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1.
Cell Host Microbe ; 32(7): 1103-1113.e6, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38838675

ABSTRACT

Antibiotic treatment promotes the outgrowth of intestinal Candida albicans, but the mechanisms driving this fungal bloom remain incompletely understood. We identify oxygen as a resource required for post-antibiotic C. albicans expansion. C. albicans depleted simple sugars in the ceca of gnotobiotic mice but required oxygen to grow on these resources in vitro, pointing to anaerobiosis as a potential factor limiting growth in the gut. Clostridia species limit oxygen availability in the large intestine by producing butyrate, which activates peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling to maintain epithelial hypoxia. Streptomycin treatment depleted Clostridia-derived butyrate to increase epithelial oxygenation, but the PPAR-γ agonist 5-aminosalicylic acid (5-ASA) functionally replaced Clostridia species to restore epithelial hypoxia and colonization resistance against C. albicans. Additionally, probiotic Escherichia coli required oxygen respiration to prevent a post-antibiotic bloom of C. albicans, further supporting the role of oxygen in colonization resistance. We conclude that limited access to oxygen maintains colonization resistance against C. albicans.


Subject(s)
Candida albicans , Oxygen , Candida albicans/drug effects , Animals , Mice , Oxygen/metabolism , PPAR gamma/metabolism , Anti-Bacterial Agents/pharmacology , Escherichia coli/drug effects , Candidiasis/microbiology , Anaerobiosis , Hypoxia/metabolism , Mice, Inbred C57BL , Streptomycin/pharmacology , Humans , Cecum/microbiology , Intestinal Mucosa/microbiology , Intestinal Mucosa/metabolism , Germ-Free Life
2.
Open Forum Infect Dis ; 11(2): ofad679, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38370292

ABSTRACT

Background: Severe coccidioidomycosis presenting with respiratory failure is an uncommon manifestation of disease. Current knowledge of this condition is limited to case reports and small case series. Methods: A retrospective multicenter review of patients with coccidioidomycosis-associated acute respiratory distress syndrome (CA-ARDS) was conducted. It assessed clinical and laboratory variables at the time of presentation, reviewed the treatment course, and compared this cohort with a national database of patients with noncoccidioidomycosis ARDS. Survivors and nonsurvivors of coccidioidomycosis were also compared to determine prognostic factors. Results: In this study, CA-ARDS (n = 54) was most common in males, those of Hispanic ethnicity, and those with concurrent diabetes mellitus. As compared with the PETAL network database (Prevention and Early Treatment of Acute Lung Injury; n = 1006), patients with coccidioidomycosis were younger, had fewer comorbid conditions, and were less acidemic. The 90-day mortality was 15.4% for patients with coccidioidomycosis, as opposed to 42.6% (P < .0001) for patients with noncoccidioidomycosis ARDS. Patients with coccidioidomycosis who died, as compared with those who survived, were older, had higher APACHE II scores (Acute Physiology and Chronic Health Evaluation), and did not receive corticosteroid therapy. Conclusions: CA-ARDS is an uncommon but morbid manifestation of infection. When compared with a national database, the overall mortality appears favorable vs other causes of ARDS. Patients with CA-ARDS had a low overall mortality but required prolonged antifungal therapy. The utility of corticosteroids in this condition remains unconfirmed.

3.
Med Mycol ; 62(1)2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38061838

ABSTRACT

The incidence of coccidioidomycosis continues to increase. The diagnosis frequently relies on non-invasive diagnostic testing with immunodiffusion and complement fixation (CF) testing the current gold standard. A direct comparison of quantitative immunodiffusion and CF for IgG antibodies has not been previously reported. In a comparison of 368 samples, there was close concordance observed (360/368 = 97.8%) (P-value < .001). These tests can be considerably interchangeable in the reference laboratory setting.


There are several diagnostic methodologies available in coccidioidomycosis. Direct comparisons of these methods are limited. Prior studies have not compared quantitative immunodiffusion to complement fixation testing. Our results show these tests are highly concordant.


