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Coccidioidomycosis is a common cause of community-acquired pneumonia in endemic regions. Approximately 20 000 cases of coccidioidomycosis occur annually; however, this statistic is limited by a widespread lack of testing. Here, we analyze emergency medicine provider attitudes toward coccidioidal testing and assess the effect of an intervention to improve testing rates. [ABSTRACT FROM AUTHOR]

Deep sternal wound infection is a rare complication of cardiac surgery that is typically caused by skin resident flora, such as species of Staphylococcus and Streptococcus. Infections caused by fungi are less common and are generally caused by Candida species. Regardless of etiology, these infections are associated with significant morbidity and mortality. We present a case of postoperative mediastinitis that occurred following a 5-vessel coronary artery bypass graft and was caused by a filamentous fungus of the Rhizopus genus. The patient was treated with serial debridement, liposomal amphotericin B, and isavuconazonium and was discharged from the hospital in stable condition. Fungal mediastinitis is a rare entity, and clinicians must maintain a high level of suspicion to make the diagnosis. A fungal cause of postoperative mediastinitis should be considered in patients with negative bacterial cultures, uncontrolled diabetes, or current immunosuppression or those who present weeks after surgery with a subacute onset of symptoms. [ABSTRACT FROM AUTHOR]

Central nervous system infection with Coccidioides spp. is fatal if untreated and complications occur even when therapy is directed by experienced clinicians. We convened a panel of clinicians experienced in the management of coccidioidal meningitis to summarize current controversies and provide consensus for the management of this difficult infection. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis is a fungal disease endemic to the southwestern United States, Mexico, and Central and South America. Prevalence rates are increasing steadily, and new endemic areas of Coccidioides are emerging. Standard treatment is often administered for months to decades, and intolerance to medications and treatment failures are common. No new treatments for coccidioidomycosis have been approved in the United States in nearly 40 years. On 5 August 2020, the US Food and Drug Administration convened experts in coccidioidomycosis from academia, industry, patient groups, and other government agencies to discuss the disease landscape and strategies to facilitate product development for treatment of coccidioidomycosis. This article summarizes the key topics concerning drug development for coccidioidomycosis presented by speakers and panelists during the workshop, such as unmet need, trial designs, endpoints, incentives, research and development support, and collaborations to facilitate antifungal drug development. [ABSTRACT FROM AUTHOR]

Approximately 5 to 15% of patients with pulmonary coccidioidomycosis subsequently develop pulmonary cavities. These cavities may resolve spontaneously over a number of years; however, some cavities never close, and a small proportion causes complications such as hemorrhage, pneumothorax or empyema. The impact of azole antifungal treatment on coccidioidal cavities has not been studied. Because azoles are a common treatment for symptomatic pulmonary coccidioidomycosis, we aimed to assess the impact of azole therapy on cavity closure. From January 1, 2004, through December 31, 2014, we retrospectively identified 313 patients with cavitary coccidioidomycosis and excluded 42 who had the cavity removed surgically, leaving 271 data sets available for study. Of the 271 patients, 221 (81.5%) received azole therapy during 5-year follow-up; 50 patients did not receive antifungal treatment. Among the 271 patients, cavities closed in 38 (14.0%). Statistical modeling showed that cavities were more likely to close in patients in the treated group than in the nontreated group (hazard ratio, 2.14 [95% CI: 1.45–5.66]). Cavities were less likely to close in active smokers than nonsmokers (11/41 [26.8%] vs 97/182 [53.3%]; P  = 0.002) or in persons with than without diabetes (27/74 [36.5%] vs 81/149 [54.4%]; P  = 0.01).We did not find an association between cavity size and closure. Our findings provide rationale for further study of treatment protocols in this subset of patients with coccidioidomycosis. Lay Summary Coccidioidomycosis, known as valley fever, is a fungal infection that infrequently causes cavities to form in the lungs, which potentially results in long-term lung symptoms. We learned that cavities closed more often in persons who received antifungal drugs, but most cavities never closed completely. [ABSTRACT FROM AUTHOR]

