Complement Fixation Titers Research Articles

Serologic Rebound after Stopping Azoles for Primary Pulmonary Coccidioidomycosis: A Case-Controlled Observational Study.

We sought to characterize the outcomes of patients with primary pulmonary coccidioidomycosis whose post-treatment complement fixation (CF) titer increased by more than 2 dilutions (serologic rebound) after discontinuation of antifungal treatment. We conducted a retrospective chart review of patients with primary pulmonary coccidioidomycosis and identified immunocompetent, non-pregnant adults who received antifungal treatment and then experienced a serologic rebound after treatment discontinuation. We compared these to matched controls similarly treated who did not have serologic rebound. Fifty-eight patients experienced serologic rebound. Thirty (52%) of these were associated with symptoms. Nine were associated with radiographic progression. The median time to serologic rebound was 3.5 months. Antifungal treatment was reinitiated in 37 (63.7%) patients. Four of the 58 (6.9%) with rebounded serology subsequently developed extra-thoracic dissemination. Compared with matched controls, patients with rebounded serology were more likely to have post-treatment symptoms, reinitiation of antifungal therapy, and a longer duration of clinical follow-up. However, they were not more likely to experience extra-thoracic dissemination. Serological rebound, manifested in at least 2-dilution rise of CF titer following antifungal treatment of primary pulmonary coccidioidomycosis, was uncommon, but resulted in longer clinical follow-up. Continued monitoring of such patients is important to identify the patients who develop subsequent symptoms, as well as extra-thoracic dissemination.

Development of a rapid lateral flow assay for detection of anti-coccidioidal antibodies.

Coccidioides spp. are dimorphic fungi that are capable of infecting human and non-human mammals and can cause diverse manifestations of coccidioidomycosis or Valley fever (VF). In combination with clinical symptoms and radiographic findings, antibody-based diagnostic tests are often used to diagnose and monitor patients with VF. Chitinase 1 (CTS1) has previously been identified as the seroreactive antigen used in these diagnostic assays to detect anticoccidial IgG. Here, an indirect enzyme-linked immunosorbent assay to detect IgG to CTS1 demonstrated 165 of 178 (92.7%) patients with a positive result by immunodiffusion (ID) and/or complement fixation (CF) had antibodies to the single antigen CTS1. We then developed a rapid antibody lateral flow assay (LFA) to detect anti-CTS1 antibodies. Out of 143 samples tested, the LFA showed 92.9% positive percent agreement [95% confidence interval (CI), 84.3%-96.9%] and 97.7% negative percent agreement (95% CI, 87.9%-99.6%) with ID and CF assays. Serum or plasma from canines, macaques, and dolphins was also tested by the CTS1 LFA. Test line densities of the CTS1 LFA correlated in a linear manner with the reported CF and ID titers for human and non-human samples, respectively. This 10-min point-of-care test for the rapid detection of anti-coccidioidal antibodies could help to inform healthcare providers in real-time, potentially improving the efficiency of healthcare delivery.

Pediatric Laryngeal Coccidioidomycosis: A Case Series in an Endemic Region.

Laryngeal coccidioidomycosis is a rare but life-threatening manifestation of coccidioidomycosis. Data in children are sparse and limited to case reports. We conducted this study to review the characteristics of laryngeal coccidioidomycosis in children. We performed a retrospective review of patients ≤21 years of age with laryngeal coccidioidomycosis who were treated from January 2010 to December 2017. We collected demographic data, clinical and laboratory studies and patient outcomes. Five cases of pediatric laryngeal coccidioidomycosis were reviewed. All children were Hispanic and 3 were female. The median age was 1.8 years and the median duration of symptoms before diagnosis was 24 days. The most common symptoms included fever (100%), stridor (60%), cough (100%) and vocal changes (40%). Airway obstruction requiring tracheostomy and/or intubation for airway management was present in 80%. The most frequent location of lesions was the subglottic area. Coccidioidomycosis complement fixation titers were frequently low and culture/histopathology of laryngeal tissue was necessary to make a definitive diagnosis. All patients required surgical debridement and were treated with antifungal agents. None of the patients had recurrence during the follow-up period. This study suggests that laryngeal coccidioidomycosis in children presents with refractory stridor or dysphonia and severe airway obstruction. Favorable outcomes can be achieved with a comprehensive diagnostic work-up and aggressive surgical and medical management. With the rise in cases of coccidioidomycosis, physicians should have a heightened awareness regarding the possibility of laryngeal coccidioidomycosis when encountering children who have visited or reside in endemic areas with stridor or dysphonia.

