clinical and radiographic), all causing mortality and IA attributable mortality.

Results

The patients’ median age was 54 years and 59% were males. By multivariate analysis, factors that were predictive of a favorable response included: localized/sinus IA vs. disseminated/pulmonary IA (P < 0.0001), not receiving WBC transfusion (P < 0.01), and DDA-VORI vs. EMP-non-Vori (P < 0.0001). On the other hand, predictors of mortality within 6 weeks of initiation of IA therapy included disseminated/pulmonary infection vs. localized/sinus IA (P < 0.01), not having stem-cell transplant within 1 year prior of IA (P = 0.01) and EMP-non-Vori vs. DDA-Vori (P < 0.001).

Conclusion

DDA-Vori is associated with a better outcome (response and survival) when compared with EMP-non-Vori and equivalent outcome to EMP-Vori. The superior to equivalent outcome associated with the DDA approach could also reduce unnecessary costs and adverse events associated with widespread use of empiric therapy.

Disclosures

I. Raad, Merck: Grant Investigator, Research grant. Allergan: Grant Investigator, Research grant. Infective Technologies, LLC: Co-Inventor of the Nitroglycerin-Citrate-Ethanol catheter lock solution technology which is owned by the University of Texas MD Anderson Cancer Center (UTMDACC) and has been licensed by Novel Anti-Infective Technologies, LLC in which Dr. Raad is a s and Shareholder, Licensing agreement or royalty
In Vitro Interactions of Echinocandins with Triazoles Against Multidrug-Resistant Candida auris
Authors: Badalii Hamid
Published: October 2017

Background

Blood stream infections due to Candida auris are related to a high mortality rate and treatment failure attributed to resistance to fluconazole, voriconazole, amphotericin B, and caspofungin. Thus, the precise identification of agents and in vitro antifungal susceptibility testing is highly recommended. Novel therapeutic strategies, such as combination therapy, are essential for increasing the efficacy and reducing the toxicity of antifungal agents. Therefore, we investigated the in vitro combination of micafungin plus voriconazole against multidrug-resistant C. auris isolated from cases of candidemia.

Methods

The in vitro interactions between echinocandins and azoles were determined against ten multidrug-resistant Candida auris strains by using a microdilution checkerboard technique.

Results

Results revealed that MICs range for voriconazole and micafungin were 0.5–8 and 0.25–8 mg/l, respectively. The checkerboard analysis revealed that the combination of micafungin with voriconazole exhibited synergistic activity against all 10 multidrug-resistant C. auris isolates (FICI range: 0.15–0.5). Overall, no antagonistic effects were observed in this experiments.

Conclusion

In vitro studies have previously suggested that among azoles isavuconazole and posaconazole are more active drugs against C. auris. In addition, the majority of isolates reported are resistant to fluconazole. Remarkably, unsuccessful treatment of C. auris infections with fluconazole, voriconazole, amphotericin B, caspofungin, and anidulafungin has been already on record. Here in we demonstrates that interaction between micafungin with voriconazole exhibited synergistic activity against multidrug-resistant C. auris isolates. It seems that lower concentrations of drugs cause fewer side-effects and improve the treatment outcomes. However, in vivo studies with suitable animal models of C. auris infection is highly recommended.

Disclosures

All authors: No reported disclosures.
Clinical Outcomes of the Oral Suspension vs Delayed-Release Tablet Formulations of Posaconazole for Prophylaxis of Invasive Fungal Infections
Authors: Tallman Gregory B , Furuno Jon P , Noble Brie N , Bubalo Joseph S , Forrest Graeme N , Lewis James S , Bienvenida Ana F , Holmes Courtney A , Weber Bo R , McGregor Jessina C
Published: October 2017

Background

Posaconazole is effective prophylaxis for invasive fungal infections (IFIs). We compared incidence of breakthrough IFI (bIFI) and early posaconazole discontinuation between patients receiving delayed-release tablet and oral suspension formulations.

Methods

This was a retrospective cohort study of patients receiving posaconazole at Oregon Health & Science University Hospital between 1/1/2010 and 6/30/2016. Oral suspension was the preferred formulation until 2/2014; afterwards the tablet was preferred. We included all courses of primary prophylaxis for each patient during the study period. Data were extracted from an electronic health record repository and via chart review. Three independent reviewers identified bIFI using European Organization for Research and Treatment of Cancer criteria. We assessed rationale for early discontinuation of posaconazole for patients that were still indicated for antifungal prophylaxis based on National Comprehensive Cancer Network (NCCN) criteria.