Subject(s)
Coccidioides , Coccidioidomycosis , Animals , Complement Fixation Tests/veterinary , Antibodies, Fungal , Coccidioidomycosis/diagnosis , Coccidioidomycosis/veterinary , Immunodiffusion/veterinary
4.
bioRxiv ; 2023 Apr 19.
Article in English | MEDLINE | ID: mdl-37131682

ABSTRACT

Antibiotic prophylaxis sets the stage for an intestinal bloom of Candida albicans , which can progress to invasive candidiasis in patients with hematologic malignancies. Commensal bacteria can reestablish microbiota-mediated colonization resistance after completion of antibiotic therapy, but they cannot engraft during antibiotic prophylaxis. Here we use a mouse model to provide a proof of concept for an alternative approach, which replaces commensal bacteria functionally with drugs to restore colonization resistance against C. albicans . Streptomycin treatment, which depletes Clostridia from the gut microbiota, disrupted colonization resistance against C. albicans and increased epithelial oxygenation in the large intestine. Inoculating mice with a defined community of commensal Clostridia species reestablished colonization resistance and restored epithelial hypoxia. Notably, these functions of commensal Clostridia species could be replaced functionally with the drug 5-aminosalicylic acid (5-ASA), which activates mitochondrial oxygen consumption in the epithelium of the large intestine. When streptomycin-treated mice received 5-ASA, the drug reestablished colonization resistance against C. albicans and restored physiological hypoxia in the epithelium of the large intestine. We conclude that 5-ASA treatment is a non-biotic intervention that restores colonization resistance against C. albicans without requiring the administration of live bacteria.

5.
JCI Insight ; 7(22)2022 11 22.
Article in English | MEDLINE | ID: mdl-36166305

ABSTRACT

Disseminated coccidioidomycosis (DCM) is caused by Coccidioides, pathogenic fungi endemic to the southwestern United States and Mexico. Illness occurs in approximately 30% of those infected, less than 1% of whom develop disseminated disease. To address why some individuals allow dissemination, we enrolled patients with DCM and performed whole-exome sequencing. In an exploratory set of 67 patients with DCM, 2 had haploinsufficient STAT3 mutations, and defects in ß-glucan sensing and response were seen in 34 of 67 cases. Damaging CLEC7A and PLCG2 variants were associated with impaired production of ß-glucan-stimulated TNF-α from PBMCs compared with healthy controls. Using ancestry-matched controls, damaging CLEC7A and PLCG2 variants were overrepresented in DCM, including CLEC7A Y238* and PLCG2 R268W. A validation cohort of 111 patients with DCM confirmed the PLCG2 R268W, CLEC7A I223S, and CLEC7A Y238* variants. Stimulation with a DECTIN-1 agonist induced DUOX1/DUOXA1-derived hydrogen peroxide [H2O2] in transfected cells. Heterozygous DUOX1 or DUOXA1 variants that impaired H2O2 production were overrepresented in discovery and validation cohorts. Patients with DCM have impaired ß-glucan sensing or response affecting TNF-α and H2O2 production. Impaired Coccidioides recognition and decreased cellular response are associated with disseminated coccidioidomycosis.


Subject(s)
Coccidioidomycosis , beta-Glucans , Humans , Tumor Necrosis Factor-alpha/genetics , Hydrogen Peroxide , Coccidioidomycosis/genetics , Coccidioidomycosis/epidemiology , Coccidioidomycosis/microbiology , Coccidioides/genetics
6.
Med Mycol ; 60(10)2022 Oct 28.
Article in English | MEDLINE | ID: mdl-36166843

ABSTRACT

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 3-3.9 cm (IQR: 2-2.9-4-4.9 cm), with heterogeneous wall thickness and no fluid level, while nodules had a median size of 1-1.19 cm (Interquartile range [IQR] 1-1.9-2-2.9 cm) 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.


Coccidioidomycosis (CM), also known as San Joaquin Valley Fever, causes a variety of symptoms including pneumonia. This historical study investigates CM of the lungs in American soldiers with CM in the 1950s, prior to modern antifungals, to better understand the natural history.


Subject(s)
Coccidioidomycosis , Animals , Coccidioidomycosis/diagnosis , Coccidioidomycosis/epidemiology , Coccidioidomycosis/veterinary , Antifungal Agents/therapeutic use , Retrospective Studies , Radiography
7.
Open Forum Infect Dis ; 9(3): ofab543, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35252466

ABSTRACT

To assess sex-specific differences in coccidioidomycosis, a retrospective analysis of human patients, nonhuman primates, and veterinary patients (including the neutered status of the animal) was performed. We found higher rates of infection and severity in males. This observed increased infection risk suggests deeper biological underpinnings than solely occupational/exposure risks.