CALCIFIED CAVITARY CONUNDRUM: DELAYED DIAGNOSIS OF HISTOPLASMOSIS

CALCIFIED CAVITARY CONUNDRUM: DELAYED DIAGNOSIS OF HISTOPLASMOSIS

Natural history of pulmonary coccidioidomycosis: Further examination of the VA-Armed Forces Database.

There are still many limitations related to the understanding of the natural history of differing forms of coccidioidomycosis (CM), including characterizing the spectrum of pulmonary disease. The historical Veterans Administration-Armed Forces database, recorded primarily before the advent of antifungal therapy, presents an opportunity to characterize the natural history of pulmonary CM. We performed a retrospective cohort study of 342 armed forces service members who were diagnosed with pulmonary CM at VA facilities between 1955 to 1958, followed through 1966, who did not receive antifungal therapy. Patients were grouped by predominant pulmonary finding on chest radiographs. The all-cause mortality was low for all patients (4.6%). Cavities had a median size of 3-3.9cm (IQR: 2-2.9-4-4.9cm), with heterogeneous wall thickness and no fluid level, while nodules had a median size of 1-1.19cm (Interquartile range [IQR] 1-1.9-2-2.9cm) and sharp borders. The majority of cavities were chronic (85.6%), and just under half were found incidentally. Median complement fixation titers in both the nodular and cavitary groups were negative, with higher titers in the cavitary group overall. This retrospective cohort study of non-disseminated coccidioidomycosis, the largest to date, sheds light on the natural history, serologic markers, and radiologic characteristics of this understudied disease. These findings have implications for the evaluation and management of CM.

Pediatric Musculoskeletal Coccidioidomycosis in Central California: A Single Center Experience.

Published literature on musculoskeletal coccidioidomycosis is sparse and limited to case reports and case series. This is one of the largest case series to describe the clinical presentation, diagnosis, medical and surgical management and outcomes of pediatric musculoskeletal coccidioidomycosis at a tertiary care hospital. A retrospective case review was performed on patients ≤ 21 years old who were followed at a tertiary care center with a diagnosis of musculoskeletal coccidioidomycosis from January 1, 2007, to December 31, 2020. Descriptive data are expressed as medians and interquartile range (IQR) for continuous variables or as frequency and percentage for categorical variables. Categorical values were compared using the χ2 test. Forty-one patients were identified. The median age was 12.8 years, and most were male (71%), Latinx (66%) and healthy (71%). Limb swelling (66%), bone pain (54%) and joint pain (46%) were the most common presenting symptoms. Multiple bone involvement was present in 29% while 12% had the joint disease, and craniofacial (n = 10) and metacarpal/metatarsal bones (n=9) were the most commonly involved sites. Elevated Coccidioides complement fixation (CF) titers ≥1:32 were seen in 90% of the patients. Thirty-three patients (81%) required surgical interventions and of these 16 (48%) required additional surgical procedures. Eleven patients (27%) had disease relapse. Children >13 years of age were more likely to have > 1 organ involvement (16 vs. 7, P = 0.04), multiple bone involvement (10 vs. 2, P = 0.004) and maximum Coccidioides CF titers >1:128 (13 vs. 6, P = 0.02). In endemic areas, musculoskeletal coccidioidomycosis causes a substantial disease burden in children and should be considered in the differential diagnosis of those presenting with bone and joint pain or swelling. Early diagnosis and treatment are essential to minimize long-term morbidity and mortality.

