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BACKGROUND To better understand clinical and epidemiologic patterns of blastomycosis, we report on a large series of blastomycosis in Indiana. Methods: All microbiologically and histopathologically confirmed cases of blastomycosis from four hospitals serving Central Indiana from 1985 to 2014 were identified. Available data were collected. Data on population estimates, annual precipitation, and construction in Indiana were evaluated for correlations with incidence rates of blastomycosis. Results: A total of 114 patients were identified. The mean age was 44.4 years; 27% had diabetes mellitus, and 16% were immunosuppressed. Most presented with pneumonia (90%); 48% had extrapulmonary disease (CNS involvement in 9%), and 15% developed ARDS. Cultures, cytopathology, and histopathology were positive in 86%, 27%, and 85% of the sample, respectively, and fungal antigen was positive in 76%. Amphotericin B was administered in 49%, and 87% received an azole. Total mortality was 12%. Immunosuppression (OR = 3.0), diabetes mellitus (OR = 2.9), and multilobar pneumonia (OR = 2.9) were associated with increased likelihood of ICU admission. There was a significant increase in incidence over time in Marion County. There was no correlation with amount of precipitation, but the rise in incidence coincided with a 2005 state initiative to expand Indiana's highway infrastructure. Conclusions The incidence of blastomycosis in Central Indiana may be on the rise. Physicians in endemic areas should be aware of the potentially fulminant consequences of the disease.

Invasive pulmonary aspergillosis (IPA) is a major cause of mortality in patients with stem cell transplants and hematologic malignancies. Timely diagnosis of IPA improves survival but is difficult to make. We evaluated the effectiveness of bronchoalveolar lavage (BAL) galactomannan (GM) in diagnosing IPA in these populations by retrospectively reviewing records of 67 consecutive patients, in whom 89 BAL GM tests were performed. For patients with IPA, only the first BAL sample linked to the IPA episode was analyzed. Eighty samples were associated with proven, 12 with probable, and 32 with possible invasive fungal infections (IFI), and 37 were associated with no IFI. Among patients with IFIs, 4 had proven, 11 probable, and 32 possible IPA. Using BAL GM ≥ 0.5 (cutoff for serum GM) and ≥ 0.85 (optimal cutoff identified by receiver-operating characteristic curve), the sensitivity in diagnosing proven or probable IPA was 73% (11/15) and 67% (10/15), respectively, and specificity was 89% (33/37) and 95% (35/37). At these cutoffs, positive and negative predictive values were 73% (11/15) and 83% (10/12), and 89% (33/37) and 87% (35/40), respectively. BAL GM was more sensitive than cytology (0%, 0/14), BAL culture (27%, 4/15), transbronchial biopsy (40%, 2/5), or serum GM (67%, 10/15) for diagnosing IPA. BAL GM was ≥ 0.85 and ≥ 0.5 in 86% (6/7) and 100% (7/7) of patients with proven or probable IPA who received a mold-active agent for ≤ 3 days. BAL GM added sensitivity to serum GM and other means of diagnosing IPA, and was not impacted by short courses of mold-active agents.

Background The endemic region of blastomycosis historically has included the state of Indiana. However, few published reports of blastomycosis exist to substantiate this distinction. A surge of patients with blastomycosis in central Indiana (Indianapolis and surrounding counties) beginning in 2005 prompted us to review our local experience. We propose that this surge was related to major highway construction around Indianapolis. Methods We reviewed all microbiologically confirmed cases from four hospitals serving central Indiana. Chart review was completed for adult patients, and data were collected on clinical presentations, methods of diagnosis, comorbidities, radiologic findings, treatment, and outcomes. We plotted patient residence addresses with sites of highway construction. Results Fifty-nine patients were identified from laboratory results and physician referral. Interestingly, a surge of blastomycosis incidence occurred in 34 patients between 2005 and 2008 during which time major highway projects were under way around the Indianapolis metropolitan area. The majority of these patients presented acutely and with pulmonary involvement. Fungal culture and antigen testing were the most sensitive means to diagnosis. Antifungal therapy was highly effective. Conclusions This urban outbreak of blastomycosis in Indianapolis should prompt clinicians to consider blastomycosis in this highly endemic area of histoplasmosis.

