Blastomycosis: A Review of Mycological and Clinical Aspects.

Blastomycosis is caused by a thermally dimorphic fungus that thrives in moist acidic soil. Blastomyces dermatitidis is the species responsible for most infections in North America and is especially common in areas around the Great Lakes, the St. Lawrence Seaway, and in several south-central and southeastern United States. Other Blastomyces species have more recently been discovered to cause disease in distinct geographic regions around the world. Infection almost always occurs following inhalation of conidia produced in the mold phase. Acute pulmonary infection ranges from asymptomatic to typical community-acquired pneumonia; more chronic forms of pulmonary infection can present as mass-like lesions or cavitary pneumonia. Infrequently, pulmonary infection can progress to acute respiratory distress syndrome that is associated with a high mortality rate. After initial pulmonary infection, hematogenous dissemination of the yeast form of Blastomyces is common. Most often this is manifested by cutaneous lesions, but osteoarticular, genitourinary, and central nervous system (CNS) involvement also occurs. The diagnosis of blastomycosis can be made by growth of the mold phase of Blastomyces spp. in culture or by histopathological identification of the distinctive features of the yeast form in tissues. Detection of cell wall antigens of Blastomyces in urine or serum provides a rapid method for a probable diagnosis of blastomycosis, but cross-reactivity with other endemic mycoses commonly occurs. Treatment of severe pulmonary or disseminated blastomycosis and CNS blastomycosis initially is with a lipid formulation of amphotericin B. After improvement, therapy can be changed to an oral azole, almost always itraconazole. With mild to moderate pulmonary or disseminated blastomycosis, oral itraconazole treatment is recommended.

Infectious complications after second allogeneic hematopoietic cell transplant in adult patients with hematological malignancies.

We conducted a retrospective review of the infectious complications and outcomes over a 2-year follow-up period of adult patients who received a second allogeneic hematopoietic cell transplant (2nd allo-HCT) during a five-year period at two cancer centers in Michigan. Sixty patients, of whom 44 (73%) had acute leukemia or myelodysplastic syndrome, were studied. The majority (n = 37,62%) received a 2nd allo-HCT because of relapsed leukemia. Infection episodes after the 2nd allo-HCT totaled 112. Bacteria were identified in 76 episodes, the majority of which occurred pre-engraftment. The most common infecting organisms were Enterococcus species and Clostridioides difficile. Viral infections, predominantly cytomegalovirus, accounted for 59 infection episodes and occurred mostly in pre-engraftment and early post-engraftment periods. There were 16 proven/probable fungal infections, of which 9 were invasive aspergillosis or candidiasis. Mortality was 45% (n = 27) at one year and 65% (n = 39) at 2 years after transplant, and 16 deaths (41%) were due to infection. Of those 16 infection deaths, 8 were bacterial, 4 fungal, 2 both bacterial and fungal, and 2 viral. Failure to engraft neutrophils or platelets was significantly associated with decreased survival, p < 0.0001 and p < 0.001, respectively. Infections are common after a 2nd allo-HCT and are associated with a high mortality rate.

Noninvasive Testing and Surrogate Markers in Invasive Fungal Diseases.

Invasive fungal infections continue to increase as at-risk populations expand. The high associated morbidity and mortality with fungal diseases mandate the continued investigation of novel antifungal agents and diagnostic strategies that include surrogate biomarkers. Biologic markers of disease are useful prognostic indicators during clinical care, and their use in place of traditional survival end points may allow for more rapid conduct of clinical trials requiring fewer participants, decreased trial expense, and limited need for long-term follow-up. A number of fungal biomarkers have been developed and extensively evaluated in prospective clinical trials and small series. We examine the evidence for these surrogate biomarkers in this review and provide recommendations for clinicians and regulatory authorities.

Invasive Fungal Disease in Patients with Newly Diagnosed Acute Myeloid Leukemia.

