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

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S238-S238
Author(s):  
Renee E Newby ◽  
Danny L Sam ◽  
Joseph Cooper

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

2020 ◽  
Vol 8 ◽  
pp. 232470962097489
Author(s):  
Faisal Nasrawi ◽  
Arash Heidari ◽  
Thulfiqar Aljashamy ◽  
Nishan Mangat ◽  
Jasbir Bhaika ◽  
...  

Coccidioidomycosis a fungal infection endemic to southwestern United States. It is caused by inhalation of spores of Coccidioides immitis. Sixty percent of infections are asymptomatic; the remaining 40% are primarily pulmonary disease. In <1% of infections, dissemination can occur. Dissemination usually affects those with impaired cellular immunity and pregnant women, and can involve bones, joints, meninges, and skin. We present the case of a 29-year-old Hispanic male who presented to the emergency department (ED) complaining of pain and swelling of right wrist and ankle as well as left knee for 2 months. He was referred to rheumatology clinic but returned to the ED as he developed spontaneous purulent drainage from his wrist. In the ED, an arthrocentesis of 2 of the joints showed total nucleated cells of 520 000/cm2 and 90 000/cm2 with 61% and 93% neutrophils, respectively. Fungal culture eventually grew Coccidioides immitis from his wrist and knee. Coccidioidomycosis complement fixation titer came back >1:512. Bone scan showed uptake of adjacent bones in the affected joints. Superimposed bacterial infection of the wrist complicated the treatment course and delayed the start of liposomal amphotericin B. Eventually patient received 12 weeks of intravenous liposomal amphotericin-B with slow clinical improvement and then switched to oral isavuconazonium for maintenance therapy. This case shows that although disseminated polyarthritis coccidioidomycosis is very rare, clinicians should keep the diagnosis of disseminated synovial coccidioidomycosis in mind in patients with risk factors.


2002 ◽  
Vol 46 (8) ◽  
pp. 2420-2426 ◽  
Author(s):  
Karl V. Clemons ◽  
Raymond A. Sobel ◽  
Paul L. Williams ◽  
Demosthenes Pappagianis ◽  
David A. Stevens

ABSTRACT The efficacy of intravenously administered liposomal amphotericin B (AmBisome [AmBi]) for the treatment of experimental coccidioidal meningitis was compared with those of oral fluconazole (FLC) and intravenously administered conventional amphotericin B (AMB). Male New Zealand White rabbits were infected by intracisternal inoculation of arthroconidia of Coccidioides immitis. Starting 5 days postinfection, animals received one of the following: 5% dextrose water diluent; AMB given at 1 mg/kg of body weight; AmBi given at 7.5, 15, or 22.5 mg/kg intravenously three times per week for 3 weeks; or oral FLC given at 80 mg/kg for 19 days. One week after the cessation of therapy, all survivors were euthanatized, the numbers of CFU remaining in the spinal cord and brain were determined, and histological analyses were performed. All AmBi-, FLC-, or AMB-treated animals survived and had prolonged lengths of survival compared with those for the controls (P < 0.0001). Treated groups had significantly lower numbers of white blood cells and significantly lower protein concentrations in the cerebrospinal fluid compared with those for the controls (P < 0.01 to 0.0005) and had fewer clinical signs of infection (e.g., weight loss, elevated temperature, and neurological abnormalities including motor abnormalities). The mean histological scores for AmBi-treated rabbits were lower than those for FLC-treated and control rabbits (P < 0.016 and 0.0005, respectively); the scores for AMB-treated animals were lower than those for the controls (P < 0.0005) but were similar to those for FLC-treated rabbits. All regimens reduced the numbers of CFU in the brain and spinal cord compared with those for the controls (P ≤0.0005). AmBi-treated animals had 3- to 11-fold lower numbers of CFU than FLC-treated rabbits and 6- to 35-fold lower numbers of CFU than AmB-treated rabbits. Three of eight animals given 15 mg of AmBi per kg had no detectable infection in either tissue, whereas other doses of AmBi or FLC cleared either the brain or the spinal cord of infection in fewer rabbits. In addition, clearance of the infection from both tissues was achieved in none of the rabbits, and neither tissue was cleared of infection in AMB-treated animals. Overall, these data indicate that intravenously administered AmBi is superior to oral FLC or intravenous AMB and that FLC is better than AMB against experimental coccidioidal meningitis. These data indicate that AmBi may offer an improvement in the treatment of coccidioidal meningitis. Additional studies are warranted.


