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.

Histoplasmosis in patients with acquired immunodeficiency syndrome. Hematologic and bone marrow manifestations.

In areas where Histoplasma capsulatum infections are endemic in the United States, there is an increasing frequency of progressive disseminated histoplasmosis (PDH) as an opportunistic infection in patients with acquired immune deficiency syndrome (AIDS). The bone marrow and peripheral blood (PB) specimens in 13 patients with AIDS and PDH were reviewed. Anemia, leukopenia, and thrombocytopenia were found in 12, 10, and 7 patients, respectively. Circulating organisms were detected in the blood smears or buffy coat preparations from five patients and were associated with PB nRBCs and severe absolute monocytopenia. Morphologically, the marrow specimens showed one of four patterns: (1) no morphologic evidence of infection (two patients, one with a positive marrow culture); (2) discrete granulomas (two patients, both with positive marrow cultures); (3) lymphohistiocytic aggregates (six patients, four with positive marrow cultures); and (4) diffuse macrophage infiltrates (three patients, all with positive marrow cultures). Morphologic examination of the bone marrow combined with cultures is useful in diagnosing disseminated histoplasmosis in patients with AIDS. However, the morphologic findings in the bone marrow may be different in patients with AIDS compared with non-AIDS patients, and seemingly nondiagnostic morphologic features must be approached with a high degree of suspicion in diagnosing infections with H. capsulatum in this population.

Histoplasmosis in Missouri: historical review and current clinical concepts.

Histoplasmosis is particularly common in Missouri, and many important clinical observations about the disease were made in this state in the 1950s and 1960s. When the AIDS epidemic spread to Missouri in the mid-1980s, histoplasmosis became recognized as a common and important opportunistic infection among Missourians with AIDS. Clinicians must maintain a high level of suspicion for histoplasmosis in any HIV-infected patient who presents with unexplained fever, particularly if the patient has evidence of hepatosplenomegaly, generalized lymphadenopathy, pancytopenia, abnormal liver function tests, or bilateral pulmonary infiltrates. The diagnosis of histoplasmosis can be established rapidly by observation of organisms on peripheral blood smear or bone marrow biopsy specimens or by Histoplasma Polysaccharide Antigen testing. The diagnosis can be confirmed by blood cultures in most cases. Histoplasmosis in AIDS is invariably fatal if not treated. Treatment consists of two phases: initial induction therapy and subsequent lifelong maintenance therapy. Amphotericin B and itraconazole are extremely effective for induction and maintenance therapy; fluconazole appears to be effective maintenance therapy. Strategies for the prevention of histoplasmosis in high risk patients are being evaluated currently.

Nosocomial pneumonia in the intubated patient.

The intubated patient receiving mechanical ventilation is at high risk for nosocomial pneumonia. Epidemiologic data, pathogenic mechanisms, and risk factors for the development of nosocomial pneumonia are reviewed in this subset of patients. Exogenous and endogenous factors for bacterial colonization of the oropharynx are summarized with particular emphasis on the effects of bacterial overgrowth in the stomach. In addition, we review the role of respiratory therapy equipment in the pathogenesis of pneumonia. Overall fatality rates for patients receiving mechanical ventilation in an intensive care unit is approximately 40%. Patients who develop ventilator-associated pneumonia have fatality rates that exceed 50% and are more than two-fold higher than intubated patients without pneumonia. Measures for altering oropharyngeal colonization, reducing gastric colonization, and the use of sound infection control practices are cornerstones for the prevention of ventilator-associated pneumonia.

Colonic histoplasmosis in acquired immunodeficiency syndrome. Report of two cases.

Colonic histoplasmosis is a rare entity. There have been four previous reported cases within the population of patients with human immunodeficiency virus (HIV) infection. Because of the increasing incidence of HIV infection within regions where histoplasmosis is endemic, this condition may become more common. Gastrointestinal histoplasmosis has protean clinical manifestations, and symptoms are often nonspecific. Any patient with HIV infection who has unexplained GI symptoms should undergo evaluation for possible histoplasmosis. Aggressive long-term amphotericin B therapy has been effective in HIV patients with histoplasmosis. Resection or diversion of symptomatic colonic strictures caused by histoplasmosis may be necessary in addition to medical therapy.

Long-term amphotericin B therapy for disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome (AIDS).

STUDY OBJECTIVE: To assess the efficacy and toxicity of long-term maintenance amphotericin B therapy in preventing relapses after treatment in patients with the acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. DESIGN: Open, nonrandomized pilot study. SETTING: Three private, university-affiliated community hospitals. PATIENTS: We studied 22 consecutive patients with disseminated histoplasmosis and human immunodeficiency virus (HIV) infection. Sixteen patients completed the study, 5 patients died before completing the initial intensive phase of treatment, and 1 patient received a different treatment regimen. INTERVENTIONS: Seven patients were treated with an initial intensive course of 1000 mg of amphotericin B, followed by weekly infusions of 50 to 80 mg until a cumulative dose of 2000 mg was attained; biweekly infusions of 50 to 80 mg were then continued indefinitely. Nine patients received an initial amphotericin B course of 2000 mg followed by weekly infusions of 80 mg. MEASUREMENTS AND MAIN RESULTS: Of the 7 patients in the 1000-mg intensive regimen group, 6 patients have survived without clinical or laboratory evidence of a histoplasmosis relapse, and 1 died of unrelated causes. Of the 9 patients in the 2000-mg intensive regimen group, 7 patients have survived, 1 patient died of a histoplasmosis relapse, and 1 patient died of other causes. Thus, 13 of 14 patients (93%) who did not die of other causes remained relapse-free. The median follow-up period was 14 months (range, 2 to 23 months). No apparent differences in outcome were observed between patients treated with weekly maintenance regimens and those treated with biweekly maintenance regimens. Sixty-three percent of patients developed intravascular device-related complications. CONCLUSIONS: Long-term, intermittent maintenance amphotericin B therapy in HIV-infected patients with disseminated histoplasmosis is well tolerated and is highly effective in suppressing relapses after treatment.