8.
Infect Dis Clin North Am ; 35(2): 453-469, 2021 06.
Article in English | MEDLINE | ID: mdl-34016286

ABSTRACT

Coccidioidomycosis, caused by the dimorphic pathogenic fungi Coccidioides immitis and Coccidioides posadassi, is endemic to the southwestern United states and Central and South America. The incidence of coccidioidomycosis continues to increase. Coccidioidomycosis is typically a self-limiting influenza-like respiratory illness; however, it can lead to disseminated disease outside of the lungs. Not all nondisseminated cases require therapy, but antifungal therapy is typically beneficial requiring treatment ranging from months to lifelong. Clinical factors related to treatment decisions include severity of symptoms, radiography, coccidioidomycosis serologic results, and concurrent medical problems including immunosuppression. This review summarizes the epidemiology, clinical manifestations, and treatment options.


Subject(s)
Antifungal Agents/therapeutic use , Coccidioides/pathogenicity , Coccidioidomycosis/drug therapy , Adjuvants, Immunologic , Coccidioides/isolation & purification , Coccidioidomycosis/diagnosis , Coccidioidomycosis/epidemiology , Humans , Immunocompromised Host , Lung Diseases, Fungal/epidemiology , Meningitis
9.
Clin Infect Dis ; 73(11): e3814-e3819, 2021 12 06.
Article in English | MEDLINE | ID: mdl-32778863

ABSTRACT

BACKGROUND: The natural history of non-central nervous system (non-CNS) disseminated coccidioidomycosis (DCM) has not been previously characterized. The historical Veterans Affairs (VA)-Armed Forces coccidioidomycosis patient group provides a unique cohort of patients not treated with standard antifungal therapy, allowing for characterization of the natural history of coccidioidomycosis. METHODS: We conducted a retrospective study of 531 VA-Armed Forces coccidioidomycosis patients diagnosed between 1955-1958 and followed to 1966. Groups were identified as non-DCM (462 patients), DCM (44 patients), and CNS (25 patients). The duration of the initial infection, fate of the primary infection, all-cause mortality, and mortality secondary to coccidioidomycosis were assessed and compared between groups. RESULTS: Mortality due to coccidioidomycosis at the last known follow-up was significantly different across the groups: 0.65% in the non-DCM group, 25% in the DCM group, and 88% in the CNS group (P < .001). The primary fate of pulmonary infection demonstrated key differences, with pulmonary nodules observed in 39.61% of the non-DCM group, 13.64% of the DCM group, and 20% of the CNS group (P < .001). There were differences in cavity formation, with 34.20% in the non-DCM group, 9.09% in the DCM group, and 8% in the CNS group (P < .001). Dissemination was the presenting manifestation or was concurrent with the initial infection in 41% and 56% of patients in the non-CNS DCM and CNS groups, respectively. CONCLUSIONS: This large, retrospective cohort study helps characterize the natural history of DCM, provides insight into the host immunologic response, and has direct clinical implications for the management and follow-up of patients.


Subject(s)
Coccidioidomycosis , Veterans , Antifungal Agents/therapeutic use , Coccidioides , Coccidioidomycosis/diagnosis , Coccidioidomycosis/drug therapy , Coccidioidomycosis/epidemiology , Humans , Retrospective Studies
10.
Infect Control Hosp Epidemiol ; 42(9): 1046-1052, 2021 09.
Article in English | MEDLINE | ID: mdl-32618530