PEDIATRICS ◽  
1972 ◽  
Vol 49 (1) ◽  
pp. 133-136
Author(s):  
Dale E. Dietzman ◽  
Luiz Horta-Barbosa ◽  
Helen M. Krebs ◽  
David L. Madden ◽  
David A. Fuccillo ◽  
...  

A double-diffusion gel precipitation test is described which provides an easy, rapid, and reliable procedure for assistance in the diagnosis of subacute sclerosing penencephalitis by detecting measles antibody in concentrated cerebrospinal fluid. The test is based on the precipitation of rubeola antibodies with a high titered SSPE measles-virus antigen. The sensitivity of the test is comparable to the sensitivity of rubeola complement-fixation and hemagglutination-inhibition determinations on unconcentrated spiral fluid. The method could be available to hospitals or institutions if the antigen were prepared commercially or by a national center.


2021 ◽  
Author(s):  
Shuang Liu ◽  
Zheng Lin ◽  
Jianwen Wang ◽  
Zerong Zheng ◽  
Wenqing Rao ◽  
...  

Abstract Background: To explore the miR-4787-3p expression levels in the serum exosome and tissue and its role in lymph node metastasis and prognosis in ESCC. Methods: The miRNA array was conducted to detect the ESCC serum exosomal miRNAs expression. A receiver operating characteristic (ROC) curve was constructed to determine the predictive ESCC with lymph node metastasis efficacy of serum exosomal miR-4784-3p. The Cox regression analysis was preformed to explore prognostic factors for ESCC. Transwell assay and CCK-8 assays were utilized to evaluate cell migration, invasion, and proliferation, respectively. Results: High serum exosomal miR-4787-3p expression was demonstrated in lymph node metastasis group (P =0.011). The serum exosomal miR-4787-3p expression was significantly associated with histologic grade (P = 0.010), and TNM stage (P = 0.033). However, there was no significant relationship between tissue miR-4787-3p expression and clinical characteristics (P >0.05). ROC analyses revealed that the AUCs of serum exosomal miR-4787-3p for lymph node metastasis prediction was 0.787. The Cox regression analysis found that high expression serum exosomal miR-4787-3p were correlated with poor prognoses (for OS, HR=2.68, 95% CI: 1.02~7.04; for DFS, HR = 2.65, 95% CI: 1.05~6.68). Nevertheless, no association between tissue miR-4787-3p expression and ESCC prognosis. In addition, upregulated expression of miR-4787-3p could promote migration and invasion in vitro. Conclusions: Serum exosomal miR-4787-3p can be promising biomarkers for ESCC metastasis and prognosis


2000 ◽  
Vol 44 (6) ◽  
pp. 1734-1736 ◽  
Author(s):  
Ren-Kai Li ◽  
Meral A. Ciblak ◽  
Nicole Nordoff ◽  
Lester Pasarell ◽  
David W. Warnock ◽  
...  

ABSTRACT The in vitro activity of voriconazole was compared to those of itraconazole and amphotericin B against the mold forms of 304 isolates of three dimorphic fungi, Blastomyces dermatitidis,Coccidioides immitis, and Histoplasma capsulatum. MICs were determined by a broth microdilution adaptation of the National Committee for Clinical Laboratory Standards M27-A procedure. RPMI 1640 medium was used for tests with voriconazole and itraconazole, whereas Antibiotic Medium 3 with 2% glucose was used for amphotericin B. Minimum fungicidal concentrations (MFCs) were also determined. Amphotericin B was active against all three dimorphic fungi, with MICs at which 90% of the isolates tested are inhibited (MIC90s) of 0.5 to 1 μg/ml. Itraconazole had MIC90s of 0.06 μg/ml for H. capsulatum, 0.125 μg/ml for B. dermatitidis, and 1 μg/ml for C. immitis. The MIC90s of voriconazole were 0.25 μg/ml for all three fungi. Amphotericin B was fungicidal for B. dermatitidis and H. capsulatum with MFCs at which 90% of strains tested are killed (MFC90s) of 0.5 and 2 μg/ml, respectively. It was less active against C. immitis, with MFCs ranging from 0.5 to >16 μg/ml. Voriconazole and itraconazole were lethal for most isolates of B. dermatitidis, with MFC50s and MFC90s of 0.125 and 4 μg/ml, respectively. Both azoles were fungicidal for some isolates of H. capsulatum, with MFC50s of 2 and 8 μg/ml for itraconazole and voriconazole, respectively; neither had a lethal effect upon C. immitis. Our results suggest that voriconazole possesses promising activity against these important human pathogens.


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