Neil M. Ampel

Practice Guidelines for the Treatment of Coccidioidomycosis

Management of patients diagnosed with coccidioidomycosis involves defining the extent of infection and assessing host factors that predispose to disease severity. Patients with relatively 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 at high risk of complications because of immunosuppression or other preexisting factors require a variety of treatment strategies that may include antifungal therapy, surgical debridement, or both. Amphotericin B is often selected for treatment of patients with respiratory failure due to Coccidioides immitis or rapidly progressive coccidioidal infections. With other more chronic manifestations of coccidioidomycosis, treatment with fluconazole, itraconazole, or ketoconazole is common. Duration of therapy often ranges from many months to years, and, for some patients, chronic suppressive therapy is needed to prevent relapses.

An Official American Thoracic Society Statement: Treatment of Fungal Infections in Adult Pulmonary and Critical Care Patients

With increasing numbers of immune-compromised patients with malignancy, hematologic disease, and HIV, as well as those receiving immunosupressive drug regimens for the management of organ transplantation or autoimmune inflammatory conditions, the incidence of fungal infections has dramatically increased over recent years. Definitive diagnosis of pulmonary fungal infections has also been substantially assisted by the development of newer diagnostic methods and techniques, including the use of antigen detection, polymerase chain reaction, serologies, computed tomography and positron emission tomography scans, bronchoscopy, mediastinoscopy, and video-assisted thorascopic biopsy. At the same time, the introduction of new treatment modalities has significantly broadened options available to physicians who treat these conditions. While traditionally antifungal therapy was limited to the use of amphotericin B, flucytosine, and a handful of clinically available azole agents, current pharmacologic treatment options include potent new azole compounds with extended antifungal activity, lipid forms of amphotericin B, and newer antifungal drugs, including the echinocandins. In view of the changing treatment of pulmonary fungal infections, the American Thoracic Society convened a working group of experts in fungal infections to develop a concise clinical statement of current therapeutic options for those fungal infections of particular relevance to pulmonary and critical care practice. This document focuses on three primary areas of concern: the endemic mycoses, including histoplasmosis, sporotrichosis, blastomycosis, and coccidioidomycosis; fungal infections of special concern for immune-compromised and critically ill patients, including cryptococcosis, aspergillosis, candidiasis, and Pneumocystis pneumonia; and rare and emerging fungal infections.

Coccidioidomycosis during human immunodeficiency virus infection: results of a prospective study in a coccidioidal endemic area

PURPOSE To determine the incidence of active coccidioidomycosis among subjects infected with the human immunodeficiency virus (HIV) living in an area endemic for coccidioidomycosis and to identify factors associated with the development of active coccidioidomycosis in these patients. PATIENTS AND METHODS This was a prospective cohort analysis of HIV-infected subjects living in an area endemic for coccidioidomycosis in Arizona. On entry and at approximately 4-month intervals, subjects were interviewed and examined, and had spherulin skin testing and CD4 lymphocyte counts performed along with other tests. During each interval, it was determined whether the subject had developed active coccidioidomycosis according to established criteria. RESULTS One hundred seventy subjects entered the study. Median follow-up was 11.3 months (range: 0 to 44 months). Thirteen subjects developed active coccidioidomycosis, with an estimated cumulative incidence of 24.6% by 41 months (95% confidence limits 8.2% and 41.1%). Risk factors associated with the development of active coccidioidomycosis in the cohort were a CD4 lymphocyte count of less than 0.250 x 10(9)/L and a diagnosis of acquired immunodeficiency syndrome. Factors associated with prior coccidioidal infection, including a positive spherulin skin test, length of residence in the endemic area for more than 25 months, and a prior history of coccidioidomycosis, were not associated with the development of active infection. CONCLUSION Active coccidioidomycosis among individuals infected with HIV is common in the coccidioidal endemic area. Immunodeficiency appears to be the major risk factor for the development of disease. Evidence of prior coccidioidomycosis, including a positive spherulin skin test, does not appear to predict the development of active infection.

Coccidioidomycosis during human immunodeficiency virus infection: A review of 77 patients

Through a retrospective review, we identified 77 previously unreported cases of coccidioidomycosis during HIV infection. Patients were classified into 1 of 6 categories based on their primary clinical presentation: 20 had focal pulmonary disease (Group 1), 31 had diffuse pulmonary disease (Group 2), 4 had cutaneous coccidioidomycosis (Group 3), 9 had meningitis (Group 4), 7 had extrathoracic lymph node or liver involvement (Group 5), and 6 has positive coccidioidal serology without a clinical focus of infection (Group 6). Coccidioidal serologies were positive on initial testing in 83% of the patients in whom such serologic testing was performed. Sera from 39% of patients were positive for TP antibodies while 74% had CF antibodies. Eleven of 12 seronegative patients had pulmonary disease (Group 1 or 2). Serologic results of other patients sent to a single reference laboratory were similar, with 26% positive for immunodiffusion TP antibodies and 79% positive for immunodiffusion CF antibodies. For the 77 patients in this study, the CD4-lymphocyte count was below 0.250 X 10(9) cells/L in 46 of the 55 patients who had this test performed, and a low CD4 count was significantly associated with mortality (p less than 0.01). At the time of follow-up, 32 of the 77 patients (42%) had died. There were significantly more deaths in those with diffuse pulmonary disease (Group 2) than in other groups (p less than 0.001). Amphotericin B, ketoconazole, fluconazole, and itraconazole were all used as antifungal therapies. Outcome could not be related to the therapy used. Of note, 3 patients developed coccidioidomycosis while receiving ketoconazole for other conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Coccidioidomycosis as a Common Cause of Community-acquired Pneumonia

The early manifestations of coccidioidomycosis (valley fever) are similar to those of other causes of community-acquired pneumonia (CAP). Without specific etiologic testing, the true frequency of valley fever may be underestimated by public health statistics. Therefore, we conducted a prospective observational study of adults with recent onset of a lower respiratory tract syndrome. Valley fever was serologically confirmed in 16 (29%) of 55 persons (95% confidence interval 16%–44%). Antimicrobial medications were used in 81% of persons with valley fever. Symptomatic differences at the time of enrollment had insufficient predictive value for valley fever to guide clinicians without specific laboratory tests. Thus, valley fever is a common cause of CAP after exposure in a disease-endemic region. If CAP develops in persons who travel or reside in Coccidioides-endemic regions, diagnostic evaluation should routinely include laboratory evaluation for this organism.

