Osteomyelitis due to Aspergillus spp. in patients with chronic granulomatous disease: comparison of Aspergillus nidulans and Aspergillus fumigatus.

OBJECTIVE: Chronic granulomatous disease (CGD) is a rare inherited disorder of NADPH oxidase in which phagocytes fail to generate reactive antimicrobial oxidants. Invasive fungal infections are an important cause of morbidity and mortality in CGD patients, with Aspergillus spp. being the most frequent fungal pathogens. We reviewed the reported cases of osteomyelitis in CGD patients due to Aspergillus nidulans and compared them with those due to Aspergillus fumigatus. METHODS: Twenty-four cases of osteomyelitis due to Aspergillus spp. in 22 male CGD patients were found in MEDLINE. RESULTS: Fourteen cases (58%) were due to Aspergillus nidulans and ten cases to Aspergillus fumigatus. No other aspergilli were reported as causes of osteomyelitis. Osteomyelitis due to Aspergillus nidulans was associated with pulmonary infection and involved 'small bones' more frequently than Aspergillus fumigatus osteomyelitis (p=0.032). Half of the CGD patients with Aspergillus nidulans osteomyelitis died compared with none of those with Aspergillus fumigatus osteomyelitis (p=0.019). In both Aspergillus nidulans and Aspergillus fumigatus cases, cure was achieved by prompt antifungal treatment combined with surgery and immunotherapy. CONCLUSION: Aspergillus nidulans causes osteomyelitis in CGD patients relatively frequently compared with Aspergillus fumigatus and may be accompanied by higher mortality. This contrasts with the low frequency with which Aspergillus nidulans causes osteomyelitis in patients with other types of immunodeficiency.     

Cryptococcal meningitis: outcome in patients with AIDS and patients with neoplastic disease.

A retrospective analysis of 41 patients with cryptococcal meningitis and AIDS or neoplastic disease was done. Patients with AIDS were younger and predominantly male; they had a shorter duration of prior illness, higher initial serum cryptococcal antigen titers, and lower initial cerebrospinal fluid white blood cell counts than those with neoplastic disease. The median overall survival for patients with AIDS was 9 months compared with 2 months for those with neoplastic disease (P = .004). Seventy-eight percent of patients with AIDS and 43% of those with neoplastic disease were cured or improved 6 months after diagnosis (P = .039). Toxicity from amphotericin B and flucytosine was similar for both groups. One patient with AIDS relapsed. Multivariate predictors of survival included headache (P = .007) and an AIDS diagnosis (P = .009). Examination of outcomes for other opportunistic infections associated with AIDS and other immunosuppressive illness may distinguish prognostic features for different patient populations.     

The prevalence of invasive amebiasis is not increased in patients with AIDS.

OBJECTIVE: To determine whether the frequency or severity of invasive amebiasis is increased in patients with AIDS. DESIGN: A case-control sampling approach, based on an autopsy registry. SETTING: General Hospital of Mexico City, Mexico, a large government-supported, tertiary care medical institution. PATIENTS, PARTICIPANTS: Ninety-four patients with AIDS and 335 historical and contemporary, age- and sex-matched controls who were defined as dying, but not because of AIDS. RESULTS: The odds ratio (OR) for mortality from invasive amebiasis was the same for cases and controls (0.7; 95% confidence interval, 0.07-7.2). By contrast, the OR for other diseases, such as miliary tuberculosis, cytomegalovirus infection, Pneumocystis carinii pneumonia and toxoplasmosis was greatly increased. Only one patient with AIDS had amebiasis of the common amebic ulcerative colitis type, without extraintestinal involvement. CONCLUSION: In conclusion, we show that the frequency and severity of invasive amebiasis is not increased in Mexican patients with AIDS.     

Clinical significance of Aspergillus fungaemia in patients with haematological malignancies and invasive aspergillosis

The clinical significance of Aspergillus fungaemia in the setting of a deep-seated aspergillosis has not been clearly established. Among 107 microbiologically documented Aspergillus infections in patients with haematological diseases observed over a 17-year period, blood cultures grew Aspergillus species from 10 cases. Aspergillus fungaemia was documented in 9 out of 89 (10.1%) patients with pulmonary aspergillosis at a median of 5 d from the onset of clinical signs of infection, and in one patient with central venous catheter focal infection. Five (50%) patients died as a result of fungal infection a median of 12 d (range 4--48) from the documentation of Aspergillus fungaemia. A comparison between cases of invasive aspergillosis with or without fungaemia showed that fungaemic patients were similar to those without positive blood cultures regarding clinical presentation, risk factors, clinical course and outcome. The diagnostic role of Aspergillus fungaemia in the setting of a deep-seated infection is limited because blood cultures become positive when a microbiological or clinical diagnosis of aspergillosis has already been performed. Aspergillus fungaemia does not necessarily seem to be correlated with a disseminated infection or a poorer prognosis.     