This single-center retrospective study of invasive fungal disease (IFD) enrolled 251 adult patients undergoing induction chemotherapy for newly diagnosed acute myeloid leukemia (AML) from 2014-2019. Patients had primary AML (n = 148, 59%); antecedent myelodysplastic syndrome (n = 76, 30%), or secondary AML (n = 27, 11%). Seventy-five patients (30%) received an allogeneic hematopoietic cell transplant within the first year after induction chemotherapy. Proven/probable IFD occurred in 17 patients (7%). Twelve of the 17 (71%) were mold infections, including aspergillosis (n = 6), fusariosis (n = 3), and mucomycosis (n = 3). Eight breakthrough IFD (B-IFD), seven of which were due to molds, occurred in patients taking antifungal prophylaxis. Patients with proven/probable IFD had a significantly greater number of cumulative neutropenic days than those without an IFD, HR = 1.038 (95% CI 1.018-1.059), p = 0.0001. By cause-specific proportional hazards regression, the risk for IFD increased by 3.8% for each day of neutropenia per 100 days of follow up. Relapsed/refractory AML significantly increased the risk for IFD, HR = 7.562 (2.585-22.123), p = 0.0002, and Kaplan-Meier analysis showed significantly higher mortality at 1 year in patients who developed a proven/probable IFD, p = 0.02. IFD remains an important problem among patients with AML despite the use of antifungal prophylaxis, and development of IFD is associated with increased mortality in these patients.

Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology.

The global burden of the endemic mycoses (blastomycosis, coccidioidomycosis, emergomycosis, histoplasmosis, paracoccidioidomycosis, sporotrichosis, and talaromycosis) continues to rise yearly and these infectious diseases remain a leading cause of patient morbidity and mortality worldwide. Management of the associated pathogens requires a thorough understanding of the epidemiology, risk factors, diagnostic methods and performance characteristics in different patient populations, and treatment options unique to each infection. Guidance on the management of these infections has the potential to improve prognosis. The recommendations outlined in this Review are part of the "One World, One Guideline" initiative of the European Confederation of Medical Mycology. Experts from 23 countries contributed to the development of these guidelines. The aim of this Review is to provide an up-to-date consensus and practical guidance in clinical decision making, by engaging physicians and scientists involved in various aspects of clinical management.

Evaluation of targeted versus universal prophylaxis for the prevention of invasive fungal infections following lung transplantation.

BACKGROUND: Antifungal prophylaxis to prevent invasive fungal infections (IFI) is widely used following lung transplantation, but the optimal strategy remains unclear. We compared universal with targeted antifungal prophylaxis for effectiveness in preventing IFI. METHODS: Adult patients who underwent lung transplantation at the University of Michigan from /1 July 2014-31 December 2017 were studied for 18 months post-transplant. Universal prophylaxis consisted of itraconazole with or without inhaled liposomal amphotericin B. Using specific criteria, targeted prophylaxis was given with voriconazole for patients at risk for invasive pulmonary aspergillosis (IPA) and with fluconazole or micafungin for patients at risk for invasive candidiasis. Risk factors, occurrence of proven/probable IFI, and mortality were analyzed for the two prophylaxis cohorts. RESULTS: Of 105 lung transplant recipients, 84 (80%) received a double lung transplant, and 38 (36%) of patients underwent transplant for pulmonary fibrosis. Fifty-nine (56%) patients received universal antifungal prophylaxis, and 46 (44%), targeted antifungal prophylaxis. Among 20 proven/probable IFI, there were 14 IPA, 4 invasive candidiasis, 1 cryptococcosis, and 1 deep sternal mold infection. Six (10%) IFI occurred in the universal prophylaxis cohort and 14 (30%) in the targeted prophylaxis cohort. Five of 6 (83%) IFI in the universal prophylaxis cohort, compared with 9/14 (64%) in the targeted prophylaxis cohort, were IPA Candida infections occurred only in the targeted prophylaxis cohort. The development of IFI was more likely in the targeted prophylaxis cohort than the universal prophylaxis cohort, HR = 4.32 (1.51-12.38), P = .0064. CONCLUSIONS: Universal antifungal prophylaxis appears to be more effective than targeted antifungal prophylaxis for prevention of IFI after lung transplant.

Performance of Aspergillus Galactomannan Lateral Flow Assay on Bronchoalveolar Lavage Fluid for the Diagnosis of Invasive Pulmonary Aspergillosis.