263. Antibody Spill-Over vs. True Coccidioidal Meningitis in a Patient with HIV/AIDS and Disseminated Coccidioidomycosis

Abstract Background The diagnosis of coccidioidal meningitis merits life-long antifungal therapy given high rates of disease recurrence. Accurate diagnosis is important. Antibody spill-over into cerebrospinal fluid (CSF) can happen when serum titers are high. We present a case of antibody spill-over vs. true fluconazole-resistant coccidioidal meningitis. Methods A 49-year-old man presented with 6 months of intermittent fever, myalgias, decreased appetite, vomiting, diarrhea, unsteadiness and 60-pound weight loss. He was recently diagnosed with HIV and a prior lymph node biopsy had grown Coccidioides immitis (C. i) for which he was given fluconazole 100 mg twice daily. Figure 1. Timeline of Coccidioides immitis lab results in relation to treatment regimen. CF: Complement fixation, EIA: Enzyme immunoassay for Coccidioides antigen, CSF: Cerebrospinal fluid, c/mL: copies/mL, R: resistant, S: susceptible. Results Vitals revealed a temperature of 102°F. He was cachectic and a 0.5 cm right supraclavicular lymph node was palpable. No meningeal signs were appreciated. CD4 count was 50/µL (18%), HIV-1 viral load 2,969,945 copies/mL. Computed tomography (CT) of the abdomen/pelvis suggested lung and spleen involvement. Serum C. i enzyme immunoassay (EIA) was 1.38 ng/mL, immunodiffusion (ID) was positive and complement fixation (CF) titer was 1:256. C. i was isolated from expectorated sputum. CSF cell count was normal, but ID was positive and CF titer was 1:2 however, lab reported concern for spill-over due to high serum IgG titers. He left against medical advice with fluconazole 400 mg daily. He was hospitalized a month later for failure to thrive. MRI head revealed enlarged lateral and third ventricles with increased periventricular hyperintensity concerning for coccidioidal meningitis. Repeat serum studies were stable. CSF revealed CF 1:4 and C. i antigen by EIA 1.31ng/mL, distinguishing between spill-over and meningitis. Susceptibility results showed resistance to fluconazole and amphotericin B with minimum inhibitory concentrations (MICs) of 50 and 4 respectively, posaconazole susceptibility (MIC < 1) and itraconazole borderline (MIC 3.7). Despite amphotericin B resistance, it was used for bridge to posaconazole. ART was initiated after concern for immune reconstitution had resolved. Conclusion This case highlights the difficulty in making an accurate diagnosis of coccidioidal meningitis. It also describes a fluconazole-resistant C. i isolate in the setting of prolonged low-dose fluconazole therapy. Disclosures All Authors: No reported disclosures

703. Peritoneal Coccidioidomycosis in a Pediatric Patient: An Extremely Rare Presentation and Literature Review

BackgroundChronic peritonitis is an unusual manifestation of coccidiomycosis (CM) that is challenging to diagnose and manage due to its propensity for relapse. It is even more unusual to diagnose peritoneal CM in the pediatric population, with only two other cases reported in the literature. MethodsWe present the case of a previously healthy 5-year-old Filipino female in Florida who was diagnosed with peritoneal CM. After months of unintentional weight loss and worsening abdominal distention, she presented to medical care. Imaging revealed significant abdominal ascites and nodularities throughout the peritoneum. The peritoneal fluid demonstrated a lymphocytic pleocytosis and infectious workup was benign. CA125 levels were elevated, but peritoneal adenosine deaminase was within normal limits. A biopsy of the affected tissue revealed diffuse granulomas surrounding spherules that were positive on GMS and PAS staining, concerning for CM. Exposure history revealed that she was raised in California and moved to Florida one year prior to presentation. Complement fixation titers were significantly elevated at ≥ 1:512 and immunodiffusion titers were positive. A Coccidioides PCR was sent from the tissue to the Mayo clinic and was positive, and fungal cultures from the tissue grew C. immitis/posadasii. Immunologic workup was reassuring. She was started on oral Fluconazole with rapid resolution of her symptoms. ResultsInvolvement of the peritoneum in CM is extremely rare. Abdominal distention due to ascites is the most common presentation, and the peritoneal fluid is typically exudative. Imaging may reveal peritoneal deposits which can mimic other infections and malignancy. Diagnosis can be based on histopathological demonstration of fungal structures, cultures, antibody testing, antigen detection and/or PCR. Treatment guidelines suggest azole therapy for nonmeningeal disseminated CM with at least 6–12 months of treatment for extrapulmonary coccidioidal soft tissue infection. ConclusionPeritoneal CM is an extremely uncommon condition and it is even more rare in the pediatric population, but should be considered in those in the appropriate clinical settings, particularly if they have history to suggest exposure to regions where this fungus is endemic. Disclosures All Authors: No reported disclosures