Aspergillus antigen detection in bronchoalveolar lavage fluid from patients with invasive aspergillosis and aspergillomas

Improved diagnostic techniques have been needed for pulmonary aspergillosis, a common opportunistic fungal infection with a high mortality rate. Radioimmunoassay was used in this study to detect Aspergillus antigen in bronchoalveolar lavage fluid. In four patients with invasive aspergillosis or aspergillomas, Aspergillus antigen was detected in bronchoalveolar lavage fluid. In two patients, results of fungal cultures were negative or delayed. The specificity of antigen detection in bronchoalveolar lavage fluid was 91 percent in 35 control patients with a variety of pulmonary disorders. The technique of radioimmunoassay detection of microbial antigen in bronchoalveolar lavage fluid appears promising for the diagnosis of aspergillosis.     

Non invasive evaluation of endothelial function in patients with Anderson-Fabry disease.

AIM: Fabry's disease is an X-linked recessive abnormality of glycosphingolipid metabolism. Increased levels of endothelial prothrombotic factors have recently been demonstrated in Fabry's disease, whereas endothelial function has not been studied using high resolution ultrasound. METHODS: We enrolled 6 patients (4 male, 2 female; mean age, 37 years) and 12 sex matched control subjects (mean age, 37 years). Patients' exclusion criteria included a prior history of cardiac disease, diabetes and treated or untreated hypertension. Patients underwent: anamnesis, physical examination, EKG, 2-dimensional echocardiography with tissue Doppler, measurement of body weight and height, blood pressure. Biochemistry variables were also considered: fasting blood sugar, total cholesterol, HDL-C, LDL-C, triglycerides, fibrinogen, C reactive protein and homocysteine. Using high resolution ultrasound, we assessed the brachial vasodilator response to reactive hyperemia (endothelium-dependent) and sublingual nitroglycerin (NTG) (endothelium-independent). Flow-mediated dilatation (FMD) was expressed as percentage change in post-stimulus diameter in comparison with the baseline. RESULTS: In baseline condition, there was no significant difference between patients and controls in the brachial artery diameter (3.5+/-0.55 vs 3.1+/-0.4). After reactive hyperemia, the FMD change was significantly higher in controls than in patients (16.5+/-6.3% vs 9.3+/-6.2%, P<0.05). After NTG, endothelium-independent vasodilation did not show a significant difference between cases and controls (15+/-7.7% vs 13.8+/-7.1%). CONCLUSIONS: Our study demonstrated the presence of endothelial dysfunction in patients with Fabry's disease in comparison to controls. We hypothesized that endothelial dysfunction may contribute to the pathogenesis of ischemic events in patients with Fabry's disease.     

Pulmonary disease in AIDS patients

Pulmonary disease remains a major complication of the human immunodeficiency virus (HIV). Over the past decade several changes in the pattern of disease have occurred. Pneumocystis carinii pneumonia (PCP) remains the most common opportunistic pathogen in AIDS patients, though its incidence on bronchoscopy has declined and empiric therapy often occurs without a specific diagnosis. Changes in the management of patients with PCP have included different dosages and routes of administration for chemotherapy, improved overall survival, and a recent increase in the number of patients surviving episodes of respiratory failure. In addition, infection with mycobacteria tuberculosis (M.Tb.) has emerged as a major public health problem. The pattern of M.Tb. is distinct from non-immunocompromised patients though response to therapy usually occurs.     

