The role of extracorporeal membrane oxygenation in severe pulmonary coccidioidomycosis.

BACKGROUND: Severe coccidioidal pneumonia with acute respiratory distress syndrome (ARDS) is associated with high mortality. Extracorporeal membrane oxygenation (ECMO) has been applied successfully to other severe fungal pneumonia associated with ARDS. We review our experience with the use of ECMO in severe coccidioidal ARDS. OBJECTIVES: To review indications and outcome of ECMO in severe pulmonary coccidioidomycosis. METHODS: Three cases of severe ARDS caused by coccidioidomycosis are presented. All were managed with ECMO. Clinical course, complications, antifungal therapy and outcome are reviewed. RESULTS: Three cases of severe coccidioidal ARDS survived after treatment with ECMO. Common complications included bacterial pneumonia, encephalopathy and critical illness myopathy. They received liposomal amphotericin during ECMO, and transitioned to azole therapy. All required prolonged hospitalization and rehabilitation. CONCLUSIONS: ECMO was life-saving in cases of coccidioidal ARDS. Common complications included pneumonia, encephalopathy and critical illness myopathy. All cases were successfully managed with liposomal amphotericin followed by azole therapy. They required prolonged hospitalization and rehabilitation.

Coccidioidomycosis: An underreported cause of death-Arizona, 2008-2013.

In Arizona during 1997-2013, coccidioidomycosis increased from 21 to 90 cases/100,000 population, but coccidioidomycosis-associated deaths remained stable at 3-6 deaths/million population. We used the capture-recapture method by using death certificates and hospital discharge data to more fully estimate the total number of coccidioidomycosis-attributable deaths and compared this with published estimates. Death certificates were included if any cause of death included coccidioidomycosis; hospital discharge data deaths were included if any discharge diagnosis included coccidioidomycosis and laboratory confirmation. Among deaths during 2008-2013, we identified 529 coccidioidomycosis-attributable deaths from death certificates and 560 from hospital discharge data, with 251 deaths identified in both databases. Capture-recapture estimated 1,178 total coccidioidomycosis-attributable deaths, compared with 164 deaths (underlying cause of death) or 529 deaths (any cause of death) on death certificates. Coccidioidomycosis-attributable deaths are underreported from two- to sevenfold on Arizona death certificates, demonstrating an education need for death certifiers to document coccidioidomycosis mortality.

Hospitalized burden and outcomes of coccidioidomycosis: A nationwide analysis, 2005-2012.

The incidence of coccidioidomycosis (CM) infection has increased over the last 20 years. We investigated recent trends of CM-associated hospitalization in the United States. patients with CM-associated hospitalization were identified from the Nationwide Inpatient Sample, 2005-2012. The outcomes of interest were the trend of annual hospitalization, in-hospital mortality, and independent risk factors for mortality. A total of 30,870 hospitalizations with CM (29,584 of adults; 1,286 of children) were identified. Over the 8-year study period, the number of hospitalizations for CM fluctuated but increased overall with successively higher peaks in 2009 and 2011. The annual median length of stay (LOS) shortened from 6 to 7 days in 2005-2010 to 4 days in 2011 and 5 days in 2012. The inflation-adjusted hospital charges were highest in 2006 then trended down by 21% in 2012. The in-hospital mortality declined from the highest level in 2005 (5.2%) to a low in 2010 (1.1%), then increased modestly in 2011 (1.9%) and 2012 (1.5%). Hospitalizations were identified in 46 states, with nearly half in Arizona (49.1%), followed by California (36.8%), Texas (3.3%), and Nevada (1.6%). Logistic regression analysis in adults revealed that in-hospital mortality was associated with age groups 61-70 years and >70 years (OR = 3.3 and 3.5, respectively. Ref: 18-30 years) and Charlson Index ≥1 (OR = 2.0-8.3). In children, males had lower risk for mortality than females (OR = 0.2). This study shows that CM-associated hospitalizations occur widely throughout the United States with an increasing admission trend; however, patient outcomes have improved and the cost of hospitalization has decreased.

Effect of Geography on the Analysis of Coccidioidomycosis-Associated Deaths, United States.

Because coccidioidomycosis death rates vary by region, we reanalyzed coccidioidomycosis-associated mortality in the United States by race/ethnicity, then limited analysis to Arizona and California. Coccidioidomycosis-associated deaths were shown to increase among African-Americans but decrease among Native Americans and Hispanics. Separately, in a Native American cohort, diabetes co-varied with coccidioidomycosis-associated death.