Background: Several newly developed biomarker tests for invasive pulmonary aspergillosis (IPA) have been developed, including the IMMY Aspergillus galactomannan lateral flow assay (Aspergillus GM-LFA) evaluated in this study. Methods: Twenty patients with proven/probable IPA (EORTC/MSGERC criteria) were matched by age and underlying disease with 20 patients without IPA. Bronchoalveolar lavage fluid (BALF) was analyzed in duplicate using the Aspergillus GM-LFA. Results were read visually by two blinded observers, and the optical density index (ODI) was obtained digitally with a cube reader. Results: Using a cutoff of ≥0.5 ODI, the Aspergillus GM-LFA had a sensitivity of 40%, specificity of 80%, positive predictive value (PPV) of 67% and negative predictive value (NPV) of 57%. When the cutoff was increased to ≥1.0 ODI, sensitivity remained at 40%, specificity rose to 95%, PPV was 89%, and NPV was 61%. Excellent agreement was found when duplicate samples were read either visually (κ = 1) or with the cube reader (κ = 0.89). Correlation of results obtained by visual inspection and those obtained using the cube reader was excellent (κ = 0.82). Conclusion: The Aspergillus GM-LFA had poor sensitivity but excellent specificity for proven/probable IPA in BALF. The assay was easy to interpret, and there was high concordance between results obtained visually and with a cube reader.

Diagnostic Performance of Bronchoalveolar Lavage (1,3)-ß-d-Glucan Assay for Pneumocystis jirovecii Pneumonia.

We evaluated the performance of the (1,3)-ß-d-glucan (BDG) assay on bronchoalveolar lavage fluid (BALF) as a possible aid to the diagnosis of Pneumocystis jirovecii pneumonia. BALF samples from 18 patients with well-characterized proven, probable, and possible Pneumocystis pneumonia and 18 well-matched controls were tested. We found that the best test performance was observed with a cut-off value of 128 pg/mL; receiver operating characteristic/area under the curve (ROC/AUC) was 0.70 (95% CI 0.52-0.87). Sensitivity and specificity were 78% and 56%, respectively; positive predictive value was 64%, and negative predictive value was 71%. The low specificity that we noted limits the utility of BALF BDG as a diagnostic tool for Pneumocystis pneumonia.

Performance of the (1,3)-Beta-D-Glucan Assay on Bronchoalveolar Lavage Fluid for the Diagnosis of Invasive Pulmonary Aspergillosis.

Detection of (1,3)-beta-D-glucan (BDG), a component of the cell wall of many fungi, was studied in bronchoalveolar lavage fluid (BALF) as a possible aid for the diagnosis of proven/probable invasive pulmonary aspergillosis (IPA). BDG was measured on stored BALF from 13 patients with EORTC/MSGERC defined proven/probable IPA and 26 matched control patients without IPA. The median BALF BDG was 80 pg/mL (range < 45-8240 pg/mL) in the IPA cohort and 148 pg/mL (range < 45-5460 pg/mL) in the non-IPA cohort. Using a positive cutoff of ≥ 80 pg/mL, sensitivity was 54% and specificity was 38%. Higher cutoff values led to improvement in specificity but a dramatic decrease in sensitivity. ROC/AUC analysis was unable to identify an optimal cutoff value at which test performance was enhanced: AUC 0.43, 95% CI 0.24-0.63. When the BDG assay was performed on BALF, neither sensitivity nor specificity was sufficient for use in the diagnosis of IPA.

Long-term Outcomes of Patients With Fungal Infections Associated With Contaminated Methylprednisolone Injections.