ABSTRACT

OBJECTIVE: To describe the pattern of transmission of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) during 2 nosocomial outbreaks of coronavirus disease 2019 (COVID-19) with regard to the possibility of airborne transmission. DESIGN: Contact investigations with active case finding were used to assess the pattern of spread from 2 COVID-19 index patients. SETTING: A community hospital and university medical center in the United States, in February and March, 2020, early in the COVID-19 pandemic. PATIENTS: Two index patients and 421 exposed healthcare workers. METHODS: Exposed healthcare workers (HCWs) were identified by analyzing the electronic medical record (EMR) and conducting active case finding in combination with structured interviews. Healthcare coworkers (HCWs) were tested for COVID-19 by obtaining oropharyngeal/nasopharyngeal specimens, and RT-PCR testing was used to detect SARS-CoV-2. RESULTS: Two separate index patients were admitted in February and March 2020, without initial suspicion for COVID-19 and without contact or droplet precautions in place; both patients underwent several aerosol-generating procedures in this context. In total, 421 HCWs were exposed in total, and the results of the case contact investigations identified 8 secondary infections in HCWs. In all 8 cases, the HCWs had close contact with the index patients without sufficient personal protective equipment. Importantly, despite multiple aerosol-generating procedures, there was no evidence of airborne transmission. CONCLUSION: These observations suggest that, at least in a healthcare setting, most SARS-CoV-2 transmission is likely to take place during close contact with infected patients through respiratory droplets, rather than by long-distance airborne transmission.


Subject(s)
COVID-19 , Cross Infection , Cross Infection/epidemiology , Health Personnel , Humans , Infectious Disease Transmission, Patient-to-Professional , Pandemics , SARS-CoV-2
11.
Infect Dis Clin North Am ; 33(2): 545-566, 2019 06.
Article in English | MEDLINE | ID: mdl-31005138

ABSTRACT

Despite advances in chemotherapy and supportive care, morbidity and mortality remain high for patients with hematologic malignancies (HMs). Those who require hematopoietic stem cell transplantation (HSCT) often require significant immunosuppression and are subject to a variety of complications. These patients carry multiple risk factors for infectious complications, including the development of invasive fungal infections, compared with the general population. Because antifungal prophylaxis has been widely adopted, there has been a shift away from invasive candidiasis toward invasive mold infections, including breakthrough infections. For patients with HM and HSCT, we outline the epidemiology, manifestations, diagnosis, and treatment of invasive fungal infections.


Subject(s)
Hematologic Neoplasms/complications , Hematologic Neoplasms/microbiology , Hematopoietic Stem Cell Transplantation/adverse effects , Invasive Fungal Infections/etiology , Candidiasis, Invasive/drug therapy , Candidiasis, Invasive/etiology , Clinical Trials as Topic , Humans , Immunosuppression Therapy/adverse effects , Invasive Fungal Infections/drug therapy , Meta-Analysis as Topic , Risk Factors , Systematic Reviews as Topic
12.
J Clin Microbiol ; 56(12)2018 12.
Article in English | MEDLINE | ID: mdl-30257902

ABSTRACT

Coccidioidomycosis is associated with a broad spectrum of illness severity, ranging from asymptomatic or self-limited pulmonary infection to life-threatening manifestations of disseminated disease. Serologic studies before the widespread availability of antifungals established current understanding of serologic kinetics and dynamics. Chart histories and complement fixation (CF) titer trends were analyzed for 434 antifungal-treated coccidioidomycosis patients, who were classified by three infectious disease physicians as having either pulmonary uncomplicated coccidioidomycosis (PUC) (n = 248), pulmonary chronic coccidioidomycosis (PCC) (n = 64), disseminated coccidioidomycosis (DC) not including meningitis (n = 86), or coccidioidal meningitis (CM) (n = 36). The median maximal CF titers were 1:4 for PUC patients, 1:24 for PCC patients, 1:128 for DC patients, and 1:32 for CM patients. Approximately 25.4% of PUC patients, 6.2% of PCC patients, 2.3% of DC patients, and 8.3% of CM patients did not develop detectable titers during the study period. Maximal titers developed a mean of 31 days (95% confidence interval [CI], 13 to 50 days) after initial serologic positivity, with no significant differences between groups. Serologic recurrence occurred in 9% of PUC patients, 36% of PCC patients, 50% of DC patients, and 52% of CM patients. Median titer improvement rates were 91 days/dilution for PUC patients, 112 days/dilution for PCC patients, 136 days/dilution for DC patients, and 146 days/dilution for CM patients. Receiver operating characteristic (ROC) analysis revealed that CF testing retains moderate classification value for disseminated infections (area under the curve [AUC], 0.82 [95% CI, 0.78 to 0.87]) and complicated infections (AUC, 0.82 [95% CI, 0.77 to 0.86]). A suitable cutoff value for complicated infections is ≥1:32. Findings update serologic parameters that are relevant for clinical assessment of coccidioidomycosis patients in the triazole era.