Mortality From Fungal Diseases in the US Air Force From 1970 to 2013.

We review a unique set of documents, death certificates, catalogued in the US Air Force Mortality Registry, which tracks deaths for current and retired Air Force service members. We screened the records for all deaths caused by fungal diseases between 1970 and 2013. There were 216 deaths caused by a variety of diseases such as aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis, histoplasmosis, mucormycosis, pneumocystosis, sporotrichosis, and zygomycosis. The single most common identified cause of death was opportunistic candidiasis. Of the total 216 deaths, only 7 were active duty or active reserve personnel.

Coccidioidomycosis-Associated Deaths in California, 2000-2013.

The number of cases of coccidioidomycosis and associated hospitalizations increased in California during 2000-2013. During that period, a total of 1,098 death records listed coccidioidomycosis as a cause, averaging 78 deaths annually (range: 43-108). The death rate peaked in 2006 and was significantly higher among males than among females, among African American patients than among white patients, and among residents of the coccidioidomycosis-endemic region of California than among residents of the less endemic regions (p<0.001). A higher death rate was associated with increasing age and was highest (8.8 per 1 million population) among adults aged ≥75 years. Of coccidioidomycosis-associated deaths, 31.9% had a contributing cause of death of severe/disseminated disease, 31.8% of unspecified -coccidioidomycosis, and 28.3% of pulmonary unspecified coccidioidomycosis, per International Classification of Diseases codes. Diabetes was a contributing cause in 19.3% of deaths, and other immunocompromising conditions were a contributing cause in 15.9% of deaths. Populations at higher risk for coccidioidomycosis--associated deaths are similar to those at higher risk for coccidioidomycosis-associated hospitalizations and infection. Awareness for coccidioidomycosis among these groups and their providers is important for proper diagnosis and care.

Epidemiology of Pediatric Coccidioidomycosis in California, 2000-2012.

BACKGROUND: Reported coccidioidomycosis cases have increased in the southwestern US since 2000. However, there are few publications on pediatric coccidioidomycosis. We sought to describe the epidemiology of coccidioidomycosis in the California pediatric population during 2000-2012. METHODS: We reviewed surveillance and hospitalization datasets for years 2000-2012 and death datasets for years 2000-2010 to identify coccidioidomycosis-associated cases, hospitalizations and deaths in pediatric (≤17 years old) California residents. We calculated rates and described demographic characteristics of cases and hospitalized patients and, using Poisson regression, calculated bivariate relative risks to identify potential demographic risk factors. We identified immunocompromising conditions associated with hospitalization and death and calculated hospitalization charges. RESULTS: We identified 3453 cases, 1301 hospitalizations and 11 deaths associated with coccidioidomycosis in the California pediatric population. During 2000-2012, annual case and hospitalized patient rates increased and were highest in males, those in the 12-17 age group, and residents of the California endemic region. Compared with White children, African-American children were significantly more likely to be hospitalized (relative risk = 1.4, P = 0.01). Approximately 12.0% of those hospitalized and 27% of those who died had an immunocompromising condition. Hospitalized patients accrued $149 million in total hospital charges. CONCLUSIONS: Similar to recent increases among adults, reported pediatric coccidioidomycosis cases and hospitalizations have increased in California since 2000, disproportionately affecting certain demographic groups. The burden of coccidioidomycosis among California children emphasizes the need for more awareness and research into this reemerging fungal disease in endemic and nonendemic areas.

Evaluation of VT-1161 for Treatment of Coccidioidomycosis in Murine Infection Models.

Coccidioidomycosis, or valley fever, is a growing health concern endemic to the southwestern United States. Safer, more effective, and more easily administered drugs are needed especially for severe, chronic, or unresponsive infections. The novel fungal CYP51 inhibitor VT-1161 demonstrated in vitro antifungal activity, with MIC50 and MIC90 values of 1 and 2 µg/ml, respectively, against 52 Coccidioides clinical isolates. In the initial animal study, oral doses of 10 and 50 mg/kg VT-1161 significantly reduced fungal burdens and increased survival time in a lethal respiratory model in comparison with treatment with a placebo (P < 0.001). Oral doses of 25 and 50 mg/kg VT-1161 were similarly efficacious in the murine central nervous system (CNS) model compared to placebo treatment (P < 0.001). All comparisons with the positive-control drug, fluconazole at 50 mg/kg per day, demonstrated either statistical equivalence or superiority of VT-1161. VT-1161 treatment also prevented dissemination of infection from the original inoculation site to a greater extent than fluconazole. Many of these in vivo results can be explained by the long half-life of VT-1161 leading to sustained high plasma levels. Thus, the efficacy and pharmacokinetics of VT-1161 are attractive characteristics for long-term treatment of this serious fungal infection.