Results

547 patients received 859 courses of posaconazole (53% oral suspension and 48% tablet). Prophylaxis was indicated according to NCCN criteria in 91% of courses. The primary indications for prophylaxis were acute myelogenous leukemia (68%), graft-vs-host disease (18%), and myelodysplastic syndrome (3%). There were no significant differences in demographics or indication between patients receiving the different formulations. The overall incidence rate of bIFI was 4.15/10,000 posaconazole-days (16 total bIFI events). Incidence of bIFI was not significantly different between patients receiving the different formulations (P = 0.92). Posaconazole was discontinued early in 147 (17%) courses; frequency of discontinuation was not significantly different between the tablet (20%) and oral suspension (15%) formulations (P = 0.10). The primary reasons for early discontinuation were elevated liver function tests or QT prolongation (25%), inability to take an oral formulation (17%), and drug cost (17%).

Conclusion

Among patients receiving posaconazole prophylaxis, incidence of bIFI was low and not significantly different between those receiving the tablet vs oral suspension formulations.

Disclosures

J. P. Furuno, Merck & Co.: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium. J. S. Lewis II, Merck & Co.: Consultant, Consulting fee. J. C. McGregor, Merck & Co.: Grant Investigator, Research grant
The Trends in the Distribution of Candida species Causing Candidemia at a Community Hospital in 2005 and 2014
Authors: Ishiekwene Celestine , Kasangana Maxine Seales , Ghitan Monica , Kuhn-Basti Margaret , Chapnick Edward , Lin Yu Shia
Published: October 2017

Background

Candida remains the most common cause of invasive fungal infections, with an attributable morality of 15–35%. Although five Candida species (C. albicans, C. tropicalis, C. parapsilosis, C. glabrata, and C. krusei) account for 92% of cases of candidemia, Candida albicans remains the most common cause of candidemia. However, recent studies report that the frequency of non albicans species are increasing globally and the distribution of Candida spp. varies significantly among different geographic regions and hospitals units.

Objective

We determine the distribution of Candida species causing candidemia at an adult level 1 Trauma Center in Brooklyn, New York and compared the trends of Candida species between 2005 and 2014. The results were compared with trends of US data collected in 2004 and 2012. Knowledge of the frequency of causative species would facilitate appropriate selection of empiric antifungal therapy.

Methods

We performed a retrospective chart review of patients with candidemia who were admitted in 2005 and 2014. We determined the frequency of Candida species and compared 2005 data with those in 2014.

Results

In total, 226 and 109 patients with candidemia were admitted to our hospital in 2005 and 2014, respectively. Although, C. albicans was the most common species (43% of candidemia in 2005), its frequency decreased to 33% in 2014. The frequencies of C. glabrata and C. parapsilosis increased in 2014 compared with those in 2005 (24% vs. 16% and 33% vs. 26%, respectively). Figure 1 compared the proportion of Candida species in Maimonides Medical Center to National data.

Conclusion

Our finding of an increase in non-albicans spp. causing candidemia is consistent with published reports. We saw more cases of C. parapsilosis compared with published data. Our results may be used to inform empiric antifungal therapy.

Disclosures

All authors: No reported disclosures.
Candidemia with Ocular Manifestrations: A Review of 26 Cases in a University Hospital in Japan
Authors: Takata Tohru , Yoshimura Yoshinobu , Obata Yumiko , Togawa Atsushi , Takamatsu Yasushi
Published: October 2017

Background

Ocular candidiasis is a major complication of candidemia; however, many remains unknown for the incidence, risk factors, and outcome of eye involvement.

Methods

We retrospectively reviewed the medical records and obtained information related to fungal infection and its management, and visual outcome at Fukuoka University Hospital from 2000 to 2016.

