Richard B. Kohler

Diagnosis of Disseminated Histoplasmosis by Detection of Histoplasma capsulatum Antigen in Serum and Urine Specimens

The diagnosis of Histoplasma capsulatum infection by serologic testing for the presence of antibodies is limited by a high rate of false positive and false negative results and by the requirement that the patient have a normal immune response. We have developed a radioimmunoassay for the detection of H. capsulatum antigen in urine and serum specimens. Antigenuria was noted in 20 of 22 episodes of disseminated histoplasmosis that occurred in 16 patients, in 6 of 32 patients with self-limited infection, in 2 of 32 patients with cavitary histoplasmosis, and in 4 of 8 patients with a sarcoid-like illness caused by H. capsulatum. The detection of antigen in urine was reproducible in 38 of 41 (93 percent) retests of specimens. H. capsulatum antigen was also detected in the serum during 11 of the 22 episodes of disseminated histoplasmosis, in none of the 12 episodes of other types of histoplasmosis in patients with antigenuria, in 1 of the 33 patients with histoplasmosis who lacked the urinary antigen, and in none of the 50 controls. Antigenemia and antigenuria decreased after initiation of antifungal therapy and recurred in patients who had a relapse. We conclude that this radioimmunoassay for H. capsulatum antigen represents a useful new method for the rapid diagnosis of disseminated histoplasmosis.

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.

Unidentified Gram-Negative Rod Infection: A New Disease of Man

A Gram-negative bacillus that defies identification was isolated from blood cultures of 17 patients with fever. Fifteen patients were male adults, and 14 patients had underlying diseases, including previous splenectomy in five, which impair host defenses against infection. Illnesses occurred in the summer and autumn in 14 cases and had been recently preceded by dog bites in 10 cases. Clincal syndromes included cellulitis in seven cases, primary bacteremia without localization in four, purulent meningitis in four, and endocarditis in three. Three patients died. The organism grows slowly on blood or chocolate agar in 10% CO, is oxidase- and catalase-positive, and is negative for nitrate reduction, indole production, and urease. It produces acid from glucose, lactose, and maltose. These features distinguish it from all previously described and classified bacteria. Furthermore, the epidemiologic features of the patients suggest that this organism is an opportunistic invader and may have an animal reservoir in nature.

Histoplasma capsulation polysaccharide antigen detection in diagnosis and management of disseminated histoplasmosis in patients with acquired immunodeficiency syndrome

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.

Solid-Phase Radioimmunoassay for Immunoglobulin G Staphylococcus aureus Antibody in Serious Staphylococcal Infection

Clinical features of 99 patients with staphylococcal infection were reviewed, and sera were tested by solid-phase radioimmunoassay and gel diffusion for staphylococcal antibodies to ascertain whether these variables predict the extent of infection and the need for prolonged therapy. Clinical features, including the presence of a primary site of infection or a continuous pattern of bacteremia, were not sufficient for differentiating endocarditis or complicated bacteremia from uncomplicated bacteremia. Patients with uncomplicated bacteremia were cured by 3 weeks of antibiotic therapy. Positive serologic tests for staphylococcal antibody helped distinguish patients with endocarditis or complicated bacteremia from patients with uncomplicated bacteremia. Radioimmunoassay was more sensitive than gel diffusion for identifying patients with complicated bacteremia. Our results indicate that patients with a positive antibody result 14 days after the onset of infection should be considered to have endocarditis or complicated bacteremia, but a negative antibody result would support short-term antibiotic therapy.

Multicenter, Open-Label, Randomized Study to Compare the Safety and Efficacy of Levofloxacin versus Ceftriaxone Sodium and Erythromycin Followed by Clarithromycin and Amoxicillin- Clavulanate in the Treatment of Serious Community-Acquired Pneumonia in Adults

This randomized, multicenter, phase IV, comparative trial, which was designed to show equivalence, compared the efficacy of levofloxacin with that of a β-lactam-macrolide combination in the treatment of 269 seriously ill patients with community-acquired pneumonia. Patients were randomly assigned to 1 of 2 treatment arms: (1) levofloxacin, 500 mg intravenously, followed by oral administration, every 24 h for 7-14 days, or (2) ceftriaxone sodium, 1-2 g intravenously or intramuscularly every 24 h, with erythromycin, 500-1000 mg intravenously every 6 h, and then switched to amoxicillin-clavulanate, 875 mg orally twice daily, with clarithromycin, 500 mg orally twice daily for 7-14 days. Among patients evaluable for clinical efficacy, 89.5% of levofloxacin-treated patients (85 of 95 patients) and 83.1% of comparator-treated patients (74 of 89 patients) achieved clinical success (a cure or an improved condition). Both levofloxacin and the comparator were safe and well tolerated, with gastrointestinal disorders being the most common adverse event in both groups. Levofloxacin was as efficacious as the β-lactam-macrolide combination in the treatment of seriously ill patients with community-acquired pneumonia.

The microbiology and chemotherapy of odontogenic infections

This article reviews the complexity of the microbiological environment of odontogenic infections. With an understanding of the organisms involved, the appropriate antibiotic can be chosen. A review of current antibiotic choices and the rationale for their selection is also presented.

Cavitary Histoplasmosis Occurring During Two Large Urban Outbreaks: Analysis Of Clinical, Epidemiologic, Roentgenographic, And Laboratory Features

We have compared risk factors for cavitary histoplasmosis in 62 patients with that manifestation of the infection and in 679 patients with other forms of histoplasmosis, and we have evaluated the clinical and laboratory findings in 45 patients with cavitary histoplasmosis who were cared for at the Indiana University Medical Center hospitals during two large histoplasmosis outbreaks. Chronic obstructive lung disease and old age were the strongest risk factors for cavitary histoplasmosis but male sex, white race and immunosuppression were also important in certain patient groups. Fever, sweats, weight loss, productive cough, anemia, lymphopenia, and alkaline phosphatase elevation were common findings. The patients were occasionally incorrectly treated for presumed class 3 tuberculosis. Cultures were positive in 58% of patients, with sputum samples providing the highest yield (61%). Histoplasmal serologic tests provided useful clues to the diagnosis, positive in over 90% of cases. About one-third of patients recovered spontaneously while another 35% improved following treatment. About 4% developed chronic untreated cavitary histoplasmosis characterized by clinical and roentgenographic exacerbations and remissions. Of the deaths in four patients with untreated disease, one was caused by disseminated histoplasmosis while three died of other causes. Ketoconazole appeared effective in three of seven patients while its effect in three additional patients was uncertain. Toxicity precluded completion of ketoconazole therapy in one patient. Only amphotericin B has been proven to be effective therapy for cavitary histoplasmosis.