The Changing Epidemiology of Coccidioidomycosis in Los Angeles (LA) County, California, 1973-2011.

Coccidioidomycosis, also known as Valley Fever, is often thought of as an endemic disease of central California exclusive of Los Angeles County. The fungus that causes Valley Fever, Coccidioides spp., grows in previously undisturbed soil of semi-arid and arid environments of certain areas of the Americas. LA County has a few large areas with such environments, particularly the Antelope Valley which has been having substantial land development. Coccidioidomycosis that is both clinically- and laboratory-confirmed is a mandated reportable disease in LA County. Population surveillance data for 1973-2011 reveals an annual rate increase from 0.87 to 3.2 cases per 100,000 population (n = 61 to 306 annual cases). In 2004, case frequency started substantially increasing with notable epidemiologic changes such as a rising 2.1 to 5.7 male-to-female case ratio stabilizing to 1.4-2.2. Additionally, new building construction in Antelope Valley greatly rose in 2003 and displayed a strong correlation (R = 0.92, Pearson p<0.0001) with overall LA County incidence rates for 1996-2007. Of the 24 LA County health districts, 19 had a 100%-1500% increase in cases when comparing 2000-2003 to 2008-2011. Case residents of endemic areas had stronger odds of local exposures, but cases from areas not known to be endemic had greater mortality (14% versus 9%) with notably more deaths during 2008-2011. Compared to the 57 other California counties during 2001-2011, LA County had the third highest average annual number of cases and Antelope Valley had a higher incidence rate than all but six counties. With the large number of reported coccidioidomycosis cases, multi-agency and community partnering is recommended to develop effective education and prevention strategies to protect residents and travelers.

Diagnosis, treatment, and outcomes of coccidioidomycosis in allogeneic stem cell transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients have multiple risk factors for coccidioidomycosis, and previous reports of coccidioidomycosis in this patient population describe severe infections with poor outcomes. METHODS: We performed a retrospective chart review of allo-HSCT recipients with active coccidioidomycosis to characterize the utility of diagnostic tests for coccidioidomycosis and to determine treatment outcomes. RESULTS: Eleven of 426 (2.6%) allo-HSCT recipients experienced active coccidioidomycosis after transplantation. Of these 11 patients, 1 (9%) had extrapulmonary infection, 9 (82%) patients were hospitalized, and 5 (45%) died. Culture or histology was positive in 33% (3/9) of the patients tested. Most (64% [7/11]) had at least 1 positive serologic test result, and the enzyme immunoassay immunoglobulin G test was positive most often (overall 55% [6/11]). Chest radiographs and chest computed tomography scans showed miliary or multifocal nodular infiltrates or consolidations, consistent with coccidioidomycosis, in 80% (8/10) and 100% (9/9), respectively, of patients tested throughout the course of active illness. Rapid polymerase chain reaction testing was positive in 71% (5/7) of the patients tested. Peripheral eosinophilia was present in 18% (2/11) of patients. CONCLUSION: Coccidioidomycosis is associated with high morbidity and mortality in allo-HSCT recipients in an area endemic for Coccidioides. Diagnosis of this infection can be difficult and often requires multiple and frequently invasive tests. Antifungal prophylaxis should be considered for patients at highest risk.

Factores de riesgo en pacientes con coccidioidomicosis diseminada fatal. Estudio de casos y controles / Risk factors in patients with fatal disseminated coccidioidomycosis