Results

Of 143 patients with candidemia for whom an ophthalmology consult was requested, 26 had findings consistent with the diagnosis of ocular candidiasis. Patients with ocular candidiasis were mostly infected with Candida albicans (n = 20), followed by C. glabrata (n = 4), and C. tropicalis (n = 2). In contrast, only one patient infected with C. parapsilosis had ocular involvement although the number of the patients with C. parapsilosis candidemia was second the most among candidemia. No difference was seen for the β-d-glucan in patients with or without ocular candidiasis (128.6 vs. 106.1, P = 0.654). All of the isolates other than C. glabrata were susceptible to fluconazole. In all of 23 patients with existing central venous cathers, CVCs were removed after the diagnosis of candidemia. Four-week mortality rate in patients with ocular candidiasis was 16.7% (three of 18 patients) which was not significantly different from that in patients without ocular manifestations. All treated patients were confirmed for clearance of candidemia, received systemic antifungals, and improved for visual outcome or remained stable, and no patients complicated visual loss without surgical treatment. Therapy with micafungin or caspofungin followed by fluconazole (12 patients) was successful in all patients.

Conclusion

Ocular involvement occurred in 18% of patients with candidemia, and treatment with echinocandins followed by fluconazole was successful in most cases with follow-up.

Disclosures

T. Takata, Taisho Toyama Pharma: Speaker’s Bureau, Speaker honorarium
Epidemiology and Outcomes of Hospitalizations with Invasive Aspergillosis in the United States, 2010–2013
Authors: Zilberberg Marya D , Nathanson Brian , Harrington Rachel , Spalding James , Shorr Andrew F
Published: October 2017

Background

Invasive aspergillosis (IA) complicates the care of up to 13% of patients with varying forms of immune compromise. The accompanying morbidity and mortality associated with IA remains high. We sought to describe the epidemiology and outcomes for all hospitalizations associated with IA in the United States.

Methods

We analyzed the National Inpatient Sample (NIS) from the Agency for Healthcare Research and Quality (AHRQ) for 2010–2013. We identified subjects with high-risk conditions for IA (stem cell or solid organ transplant, critical illness, major surgery, mild-to-moderate immune compromise, severe immune compromise, and other [human immunodeficiency virus, pneumonia, chronic obstructive pulmonary disease]). IA was identified via ICD-9-CM codes 117.3, 117.9, and 484.6. We compared characteristics and outcomes between those with (IA) and without IA (non-IA). We calculated the IA-associated excess mortality, length of stay (LOS) and costs using propensity-score (PS) matching.

Results

Of the 66,634,683 discharges who met the study inclusion criteria, 154,888 (0.2%) had a diagnosis of IA. Patients with IA were more likely to be male (50.9% IA vs. 46.7% non-IA, P < 0.001), and African American (15.3% IA vs. 12.5% non-IA, P < 0.001). The most common high-risk condition among those not classified as IA was major surgery (50.1%). In the IA group critical illness was noted most frequently (41.0%). The burden of both chronic (median [interquartile range, IQR] number of Elixhauser comorbidities 3 [1, 5] non-IA vs. 4 [3, 6] IA, P < 0.001) and acute (median [IQR] number of procedures during the hospitalization 2 [1, 3] non-IA vs. 3 [1, 6] IA, P < 0.001) illnesses was higher in the IA group than the non-IA. After PS-matching, mortality in IA (14.1%) was 37% higher than in non-IA (10.3%, P < 0.001), translating to an odds ratio = 1.43; 95% CI (1.36, 1.51). IA was associated with 6.0 (95% CI 5.7, 6.4) excess days in the hospital and excess $15,542 (95% CI $13,869, $17,215) in costs/hospitalization.

Conclusion

Although rare even among high-risk groups, IA is associated with high hospital mortality, excess duration of hospitalization, and costs. Given nearly 40,000 annual IA admissions in the United States, we estimate that the aggregate IA-attributable excess costs may reach $600 million annually.

Disclosures

M. D. Zilberberg, Astellas: Grant Investigator, Research support. B. Nathanson, EviMed, LLC: Consultant, Consulting fee. R. Harrington, Astellas Pharma Global Development, Inc.: Employee, Salary. J. Spalding, Astellas Pharma Global Development, Inc.: Employee, Salary. A. F. Shorr, Astellas: Consultant and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium. Cidara: Consultant, Consulting fee. Merck: Consultant, Scientific Advisor and Speaker’s Bureau, Research support and Speaker honorarium
Validation of an Empiric Candidemia Treatment Algorithm
Authors: Stack Conor M , Olafsdottir Lovisa B , Mahoney Monica V , McCoy Christopher , Gold Howard S , Lasalvia Mary , Yassa David S , Wright Sharon B , Snyder Graham M
Published: October 2017

Background

Judicious use of echinocandins may limit the development of resistance in Candida species. Guidelines endorse the use of echinocandins as initial therapy in candidemia, with fluconazole as an alternate choice in select patients. We compared the ability of providers to predict the need for echinocandin therapy in Candida bloodstream infections to that of a proposed institutional treatment algorithm designed to optimize empiric antifungal use.