692. Coccidioides sp. Infective Endocarditis: A Review of the Literature

BackgroundDespite the endemic nature of Coccidioides sp. to the American Southwest, the incidence Coccidioides sp. infective endocarditis (CIE) is rare. Following successful treatment of a patient with CIE at our institution, we reviewed the literature to identify trends in disease presentation, patient characteristics, and outcomes.MethodsWe reviewed all cases of CIE reported since 1938. Details including patient demographics, underlying immunodeficiency, time to diagnosis, treatment, and outcome were collected for analysis of diagnostic challenges and survival.ResultsIncluding ours, we identified 11 published cases of CIE. The majority (7) occurred in men. 5 patients were of either African American or Hispanic descent. Of the 10 patients with reported ages, the median age was 35.5 years (range 3 weeks – 61 years). 5 patients had a previous diagnosis of coccidioidomycosis and only 3 had an immunocompromising condition. These comprised pregnancy, heart transplant, and juvenile inflammatory arthritis. Three cases had multi-valvular involvement, but the majority affected the mitral (5) and the aortic (4) valves. Only 2 of the 11 cases involved a prosthetic valve. Of the 8 cases with reported blood cultures, only 2 were positive. Ten of the 11 cases had extra-cardiac disease. Complement fixation (CF) titers were heterogenous with a median of 1:32 and a range of 1:1 to 1:2048. There was no obvious correlation between a patient’s CF titer and their survival. Average time to diagnosis was 3.5 months (range 2.5 – 36 months). Diagnosis was made post-mortem in 4 of the 11 cases. 6 patients (54%) did not survive. Notably, 2 of the fatal cases preceded the discovery of amphotericin B (1969) and 4 occurred prior to the discovery of fluconazole (1990). Of the five patients that survived, four required surgical intervention in addition to azole therapy.ConclusionCIE is a diagnostic and therapeutic challenge. The diagnosis itself is rare, culture incubation times are long, and the symptoms are often non-specific thus delaying definitive therapy. The introduction of azole therapy appears to have had significant impact on rates of survival. Despite this, successful management of CIE still requires concurrent surgical intervention with aggressive, indefinite anti-fungal therapy.Disclosures All Authors: No reported disclosures