Clinical courses of seven survivors of Clostridium septicum infection and their immunologic responses to alpha toxin.

Clostridium septicum bacteremia typically portends a fulminant disease associated with high mortality. We describe the clinical courses of seven survivors of C. septicum infection and their antibody responses to the alpha toxin produced by C. septicum. Three patients had clinical syndromes ranging from uncomplicated bacteremia to early typhlitis, and three patients had syndromes ranging from abscess to myonecrosis and septic shock. In addition, an AIDS patient who developed septic shock and who had extensive gas in the retroperitoneal musculature did not undergo surgery but survived after receiving antimicrobial therapy and intensive supportive care. Both immunocompetent patients with myonecrosis had detectable IgG to alpha toxin by immunoblot analysis. IgG to alpha toxin was not detected in the four immunocompetent patients who had C. septicum bacteremia but who did not have myonecrosis or in the AIDS patient with myonecrosis. Therefore, humoral responses to alpha toxin during C. septicum infection may be related to the host's clinical syndrome and immune status.

Mycobacterium kansasii among patients infected with human immunodeficiency virus in Kansas City. Kansas City AIDS Research Consortium.

Previous reports of infection due to Mycobacterium kansasii among patients infected with human immunodeficiency virus (HIV) have conflicted with regard to the significance of the isolate; the clinical, radiographic, and laboratory features of the disease; and the response to therapy. To clarify the spectrum of M. kansasii infection in this population, we conducted a retrospective study of 35 patients. Twenty-eight of these patients were believed to have disease due to M. kansasii, while the remaining seven patients were probably colonized with the organism. All but two patients presented with advanced HIV infection; the median CD4 cell count was 12/microL. Most patients with pulmonary disease presented with fever, cough, and dyspnea, but only eight of these 22 patients had radiographic findings of either pulmonary cavitation or predominantly upper-lobe disease. Ten patients had M. kansasii isolated from blood or bone marrow. The majority of patients with pulmonary or disseminated disease responded to therapy. However, 11 patients died either before mycobacterial infection was diagnosed or early in the course of treatment, and two had a relapse of infection during therapy.

Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. The role of gastric colonization.

Gram-negative nosocomial pneumonia may result from retrograde colonization of the pharynx from the stomach, and this may be more likely when the gastric pH is relatively high. We studied the rate of nosocomial pneumonia among 130 patients given mechanical ventilation in an intensive care unit who were receiving as prophylaxis for stress ulcer either sucralfate (n = 61), which does not raise gastric pH, or conventional treatment with antacids, histamine type 2 (H2) blockers, or both (n = 69). At the time of randomization to treatment, the two groups were similar in age, underlying diseases, and severity of acute illness. Patients in the sucralfate group had a higher proportion of gastric aspirates with a pH less than or equal to 4 (P less than 0.001) and significantly lower concentrations of gram-negative bacilli (P less than 0.05) in gastric aspirates, pharyngeal swabs, and tracheal aspirates than did patients in the antacid-H2-blocker group. The rate of pneumonia was twice as high in the antacid-H2 group as in the sucralfate group (95 percent confidence interval, 0.89 to 4.58; P = 0.11). Gram-negative bacilli were isolated more frequently from the tracheal aspirates of patients with pneumonia who were receiving antacids or H2 blockers. Mortality rates were 1.6 times higher in the antacid-H2 group than in the sucralfate group (95 percent confidence interval, 0.99 to 2.50; P = 0.07). Although our results fell just short of statistical significance when they were analyzed according to intention to treat, they suggest that agents that elevate gastric pH increase the risk of nosocomial pneumonia in patients receiving ventilation by favoring gastric colonization with gram-negative bacilli. We conclude that in patients receiving mechanical ventilation, the use of a prophylactic agent against stress-ulcer bleeding that preserves the natural gastric acid barrier against bacterial overgrowth may be preferable to antacids and H2 blockers.

Prospective study of histoplasmosis in patients infected with human immunodeficiency virus: incidence, risk factors, and pathophysiology.

Histoplasmosis is a common opportunistic infection in patients with human immunodeficiency virus (HIV) infection who reside in areas where Histoplasma capsulatum is endemic. We undertook a prospective study of a cohort of 304 HIV-Infected patients in Kansas City from October 1990 through March 1993 to define the incidence-specific risk factors, and pathophysiology of histoplasmosis. The annual incidence of histoplasmosis was 4.7%; 74% of the patients with histoplasmosis were symptomatic (all of whom had disseminated disease). A history of exposure to chicken coops, a positive baseline serology for complement-fixing antibodies to Histoplasma mycelium antigen, and a baseline CD4+ lymphocyte count of < 150/microL were associated with an increased risk for histoplasmosis. Histoplasmin reactivity and the presence of pulmonary calcifications were not useful markers for patients at high risk. Symptomatic infection occurred in 9.9% of patients with evidence of prior exposure to H. capsulatum, in 4.0% of patients without documented prior exposure, and in 3.0% of patients who were anergic; these findings suggest that the pathophysiology of histoplasmosis in patients with AIDS involves reactivation of latent infection in some cases and dissemination of exogenously acquired infection in other cases.