BACKGROUND: The largest health care-associated infection outbreak in the United States occurred during 2012-2013. Following injection of contaminated methylprednisolone, 753 patients developed infection with a dematiaceous mold, Exserohilum rostratum. The long-term outcomes of these infections have not been described. METHODS: This retrospective cohort study of 440 of a total of 753 patients with proven or probable Exserohilum infection evaluated clinical and radiographic findings, antifungal therapy and associated adverse effects, and outcomes at 6 weeks, 3, 6, 9, and 12 months after diagnosis. Patients were grouped into 4 disease categories: meningitis with/without stroke, spinal or paraspinal infections, meningitis/stroke plus spinal/paraspinal infections, and osteoarticular infections. RESULTS: Among the 440 patients, 223 (51%) had spinal/paraspinal infection, 82 (19%) meningitis/stroke, 123 (28%) both, and 12 (3%) osteoarticular infection. Of 82 patients with meningitis/stroke, 18 (22%) died; among those surviving, 87% were cured at 12 months. Only 7 (3%) of 223 patients with spinal/paraspinal infection died, but at 12 months, 68% had persistent or worsening pain and only 47% were cured. For the 123 patients with both meningitis/stroke and spinal/paraspinal infection, 10 (8%) died, pain persisted in 72%, and 52% were cured at 12 months. Only 37% of those with osteoarticular infection were cured at 12 months. Adverse events from antifungal therapy were noted at 6 weeks in 71% of patients on voriconazole and 81% on amphotericin B. CONCLUSIONS: Fungal infections related to contaminated methylprednisolone injections culminated in death in 8% of patients. Persistent pain and disability were seen at 12 months in most patients with spinal/paraspinal infections.

Breakthrough Invasive Fungal Infections in Patients with Acute Myeloid Leukemia.

OBJECTIVES: We sought to determine the occurrence, risk factors, effect of antifungal prophylaxis, and outcomes of invasive fungal infections (IFIs) in patients with acute myeloid leukemia (AML). PATIENTS AND METHODS: We performed a retrospective analysis of all adult patients admitted to the University of Michigan Health System for AML over a 3-year period from 2010 to 2013. We determined comorbidities, hematopoietic cell transplant (HCT) status, antifungal prophylaxis, proven and probable IFI, and outcomes at 12 weeks after initiation of appropriate antifungal therapy. RESULTS: Of 333 patients in our cohort, 116 of whom had received a HCT, 98 (29%) developed an IFI. Of the 30 (9%) patients who had a proven or probable IFI, 18 had breakthrough infection while on micafungin (n = 5), voriconazole (n = 4), posaconazole (n = 5), or fluconazole (n = 4). Breakthrough IFIs were due to Aspergillus species (n = 11), other molds (n = 4), and Candida species (n = 3). Factors associated with breakthrough IFI were prolonged severe neutropenia (p = .05) and having received tacrolimus (p = .04). Antifungal therapy was successful in 7 of the 18 (39%) patients with breakthrough IFI and 8 of the 12 (67%) patients with non-breakthrough IFI, p = .13. Mortality at 12 weeks was 27%, 5 with breakthrough IFI and 3 with non-breakthrough IFI and was associated with prolonged severe neutropenia, p = .04. CONCLUSIONS: Patients with AML remain at risk for IFI despite the use of several different antifungal agents for prophylaxis. Mortality remains high in patients with AML who develop IFI.

Blastomycosis.

Blastomycosis is a serious fungal disease of humans and other mammals caused by environmentally acquired infection with geographically restricted, thermally dimorphic fungi belonging to the genus Blastomyces. The genetic and geographic diversity of these pathogens is greater than previously appreciated. In addition to Blastomyces dermatitidis and the cryptic species Blastomyces gilchristii, which cause blastomycosis in mid-western and various eastern areas of North America, atypical blastomycosis is occasionally caused by Blastomyces helicus in western parts of North America and Blastomyces percursus in Africa. Blastomycosis is acquired by inhalation of the conidia that are produced in the mold phase; in the lungs, temperature-dependent transformation occurs to the yeast phase. In this form, the organism is phagocytized by macrophages and can spread hematogenously to various organs causing disseminated infection. Pulmonary disease is most common and varies from mild, self-limited infection to severe, potentially fatal adult respiratory distress syndrome. Disseminated infection is manifested primarily by skin lesions, but many other organs can be involved. Diagnosis is established by growth of the organism in culture; however, a tentative diagnosis can be made quickly by histopathological identification of the classic yeast form in tissues or by finding Blastomyces antigen in urine or serum. Blastomycosis is treated initially with amphotericin B when the disease is severe, involves the central nervous system, or the host is immunosuppressed. Itraconazole is recommended for primary therapy in mild-to-moderate infection and for step-down therapy after initial amphotericin B treatment. Voriconazole and posaconazole can be used for patients in whom itraconazole is not tolerated.