Methods

In this retrospective study (10/2015–10/2016), patients were included with Candida isolated in ≥1 blood culture, without candidemia in the prior 14 days. Empiric treatment (the first antifungal prescribed for ≥24 hours after index blood culture draw) was considered “overly broad” if an echinocandin was administered to a fluconazole-susceptible isolate and “inappropriate” if fluconazole was administered to a fluconazole-non-susceptible isolate. An institutional algorithm was created recommending empiric echinocandin use based on the presence of ≥1 risk factors (Table 1). Provider choice and the recommended agent according to the algorithm were compared with the final fluconazole susceptibility of the organism.

Results

Among 65 episodes of candidemia, the majority of isolates were C. glabrata (Figure 1). Ninety-one percent of patients received non-azole therapy, primarily micafungin. Fluconazole was recommended by the algorithm in 25% of cases but initially prescribed in only 9% (Figure 2). Providers prescribed both overly broad and inappropriate treatment at a higher rate than algorithm recommendations (Figure 3).

Conclusion

An algorithm using risk factors for fluconazole-non-susceptible Candida was able to predict appropriate empiric antifungal therapy better than provider decision making in cases of candidemia. Implementation of this algorithm into local treatment guidelines may improve empiric antifungal prescribing.

Disclosures

All authors: No reported disclosures.
Low Rate of Microbiologic Relapse in Two-Stage Exchange for Hip Prosthetic Joint Infections
Authors: Henry Michael , Russell Celeste , Nocon Allina , Westrich Geoffrey , Brause Barry , Miller Andy
Published: October 2017

Background

Prosthetic joint infection (PJI) is a grave complication of total hip arthroplasty (THA). Historically, two-stage arthroplasty exchange has been considered to be the definitive approach to eradicating infection and preserving joint function. However, patients are increasingly presenting with higher rates of comorbidities traditionally associated with poorer orthopedic surgical outcome, including advanced age, obesity and diabetes. We investigated whether two-stage exchange remains effective for THR PJI at an orthopedic specialty hospital, and what were the microbiologic etiologies in repeat infections.

Methods

A retrospective cohort of THA PJI treated with two-stage exchange was identified by query of hospital coding records from 2009 to 2014. The primary endpoint was defined as 2-year implant retention without further surgery. Failure was defined as a recurrence within in 2 years. Microbiologic failure was defined as a recurrence of the previously treated organism. Descriptive statistics were completed using the Fisher’s exact test for categorical variables and the Mann–Whitney U-test for continuous variables.

Results

One hundred and forty-four patients meeting Musculoskeletal Infection Society International Consensus criteria for THA PJI were identified. The average age was 65 years and 60% were female. One hundred and twenty-seven (88.2%) were cured at 2 years. Pathogens included Staphylococcus aureus (MSSA, 23%; MRSA, 13%), coagulase-negative staphylococci (17%), and streptococci (17%). In univariate analysis, no links were noted between primary outcome and patient age, comorbidities (including diabetes and tobacco), BMI, microbiology, or symptom duration. Of the 17 patients who did not meet criteria for success, 11 (65%) were diagnosed with new, microbiologically distinct infection. The remaining six met our criteria for microbiologic failure; four of the six patients had S. aureus infection (three MSSA).

Conclusion

We present 2-year outcomes on a large cohort of THA PJI treated with two-stage exchange arthroplasty. Nearly, two-thirds of the patients who failed were found to have a new infection at the time of relapse. Only 4% of the patients in our cohort failed to achieve cure of the primary infection. Two-stage exchange continues to be an effective approach to PJI treatment with a low rate of microbiologic failure.

Disclosures

All authors: No reported disclosures.
Clinical Characteristics and Outcomes of Healthcare-Associated Hematogenous Vertebral Osteomyelitis
Authors: Park Ki-Ho , Lee Yu-Mi , Moon Song Mi , Park Seong Yeon , Cho Oh-Hyun , Lee Mi Suk , Bae In-Gyu
Published: October 2017

Background

The incidence of hematogenous vertebral osteomyelitis (HVO) has increased over recent years, likely due to longer life expectancies, higher prevalence of chronic disease, and more effective diagnostic techniques. Recently, healthcare-associated infections, such as catheter-related and procedure-related bloodstream infections, also increase the risk of HVO. The aim of our study was to evaluate the clinical characteristics and outcomes of healthcare-associated HVO (HCA-HVO).