Background Coccidioidomycosis is often diagnosed with a collection of tests that rely on the patient's ability to mount an immune response to the fungus (antibody-based diagnostics), making diagnosis of this infection challenging. Here we present an antigen-based assay that detects and quantifies coccidioidal chitinase-1 (CTS1) in human serum. Methods An inhibition-based enzyme-linked immunoassay (ELISA) was developed that utilizes a monoclonal antibody specific for coccidioidal CTS1. CTS1 was quantified in commercial antigen preparations using recombinant CTS1 as a standard. Sera from 192 individuals from an endemic area were tested, which included 78 patients (40.6%) with proven or probable coccidioidomycosis. Results The quantity of CTS1 in diagnostic commercial antigen preparations from different suppliers varied. CTS1 antigenemia was detected in 87.2% of patients with proven or probable coccidioidomycosis. Specificity was determined to be 96.94% using serum from individuals who reside in the Phoenix, Arizona area who did not have coccidioidomycosis. Levels of CTS1 correlated with low- and high-titer serology from patients with a coccidioidomycosis diagnosis. Conclusions Since the CTS1 inhibition ELISA described in this report does not depend on the host immune response, it is a promising diagnostic tool to aid in diagnosis and disease monitoring of coccidioidomycosis. [ABSTRACT FROM AUTHOR]

Coccidioides fungi are found primarily in the southwestern United States and are the cause of coccidioidomycosis. Tumor necrosis factor α inhibitors (TNFIs) are therapies for autoimmune and inflammatory conditions; their association with coccidioidomycosis is not well characterized. We aimed to determine the prevalence and characteristics of coccidioidomycosis among TNFI recipients with different inflammatory disorders at a tertiary care center. We retrospectively reviewed the electronic health records of patients at our institution from April 4, 2010 to December 17, 2017, who received TNFIs (infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab) and had positive culture, pathologic, and/or serologic results for coccidioidomycosis. Among 1770 patients identified who received TNFIs, 49 (2.8%) had proven or probable coccidioidomycosis. Of these 49, 28 (57%) were men, 47 (96%) were White, and 42 (86%) had pulmonary coccidioidomycosis. The most common TNFIs used were adalimumab, infliximab, and etanercept. Coccidioidomycosis was identified in 25 of 794 patients with rheumatologic disorders (3.1%), 18 of 783 patients with inflammatory bowel disease (IBD) (2.3%), and six of 193 patients with dermatologic disorders (3.1%) (P  = .34). There was no difference in coccidioidal infections among recipients of any particular TNFI agents. A minority of patients (7/49, 14%) had an extrapulmonary infection, and the majority of these (6/7) had IBD. Our study shows a low prevalence of coccidioidomycosis in TNFI recipients, even within the Coccidioides -endemic area. Persons with IBD were disproportionately represented among those with extrapulmonary coccidioidomycosis. Treatment with azoles was effective. Lay Summary Among 1770 patients who received tumor necrosis factor α inhibitors, 49 (2.8%) had newly acquired coccidioidomycosis over a 7-year period. Dissemination occurred in 14.3%, but disproportionately among those with underlying inflammatory bowel disease. All patients recovered with medical management. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis is an endemic fungal infection of the desert southwestern United States. Intact cellular immunity is critical to the control of this infection. A recently released reformulated spherulin antigen (Spherusol; Nielsen BioSciences, Inc.) was approved to detect delayed-type hypersensitivity, which implies the presence of cellular immunity, to Coccidioides species. We aimed to summarize our experience with this test in patients with primary pulmonary coccidioidomycosis. We retrospectively reviewed clinical data for all patients with primary pulmonary coccidioidomycosis who had a Coccidioides (spherulin) skin test (CST) placed at our institution between January 1, 2015, and August 31, 2017. During the study period, 172 patients had a CST placed, and 122 met our inclusion criteria for proven or probable pulmonary coccidioidomycosis. Of these 122, 88 (72.1%) had a positive CST result and 34 (27.9%) had a negative result. In the positive CST group, 74 of the 79 treated patients (93.7%) had antifungal treatment stopped, 1 of whom (1.4%) had relapsed infection. In contrast, 27 of the 33 treated patients in the negative CST group (81.8%) had their antifungal treatment stopped, and none had a relapse. Seven patients overall (5.7%), all of whom had a positive CST, experienced mild local adverse reactions to the CST. Although previous controlled studies of CST showed sensitivity and specificity greater than 98%, our real-world experience with the CST showed lower rates of positivity. Negative CST results did not predict relapse with antifungal agent withdrawal. [ABSTRACT FROM AUTHOR]

The care of primary pulmonary coccidioidomycosis remains challenging. Such infections produce a variety of signs, symptoms, and serologic responses that cause morbidity in patients and concern in treating clinicians for the possibility of extrapulmonary dissemination. Illness may be due to ongoing fungal growth that produces acute inflammatory responses, resulting in tissue damage and necrosis, and for this, administering an antifungal drug may be of benefit. In contrast, convalescence may be prolonged by other immunologic reactions to infection, even after fungal replication has been arrested, and in those situations, antifungal therapy is unlikely to yield clinical improvement. In this presentation, we discuss what findings are clinical indicators of fungal growth and what other sequelae are not. Understanding these differences provides a rational management strategy for deciding when to continue, discontinue, or reinstitute antifungal treatments. [ABSTRACT FROM AUTHOR]