Introducción. La coccidioidomicosis es una enfermedad endémica con una mortalidad inferior al 1%. Objetivo. Evaluar los factores de riesgo para mortalidad en pacientes con coccidioidomicosis diseminada (CMD) y describir los casos fatales. Métodos. Estudio de casos (fatales) y controles (no fatales) realizado entre enero de 2006 a diciembre de 2011. Se analizaron los factores de riesgo para desarrollo de CMD fatal. Se utilizó la prueba de Haldane para proporciones y se calculó la razón de momios con intervalo de confianza al 95% con el programa SPSS 15.0. Resultados. Se analizaron 20 casos de CMD, de los cuales 5 fueron fatales. La insuficiencia renal crónica y el trasplante renal se presentaron más frecuentemente en pacientes con CMD fatal. El 40% de los casos con CMD no fatal eran portadores del VIH. La anemia de 10 g/dl de hemoglobina o menos fue un hallazgo constante en CMD fatal. Conclusiones. En este estudio no se encontró diferencia significativa entre los factores de riesgo para CMD fatal y no fatal. Sin embargo, los pacientes que fallecieron tuvieron un curso de menos de 6 meses y presentaron anemia con hemoglobina de 10 g/dl o menos. Todos desarrollaron pulmón de shock con membranas hialinas. La CMD puede presentarse en forma atípica sin patología pulmonar. Se debe investigar la posibilidad de CMD en pacientes con patrón pulmonar de lesiones de tipo miliar, sobre todo en aquellos con deficiencia inmunológica y que habitan áreas endémicas (AU)

Introduction: Coccidioidomycosis is an endemic disease that has a mortality rate of less than 1%. Aim: To evaluate the risk factors for mortality in patients with disseminated coccidioidomycosis (DCM) and describe the fatal cases. Method: Fatal cases and non-fatal controls were studied between January 2006 and December 2011. Risk factors leading to fatal DCM were analysed. The Haldane test was used for propor- tions and the odd’s ratio was calculated with a confidence interval of 95% with the SPSS 15.0 programme. Results: Twenty cases of DCM were analysed, of which 5 were fatal. Chronic renal insufficiency and renal transplant were the most frequent conditions in patients with fatal DCM. 40% of non- fatal cases of DCM were HIV carriers. Anaemia of 10 g/dL or less of haemoglobin was a constant feature of fatal DCM cases. Conclusions: No significant difference in risk factors for fatal or non-fatal DCM was found. However, patients who died had a disease course of less than 6 months and anaemia of 10 g/dL or less. All developed shock lung with hyaline membranes. DCM can present atypically, with no pulmonary pathology. A diagnosis of DCM should be considered in patients with a pulmonary pattern of miliary type lesions, especially when the patient has an immunological deficiency and/or lives in areas endemic for coccidioidomycosis (AU)

Coccidioidomycosis-associated hospitalizations, California, USA, 2000-2011.

In the past decade, state-specific increases in the number of reported cases of coccidioidomycosis have been observed in areas of California and Arizona where the disease is endemic. Although most coccidioidomycosis is asymptomatic or mild, infection can lead to severe pulmonary or disseminated disease requiring hospitalization and costly disease management. To determine the epidemiology of cases and toll of coccidioidomycosis-associated hospitalizations in California, we reviewed hospital discharge data for 2000-2011. During this period, there were 25,217 coccidioidomycosis-associated hospitalizations for 15,747 patients and >$2 billion US in total hospital charges. Annual initial hospitalization rates increased from 2.3 initial hospitalizations/100,000 population in 2000 to 5.0 initial hospitalizations/100,000 population in 2011. During this period, initial hospitalization rates were higher for men than women, African Americans and Hispanics than Whites, and older persons than younger persons. In California, the increasing health- and cost-related effects of coccidioidomycosis-associated hospitalizations are a major public health challenge.

Coccidioidomycosis-associated Deaths, United States, 1990-2008.

Coccidioidomycosis is endemic to the Americas; however, data on deaths caused by this disease are limited. To determine the rate of coccidioidomycosis-associated deaths in the United States, we examined multiple cause-coded death records for 1990-2008 for demographics, secular trends, and geographic distribution. Deaths were identified by International Classification of Diseases, 9th and 10th Revision, codes, and mortality rates were calculated. Associations of deaths among persons with selected concurrent conditions were examined and compared with deaths among a control group who did not have coccidioidomycosis. During the 18-year period, 3,089 coccidioidomycosis-associated deaths occurred among US residents. The overall age-adjusted mortality rate was 0.59 per 1 million person-years; 55,264 potential life-years were lost. Those at highest risk for death were men, persons >65 years, Hispanics, Native Americans, and residents of California or Arizona. Common concurrent conditions were HIV and other immunosuppressive conditions. The number of deaths from coccidioidomycosis might be greater than currently appreciated.

The role of reactive oxygen intermediates in experimental coccidioidomycois in mice.