Methods

We conducted a retrospective chart review of adult patients with microbiologically diagnosed HVO from five tertiary-care hospitals over 8-year period. HCA-HVO was defined as onset of symptoms after 1 month of hospitalization or within 6 months after hospital discharge, or ambulatory manipulations in the 6 months before the diagnosis [Pigrau et al. Medicine (Baltimore) 2015; 94:e365]. We compared the clinical characteristics and outcomes of HCA-HVO with community-acquired HVO (CA-HVO) cases.

Results

In total, 358 patients with microbiologically diagnosed HVO were included in final analysis. Of these 358 cases, 256 (63.1%) were CA-HVO and 132 (36.9%) were HCA-HVO according to the predefined criteria. The main causative pathogens identified were methicillin-susceptible Staphylococcus aureus (32%), followed by methicillin-resistant S. aureus (MRSA) (26%), aerobic gram-negative bacteria (24%), and Streptococcus species (11%). Compared with CA-HVO cases, patients with HCA-HVO had more neoplasm (13.6% vs. 5.8%, P = 0.01) and end-stage renal disease (8.3% vs. 2.2%, P = 0.007). MRSA was more frequent pathogens in HCA-HVO cases than in CA-HVO (37.1% vs. 17.7%, P = 0.01). Patients with HCA-HVO were more likely to be have the higher rates of persistent bacteremia for ≥7 days (24.2% vs. 15.5%, P = 0.04), 1-year mortality (18.2% vs. 11.5%, P = 0.08) and 1-year relapse (12.1% vs. 6.2%, P = 0.051).

Conclusion

In this study, more than one-third of HVO is health care associated. Patients with HCA-HVO were more likely to have underlying illness, and their causative pathogens were more frequently MRSA. Outcomes of HCA-HVO were poorer, which require prevention measures and early diagnosis.

Disclosures

All authors: No reported disclosures.
Utility of Diagnostic Bone Biopsies in the Management of Osteomyelitis Through Retrospective Analysis: How Golden Is This Gold Standard?
Authors: Hirschfeld Cole , Kapadia Shashi , Bryan Joanna , Jannat-Khah Deanna , May Benjamin , Friedman Tamir , Vielemeyer Ole , Esquivel Ernie
Published: October 2017

Background

Bone biopsy is considered the gold standard for diagnosis and treatment of osteomyelitis (OM), but few studies have investigated the extent to which it influences antimicrobial therapy in non-vertebral bones. The purpose of this study was to evaluate clinician-initiated changes to empiric antimicrobial therapy after obtaining bone biopsy results. A secondary aim was to identify predictors of a positive bone culture.

Methods

We retrospectively reviewed all cases of non-vertebral OM in patients who underwent image-guided bone biopsies between 2009 and 2016. Data on pathologic and microbiologic yield were collected and logistic regression was used to determine potential factors affecting the microbiologic yield. Post-biopsy empiric antibiotics and final antibiotics were compared with determine if there was a change in antibiotic treatment after biopsy results were reported.

Results

We evaluated 203 bone biopsies in 185 patients. Samples from 115 (57%) cases were sent to pathology, of which 33 (29%) confirmed OM. All samples were sent to microbiology and 57 (28%) yielded a positive result. Diabetes (OR=2.39, P = 0.021) and white blood cell count (OR=1.13, P = 0.006) were significantly associated with positive bone cultures in multivariate analyses. There was no association between positive cultures and number of samples cultured, needle size, prior antibiotic use, or antibiotic-free days. Post-biopsy empiric antibiotics were given in 138 (68%) cases. Therapy was narrowed to target specific organisms in seven cases and changed due to inadequate empiric treatment in three cases. Targeted therapy was initiated in 4/65 cases, in which empiric antibiotics had been initially withheld. While final antibiotics were withheld in 38/146 with negative bone cultures, empiric antibiotics were discontinued in only eight cases.

Conclusion

In patients with non-vertebral OM, bone biopsy cultures rarely yielded results that necessitated changes in antibiotic management. Identified bone organisms were treated by empiric therapy in most patients. While bone biopsy remains the gold standard diagnostic test for OM, further work is needed to identify patients whose management may be impacted by this procedure.