Background Tumor necrosis factor α inhibitors (TNFi) are commonly used to treat immune-mediated disorders, but they are associated with an increased risk of mycobacterial and fungal infections. We compared the outcomes of TNFi recipients screened for asymptomatic coccidioidomycosis with those of unscreened patients to compare the development of symptomatic coccidioidomycosis and to describe its outcomes for patients with abnormal coccidioidal screenings. Methods We searched electronic health records from 4 September 2010 through 26 September 2016 for all patients receiving a TNFi for dermatologic, rheumatologic, or gastroenterologic diagnoses, then categorized patients by whether or not they had undergone coccidioidal serologic testing for screening or diagnostic purposes. Results A total of 2793 patients had a TNFi prescribed. Of those, 1951 met the inclusion criteria: 1025/1951 (52.5%) never had coccidioidal screening; 925/1951 (47.4%) had serologic screening either before beginning TNFi therapy or annually, or both after beginning a TNFi. Symptomatic coccidioidomycosis developed in 35/1025 (3.4%) unscreened patients. Of those screened, 861/925 (93.1%) had negative serologic tests, of which 11/861 (1.3%) subsequently developed symptomatic coccidioidomycosis; 36/925 (3.9%) had coccidioidomycosis at screening (7, probable infection; 11, possible infection; 18, asymptomatic seropositive result); and 17 had only positive findings for immunoglobulin M antibodies and did not meet the definition for coccidioidomycosis. The unscreened cohort was more likely to have symptomatic coccidioidomycosis than the screened cohort (35/1025 vs 11/861, P <.01). Conclusions Screening for asymptomatic coccidioidomycosis within a Coccidioides -endemic area allowed for identifying and managing asymptomatic coccidioidomycosis before patients began TNFi therapy. Less symptomatic infection developed in the screened than the unscreened cohort. [ABSTRACT FROM AUTHOR]

After contracting coccidioidomycosis, persons with impaired cellular immunity are more likely than healthy persons to have severe infection, disseminated infection, and higher mortality rates. In this brief review, we summarize the clinical manifestations, diagnosis, treatment, and prevention of coccidioidomycosis in persons infected with human immunodeficiency virus (HIV), recipients of solid organ or hematopoietic stem cell transplants, and recipients of biologic response modifiers. Among individuals infected with HIV, a diagnosis of acquired immunodeficiency syndrome (AIDS) and a CD4 T-lymphocyte count <250 cells/μl were associated with more severe coccidioidomycosis, whereas less severe disease occurred among those with undetectable HIV-RNA and higher CD4 T-lymphocyte counts, indicating that controlled HIV viremia and improved cellular immune status are important in limiting disease. For transplant recipients whose immunosuppression typically peaks in the first 3 to 6 months and tapers thereafter, the greatest risk of acute coccidioidomycosis occurs 6 to 12 months after transplantation. Relapses of recent coccidioidomycosis may occur during ongoing immunosuppression when patients are not taking suppressive antifungal medication. Recipients of biologic agents, especially those that impair tumor necrosis factor α (TNF-α), may be at increased risk for poorly controlled coccidioidomycosis; however, the best way to prevent and treat such infections has yet to be defined. [ABSTRACT FROM AUTHOR]

Coccidioidal meningitis (CM) has high morbidity, and adjunctive measures to improve outcomes are needed. Using an established multicenter retrospective cohort study of CM (N = 221), we found that patients receiving adjunctive corticosteroids had a significant reduction in secondary cerebrovascular events (P = .0049). Those with CM-associated cerebrovascular events (8%) may benefit from short-term corticosteroids. [ABSTRACT FROM AUTHOR]

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure. [ABSTRACT FROM AUTHOR]