713. Coccidioidal Meningitis Among Children: A Case Series and Single Center Experience In Central California

BackgroundCoccidioidal meningitis is a severe form of coccidioidomycosis associated with significant morbidity and mortality. Published literature in the pediatric population is limited, particularly on coccidioidal meningitis. Here we describe a large case series of pediatric coccidioidal meningitis followed at a tertiary care center in an endemic region.MethodsWe performed a retrospective case review of patients ≤21 years old followed at our facility with a diagnosis of coccidioidal meningitis from January 1, 2000, to December 31, 2018.ResultsOverall, 30 patients were identified during the study period. The median age was 10.8 years (IQR: 4.6-15). The majority of patients were previously healthy (93%) and all required hospitalization. Fever (90%), headache (70%), vomiting (53%), and fatigue (57%) were the most common clinical manifestations. More than one-third (40%) had concurrent pulmonary disease. Only 20 patients (67%) had initial Coccidioides complement fixation (CF) titers >=1:16. The majority had extra-axial brain involvement (60%) and seven (23%) had associated spinal canal disease. Over two-third required shunt placement (70%) and almost half of them (43%) underwent revision. Neurological complications including paresis/paralysis, stroke, neuropathy, seizures, and cognitive delay were observed in 20% of patients. Two-thirds (73%) of patients received fluconazole as the initial drug. However, 37% of those had fluconazole failure, requiring alternative treatment. Due to refractory disease, two patients required a novel triazole, isavuconazole, while adjunctive therapy with steroids and interferon-gamma (IFNγ) was used in 20% of patients. Most cases (83%) stabilized, 13% experienced relapses and/or progressive disease, and 3% were fatal.ConclusionPediatric coccidioidal meningitis is an uncommon and sometimes devastating complication of disseminated coccidioidomycosis. Many patients present with relatively low CF titers, and communicating hydrocephalus and long term neurologic complications are common. Fluconazole treatment failures are common, and management remains difficult despite recent advances in therapy. Most patients do well once the disease is stabilized and require lifelong therapy. Newer therapeutic agents are needed. Disclosures All Authors: No reported disclosures

REACTIVATION OF PULMONARY COCCIDIOIDES IN THE SETTING OF COVID-19 INFECTION

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Clinical course and management of severe acute respiratory syndrome COVID-2 (Covid-19) infection has been full of uncertainties. As a viral respiratory illness, its presentation can be very similar to other respiratory diseases. Therefore, it is essential to have a high degree of suspicion for superimposed bacterial and fungal infections. CASE PRESENTATION: A 65-year-old male with insulin-dependent diabetes mellitus presented to the emergency department with fever, sudden shortness of breath, cough, and diffuse chest discomfort. Upon arrival his blood pressure was 155/76 mmhg, heart rate 91 bpm, respiratory rate of 22, with temperature of 101.9 F. The patient's Covid-19 PCR nasopharyngeal swab resulted positive. Imaging showed moderate to severe bilateral lung ground-glass infiltrates and consolidation pattern and a 1.9 cm, left upper lobe cavitary lesion. No prior imaging was available for review. Patient was treated with supplemental oxygen, antibiotic therapy for community acquired pneumonia, Remdicivir, and convalescent plasma therapy. Given low suspicion for active TB, steroid therapy was continued. Patient's QuantiFERON gold resulted positive, and he was found to have positive coccidioides IgG, but the complement fixation titer was negative on the day of admission. Three AFB samples, serum (1-3)-beta-D-Glucan assay and Aspergillus assay resulted negative. Bronchoalveolar lavage was performed. Serum coccidioides antibody complement fixation and immunodiffusion results were made available after the patient's passing, which showed positive for IgG and IgM with titers 1:256. Bronchoalveolar lavage cultures revealed Coccidioides Posadasii and Immitis. DISCUSSION: Coccidioidomycosis, commonly known as valley fever, is caused by dimorphic fungi of the Coccidioides family, which is endemic to California, south-central Washington, and northern Mexico. Pulmonary Coccidioides has a similar clinical presentation to Covid-19 infection and seldom, associated with cavitary lesions. Fever, cough, and shortness of breath are the most common presenting symptoms. Radiographic findings vary with COVID -19 showing bilateral peripheral ground glass opacifications with or without consolidations. Among the bacterial co-infections, streptococcus pneumoniae is the most common followed by Klebsiella pneumoniae and Haemophilus influenzae. Due to lengthy wait periods for many laboratory studies to be resulted, it is challenging to distinguish co-infection cases. Reactivation of coccidiodes has been seen in patients with HIV, and patients on chemo and immunotherapy despite antifungal prophylaxes. CONCLUSIONS: Given nonspecific radiological findings of Covid-19 infection that are seen with other causes of pneumonia and its uncertain and similar clinical course to other respiratory infections, it is crucial to have a high degree of suspicion for superimposed bacterial and fungal infections. REFERENCE #1: Freedman M, Jackson BR, McCotter O, Benedict K. Coccidioidomycosis Outbreaks, United States and Worldwide, 1940-2015. Emerg Infect Dis. 2018;24(3):417-423. doi:10.3201/eid2403.170623 REFERENCE #2: Galgiani JN, Ampel NM, Blair JE, et al. 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Clin Infect Dis. 2016;63(6):e112-e146. doi:10.1093/cid/ciw360 REFERENCE #3: Zhu X, Ge Y, Wu T, et al. Co-infection with respiratory pathogens among COVID-2019 cases. Virus Res. 2020;285:198005. doi:10.1016/j.virusres.2020.198005 DISCLOSURES: No relevant relationships by Nami Moradi, source=Web Response No relevant relationships by Paloma Rivero-Moragrega, source=Web Response