Subject(s)
Coccidioidomycosis/classification , Coccidioidomycosis/immunology , Complement Fixation Tests , Adolescent , Adult , Aged , Aged, 80 and over , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Child , Child, Preschool , Coccidioides/drug effects , Coccidioides/immunology , Coccidioidomycosis/drug therapy , Female , Humans , Infant , Male , Middle Aged , ROC Curve , Sensitivity and Specificity , Time Factors , Triazoles/pharmacology , Triazoles/therapeutic use , Young Adult
13.
Cornea ; 36(11): 1423-1425, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28872517

ABSTRACT

PURPOSE: To describe a case of Coccidioides endophthalmitis that resulted in a favorable visual outcome after a combined medical and surgical approach. METHODS: A 33-year-old previously healthy woman was referred for evaluation of dyspnea and left-sided vision loss, which began 3 months before, after a trip to Nevada. She was found to have a pulmonary cavitary lesion and fluffy white material in the anterior chamber. An aqueous and vitreous paracentesis grew Coccidioides species. She was managed medically with a total of 7 weekly intravitreal injections of amphotericin B and intravenous liposomal amphotericin B followed by transition to oral posaconazole. Seven months after presentation, to ensure ocular sterilization and to clear the visual axis, she underwent temporary keratoprosthesis implantation, anterior segment reconstruction, removal of a cyclitic membrane and the crystalline lens, pars plana vitrectomy, placement of a pars plana Ahmed drainage device, and penetrating keratoplasty. RESULTS: After surgical intervention and with maintenance posaconazole therapy, the patient had resolution of her dyspnea and improved uncorrected (aphakic) vision with a clear corneal graft, quiet anterior chamber, and normal optic nerve and retina. CONCLUSIONS: A combined medical and surgical approach resulted in a favorable visual outcome and avoided the need for enucleation.


Subject(s)
Antifungal Agents/therapeutic use , Coccidioides/isolation & purification , Coccidioidomycosis/therapy , Endophthalmitis/therapy , Eye Infections, Fungal/therapy , Ophthalmologic Surgical Procedures , Adult , Amphotericin B/therapeutic use , Aqueous Humor/microbiology , Coccidioidomycosis/drug therapy , Coccidioidomycosis/microbiology , Coccidioidomycosis/surgery , Combined Modality Therapy , Endophthalmitis/drug therapy , Endophthalmitis/microbiology , Endophthalmitis/surgery , Eye Infections, Fungal/drug therapy , Eye Infections, Fungal/microbiology , Eye Infections, Fungal/surgery , Female , Humans , Intravitreal Injections , Treatment Outcome , Triazoles/therapeutic use , Vitreous Body/microbiology
14.
Infect Immun ; 82(7): 3058-65, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24799631

ABSTRACT

Compared to Cryptococcus neoformans, little is known about the virulence of the molecular types in Cryptococcus gattii. We compared in vitro virulence factor production and survival data using a Drosophila model of infection to further characterize the phenotypic features of different cryptococcal molecular types. Forty-nine different isolates were inoculated into wild-type flies and followed for survival. In vitro, isolates were assessed for growth at 30 and 37°C, melanin production, capsule size, resistance to H(2)O(2), and antifungal susceptibility. A mediator model was used to assess molecular type and virulence characteristics as predictors of survival in the fly model. VGIII was the most virulent molecular type in flies (P < 0.001). At 30°C, VGIII isolates grew most rapidly; at 37°C, VNI isolates grew best. C. gattii capsules were larger than those of C. neoformans (P < 0.001). Mediator model analysis found a strong correlation of Drosophila survival with molecular type and with growth at 30°C. We found molecular-type-specific differences in C. gattii in growth at different temperatures, melanin production, capsule size, ability to resist hydrogen peroxide, and antifungal susceptibility, while growth at 30°C and the VGIII molecular type were strongly associated with virulence in a Drosophila model of infection.