Primary pulmonary coccidioidomycosis is characterized by prolonged respiratory and systemic symptoms and fatigue. We prospectively administered the fatigue severity scale (FSS) and Short Form-36 Health Status Questionnaire (SF-36) to patients with proven or probable primary pulmonary coccidioidomycosis to quantify disease effect on quality of life (QOL). The 24-week observational study did not specify whether antifungal treatment would be provided; the treating physician made treatment decisions. FSS and SF-36 were completed at 4-week intervals. Thirty-six patients participated, of whom 20 received antifungal treatment. At onset of coccidioidal illness, mean FSS score was higher (ie, more fatigue) in the treatment group. However, in early illness, both groups had higher fatigue levels than reference populations with other diseases (eg, multiple sclerosis). FSS scores gradually improved, and scores in each group were below the severe fatigue level at week 12 and week 16 in the nontreatment and treatment groups, respectively. By week 24, mean FSS score of the nontreatment group equaled the general population. SF-36 component and profile scores were lower (with more symptoms) in the treatment group at each time point than the nontreatment group; both groups showed similar improvement. Mental and emotional health SF-36 scores were not as severely affected as physical scores. Most patients reached a physical functioning level similar to the general population at week 12. Pulmonary coccidioidomycosis causes severe fatigue and substantially affects physical abilities. Fatigue was found to be prolonged, with gradual improvement in QOL, regardless of antifungal administration. [ABSTRACT FROM AUTHOR]

Background. Tenosynovitis is an uncommon manifestation of disseminated infection with Coccidioides fungal species. Most experts treat this infection with combined surgical debridement and antifungal medication. The aim of our study was to examine the outcomes of patients with coccidioidal tenosynovitis of the hand and wrist. Methods. We retrospectively searched for the records of patients with coccidioidal tenosynovitis of the hand and wrist at our institution. between 1987 and 2013. We also conducted a review of the literature from 1950 to 2014 to identify additional cases. Results. We identified 9 cases of coccidioidal tenosynovitis of the hand and wrist at our institution, along with 5 other cases found in a review of the literature. The relapse rate was high overall (50%) and was higher after discontinuation of antifungal therapy (71%) in both immunocompromised and immunocompetent patients. Results of serologic testing were not predictive of relapse. Conclusions. A treatment strategy for coccidioidal tenosynovitis should focus on long-term administration of antifungal agents. [ABSTRACT FROM AUTHOR]

Patients with coccidioidomycosis often report prolonged and debilitating fatigue after other evidence of infection has resolved. In this study, we quantify fatigue, muscle weakness, and impaired aerobic capacity in 5 such individuals. A closer examination of the cardiorespiratory system may contribute to a better understanding of underlying mechanisms and potential interventions. [ABSTRACT FROM AUTHOR]

Background. Coccidioidomycosis is a fungal infection of the desert southwestern United States. It may be selflimited or may require antifungal therapy. Currently used triazoles (eg, fluconazole and itraconazole) have largely supplanted amphotericin B, which is fraught with adverse effects. Limited case reports and small open-label trials show that voriconazole and posaconazole benefit patients with coccidioidomycosis refractory to first-line agents. Methods. We conducted a retrospective review of patients prescribed voriconazole or posaconazole for coccidioidomycosis at our institution between 1 January 2006 and 1 August 2010. Outcomes were assessed with both a retrospectively applied Mycosis Study Group score (ie, a composite score for symptoms, serology, and radiographic findings) and the documented impressions of treating medical practitioners. Results. Twenty-one patients who received voriconazole and 16 who received posaconazole met study criteria. After a median duration of 6 months of voriconazole treatment, 14 of 21 patients (67%) were improved in overall status, 5 were unchanged, and 2 were unresponsive to voriconazole. After a median of 17 months of posaconazole treatment, 12 of 16 patients (75%) showed improvement, 1 was unchanged, and 3 were unresponsive due to medication intolerance or relapsed infection. Conclusions. Voriconazole and posaconazole are reasonable but not infallible options for salvage treatment of refractory coccidioidomycosis. Prospective comparative trials are required to provide further insights into their efficacy and utility. [ABSTRACT FROM AUTHOR]