Recent Advances in Our Understanding of the Environmental, Epidemiological, Immunological, and Clinical Dimensions of Coccidioidomycosis

SUMMARY Coccidioidomycosis is the endemic mycosis caused by the fungal pathogens Coccidioides immitis and C. posadasii. This review is a summary of the recent advances that have been made in the understanding of this pathogen, including its mycology, genetics, and niche in the environment. Updates on the epidemiology of the organism emphasize that it is a continuing, significant problem in areas of endemicity. For a variety of reasons, the number of reported coccidioidal infections has increased dramatically over the past decade. While continual improvements in the fields of organ transplantation and management of autoimmune disorders and patients with HIV have led to dilemmas with concurrent infection with coccidioidomycosis, they have also led to advances in the understanding of the human immune response to infection. There have been some advances in therapeutics with the increased use of newer azoles. Lastly, there is an overview of the ongoing search for a preventative vaccine.

Barriers to Use of Electronic Adherence Monitoring in an HIV Clinic

OBJECTIVE: To evaluate barriers to Medication Event Monitoring System (MEMS) measurement of adherence to combination antiretroviral therapy in an HIV clinic. DESIGN: Descriptive, cross-sectional study measured MEMS adherence to one antiretroviral for one month. SETTING: HIV clinic in a Veterans Affairs Medical Center. PARTICIPANTS: Sixty-four men on a stable antiretroviral treatment regimen. MAIN OUTCOME MEASURES: Decanting (removing >1 dose at a time) before and during monitoring over a 30-day observation period was used to determine the qualitative impact of MEMS on adherence. The adherence index was the proportion of prescribed doses not missed. RESULTS: Subjects were primarily white (73%) with mean CD4+ count 408 cells/mm3, log viral load 1.81 copies/mL, and duration of antiretroviral therapy 5.5 years. Twenty-seven (42%) had some decanting routine established prior to monitoring; 12 (44%) of these patients used daily decanters and 15 (56%) used weekly pillboxes. Of those who decanted prior to the study, 10 (37%) did not stop decanting during monitoring, 14 (52%) stopped decanting only the capped medication, and three (11%) stopped decanting all antiretrovirals. Other adherence strategies did not accommodate MEMS. Eight (13%) subjects said MEMS made adherence more difficult, six (9%) said MEMS was a reminder to adhere, and two (3%) mentioned both. Two subjects attributed skipped doses or time changes to the MEMS cap. The majority who refused to participate used pillboxes. CONCLUSIONS: Personal adherence strategies incompatible with MEMS are common in persons on complex treatment regimens. Although MEMS data on decanters underestimate adherence, excluding decanters erodes applicability of descriptive measures. MEMS use may have affected adherence behavior. Measures in conjunction with MEMS should include self-reported adherence and decanting assessment.

Coccidioidomycosis in Human Immunodeficiency Virus-Infected Persons in Arizona, 1994–1997: Incidence, Risk Factors, and Prevention

From 1 January 1995 through 31 June 1997, 153 cases of coccidioidomycosis in human immunodeficiency virus (HIV)-infected persons were identified in Arizona (incidence, 41/1000 persons living with AIDS). A case-control study was conducted to evaluate risk factors for coccidioidomycosis in HIV-infected persons. A case was defined as laboratory-confirmed, incident coccidioidomycosis in a person infected with HIV for > or =3 months, and each case patient had 3 control patients matched by county, age group, sex, HIV/AIDS status, and CD4 lymphocyte count. Multivariable analysis identified black race and a history of oropharyngeal or esophageal candidiasis to be associated with increased risk of coccidioidomycosis; protease inhibitor therapy was associated with a reduced risk. In persons with previous history of oropharyngeal or esophageal candidiasis, having received an azole drug was associated with a reduced risk (odds ratio, 0.4; 95% confidence interval, 0.2-0.9; P=.04). Physicians may need to consider azole chemoprophylaxis for HIV-infected persons who live in areas of endemicity, have CD4 cell counts <200/microL, are black, or have a history of thrush.

2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis

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 patients 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.

Coccidioidomycosis in Persons Infected with HIV Type 1

Coccidioidomycosis is a recognized opportunistic infection among persons infected with human immunodeficiency virus (HIV). Early in the HIV epidemic, most cases presented as overwhelming diffuse pulmonary disease with a high mortality rate. Although these cases are still seen, patients without significant immunodeficiency frequently present with a community-acquired pneumonia syndrome. Diagnosis can be established by cytological staining, culture, or serologic testing. All patients with HIV infection and symptomatic coccidioidomycosis should be treated with antifungal therapy. Severe cases frequently require a combination of therapy with amphotericin B and a triazole antifungal. Therapy for at least 1 year is recommended, but for patients with a focal pulmonary infection and peripheral blood CD4 lymphocyte counts of >250 cells/microL, it may be reasonable to stop therapy after this time. Other manifestations of coccidioidomycosis require prolonged therapy, and life-long treatment is recommended for persons with meningitis.