Subject(s)
Cryptococcus gattii/genetics , Cryptococcus gattii/pathogenicity , Drosophila melanogaster/microbiology , Animals , Antifungal Agents/therapeutic use , Cryptococcus gattii/cytology , Cryptococcus gattii/drug effects , Cryptococcus gattii/physiology , Drug Resistance, Fungal , Gene Expression Regulation, Bacterial , Melanins/metabolism , Virulence
15.
Med Mycol ; 51(3): 319-23, 2013 Apr.
Article in English | MEDLINE | ID: mdl-22680977

ABSTRACT

The clinical manifestations of coccidioidomycosis vary depending upon the extent of exposure and immune status of the host. Recent studies have demonstrated an essential role for vitamin D in both innate and acquired immunity and serum levels strongly correlate with the development of upper respiratory tract infections, including tuberculosis. Despite similar pathophysiologic processes at play in the control of tuberculosis and invasive fungal infections, a possible association of low serum 25(OH) vitamin D levels had not previously been assessed in the latter patient group. Therefore, we performed a case-control study examining serum 25(OH) vitamin D levels in three distinct groups of patients with coccidioidomycosis as compared to healthy uninfected controls. Of the 89 patients included in this study, there were 26 negative controls, 23 who were immune, 22 with primary coccidioidal pneumonia, and 18 who had disseminated/meningeal infection. Serum 25(OH) vitamin D levels varied between groups with lowest levels seen in the group with disseminated/meningeal coccidioidomycosis (P= 0.14). In this evaluation of a diverse group of patients with varying forms of coccidioidomycosis we found no association of vitamin D with the acquisition or resolution of this infection. Vitamin D does not play a significant role in host susceptibility to coccidioidomycosis.


Subject(s)
Coccidioidomycosis/epidemiology , Coccidioidomycosis/pathology , Vitamin D/analogs & derivatives , Adult , Aged , Case-Control Studies , Disease Susceptibility , Female , Humans , Lung Diseases, Fungal/epidemiology , Lung Diseases, Fungal/pathology , Male , Meningitis, Fungal/epidemiology , Meningitis, Fungal/pathology , Middle Aged , Serum/chemistry , Vitamin D/blood
16.
Chest ; 143(3): 776-781, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23187746

ABSTRACT

BACKGROUND: In a patient with positive serum serology for coccidioidomycosis, the differential diagnosis of concurrent pleural effusions can be challenging. We, therefore, sought to clarify the performance characteristics of biochemical, serologic, and nucleic-acid-based testing in an attempt to avoid invasive procedures. The utility of adenosine deaminase (ADA), coccidioidal serology, and polymerase chain reaction (PCR) in the evaluation of pleuropulmonary coccidioidomycosis has not been previously reported. METHODS: Forty consecutive patients evaluated for pleuropulmonary coccidioidomycosis were included. Demographic data, pleural fluid values, culture results, and clinical diagnoses were obtained from patient chart review. ADA testing was performed by ARUP Laboratories, coccidioidal serologic testing was performed by the University of California-Davis coccidioidomycosis serology laboratory, and PCR testing was performed by the Translational Genomics Research Institute using a previously published methodology. RESULTS: Fifteen patients were diagnosed with pleuropulmonary coccidioidomycosis by European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria. Pleural fluid ADA concentrations were < 40 IU/L in all patients (range, < 1.0-28.6 IU/L; median, 4.7). The sensitivity and specificity of coccidioidal serologic testing was 100% in this study. The specificity of PCR testing was high (100%), although the overall sensitivity remained low, and was comparable to the experience of others in the clinical use of PCR for coccidioidal diagnostics. CONCLUSION: Contrary to prior speculation, ADA levels in pleuropulmonary coccidioidomycosis were not elevated in this study. The sensitivity and specificity of coccidioidal serologic testing in nonserum samples remained high, but the clinical usefulness of PCR testing in pleural fluid was disappointing and was comparable to pleural fluid culture.