Current and New Perspectives in the Diagnosis of Blastomycosis and Histoplasmosis.

The diagnosis of blastomycosis and histoplasmosis can be difficult for clinicians who rarely see infections caused by these environmentally restricted dimorphic fungi. Historically, the diagnosis of blastomycosis has been established by culture and sometimes by histopathologic identification. Currently, antigen detection in urine and serum has been shown to aid in the rapid diagnosis of blastomycosis, and newer antibody assays are likely to contribute to our diagnostic capability in the near future. The gold standard for the diagnosis of histoplasmosis has been culture of the organism from involved tissues, aided in some patients by histopathological verification of the typical yeast forms in tissues. Antigen detection has contributed greatly to the ability of clinicians to rapidly establish the diagnosis of histoplasmosis, especially in severely ill and immunocompromised patients, and antibody testing for Histoplasma capsulatum provides important adjunctive diagnostic capability for several forms of both acute and chronic histoplasmosis. For both of these endemic mycoses, novel molecular tests are under active investigation, but remain available in only a few reference laboratories. In this review, we provide a synopsis of diagnostic test options that aid in establishing whether a patient has blastomycosis or histoplasmosis.

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.

Clinical application of Aspergillus lateral flow device in bronchoalveolar lavage fluid of patients with classic risk factors for invasive pulmonary aspergillosis.

BACKGROUND: The diagnosis of invasive pulmonary aspergillosis (IPA) remains challenging. We evaluated the performance characteristics of a newly formatted Aspergillus lateral flow test, AspLFD, in bronchoalveolar lavage (BAL) fluid from patients with classic risk factors for IPA. METHODS: Prospectively banked BAL samples from 14 patients with proven or probable IPA defined by EORTC/MSG criteria and 28 BAL samples from age-matched high-risk patients without IPA were tested with AspLFD according to manufacturer's directions. Results were read by two independent observers, and test performance was calculated. RESULTS: Age, gender and underlying risk factors, except for neutropenia and haematological malignancy, were similar between IPA cases and controls. Seven patients (50%) in the IPA group received a mould-active agent within 5 days prior to bronchoscopy compared with only three patients (11%) in the control group, P = .004. Of 14 patients with proven/probable IPA, AspLFD was positive in 3 and negative in 9; two tests yielded invalid results. All 28 control patients had a negative AspLFD test. AspLFD showed low sensitivity (25%, 95% CI: 5.5% to 57.2%), but high specificity (100%. (95% CI: 87.7% to 100%). CONCLUSIONS: A positive AspLFD test in BAL fluid of patients with classic risk factors for IPA could be useful to support the diagnosis of proven/probable IPA because of its high specificity. However, as a stand-alone test for IPA, the use of AspLFD is limited by low sensitivity.

Central Nervous System Infection with Other Endemic Mycoses: Rare Manifestation of Blastomycosis, Paracoccidioidomycosis, Talaromycosis, and Sporotrichosis.

The central nervous system (CNS) is not a major organ involved with infections caused by the endemic mycoses, with the possible exception of meningitis caused by Coccidioides species. When CNS infection does occur, the manifestations vary among the different endemic mycoses; mass-like lesions or diffuse meningeal involvement can occur, and isolated chronic meningitis, as well as widely disseminated acute infection that includes the CNS, are described. This review includes CNS infection caused by Blastomyces dermatitidis, Paracoccidioides brasiliensis, Talaromyces marneffei, and the Sporothrix species complex. The latter is not geographically restricted, in contrast to the classic endemic mycoses, but it is similar in that it is a dimorphic fungus. CNS infection with B. dermatitidis can present as isolated chronic meningitis or a space-occupying lesion usually in immunocompetent hosts, or as one manifestation of widespread disseminated infection in patients who are immunosuppressed. P. brasiliensis more frequently causes mass-like intracerebral lesions than meningitis, and most often CNS disease is part of disseminated infection found primarily in older patients with the chronic form of paracoccidioidomycosis. T. marneffei is the least likely of the endemic mycoses to cause CNS infection. Almost all reported cases have been in patients with advanced HIV infection and almost all have had widespread disseminated infection. Sporotrichosis is known to cause isolated chronic meningitis, primarily in immunocompetent individuals who do not have Sporothrix involvement of other organs. In contrast, CNS infection in patients with advanced HIV infection occurs as part of widespread disseminated infection.