Mediastinal Mass with Unusual Etiology.

Mediastinal Mass with Unusual Etiology.

Answer to September 2020 Photo Quiz

Answer: Chronic pulmonary coccidioidomycosis. An IgG antibody to Aspergillus fumigatus was not present in the patient’s serum, and Aspergillus fumigatus was not detected in either BAL sample by PCR. However, a serum Coccidioides IgG complement fixation titer was positive at 1:32. Coccidioides immitis/Coccidioides posadasii was isolated from culture of the BAL fluid and was also detected by a specific PCR assay. Treatment with fluconazole was initiated (1). The patient’s lengthy history of pulmonary illness suggests that she had acquired her infection in Mexico or Arizona, but autochthonous coccidioidomycosis has also been reported in Washington State (2). Most coccidioidal pneumonia is self-limited, and fewer than 1% of patients develop chronic progressive pulmonary infections, which may be indistinguishable from other chronic fungal or mycobacterial infections (3). Diabetes mellitus is a risk factor for chronic infection. Radiologic manifestations of chronic disease include residual nodules, chronic cavities, persistent pneumonia with or without lymphadenopathy, pleural effusion, and regressive changes such as localized fibrosis, bronchiectasis, and calcification (4). The pulmonary imaging in this patient was not specific for Coccidioides infection; however, the presence of the air crescent sign in the dependent area of the cavitating lesion was not felt to be typical for an aspergilloma, and sparing of the lung apex reduced the likelihood of tuberculosis.

Herpes zoster laryngitis

Herpes zoster infection is due to reactivation of the latent varicella zoster virus. It is often seen in persons with impaired immunity or stress and characterized by one-side herpetic vesicular eruptions and neuralgia. A 45-year-old male presented with sore throat, hiccups, voice changes, and dry cough. Laryngeal examinations showed edema and eruptions over the left side of the larynx. He had herpetic vesicles over the left concha and external auditory canal. Elevated complement fixation titer confirmed the diagnosis of the herpes zoster. The patient was treated with acyclovir and steroid. Patients improved symptomatically after 10 days of treatment. This clinical condition should be kept in mind when the patient will present with unilateral sore throat, voice changes, and hiccups.

Extrapulmonary Coccidioidomycosis Among Children in Central California: A Retrospective Review.

The literature on pediatric extrapulmonary coccidioidomycosis is limited. We reviewed the clinical course, diagnostic studies, treatment and outcomes of children with extrapulmonary coccidioidomycosis followed at a tertiary care center in central California. Retrospective study of 78 patients ≤21 years old with extrapulmonary coccidioidomycosis diagnosed over 10 years (1/1/07-12/31/16). The median age was 9.7 years (interquartile range, 4.5-14.8). The majority of patients were males (55%), Hispanic (65%) and without comorbid conditions (85%). Over two-thirds (68%) had concurrent pulmonary disease. Organ involvements included bones and joints (33%), mediastinum (19%), central nervous system (19%), cervical lymph nodes (15%), larynx (6%) and skin (5%). Most cases (84%) resolved and/or became stable on maintenance therapy, 14% experienced relapse and/or progressive disease, and 2% were fatal. Children ≥10 years of age tended to have >1 site of involvement (47% vs. 25%, P = 0.06), and more relapsed/progressive/fatal disease (21% vs. 5%, P = 0.06) compared with those <10 years. They also required longer durations of treatment (median, 611 vs. 349 days, P = 0.02). Non-Hispanics were more likely to require >1 drug therapy (85% vs. 70%, P = 0.04) and tended to have Coccidioides complement fixation titers ≥1:32 (89% vs. 72%, P = 0.04) compared with Hispanics. Extrapulmonary coccidioidomycosis in children can be severe and spread to multiple sites and requires prolonged treatment. Non-Hispanics and those ≥10 years of age are more likely to experience severe disease, suggesting a need for early recognition and intervention in these populations.