Subject(s)
Adenosine Deaminase/blood , Coccidioidomycosis/diagnosis , Lung Diseases, Fungal/diagnosis , Pleural Effusion/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Child , Coccidioidomycosis/enzymology , Complement Fixation Tests , Female , Humans , Lung Diseases, Fungal/enzymology , Male , Middle Aged , Polymerase Chain Reaction , Sensitivity and Specificity , Young Adult
17.
J Clin Microbiol ; 50(9): 3060-2, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22692738

ABSTRACT

The serum (1→3)-ß-d-glucan assay has emerged as an important diagnostic test for invasive fungal disease. The utility of this assay in coccidioidomycosis has not been previously studied. Using a cutoff value of ≥80 pg/ml, we found the sensitivity (43.9%), specificity (91.1%), positive predictive value (81.8%), and negative predictive value (64.1%) to be similar to those of the assay in diagnosing other invasive mycoses.


Subject(s)
Coccidioidomycosis/diagnosis , Serum/chemistry , beta-Glucans/blood , Humans , Predictive Value of Tests , Proteoglycans , Sensitivity and Specificity
18.
Antimicrob Agents Chemother ; 56(1): 563-4, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22005993

ABSTRACT

The use of voriconazole, a trifluorinated antifungal, has been associated with the development of fluoride excess and periostitis/exostoses. We evaluated a cohort of patients on long-term triazole therapy and found that other fluorinated triazoles (fluconazole and posaconazole) conferred no risk for the development of hyperfluorosis and its complications in our cohort.


Subject(s)
Antifungal Agents/adverse effects , Coccidioidomycosis/drug therapy , Fluconazole/administration & dosage , Pyrimidines/adverse effects , Triazoles/administration & dosage , Triazoles/adverse effects , Adolescent , Adult , Antifungal Agents/administration & dosage , Coccidioides/drug effects , Coccidioides/growth & development , Coccidioidomycosis/microbiology , Cohort Studies , Exostoses/chemically induced , Female , Fluorides/metabolism , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Periostitis/chemically induced , Pyrimidines/administration & dosage , United States , Voriconazole
19.
Clin Infect Dis ; 53(6): e20-4, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21865185

ABSTRACT

BACKGROUND: We have observed a number of patients who fail to develop coccidioidal complement fixing (CF) antibody (immunoglobulin [IgG]) after the initiation of early antifungal therapy. Although this is the first description of this phenomenon in mycology, a precedent for the abrogation of the immune response has been observed in other conditions, including primary syphilis and primary Lyme disease. METHODS: We conducted a retrospective case-control study to determine any patient-specific risk factors associated with this observation. Additionally, in vitro analysis of the coccidioidal CF (IgG) antigen (Cts1) was performed after Coccidioides was grown under escalating fluconazole concentrations. RESULTS: Seventeen patients persistently positive for coccidioidal IgM antibodies without developing an IgG response (cases) were compared with 64 consecutive patients who did develop coccidioidal CF (IgG) antibodies (controls). Early treatment with antifungals (within 2 weeks of symptom onset) was associated with an abrogation of IgG antibody production (P < .001). With immunodiffusion testing, control serum demonstrated a lack of IgG seroreactivity when Coccidioides posadasii grown in the presence of escalating fluconazole doses (0.5-128 µg/mL) was used as the antigen; however, control serum remained seroreactive for the presence of IgM. The coccidioidal IgG antigen (Cts1) was shown to be diminished when cultures were grown in the presence of fluconazole, lending further in vitro plausibility to our findings. CONCLUSIONS: The abrogation of an IgG response in patients treated early in the course of coccidioidal infection may complicate serodiagnosis and epidemiologic studies, and further study to determine the potential clinical implications should be performed.


Subject(s)
Antibodies, Fungal/biosynthesis , Antifungal Agents/therapeutic use , Coccidioides/immunology , Coccidioidomycosis/drug therapy , Coccidioidomycosis/immunology , Fluconazole/therapeutic use , Immunoglobulin G/biosynthesis , Adaptive Immunity/drug effects , Adult , Aged , Antibodies, Fungal/blood , Antibodies, Fungal/immunology , Antigens, Fungal/genetics , Antigens, Fungal/immunology , Antigens, Fungal/metabolism , Case-Control Studies , Chitinases/genetics , Chitinases/metabolism , Female , Fungal Proteins/genetics , Fungal Proteins/metabolism , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/immunology , Humans , Immunodiffusion , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/biosynthesis , Immunoglobulin M/blood , Immunoglobulin M/immunology , Male , Middle Aged , Retrospective Studies , Risk Factors
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