BACKGROUND: Coccidioidomycosis is usually a self-limited infection in immunocompentent people. In immunocompentent human beings second infections due to Coccidioides are very rare, indicating that recovery from infection results in protective immunity. In experimental animals, immunization with several different proteins or attenuated mutants protects against a virulent challenge. To explore what mechanisms are responsible for protective immunity, we investigated the course of Coccidioides infection in the gp91phox knock out mouse that has a defect in the oxidative burst that results in chronic granulomatous disease. RESULTS: We found that the gp91phox knock out mice were somewhat more resistant to intraperitoneal infection and equally as resistant to low dose intranasal infection, but slightly more susceptible to high dose intranasal infection compared to control mice. The gp91phox knock out mice made a more robust inflammatory response to infection than controls, as measured by histology and production of inflammatory cytokines. The gp91phox knock out mice were as protected by immunization with the recombinant Coccidioides protein Ag2/PRA as the controls were against either intraperitoneal or intranasal infection. Coccidioides immitis arthroconidia and spherules were significantly more resistant to H2O2 treatment in vitro than Aspergillus fumigatus spores. CONCLUSION: These data suggest that oxidative burst may not be required for protective immunity to coccidioidomycois.

Nitric oxide synthase activity has limited influence on the control of Coccidioides infection in mice.

The functions of inducible nitric oxide synthase (iNOS) activity in protection against microbial insults are still controversial. In this study, we explored the role of iNOS in protection against Coccidioides infection in mice. We observed that wild type (WT) and iNOS(-/-) mice showed similar percent survival and fungal burden in their lungs at days 7 and 11 after intranasal challenge with Coccidioides. Vaccinated WT and iNOS(-/-) mice revealed comparable fungal burden in their lungs and spleen at 7 and 11 days postchallenge. However, at 11 days the non-vaccinated, iNOS-deficient mice had significantly higher fungal burden in their spleen compared to WT mice. Additionally, higher numbers of lung-infiltrated neutrophils, macrophages and dendritic cells were observed in WT mice at day 11 postchallenge compared to iNOS(-/-) mice. Moreover, no difference in numbers of T, B, NK or regulatory T cells, or concentrations of selected cytokines and chemokines were detected in lungs of both mouse strains at 7 and 11 days postchallenge. Although iNOS-derived NO production appears to influence the inflammatory response and dissemination of the fungal pathogen, our results suggest that iNOS activity does not play a significant role in the control of coccidioidal infection in mice and that other, still undefined mechanisms of host protection are involved.

Coccidioides fungemia in six patients, with a review of the literature.

To identify demographics, clinical manifestations, and outcomes of patients with Coccidioides fungemia, we searched our institutional medical records to identify patients with Coccidioides fungemia treated between 1998 and 2008 and conducted a comprehensive search of the medical literature to identify previously reported cases. Coccidioides fungemia is an uncommon manifestation of coccidioidomycosis, a fungal infection caused by Coccidioides sp. endemic to the southwestern United States. Six Coccidioides fungemia patients were treated at our institution during the 10-year period. All 6 had underlying comorbid disease; three were receiving immunosuppressants. Three patients survived longer than 2 years. The literature review identified 107 patients, bringing the total cohort to 113 (mean age, 42 years). Forty-three patients (38%) had infection with the human immunodeficiency virus, 20 (18%) were receiving corticosteroids, 11 (10%) had solid organ transplants, and 5 (4%) were pregnant. Sites of extrapulmonary dissemination were reported for 97 (86%); the most common sites were liver (26/97 [27%]), spleen (21/97 [22%]), and meninges/central nervous system (17/97 [18%]). No patient showed evidence of endocarditis. At least 1 serologic test was positive in 45 (87%) of 52 patients for whom results were available. Overall mortality at 30 days was 62% (70/113; mean survival, 11.4 days). Survival was significantly worse in immunocompromised versus immunocompetent patients (22/72 [31%] vs. 19/36 [53%], respectively; P = .04). Lack of antifungal therapy predicted poor survival (8/38 [21%] vs. 32/65 [49%], respectively; P = .004). Coccidioides fungemia is an uncommon manifestation of fulminant, disseminated coccidioidomycosis. Survival is poorest in immunocompromised patients or those not receiving antifungal therapy.

Comparative efficacies of lipid-complexed amphotericin B and liposomal amphotericin B against coccidioidal meningitis in rabbits.