Disseminated Coccidioidomycosis Refractory to Multi-Drug Therapies in an Immunocompetent Patient

Coccidioidomycosis is a fungal infection caused by Coccidioides immitis which thrives in dry desert climates such as the southwestern United States. Disseminated coccidioidomycosis is often seen in patients with an underlying immunodeficiency. Historically there have been few reported cases of opportunistic infections in the setting of low CD4+ count and no evidence of HIV infection. Coccidioidomycosis typically presents asymptomatically or as a minor respiratory illness in immunocompetent individuals. We report a case of disseminated coccidioidomycosis in a patient who is otherwise immunocompetent. Patient is a 24-year-old Hispanic male who presented with severe headache, fever, body pain, vomiting, and diarrhea for approximately 14 days. On admission, patient’s CD4+ count was 91 and CSF culture grew Coccidioides immitis, for which patient was started on fluconazole. Patient’s hospital stay was complicated by multiple bouts of altered mental status, fevers, hyponatremia, hydrocephalus, neurogenic bladder, new-onset Mobitz II heart arrhythmia, urinary tract infection, and sepsis. MRI studies revealed abnormal enhancement of leptomeninges, bilateral basal ganglia, thecal sac and cauda equina fibers, signifying disseminated disease. Patient’s serum Coccidioides complement fixation (IgG) titers remained elevated despite aggressive therapy with IV amphotericin B. After a total of six months of hospitalization, including treatment with intrathecal amphotericin B, patient’s last CD4+ count was 549, CSF IgG titers achieved

Coccidioidomycosis in solid organ transplant recipients.

The purpose of the review is an update of diagnosis and treatment of coccidioidomycosis infection in solid organ transplant (SOT) patients. Endemic fungal infections continue to be a cause of serious morbidity and mortality in transplant recipients. In transplant patients there are recommendations regarding screening in areas that are endemic for coccidioidomycosis. This screening involves serologic testing and chest imaging. In endemic areas pretransplant seropositivity varies from 1.4 to 5.6%. In immunocompromised patients with elevated complement fixation titers, evaluation of cerebrospinal fluid is recommended even in the absence of symptoms. Although coccidioidomycosis can be a self-limited disease in immunocompotent patients, all SOT patients should be treated regardless of severity. This may include intravenous amphotericin B in severe cases and fluconazole therapy in milder episodes. In those SOT recipients with evidence of prior coccidioidomycosis, lifelong secondary prophylaxis with fluconazole given risk of recurrent disease. Coccidioidomycosis continues to be a cause of serious morbidity and mortality in transplant recipients but with proper screening and treatment can be successfully managed.

An Analysis of Skin Test Responses to Spherulin-Based Coccidioidin (Spherusol®) Among a Group of Subjects with Various Forms of Active Coccidioidomycosis