Background Detection of antigen in BAL is useful for diagnosis of histoplasmosis. The MVista Histoplasma antigen enzyme immunoassay has been modified to permit quantification. The purpose of this study is to compare the sensitivity of the quantitative antigen detection assay with cytopathology and culture of BAL specimens. Methods BAL from patients with histoplasmosis who were evaluated at the Indiana University Medical Center and controls without histoplasmosis were studied. BAL fluid was tested in the quantitative Histoplasma antigen assay. Results Antigen was detected in the BAL in 93.5% of patients with histoplasmosis, 80% with blastomycosis, and 0% of controls with nonfungal infections. Antigen was detected in the urine of 79% and serum in 65% of patients with histoplasmosis. Cytopathology was positive in 48% and culture in 48% of patients with histoplasmosis, and 40% and 60% of patients with blastomycosis, respectively. Serology was positive in 65%. Combining BAL antigen detection and BAL cytopathology, both methods for rapid diagnosis, the sensitivity was 96.8% in histoplasmosis and 80% in blastomycosis. Conclusions Detection of antigen in BAL complements antigen detection in serum and urine as an objective diagnostic test for histoplasmosis.

Detection of galactomannan antigen in serum or bronchoalveolar lavage fluid is useful for diagnosis of invasive aspergillosis, but the current serologic tests are not useful. (1-->3)-beta-D-glucan can be detected in the serum of patients who have aspergillosis, candidiasis, and a few other mold infections, but false-positive results limit its reliability for diagnosis. None of these methods is useful for diagnosis of zygomycosis and certain other less common mold infections. This article focuses on the detection of antigen and beta-D-glucan for diagnosis of invasive aspergillosis and candidiasis.

The endemic mycoses are often overlooked in the evaluation of community-acquired pneumonia, and appropriate testing is not performed until the patient has failed to improve on antibacterial therapy. Antigen detection and fungal serology may be helpful in diagnosis of endemic mycoses as causes for pneumonia. Guidelines for recognition and evaluation of endemic mycoses as causes for community-acquired pneumonia are proposed. Performance of antigen testing on bronchial washings or lavage fluid may improve the sensitivity for diagnosis over microscopic examination and the speed of diagnosis over culture. This article focuses on antigen detection and serology for diagnosis of endemic mycoses. Of note is that isolation of the fungus by culture remains the only method for definitive diagnosis, and the only method for diagnosis in some patients.

SummaryAntigen detection is a useful adjunct for the diagnosis of histoplasmosis. The purpose of this study was to evaluate antigen detection in bronchoalveolar lavage (BAL) fluid using an improved second-generation Histoplasma antigen assay. Antigen was detected in 16 of 19 (84%) cases of histoplasmosis and 5 of 6 (83.3%) blastomycosis cases using the second-generation assay vs. 13 of 19 (68%) and 4 of 6 (66.7%), respectively, in the original assay. Ten-fold concentration permitted detection of antigen in an additional case of histoplasmosis and another with blastomycosis, for an overall sensitivity of 23 of 25 (92.0%). Specificity was 98.2% in both assays in controls with other pulmonary infections. These findings support the diagnostic utility of the second-generation assay in patients with pulmonary histoplasmosis and blastomycosis.

Invasive fungal infections are often difficult to diagnose using radiology, culture methods, histopathology, or serology, and turnaround time is often lengthy. Antigen testing has been developed for several important invasive mycoses, offering rapid turnaround time and sensitivity comparable or superior to those of other methods. This review provides an update on rapid antigen testing for several invasive fungal infections, including histoplasmosis, blastomycosis, coccidioidomycosis, and aspergillosis and is intended as an addendum to previous reviews on the subject.

We developed a colorimetric microtiter plate polymerase chain reaction enzyme immunoassay (PCR-EIA) for the detection of Histoplasma capsulatum in urine. The specificity of the PCR assay was confirmed using H. capsulatum (positive control) and Blastomyces dermatitidis (negative control) isolates. The analytical sensitivity of the PCR assay was determined by testing urine samples spiked with freshly grown H. capsulatum organisms and was 2 yeasts per reaction in urine and 0.2 yeasts per reaction in urine sediment after centrifugation. Fifty-one urine specimens positive for H. capsulatum antigen and 25 urine specimens from healthy volunteers were tested blindly. Patient specimens also were cultured for H. capsulatum. The PCR assay was positive in 4 (7.8%) of 51 urine specimens containing antigen and negative in urine specimens from healthy volunteers. The positive PCR results occurred in 4 of 5 urine specimens that were positive by culture, and each exhibited high level of antigenuria (>20 U). Urine cultures were not positive in 24 urine specimens with an antigenuria of 1-19.9 U, but were positive in 5 of 27 urine specimens with antigenuria >20 U. Thus, positive PCR results in urine specimens correlate with positive culture results, but not with antigenuria. The low sensitivity of this PCR assay in urine limits its use in the diagnosis of disseminated histoplasmosis.

