Thomas G. Slama

Histoplasmosis in the acquired immune deficiency syndrome

This report describes the experience with disseminated histoplasmosis in seven of 15 patients with the acquired immune deficiency syndrome (AIDS) diagnosed in Indianapolis since 1981. Three were homosexual, two were intravenous drug addicts, one was the spouse of another patient with AIDS and disseminated histoplasmosis, and the seventh was a hemophiliac. Six had associated infections: candidiasis in three, Pneumocystis carinii pneumonia, recurrent mucocutaneous herpes simplex infection, and disseminated Mycobacterium avium infection in two each, and disseminated infection with an unidentified mycobacterium in one. Clinical diseases suggested sepsis in four. Histoplasma fungemia occurred in five, but the diagnosis was established first by visualization of organisms in blood or bone marrow in three. Results of Histoplasma serologic tests were positive in each. Three died before receiving 50 mg of amphotericin B, three had prompt improvement with amphotericin B, and one was treated with ketoconazole to prevent dissemination. However, two of the three patients treated with amphotericin B had relapses after a 35 mg/kg course, and the third died within a month following therapy. Disseminated histoplasmosis is a major opportunistic infection in patients with AIDS from endemic areas. AIDS should be strongly considered in otherwise healthy persons with disseminated histoplasmosis, especially if risk factors for AIDS are present. Amphotericin B is not curative in these patients.

Clinical and laboratory features of disseminated histoplasmosis during two large urban outbreaks.

Clinical and laboratory features have been reviewed in 66 episodes of disseminated histoplasmosis that occurred during two large urban outbreaks in Indianapolis. Immunosuppression, age greater than 54 years, and presence of other serious underlying illnesses predisposed to the disseminated form of the disease; only 21% of patients lacked one of these risk factors. Central nervous system findings, splenomegaly, hepatomegaly, and lymphopenia suggested disseminated disease but were present in only about one-third of patients. Miliary or diffuse pulmonary infiltrates also suggested dissemination and were noted in about one-third of patients, while mediastinal lymphadenopathy was present in only 17%. Histoplasmal serologic tests, positive in 90% of patients, provided useful diagnostic clues. The diagnosis could be confirmed by culture in 88% of patients, and special stains were positive in about two-thirds. Although 10% of patients recovered without treatment, 11 patients (17%) died because of failure to suspect the diagnosis and initiate therapy promptly. Amphotericin B was effective in all patients receiving at least 500 mg, but relapse occurred if the total dose was less than 30 mg/kg. Ketoconazole appeared effective in non-immunosuppressed patients but not in those with underlying immunosuppression; however, a controlled trial comparing ketoconazole and amphotericin B is required to establish the role of this new fungistatic oral agent.

A large urban outbreak of histoplasmosis: clinical features.

An outbreak of histoplasmosis estimated to involve more than 100,000 residents in Indianapolis, Indiana, occurred between September 1978 and August 1979. In the 435 cases evaluated, 52% of the patients were between 15 and 34 years old, and 63% were black. Fifteen patients died, and 46 progressive disseminated infection. Twenty-four patients had pericarditis, and 26 had rheumatologic syndromes. Unusual manifestations that occurred in 18 patients included esophageal and vocal cord ulcers, parotitis, adrenal insufficiency, uveitis, fibrosing mediastinitis, interstitial nephritis, intestinal lymphangiectasia, and epididymitis. The highest attack rate was in the central part of the city, which is a densely populated, disproportionately black section. The source of the outbreak has not been proved by positive culture results; two sites, however, were suspected on an epidemiologic basis.

Risk Factors for Disseminated or Fatal Histoplasmosis: Analysis of a Large Urban Outbreak

An outbreak of histoplasmosis in Indianapolis involving 488 clinically recognized cases including 60 patients with disseminated or fatal infection permitted statistical analysis of risk factors. Being male, white, under 5 years of age, having chronic obstructive lung disease, and living near the presumed source of the outbreak were not risk factors for fatal or disseminated histoplasmosis. Age greater than 54 years and immunosuppression were the only risk factors for disseminated or fatal infection. Dissemination should be excluded in patients with histoplasmosis who are immunosuppressed or older than 54 years. Specific antifungal treatment is more likely to be required in those two groups rather than in patients without risk factors.

The diagnostic laboratory tests for histoplasmosis: analysis of experience in a large urban outbreak.

Of 495 patients reported in a large urban histoplasmosis outbreak, we studied 276 whose serologic tests were done in a single laboratory. Serologic test results were positive in 96% of these patients (compared with less than 5% of controls from an endemic area), cultures were positive in 22%, and special stains in 19%. The immunodiffusion test results were negative in 13% of patients who had positive findings by complement fixation, and 1% had positive results only by immunodiffusion. The complement fixation test was almost twice as sensitive as the immunodiffusion test in patients with subclinical infection. The serologic response differed significantly among the clinical syndromes with higher titers in cavitary and lower titers in disseminated disease. Factors associated with titers of 1:64 or greater to both antigens were black race and immunocompetence. High mycelial titers were also associated with more intense exposure, and high yeast titers were associated with age less than 36 years. No prognostic significance could be proved for fourfold titer rises or falls or persistence of precipitins.