Disclosures

All authors: No reported disclosures.
Comparative Analysis of Initial Antibiotic Dosing Among Healthy Weight, Overweight, and Obese Children with Osteomyelitis
Authors: Waddell Joel , Mcculloh Russell , Goldman Jennifer , Lee Brian , Teachout Warren
Published: October 2017

Background

Acute hematogenous osteomyelitis (AHO) is a common infection of childhood. Inadequately treated AHO can lead to significant morbidity. Small studies have demonstrated alterations in the pharmacokinetics of antibiotics among obese children. Consequently, there is no consensus regarding appropriate dosing of antibiotics among overweight and obese children with AHO.

Methods

This is a single center, retrospective, cohort study of children 2–17 years of age with a discharge diagnosis of acute osteomyelitis admitted between 1/1/2012 and 12/31/2015. Complicated osteomyelitis cases were excluded. Variability of the initial mg/kg antibiotic dose was determined and compared between healthy weight, overweight, and obese children.

Results

142 children were included in the cohort. In total, 83 (58%) were classified as healthy weight, 25 (18%) overweight, and 34 (24%) obese. No difference was found in the variability of mg/kg dosing of vancomycin or clindamycin across the three weight groups. Cefazolin dosing in healthy weight children (median 33.3mg/kg [IQR 32.9–36.7mg/kg]) was significantly higher as compared with obese children (24.4mg/kg  [20.0–33.3mg/kg]) (P = 0.041). Cephalexin dosing in healthy weight children (33.0mg/kg  [30.6–34.5mg/kg]) was also significantly higher than in obese children (23.0mg/kg [20.0–29.9mg/kg])(P = 0.013).

Conclusion

There was significant variability and lower overall dosing of first-generation cephalosporins among obese children compared with healthy weight children. Given the increasing incidence of invasive methicillin-susceptible Staphylococcus aureus infections, this study highlights the need for practitioners to optimize first-generation cephalosporin dosing in obese children suffering from AHO. These data also call for future studies to determine the clinical outcomes in obese children with AHO in relation to dosing adequacy.

Disclosures

All authors: No reported disclosures.
Factors Associated with Success in Revision Surgery for Infected Hip and Knee Arthroplasties
Authors: Kandel Christopher , Backstein David , Sajja Abhilash , McGeer Allison
Published: October 2017

Background

Patients with prosthetic joint infections (PJIs) often fail treatment. We aimed to describe the characteristics and outcomes of PJIs managed at a tertiary institution in Canada.

Methods

We assembled a cohort of patients undergoing surgical revision for hip or knee PJIs from January 1, 2010 until December 31, 2014 at our referral hospital by searching procedure descriptions from operative listings. Patient characteristics were abstracted by chart review. Treatment failure (TF) was defined by PJI recurrence requiring surgery, receipt of suppressive antimicrobials, amputation, excision or death.

Results

243 individuals with a PJI undergoing a revision surgery were included. Median age was 69 years, 111 (46%) were males, 118 (49%) involved hips, 125 (51%) were knees, incision and drainage was performed in 53 (22%), a two-stage procedure was undertaken in 168 (69%), and a one-stage procedure in 18 (7%). Most PJIs were monomicrobial (50%); with coagulase negative staphylococci (35%) and Staphylococcus aureus (18%) the most common. TF occurred in 85/171 (47%): 53 (62%) required revision surgery, 23 (27%) chronic suppressive antimicrobials, 5 (6%) amputation, and 4 (5%) died (Table 1). On univariate analysis incision and drainage was associated with failure (OR 2.8, 95% CI 1.3–5.8, P = 0.002) while a two-stage procedure (OR 0.4, 95% CI 0.2–0.8, P = 0.009) and chronic symptoms (OR 0.4, 95% CI 0.2–0.8, P = 0.008) were protective. No risk factors for TF were identified on multivariable analysis.

Conclusion

PJIs are challenging to eradicate. New treatment paradigms are needed.

Disclosures

A. McGeer, Hoffman La Roche: Investigator, Research grant. GSK: Investigator, Research grant. Sanofi pasteur: Investigator, Research grant
Variability in Management of Acute Osteoarticular Infections at a Children’s Hospital and Favorable Outcomes with Increasing Early Transition to Oral Therapy
Authors: Biary Nora , Wrotniak Brian , Islam Shamim
Published: October 2017

Background

To date, there is no established guideline for the treatment of acute pediatric osteoarticular infections (OAI), and considerable variability in management exists amongst providers and across institutions. This study analyzed the recent management and clinical outcomes of OAI at a children’s hospital.