Until recently, the diagnosis of invasive aspergillosis was most often made based on clinical and radiologic findings, which areinsensitive and non-specific.The Platelia Aspergillus galactomannan enzyme immunoassay, which has been available in Europe for nearly a decade and in the United States since 2003, provides an aid to the diagnosis of invasive aspergillosis. Part I of this article described the test methodology and those factors that may affect test performance. Part II of this article discusses guide lines and indications for performing the test and comparison of the galactomannan assay with other rapid methods.

Purpose: Oropharyngeal candidasis (thrush) is the most common opportunistic infection in individuals who are positive for the human immunodeficiency virus (HIV) and those who have progressed to AIDS. Itraconazole has a broad in vitro spectrum of activity, including a wide variety of Candida species. Our study determined the relative efficacy of a new oral solution formulation of itraconazole and fluconazole tablets in the treatment of oropharyngeal candidiasis. Patients and Methods: This was a prospective randomized, third-party–blind, multicenter trial conducted at 12 centers in the United States. One hundred seventy-nine HIV-positive patients with mycologically documented oropharyngeal candidiasis were treated with itraconazole oral solution 200 mg/day for 7 or 14 days, or fluconazole tablets 100 mg/day for 14 days. Severity of disease was scored clinically before treatment and at clinical evaluations on days 3, 7, 14, 21, 35, and 42. Semiquantitative cultures of mouth washings were also obtained on these days. Results: Both 14-day and 7-day regimens of itraconazole oral solution were equivalent to fluconazole for most efficacy parameters. The clinical response rate was 97% after 14 days of itraconazole and 87% after 14 days of fluconazole. Itraconazole oral solution given for 7 days was also equivalent to fluconazole treatment for 14 days. Approximately one half of patients in all three groups relapsed by 1 month after completion of treatment. There were few adverse reactions to either drug. Conclusion: Itraconazole oral solution is well tolerated and offers an alternative at least as effective as fluconazole in the treatment of oropharyngeal candidiasis.

purpose: The purpose of this study was to establish the effect of induction and maintenance treatment with amphotericin B on levels of Histoplasma capsulatum var. capsulatum polysaccharide antigen (HPA) in the urine and blood of patients with acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. patients and methods: This was a retrospective study of the effect of amphotericin B treatment on levels of HPA in the urine or serum from 70 patients with AIDS and disseminated histoplasmosis. All patients received initial intensive induction treatment with amphotericin B, and a subset continued to receive amphotericin B at less frequent intervals for maintenance therapy to prevent relapse. Treatment regimens varied in intensity and duration and specimens were obtained at irregular intervals. Urine and serum specimens were stored and retested for HPA in the same radioimmunoassay. results: HPA levels in serum decreased by at least 2 units during induction therapy in all 19 (100%) patients with initial levels of greater than or equal to 2.6 units and reverted to negative in 40.9% of those with initial levels of greater than or equal to 1.0 unit. HPA in urine decreased by at least 2 units in 84.8% and reverted to negative in 17.3% of patients. During induction treatment, HPA cleared more rapidly from serum than from urine. During maintenance treatment, HPA levels in serum decreased by at least 2 units in 100% and became negative in 66.7%. HPA in urine decreased by at least 2 units in 54.5% and reverted to negative in 20.0%. Rates of clearance of HPA from the serum and urine were similar, 0.01 unit/week compared with −0.04 unit/week, respectively, but less than rates during induction treatment. conclusions: Successful therapy of histoplasmosis with amphotericin B is associated with reduction of HPA in body fluids. Periodic measurement of HPA levels offers a method for monitoring the response to therapy and for comparing new treatments for histoplasmosis.