Infectious Diseases Specialty Intervention is Associated with Decreased Mortality and Lower Healthcare Costs

BACKGROUND Previous studies, largely based on chart reviews with small sample sizes, have demonstrated that infectious diseases (ID) specialists positively impact patient outcomes. We investigated how ID specialists impact mortality, utilization, and costs using a large claims dataset. METHODS We used administrative fee-for-service Medicare claims to identify beneficiaries hospitalized from 2008 to 2009 with at least 1 of 11 infections. There were 101 991 stays with and 170 336 stays without ID interventions. Cohorts were propensity score matched for patient demographics, comorbidities, and hospital characteristics. Regression models compared ID versus non-ID intervention and early versus late ID intervention. Risk-adjusted outcomes included hospital and intensive care unit (ICU) length of stay (LOS), mortality, readmissions, hospital charges, and Medicare payments. RESULTS The ID intervention cohort demonstrated significantly lower mortality (odds ratio [OR], 0.87; 95% confidence interval [CI], .83 to .91) and readmissions (OR, 0.96; 95% CI, .93 to .99) than the non-ID intervention cohort. Medicare charges and payments were not significantly different; the ID intervention cohort ICU LOS was 3.7% shorter (95% CI, -5.5% to -1.9%). Patients receiving ID intervention within 2 days of admission had significantly lower 30-day mortality and readmission, hospital and ICU length of stay, and Medicare charges and payments compared with patients receiving later ID interventions. CONCLUSIONS ID interventions are associated with improved patient outcomes. Early ID interventions are also associated with reduced costs for Medicare beneficiaries with select infections.

Acute Eosinophilic Pneumonia Secondary to Daptomycin: A Report of Three Cases

We describe 3 cases of daptomycin-induced pulmonary toxic effects that are consistent with drug-induced acute eosinophilic pneumonia. Patients presented similarly with dyspnea, cough, hypoxia, and diffuse ground-glass opacities at chest computed tomography. Clinical suspicion for this adverse drug event and cessation of daptomycin until definitive diagnosis can be made is crucial.

Treatment of disseminated and progressive cavitary histoplasmosis with ketoconazole

Ten patients with disseminated histoplasmosis and seven with progressive cavitary histoplasmosis were treated with ketoconazole, an imidazole derivative that is well absorbed orally and relatively nontoxic. Seven of seven noncompromised hosts with disseminated disease tolerated therapy well and achieved clinical and mycologic cures. Although well tolerated in all three compromised hosts with disseminated disease, none achieved clinical and bacteriologic cures. All patients with progressive cavitary disease tolerated therapy well and six of seven achieved clinical and radiographic cures. Therefore ketoconazole appears safe and effective in the treatment of disseminated or progressive cavitary histoplasmosis in the noncompromised host. In the compromised host with disseminated histoplasmosis, ketoconazole does not appear to be effective and more conventional therapy appears warranted.

Prevention of relapse of histoplasmosis with fluconazole in patients with the acquired immunodeficiency syndrome.

OBJECTIVE To assess the effectiveness of fluconazole for suppression of relapse of histoplasmosis in patients with acquired immunodeficiency syndrome (AIDS). DESIGN Retrospective, nonrandomized, open trial. SETTING Multicenter at two university referral centers and in five private practices. PATIENTS Seventy-six patients with AIDS and disseminated histoplasmosis who completed induction treatment with amphotericin B, itraconazole, or fluconazole and maintained on treatment with fluconazole to prevent relapse. INTERVENTIONS Fluconazole was given at dosages of 100 to 400 mg per day. Patients were followed by their primary physicians, who completed questionnaires collecting information about treatment and relapse status. Blood and urine specimens were submitted periodically for Histoplasma capsulatum var. capsulatum antigen determination. MEASUREMENTS AND MAIN RESULTS Nine of the 76 patients relapsed during fluconazole therapy and another was removed from the study because of allergic rash. Survival after initiation of therapy for histoplasmosis was 94 weeks, ranging from 74 weeks for those who received less than 1 g of amphotericin B for induction and none for maintenance therapy to 156 weeks for those who received greater than 1 g for induction and additional amphotericin B for maintenance therapy before beginning fluconazole (P < 0.02). Antigen levels fell at rates of 0.05 units/week in urine and 0.02 units/week in serum in patients who were successfully maintained in remission and increased by > or = 2 units/week in 4 of 6 patients who relapsed. CONCLUSIONS Fluconazole > or = 200 mg daily is a reasonable choice for chronic suppressive therapy of histoplasmosis in patients who cannot take itraconazole because of drug interactions, malabsorption, or side effects.

Pericarditis as a manifestation of histoplasmosis during two large urban outbreaks.

During two histoplasmosis outbreaks in Indianapolis 45 patients presented with pericarditis. The pericarditis occurred as a late complication in individual patients and during the outbreak. Risk factors for this complication included young age, immunocompetence, and male sex in persons between 20 and 39 years old. Intrathoracic adenopathy was present in 66% of cases. Since cultures were uniformly negative, including pericardial fluid or tissue from nine patients, serologic studies provided the basis for diagnosis. Although the course was usually benign, nine patients presented with tamponade and another with constrictive pericarditis. Prompt response to antiinflammatory medications and failure to identify H. capsulatum in the pericardial fluid or tissue support a noninfectious, inflammatory mechanism for this complication. Of 20 patients reexamined 1 year later, none had evidence of constriction but three had pericardial thickening by echocardiography. Histoplasmosis should be considered in patients with pericarditis from endemic areas, particularly when associated with intrathoracic adenopathy.