Methods

Patients admitted with acute osteomyelitis and septic arthritis [OAI] aged 2 months to 18 years at the Women & Children’s Hospital of Buffalo, between 1/1/2013 and 12/31/2016, were identified via billing databases. Patients with select comorbidities or >2 positive blood cultures were excluded. Patient demographics, antibiotics used, culture results, time from intravenous (IV) to oral (PO) therapy, length of hospitalization (LOH), PICC (peripherally inserted central catheter) line use, and emergency room (ER) visits and readmissions within 6 months of discharge, were collected and analyzed. The study period was divided into 2-year groups, before and after 1/1/15, a juncture when a new provider began to promote early transition to oral therapy (through ID consults and informal discussion).

Results

Thirty-one patients were admitted during Time#1 (2013–14) and 43 during Time#2 (2015–16). Time to PO therapy was widely distributed (Figure 1) throughout the 4 years, with 65% of patients in Time#2 transitioned ≤7 days, vs. 37% in Time#1 (P = 0.02). Specifically for osteomyelitis, mean time to PO decreased from Time#1 to #2 from 11.5 to 8.3 days. Sixty-one percent of patients in Time#1 vs 25% in Time#2 (P < 0.01) received a PICC line, and PICC use was associated with 1.5 day greater LOH (P = 0.02). There was no relationship between time to PO and repeat ER visit/readmission. Nearly 30% of patients in Time#1 had PICC or OAI-related ER visits/readmissions after discharge, while 0% did for Time#2 (P < 0.01).

Conclusion

Length of initial IV therapy and PICC line use continues to vary significantly for pediatric acute OAI. In our children’s hospital, a shift towards earlier transition to PO therapy has been adopted steadily – and prior to national and planned local guidelines – with a general decrease in LOH, duration of IV therapy, PICC line issues following discharge, and overall improved outcomes. Pediatric OAI management represents an ideal focus for institutional quality and antibiotic stewardship efforts.

Disclosures

S. Islam, Qiagen: Speaker’s Bureau, Speaker honorarium and travel support
Clinical Comparison between Native Vertebral Osteomyelitis with Abscess vs Without Abscess in Clinical Features and Outcomes
Authors: Matsuo Takahiro , Mori Nobuyoshi , Hoshino Eri , Sakurai Aki , Furukawa Keiichi
Published: October 2017

Background

It is well documented that native vertebral osteomyelitis (NVO) is accompanied by abscess formation (epidural, paravertebral, and psoas muscle) that is complicated by neurological deficit. There are few studies comparing between NVO with abscess and NVO without abscess in clinical features and outcomes.

Methods

We conducted a retrospective cohort study at St. Luke’s Intl. Hosp. in Tokyo, Japan (acute care hospital, 520 beds) from 2004 to 2015. Diagnosis of acute NVO was made by clinical signs and symptoms, and MRI. Clinical features and outcomes of NVO patients with abscess were compared with ones without abscess. Fisher’s exact test, Mann–Whitney U-test, and Kaplan–Meier curve with log-rank test were used in univariate analysis and the association to length of stay was analyzed by Cox-regression model controlling confounding.

Results

Among 122 patients with NVO, 83 patients (68%) had abscess (group A) and 39 patients (32%) had no abscess (group B). Median age: (group A: 69 vs. group B: 66, P = 0.641). Median length of stay (LOS) in hosp: (A: 48 vs. B: 43 days,  P = 0.007) (Table 1). Group A had higher rate of neurological symptoms (16.9 vs. 2.6%, P = 0.035), blood cultures positivity (62.7 vs. 35.9%, P = 0.007), infective endocarditis (IE) (15.7 vs. 2.6%, P = 0.036), and longer duration of therapy (75 vs. 56 days, P = 0.025) than group B in univariate analysis. Also, group A had trend toward higher rate of methicillin-susceptible S. aureus (28.9 vs. 5.1%, P = 0.056). Kaplan–Meier analysis revealed LOS was significantly longer in group A (P = 0.013) (Figure 1). The result of Cox’s proportional hazards model suggested abscess was associated with longer LOS (Table 2). Blood culture positivity was independently associated with longer LOS. No statistically significant associations were observed between abscess and 90-day mortality (5.1 vs. 3.6%, P = 0.654), or neurological sequelae (6 vs. 0%, P = 0.227).