Tuberculosis continues to be a major health care problem in the world, especially among children. In the United States, health care providers rely heavily on routine skin testing to identify cases of tuberculosis. Pediatric nurse practitioners have the opportunity to recognize high-risk children, teach preventive health practices to patients and families, and thus to decrease morbidity from the disease. This article presents an overview of the incidence of the disease, as well as the causes, pathophysiology, epidemiology, diagnosis and management of tuberculosis.

An enzyme-linked immunosorbent assay was developed to detect urinary antigen excreted by patients with Legionnaires' disease. Of 47 patients tested, antigen was detected in 39. Of these 39 specimens, 35 gave clearly positive results by visual analysis; four others required spectrophotometric verification of positive results. Antigen was not detected in any of 178 urine specimens from patients with other pulmonary, bacteremic or urinary tract infections after a quick and simple confirmatory test. The assay required more time to perform than a previously described radioimmunoassay but was of equivalent sensitivity and specificity and did not require expensive equipment or contact with radioactive reagents. We conclude that enzyme-linked immunosorbent assay is a rapid, sensitive and specific means for rapidly diagnosing Legionnaires' disease that can be performed in clinical laboratories unwilling or unable to use radioisotopes.

Staphylococcal bacteremia occurs frequently in patients undergoing long-term hemodialysis (dialysis patients). Although such bacteremia is frequently uncomplicated, it may be associated with endocarditis, metastatic infection or suppuration at the access site requiring excision of the access device for control of the infection (complicated bacteremia). To distinguish patients with uncomplicated bacteremia from those with complications, we measured staphylococcal teichoic acid antibodies by agar-gel diffusion and immunoglobulin G (IgG) antibodies by radioimmunoassay in 18 patients with staphylococcal bacteremia undergoing long-term hemodialysis. Although teichoic acid antibodies were not detected in five patients with uncomplicated bacteremia, they were observed in only three of 13 patients with complicated bacteremia. IgG staphylococcal antibodies were present in 10 of 13 patients with complicated bacteremia compared to none of five patients with uncomplicated bacteremia compared to none of five patients with uncomplicated bacteremia (p less than 0.05). Thus, radioimmunoassay was spuerior to agar-gel diffusion in identifying dialysis patients with complicated bacteremia. In patients with increased concentrations of IgG staphylococcal antibodies by radioimmunoassay, the diagnosis of endocarditis, metastatic infection and suppuration at the access site should be considered. Prolonged antibiotic therapy and/or operative removal of the access device may be necessary.

Purpose Disseminated histoplasmosis is a serious and often rapidly progressive, opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS), supporting the importance of rapid diagnostic tests. We investigated Histoplasma capsulatum polysaccharide antigen (HPA) detection, a promising new method for rapid diagnosis of histoplasmosis. Patients and methods Sixty-one cases of disseminated histoplasmosis in patients with AIDS form the basis of this report. Control cases were patients with AIDS who had other opportunistic infections and whose cultures were negative for H. capsulatum. A slightly modified radioimmunoassay procedure was used to measure the levels of HPA in urine and blood specimens. Results High levels of HPA were detected in the urine of 59 of 61 (96.7%) and the blood of 37 of 47 (78.7%) patients with AIDS complicated by disseminated histoplasmosis. Treatment with amphotericin B reduced levels of HPA in the urine in 19 of 21 (90.5%) and the serum of all 10 patients tested. HPA levels increased in the urine in all eight and in the serum in all five patients with culture-proven relapse. Conclusion In conclusion, HPA detection offers a rapid method for diagnosing disseminated histoplasmosis. Additional experience is required to establish the role of this test in monitoring the effects of treatment and in identifying relapse in patients with AIDS.

A method for rapid diagnosis of Staphylococcus aureus bacteremia by antigen detection would be useful. Detection of staphylococcal antigenemia has been hampered by formation of immune complexes with pre-formed antibodies. Subsequently, urine from patients with S. aureus bacteremia and controls have been tested by radioimmunoassay for antigen. Antigen was present in the urine of five of six patients with endocarditis, two of six with complicated bacteremia but none of eight with uncomplicated bacteremia caused by S. aureus . Antigen was also found in urine from 18 of 30 patients with staphylococcal urinary tract infections, in one of 48 with urinary tract infections caused by other bacteria (a patient infected with Escherichiae coli ), but not in 71 uninfected control urines. Detection of antigenuria offers a rapid new method for diagnosing S. aureus endocarditis or complicated bacteremia in the absence of staphylococcal bacteriuria (5 × 10 4 cfu ml −1 ).