Osseous Infections Caused by Aspergillus Species

Background: Osteomyelitis caused by Aspergillus spp. is a severe, but rare, clinical entity. However, clear guidelines regarding the most effective medical management have not yet been established. The present study is a literature review of all such cases, in an effort to elucidate epidemiology, as well as the therapeutic management and the infection’s outcome. Methods: A thorough review of all reports of osteomyelitis of the appendicular and the axial skeleton, without the skull and the spine, caused by Aspergillus spp. was undertaken. Data about demographics, imaging techniques facilitating diagnosis, causative Aspergillus, method of mold isolation, antifungal treatment (AFT), surgical treatment, as well as the infection’s outcome were recorded and evaluated. Results: A total of 63 cases of osseous infection due to Aspergillus spp. were identified. The studied population’s mean age was 37.9 years. The most commonly affected site was the rib cage (36.8%). Most hosts suffered immunosuppressive conditions (76.2%). Regarding imaging methods indicating diagnosis, computer tomography (CT) was performed in most cases (42.9%), followed by plain X-ray (41.3%) and magnetic resonance imaging (MRI) (34.9%). The most frequent isolated mold was Aspergillus fumigatus (49.2%). Cultures and/or histopathology were used for definite diagnosis in all cases, while galactomannan antigen test was additionally used in seven cases (11.1%), polymerase chain reaction (PCR) in four cases (6.3%), and beta-d-glucan testing in three cases (4.8%). Regarding AFT, the preferred antifungal was voriconazole (61.9%). Most patients underwent surgical debridement (63.5%). The outcome was successful in 77.5%. Discussion: Osteomyelitis due to Aspergillus spp. represents a severe infection. The available data suggest that prolonged AFT in combination with surgical debridement is the preferred management of this infection, while identification of the responsible mold is of paramount importance.

Incidence and risk factors for inappropriate use of non-culture based fungal assays: Implication for diagnostic stewardship

Background Non-culture-based fungal assays (NCBFAs) have been used increasingly to help diagnose invasive fungal diseases. However, little is known about inappropriate use of NCBFAs. We aimed to investigate inappropriate use of NCBFAs in a tertiary academic hospital. Methods This retrospective cohort study included patients who underwent testing with beta-D glucan (BDG) between Jan and Mar 2018, or galactomannan antigen (GMA) or cryptococcal antigen (CRAG) between Jan and Jun 2018. Testing was deemed appropriate if the clinical presentation was compatible with a fungal infection and there was a predisposing host factor at the time of ordering. We compared patients with appropriate and inappropriate use of NCBFAs using the multivariate logistic regression analysis. Results 470 patients (BDG, 394; GMA, 138; CRAG, 164) met inclusion criteria and were evaluated. About 80% of NCBFAs were deemed inappropriate. Ordering by transplant medicine physicians, repetitions of the test, the absence of predisposing factors for fungal infections, and the absence of recommendations from infectious diseases consultants were associated with an increased risk of inappropriate NCBFA use. Conclusions We found a large proportion of NCBFAs were deemed inappropriate. There is an opportunity for diagnostic stewardship to reduce avoidable fungal testing among patients at low risk for fungal infection.

721. Diagnosis of Histoplasmosis Using the MVista Histoplasma Galactomannan Antigen Qualitative Lateral Flow-Based Immunoassay; A Multicenter Study

Background Accurate and timely methods for the diagnosis of histoplasmosis in endemic resource-limited settings are largely lacking. Histoplasma galactomannan antigen detection by enzyme immunoassay (EIA) is the most widely used method for the diagnosis of acute pulmonary and disseminated histoplasmosis in the United States (USA). EIA methods have constraints in resource-limited settings including cost, turnaround time, and the need for large reference laboratories, leading to missed or delayed diagnoses and poor outcomes. Lateral flow assays (LFA) are practical methods that can be used in this setting for Histoplasma antigen detection. Methods Frozen urine specimens were submitted to MiraVista (MVista) for Histoplasma antigen EIA testing from three academic medical centers in highly endemic areas of the USA. They were also blinded and tested for the MVista Histoplasma LFA by skilled MVista technologists. Medical records were reviewed for clinical information. Patients were classified as controls or cases of histoplasmosis. Cases were divided into proven or probable, pulmonary, or disseminated, immune competent or immune suppressed, and mild, moderate, or severe. Results 352 subjects were enrolled, including 66 cases of histoplasmosis (44 proven, 22 probable) and 286 controls. Most of the cases were immunocompromised (68%). 76% had disseminated histoplasmosis. 6% were mild, 66% moderate, and 28% severe. A high degree of concordance was found between LFA and EIA results (kappa 0.837, OR 372.7, LR 204, p< 0.001). Overall, the sensitivity and specificity of the LFA were 78.8% and 99.3% respectively (kappa 0.84, p< 0.001). The sensitivity was higher in proven cases (93.2%), in patient with disseminated (94.7%), moderate (80%) and severe disease (94%), and those with galactomannan levels ≥ 2 ng/mL (97.7%). Specificity was 99.3% in proven cases, 99.3% in patient with moderate and severe disease, and 96.4% in those with galactomannan levels ≥ 2 ng/mL. Table 1. Statistical characteristics of the LFA test for histoplasmosis in different categories. PPV: Positive Predictive Value. NPV: Negative Predictive Value. EIA: Enzyme Immunoassay. The LFA test for histoplasmosis is more accurate in patients with high burden of infection. Conclusion The MVista Histoplasma galactomannan LFA may meet the need for accurate rapid diagnosis of histoplasmosis in resource-limited settings, especially in patients with relatively high disease burden, potentially reducing morbidity and mortality. Disclosures Melissa Minderman, Bachelor's Degree, Molecular Biology, MiraVista Diagnostics (Employee) Suphansa Gunn, Bachelor's Degree, psychology, MiraVista Diagnostics (Employee) Lawrence J. Wheat, MD, MiraVista Diagnostics (Employee)