Conclusion

LOS of NVO patients with abscess was longer than those without abscess. In particular, LOS was significantly longer in patients with positive blood culture than those with negative results.

Disclosures

All authors: No reported disclosures.
The Influence of Obesity on the Infection Risk of Prosthetic Joint Infection in the Geriatric Orthopedic Population
Authors: Nocon Allina , Henry Michael , Russell Celeste , Westrich Geoffrey , Brause Barry , Miller Andy
Published: October 2017

Background

Prosthetic joint infection (PJI) is a dreaded complication of arthroplasty. PJI are more common in the elderly and are associated with a substantial increase in 5-year mortality risk. PJI risk may correlate with increasing body mass index (BMI). However, the effect of BMI on PJI risk in the elderly has not been evaluated, to our knowledge. We sought to evaluate this relationship in a cohort of geriatric arthroplasty patients at an orthopedic specialty hospital.

Methods

A retrospective cohort of hip and knee arthroplasty patients (age >75) from 2009–2014 was identified through administrative hospital data using ICD-9 codes. Patients with a BMI <14 or >60 kg/m2, height <142 or >200 cm, and weight <36 or >226 kg were excluded. The presence of infection was confirmed via chart review; all PJIs met MSIS criteria. Obesity was defined as having a BMI >30. Univariate analyses were done using χ 2 tests and adjusted models were assessed using logistic regression.

Results

13,755 geriatric arthroplasty patients (6,408 total hip arthroplasties [THA] and 7,347 total hip arthroplasties [TKA]) were assessed. Mean age and BMI were 82 (±5.4) and 28.1 (±5.3), respectively. In an unadjusted model, obesity was associated with infection in THA (P = 0.02), but not TKA (P = 0.31). This association remained after adjusting for age, sex, and diabetes. Obesity was associated with an increased risk of infection in THA [OR=1.89 (95% CI 1.12–3.21); P = 0.02]. However, as with the unadjusted model, this relationship was not found in TKA (P = 0.50).

Conclusion

Obesity increases THR PJI risk in the elderly. However, no such association was found for TKA. Future studies are needed to quantify the compounded risk of obesity in the geriatric arthroplasty patient.

Disclosures

All authors: No reported disclosures.
Epidemiology and Clinical Features of Septic Arthritis in Children
Authors: Andrews Shannon , Sharon Bazak
Published: October 2017

Background

Children with acute arthritis are commonly admitted to the hospital in part due to concern for septic arthritis (SA) and its complications. Many noninfectious, non-urgent conditions are more common than SA and present similarly. The epidemiology and clinical presentation of SA influences management of patients with acute arthritis.

Methods

Utilizing the electronic medical record, we reviewed the charts of children (1–18 years old) with joint complaints who presented to the hospitals and clinics of one large academic health organization in the Upper Midwest from January 2011 to July 2016. Query criteria included the presenting symptom (“arthritis”, “joint swelling”, or “joint pain”), diagnosis (“arthritis”, “septic arthritis”, or “Lyme arthritis”), and/or positive synovial fluid culture. SA was confirmed when synovial bacterial culture or PCR were positive. SA was suspected in cases with a positive blood culture or when the patient was treated empirically with 4 weeks of antibiotic with no alternate diagnosis. All other children were excluded from the study cohort.

Results

Of the 705 children whose charts were reviewed, 609 were excluded with a noninfectious diagnosis and 72 with Lyme arthritis (Figure 1). We identified 24 children with SA. Six children diagnosed with SA were immunosuppressed. Among healthy children with SA, seven were diagnosed with contiguous musculoskeletal (MSK) infection and 11 were diagnosed with acute, isolated, monoarticular arthritis. SA was more common in boys. The most common pathogen isolated was S aureus (13). The knee (7) and hip (6) accounted for the majority of joints involved in healthy children.

Conclusion

SA is a rare cause of acute arthritis in children. In healthy children, SA may present with contiguous MSK infection or in an isolated joint. SA is more likely in boys and in the knee or hip joint. S. aureus is the most common cause of SA. Clear understanding of the epidemiology and clinical history of SA should shape clinical decision making in children with acute arthritis.

Disclosures

All authors: No reported disclosures.