In separate previous studies, we have shown that lipid-complexed amphotericin B (Abelcet [ABLC]) and liposomal amphotericin B (AmBisome [AmBi]) are efficacious against coccidioidal meningitis in rabbits. Here, we compared ABLC and AmBi directly in a coccidioidal meningitis model. Male New Zealand White rabbits were infected with 5 x 10(4) Coccidioides posadasii arthroconidia by direct cisternal puncture. Therapy with intravenous ABLC or AmBi at 7.5 or 15 mg/kg of body weight or sterile 5% dextrose water (D5W) began 5 days later. Clinical assessments were done daily; cerebrospinal fluid and blood samples were obtained on day 15 and upon euthanasia. Survivors to day 25 were euthanatized, the numbers of CFU in their tissues were determined, and histology analyses of the brains and spinal cords were done. Controls showed progressive disease, whereas animals treated with either dose of either drug showed few clinical signs of infection. All ABLC- or AmBi-treated rabbits survived, whereas eight of nine D5W-treated rabbits were euthanatized before day 25 (P < 0.0001). Numbers of CFU in the brains and spinal cords of ABLC- or AmBi-treated animals were 100- to 10,000-fold lower than those in the corresponding tissues of D5W-treated animals (P < 0.0006 to 0.0001). However, only two or fewer given a regimen of ABLC or AmBi were cured of infection in both tissues. Fewer ABLC-treated rabbits (four of eight treated with 7.5 mg/kg and five of eight treated with 15 mg/kg) than controls (nine of nine) had meningitis at any level of severity (P, 0.015 or 0.043 for animals treated with ABLC at 7.5 or 15 mg/kg, respectively). Although groups of rabbits treated with AmBi regimens did not have significantly fewer animals with meningitis than the control group (P > 0.05), ABLC and AmBi were not significantly different. In this model, intravenous ABLC and AmBi were similarly highly effective, with few clinical signs of infection, 100% survival, and significantly reduced fungal burdens among treated animals. There appeared to be little benefit in using the 15-mg/kg dosage of either formulation. There was no significant advantage of one drug over the other for this indication. Further studies are required to determine the lowest effective doses of these formulations.

Coccidioidomycosis in elderly persons.

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 >or=60 years with those in patients aged <60 years. RESULTS: We compared 210 patients aged >or=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;P=.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.

Therapeutic efficacy of caspofungin alone and in combination with amphotericin B deoxycholate for coccidioidomycosis in a mouse model.

OBJECTIVES: The therapeutic efficacy of caspofungin alone and in combination with amphotericin B deoxycholate was evaluated in treatment of murine coccidioidomycosis. METHODS: Survival and tissue burdens of the spleens and livers were used as antifungal response markers. In a monotherapy study, caspofungin was injected intraperitoneally at 0.1, 0.2, 0.5, 1 and 5 mg/kg per day on days 2 through 15. Amphotericin B deoxycholate was given at 0.1, 0.2 and 0.5 mg/kg intravenously and 1 and 5 mg/kg intraperitoneally three times per week for 2 weeks. In a combination therapy study, amphotericin B deoxycholate at 0.1 mg/kg was administered intravenously three times per week for 2 weeks, respectively, with and without caspofungin intraperitoneally given at 0.1, 0.5 and 5 mg/kg daily on days 2 through 15 post-infection. RESULTS: The study shows that caspofungin and amphotericin B deoxycholate at > or =0.5 and > or =0.1 mg/kg, respectively, were significant in both prolongation of survival and reduction of the tissue fungal burdens of mice compared with controls. No sterilization of either organ was observed with caspofungin doses. In combination therapy, any combination of caspofungin (0.1, 0.5 and 5 mg/kg) with amphotericin B deoxycholate (0.1 mg/kg) improved the period of survival and significantly reduced spleen and liver counts compared with controls. CONCLUSIONS: This study indicates that caspofungin has efficacy against systemic coccidioidomycosis in a murine model given in combination with amphotericin B deoxycholate.

Coccidioidomycosis and pregnancy: a review.

Coccidioidomycosis (CM) is a fungal infection endemic to the southwestern United States, northwestern Mexico, and parts of Central and South America. CM has been recognized as a complicating factor in pregnancy since at least the 1940s, and seems to be a relatively uncommon infection during pregnancy. The disease presentation during pregnancy includes a wide clinical spectrum that ranges from mild influenza-like illness and pneumonia, especially in the first two trimesters of pregnancy. The third trimester of pregnancy is a time of high risk for dissemination. Immunologic and hormonal changes during pregnancy and the postpartum period may account for any increased frequency and severity of disease observed during pregnancy. Early diagnosis and appropriate aggressive therapeutic intervention with careful monitoring usually result in good outcome.