A reformulated skin test for coccidioidomycosis, Spherusol®, was recently approved for use in the USA. We hypothesized that it could be useful in predicting severity of illness and outcome in various types of coccidioidomycosis. Subjects with non-meningeal coccidioidomycosis attending a clinic in the coccidioidal endemic region were skin tested with Spherusol® and clinical data were collected at the time of testing and at follow-up. Twenty-seven subjects were studied, eight of whom had extrathoracic dissemination. A total of 15 subjects had positive tests, including 11 of 19 subjects with non-disseminated pulmonary disease and four with extrathoracic disseminated coccidioidomycosis. Among those with non-disseminated pulmonary disease, age ≥ 65years, female sex, and antifungal therapy were significantly associated with a negative test on univariate but not multivariate analysis. For 23 subjects, there was a trend for those not on antifungal therapy at the time of follow-up to have a positive test but no association with coccidioidal complement-fixation titer or overall outcome. Not all subjects with non-disseminated pulmonary coccidioidomycosis were found to be skin test positive and half of those with extrathoracic disseminated disease manifested dermal hypersensitivity. In this small study, the results of the skin test were not clinically predictive of disease severity or outcome.

Curious Case of a Year-Long History of Cold Subcutaneous Abscesses

Abstract Cold subcutaneous abscess (CSA) is an abscess lacking classic inflammatory signs. This is a case of a 27-year-old incarcerated African American man who presented with 1-year history of soft, painless, mobile, masses on his limbs. Chest computed tomography scan showed diffuse reticulonodular infiltrates with right lower lobe mass. Computed tomography scan of the right upper extremity showed fluid density with no deep tissue involvement. Coccidioides complement fixation titers are 1:64, IgG 1.315, and IgM 0.242. Lung biopsy and CSA aspiration showed thick walled black spherules with endospores consistent with disseminated coccidioidomycosis (DCM). Cold subcutaneous abscess is a rarely reported manifestation of DCM. Defective cell-mediated immunity and inhibition of inflammation were thought to play a role in DCM and CSA pathogenesis. Cold subcutaneous abscess can remain unnoticed because of lack of inflammation. Our patient has longest time a CSA lasted without other symptoms of DCM. It is important to recognize it early to uncover a potentially dangerous disease.

388. New Observations in Coccidioidomycosis Serology

BackgroundCoccidioidomycosis is associated with a broad spectrum of illness severity, ranging from asymptomatic or self-limited pulmonary infection to life-threatening manifestations of disseminated disease. Current understanding of serologic kinetics and serologic features are largely based on serologic studies from the 1950s before antifungals were widely available. The effects of antifungal therapy on serologic characteristics has not previously been evaluated.MethodsWe retrospectively analyzed chart history and complement fixation titer trends of 434 patients classified by infectious disease physicians as having either uncomplicated pulmonary coccidioidomycosis (UPC) (n = 248), chronic pulmonary coccidioidomycosis (CPC) (n = 64), disseminated coccidioidomycosis not including meningitis (DC) (n = 86), or coccidioidal meningitis (CM) (n = 36). All patients received azole antifungal therapy. Serologic kinetics and features were analyzed and compared between groups.ResultsRoughly 94% of UPC, 61% of CPC, 29% of DC, and 56% of CM patients developed maximum complement fixation titers ≤1:32. Surprisingly, 25.4% of UPC, 6.3% of CPC, 2.3% of DC, and 8.3% of CM patients did not develop a detectable complement fixation titer during the study period (at least 3 years after diagnosis for each patient). The median maximum titer was 1:4 (range <1:2 – 1:512) for UPC, 1:24 (range <1:2 – 1:2,048) for CPC, 1:128 (range <1:2 – 1:4,096) for DC, and 1:32 (range <1:2 – 1:4,096) for CM patients. Few significant differences were observed in the mean time to maximum titer (overall mean 31 days, 95% CI 13–50) and serologic resolution rates (average 3–4 months/dilution reduction). However, 9% of UPC, 36% of CPC, 50% of DC, 52% of CM patients exhibited serologic reactivations (defined as ≥2 dilution titer increase >90 days from initial positive serology). Meanwhile, 15% of UPC, 25% of CPC, 31% of DC, and 25% of CM patients exhibited a serofast phenotype despite antifungal therapy.ConclusionOur findings provide an update to serologic studies performed prior to long-term triazole therapy. An understanding of the serologic features and kinetics for patients with varying forms of coccidioidomycosis receiving antifungal therapy is key to clinical evaluation and therapeutic decision making.Disclosures All authors: No reported disclosures.