Background. Coccidioidomycosis is a fungal infection acquired via inhalation of airborne fungal arthrospores of Coccidioides species in regions of endemicity in the deserts of the southwestern United States and northern Mexico. In recent years, the incidence of coccidioidomycosis has increased in areas of endemicity, and previous studies have found the highest incidence of coccidioidal infection in Arizona among persons in older age groups. Methods. We conducted a retrospective review of data for all patients with coccidioidomycosis who were treated at our institution that compared clinical manifestations of coccidioidomycosis in patients aged ⩾60 years with those in patients aged <60 years. Results. We compared 210 patients aged ⩾60 years with 186 patients aged <60 years. No significant differences were observed with regard to manifestations of coccidioidomycosis, even after adjustment for comorbid conditions, excluding immunosuppression. Regardless of age, when coccidioidal illnesses in immunosuppressed patients were compared with those in nonimmunosuppressed patients, immunosuppressed patients were significantly more likely to have extrapulmonary dissemination of infection, to require hospitalization, and to have progressive infection or to die of coccidioidomycosis. Univariate logistic regression identified immunosuppression as the only marker that increased risk of extrapulmonary dissemination of infection (odds ratio, 2.13; Pp.05), hospitalization (odds ratio, 2.68; P < .001), and death (odds ratio, 8.39; P < .001). Multivariate analysis revealed that neither age nor an interaction of age and immunosuppression had a significant impact on coccidioidal manifestations. Conclusions. Coccidioidomycosis is a serious illness in all patients, but its different manifestations in older-aged persons, compared with those in younger-aged persons, may be related to immunosuppression rather than age alone. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis is an endemic fungal infection of the desert southwestern United States that can cause devastating disseminated infection in immunocompromised persons. Clinical coccidioidomycosis, which is caused by Coccidioides species , has been well characterized in patients who have had solid organ transplants, but it has rarely been described in patients who have received a hematopoietic stem cell transplant (HSCT). We report the experience of 121 consecutive HSCT recipients at a single tertiary care institution in an endemic area. One patient had fatal disseminated coccidioidomycosis after receiving an allogeneic transplant, and 2 patients had pulmonary infection before successful autologous HSCT; 1 of these 2 had a reactivation of coccidioidal infection after HSCT but was treated and survived. Coccidioidomycosis was not commonly identified in HSCT recipients, even in the endemic area. A prospective evaluation is required to address the optimal use of coccidioidal serologic tests, antifungal protocols, and secondary prophylaxis in these patients. [ABSTRACT FROM AUTHOR]

The article offers a practice guideline to provide recommendations for treatment of coccidioidomycosis. Management of coccidioidomycosis first involves recognizing that a coccidioidal infection exists, defining the extent of infection, and identifying host factors that predispose to disease severity. After these assessments, patients with localized acute pulmonary infections and no risk factors for complications often require only periodic reassessment to demonstrate resolution of their self-limited process. On the other hand, patients with extensive spread of infection or who are at high risk of complications because of immunosuppression or other preexisting factors require a variety of treatment strategies that may include antifungal drug therapy, surgical debridement, or a combination of both. Therapy often ranges from many months to years in duration, and in some patients, lifelong suppressive therapy is needed to prevent relapses.

Provides information on coccidioidomycosis, an endemic fungal infection related to solid organ transplantation. Demographic characteristics of patients with coccidioidomycosis; Incidence of coccidioidomycosis after transplantation; Risk factors for coccidioidomycosis; Clinical manifestation of the infection.

Reports on a case of bacteremia, pyelonephritis and epididymitis due to aeromonas hydrophila following exposure to a recreational water source not previously described to be a risk factor for aeromonas infections. Clinical manifestations; Results of medical examination; Clinical findings.

Background Making the decision to stop antifungal therapy in patients with coccidioidomycosis can be challenging in patients with risk factors for relapsed infection. Spherulin-based coccidioidal skin testing was re-introduced to the market in 2014 and approved for the detection of delayed-type hypersensitivity in patients with a history of pulmonary coccidioidomycosis Methods We searched electronically for patients who had a spherulin skin test placed in our institution from January 1, 2015 through March 1, 2017, and then included patients age 18 years and older who met the definition for confirmed or probable pulmonary coccidioidomycosis. A retrospective chart review was conducted, and included details of clinical illness, antifungal treatment, serology, and chest imaging Results From January 1, 2015 to August 31, 2017, 172 patients with coccidioidomycosis had a spherulin skin test placed. We included for further study the 129 patients who had primary pulmonary coccidioidomycosis, followed for a median of 18 months (range 0–50 months); 56 (43.4/%) were male, 108 (85.7/%) Caucasian, median age was 55 years (range18–89).19/12914.7%)) were smokers, 14/129 (10.9%) were diabetic, 2 patients had HIV (1.6%) and 15/129 (11.6) we immunocompromised without HIV. 116/129(89.9%) % received antifungal treatment. Median time from illness to skin test was 13.5 months (range 0–78). Eighty-nine of 129 patients (69%) had a positive skin test, 40 (31%) had a negative test. Antifungal treatment was subsequently discontinued in 75/89 (84%), and one patient (1.2%) with a positive test, experienced relapsed infection. Among 30/40 with negative CST, antifungals were discontinued and none relapsed. Conclusion The presence of delayed-type hypersensitivity to coccidioidomycosis, manifested by a positive spherulin skin test, was associated with discontinuation of antifungal therapy, and a low percentage of relapsed infection. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]