Performance of the sōna Aspergillus Galactomannan Lateral Flow Assay in a Cancer Patient Population

Background: The diagnosis of invasive aspergillosis can be challenging in cancer patients. Herein, the analytical and clinical performance of the sōna Aspergillus Galactomannan Lateral Flow Assay (GM LFA) was evaluated and its performance compared to that of the Bio-Rad Galactomannan EIA (GM EIA). Materials/methods: Serum and Bronchoalveolar lavage (BAL) fluids received for GM EIA testing between March-August 2019 were included. Positive and negative percent agreement (PPA and NPA) were calculated for the GM LFA compared to the GM EIA. Discrepant analysis was performed by review of the patient‘s medical records assessing for any evidence of a fungal infection. Results: 533 samples (85 BALs and 448 serums) from 379 patients were included in the study. The overall PPA and NPA were 100% (95% CI: 72.2-100%) and 97.5% (95% CI: 95.5-98.4%) respectively. 14/24 samples were positive by LFA only. The sensitivity of the GM LFA for proven and probable IA was 100% (95% CI: 51.0-100%) and 87.5% (95% CI: 55.9-99.4%) with a specificity of 95.5% (95% CI: 92.3-97.2%) and 96.2% (95% CI: 93.4-97.7%) respectively. The sensitivity of the GM EIA for proven and probable IA was 25% (95% CI: 1.28-69.9%) and 62.5% (95% CI: 30.6-86.3%) with a specificity of 98.2% (95% CI: 96.2-99.1%) and 99.2% (95% CI: 97.7-99.8%) respectively. Conclusions: The Aspergillus GM LFA outperformed the Aspergillus GM EIA for the detection of the galactomannan antigen in our patient population. The simplicity and rapid time to results makes the Aspergillus GM LFA easy to implement in a wide range of laboratory settings.

90. Incidence and Risk Factors for Inappropriate Use of Non-culture Based Fungal Assays: Implication for Diagnostic Stewardship

Background Culture-based diagnostic tests are the gold standard for diagnosing invasive fungal diseases (IFDs). Because these tests have low sensitivity, non-culture-based fungal assays (NCBFAs) have been used increasingly to help diagnose IFDs. However, little is known about inappropriate use of NCBFAs. We aimed to investigate inappropriate use of NCBFAs in a tertiary academic hospital in Tokyo, Japan. Methods This retrospective cohort study included all patients who underwent testing with beta-D glucan (BDG) between January and March 2018, or galactomannan antigen (GMA) or cryptococcal antigen (CRAG) between January and June 2018. Patients who had received hematopoietic stem cell or solid organ transplantations were excluded. Appropriateness was assessed according to the previously published study. We compared patients with appropriate and inappropriate use of NCBFAs. Risk factors for inappropriate use were evaluated using multivariate logistic regression analysis. Results Of 1,140 patients (BDG, 1,009; GMA 273; CRAG, 310) who underwent tests, 470 patients (BDG, 394; GMA, 138; CRAG, 164) were included in this study. Four hundred thirty-eight patients (93.2%) were aged 18 or older. About 80% of NCBFAs (BDG, 334 patients [74.8%]; GMA, 117 patients [74.8%]; CRAG, 146 patients [89.0%]) were deemed inappropriate. The factors associated with inappropriate NCBFAs use included specialties of ordering physicians, risk factors for fungal infections, and recommendation from infectious disease physicians (Table). Sixty-four patients (13.6%) underwent three inappropriate NCBFAs simultaneously. Furthermore, during the study period, 408 patients (35.8%) with inappropriate NCBFAs underwent the same assays repeatedly during the study period; 643 times for BDG, 163 times for GMA, and 192 times for CRAG. The Factors Associated with Inappropriate Use of Non-Culture Based Fungal Assays Conclusion We found a large proportion of NCBFAs were deemed inappropriate and it was mostly driven by ordering physicians who generally care for transplant patients. Because inappropriate use of NCBFAs could lead to additional inappropriate tests and treatment with substantial costs to patients and health systems, diagnostic stewardship targeting NCBFAs is urgently needed. Disclosures All Authors: No reported disclosures