Infectious Complications After Umbilical Cord Blood Transplantation for Hematological Malignancy.

BACKGROUND: Umbilical cord blood transplant (UCBT) is used for patients who do not have a matched donor, but engraftment often takes longer than with a standard allogeneic transplant, likely increasing the risk for infection. We characterized specific infections and outcomes in adults undergoing UCBT at our 2 centers. METHODS: All adults who underwent UCBT between January 1, 2006 and December 31, 2015 were included. Infectious episodes from 6 months before to 2 years after UCBT were reviewed. RESULTS: Fifty-seven patients underwent UCBT; 47 had neutrophil engraftment. A total of 179 infectious episodes occurred in 55 patients, 73 (41%) within 30 days post-UCBT. Viruses caused 85 (47%) infections. Cytomegalovirus caused 32 infectious episodes and was most common from day 30 to 100. Human herpesvirus 6 occurred in 28 episodes, was most common within 30 days, and caused 1 death. Bacteria were responsible for 82 (46%) infections, most commonly bacteremias due to Staphylococcus spp, Enterococcus spp, and Enterobacteriaceae. Of 11 invasive fungal infections, 9 were aspergillosis, 4 of which were fatal. Overall mortality was 56% in the first year. Thirteen deaths were from infection; 11 occurred in the first 100 days and 7 in the first 30 days post-UCBT. Of 10 patients who never engrafted, 9 died, 6 from infection, within 100 days post-UCBT. CONCLUSIONS: Infectious complications were common after UCBT, especially in the first 30 days. Deaths from viral infections were fewer than expected. Delayed engraftment and nonengraftment continue to convey increased risk for fatal bacterial and fungal infections post-UCBT.

Manifestations and outcomes of nocardia infections: Comparison of immunocompromised and nonimmunocompromised adult patients.

Nocardia is a ubiquitous environmental pathogen that causes infection primarily following inhalation into the lungs. It is generally thought to cause infection primarily in immunocompromised patients, but nonimmunocompromised individuals are also at risk of infection. We sought to compare risk factors, clinical manifestations, diagnostic approach, treatment, and mortality in immunocompromised and nonimmunocompromised adults with nocardiosis.We studied all adults with culture-proven Nocardia infection at a tertiary care hospital from 1994 to 2015 and compared immunocompromised with nonimmunocompromised patients. The immunocompromised group included patients who had a solid organ transplant, hematopoietic cell transplant (HCT), hematological or solid tumor malignancy treated with chemotherapy in the preceding 90 days, inherited immunodeficiency, autoimmune/inflammatory disorders treated with immunosuppressive agents, or high-dose corticosteroid therapy for at least 3 weeks before the diagnosis of nocardiosis.There were 112 patients, mean age 55 ±â€Š17 years; 54 (48%) were women. Sixty-seven (60%) were immunocompromised, and 45 (40%) were nonimmunocompromised. The lung was the site of infection in 54 (81%) immunocompromised and 25 (55%) nonimmunocompromised patients. Pulmonary nocardiosis in immunocompromised patients was associated with high-dose corticosteroids, P = .002 and allogeneic HCT, P = .01, and in nonimmunocompromised patients with cigarette smoking, bronchiectasis, and other chronic lung diseases, P = .002.Cavitation occurred only in the immunocompromised group, P < .001. Disseminated infection was more common in the immunocompromised, P = .01, and was highest in solid organ transplant recipients, P = .007. Eye infection was more common in nonimmunocompromised patients, P = .009. Clinical signs and symptoms did not differ significantly between the 2 groups. The initial treatment for most patients in both groups was trimethoprim-sulfamethoxazole with or without a carbapenem. All-cause 1-year mortality was 19%; 18 (27%) immunocompromised and 3 (7%) nonimmunocompromised patients died, P = .01.Immunocompromised patients with nocardiosis had more severe disease and significantly higher mortality than nonimmunocompromised patients, but clinical presentations did not differ.