Cytokine profile in lung transplant recipients with Aspergillus spp colonization

We studied cytokine profiles in BAL of LTRs with Aspergillus spp colonization who did not progress to IPA in the absence of antifungal prophylaxis. This was a retrospective, single center case‐control study. BAL samples were analyzed for cytokines. Patients with Aspergillus spp in BAL who did not receive prophylaxis and did not develop IPA were compared to LTRs with Aspergillus spp that received prophylaxis, LTRs with IPA and controls. Twenty‐one patients with Aspergillus colonization who did not develop IPA, seven patients with suspected IPA who received prophylaxis, 4 IPA and 19 controls were included. IPA group had significantly higher levels (median [IQR]) of MIP‐1 beta compared to the Suspected IPA group (5 vs 5 P: 0.03). The Suspected IPA group had significantly higher levels of IL‐12 (11.38 vs 1 P: 0.0001), IL‐1 RA (86.11 vs 23.98 P: 0.0118), IP‐10 (22.47 vs 0.86 P: 0.0151), HGF (40.92 vs 16.82 P: 0.0055), and MIG (169.62 vs 5 P: 0.0005) than Colonization group. We have identified a unique cytokine signature in patients with Aspergillus colonization that do not develop IPA. Our study forms basis for a larger study to use these cytokines profile to identify patients at a lower risk of developing IPA.     

Survival of patients with AIDS and cytomegalovirus disease treated with ganciclovir or foscarnet.

We reviewed the hospital charts of 168 patients with AIDS and cytomegalovirus (CMV) disease diagnosed at San Francisco General Hospital between July 1985 and October 1989. One hundred and thirty-three patients had CMV retinitis, 33 had CMV gastrointestinal disease, and two had CMV lung disease. We found a trend towards longer survival from time of CMV disease diagnosis in patients with more recent dates of diagnosis. The median survival of patients diagnosed with CMV disease prior to 30 September 1987 was 4 months, compared with 9 months for patients diagnosed after 30 September 1987 (P = 0.001). The relative hazard of death for patients with CMV retinitis who were initially treated with foscarnet was not significantly reduced compared to those initially treated with ganciclovir. Even after controlling for age at time of CMV diagnosis, time from index AIDS diagnosis, hemoglobin, absolute lymphocyte count, absolute neutrophil count and concurrent zidovudine therapy, the relative hazard for foscarnet-treated patients compared with ganciclovir-treated patients was 1.0 (95% confidence interval, 0.5-1.8).     

Pulmonary Aspergillus colonization in humans and its impact on management of critically ill patients

Samples of lung tissues were obtained and analysed for Aspergillus carriage in 56 patients undergoing thoracic surgical intervention and 18 people who had an unexpected death. Out of 74 samples, 46 (63%) had evidence of pulmonary fungal colonization. The surgery population had a rate of 62% of fungal growth. Aspergillus was present in 39%. The autopsy population had a rate of 61% of fungal colonization. Aspergillus was present in 41%. In these cases eradication of fungal spores residing in the lung prior to aggressive chemotherapy and prevention of further spore uptake during hospitalization is indispensable in preventing pulmonary aspergillosis.     

Invasive aspergillosis in patients with AIDS.

Invasive aspergillosis is a rare complication of AIDS. We discuss the cases of 18 patients with AIDS and invasive aspergillosis who were identified at our institution and 19 patients who are described in the literature. Twenty-one patients were either homosexual or bisexual, eight were intravenous drug users, three were hemophiliacs, two attributed their disease to a heterosexual contact, and one was a transfusion recipient; risk factors for AIDS were unknown for two patients. Twenty-eight of the 37 patients had pulmonary aspergillosis; for 18 of these 28, the lung was the sole site of disease. Aspergillosis involved the brain in 12 cases, the heart in five cases, and the kidney, sinuses, or skin in six other cases. Eleven patients had multiple sites of disease, and eight patients had extrapulmonary disease alone. Possible risk factors for aspergillosis included leukopenia (7 patients, of whom 5 were also neutropenic) and use of corticosteroids (8 patients), alcohol (6 patients), broad-spectrum antibiotics (5 patients), and antineoplastic agents (4 patients); 14 patients had no identifiable risk. Death was the usual outcome, despite treatment of patients with amphotericin B. In cases of AIDS and invasive aspergillosis, early diagnosis may lead to improved outcome.     

Cytomegalovirus infection in patients with AIDS.

Advances in the field of antiviral therapy are now occurring with increasing frequency and rapidity and often generate varying degrees of confusion among those of us whose practices are focused primarily on therapy with antibacterial agents. How to treat cytomegalovirus infections in patients infected with the human immunodeficiency virus constitutes one of the best examples of the quandaries engendered by these advances, and the topic is reviewed in this first AIDS Commentary update. Given the U.S. Food and Drug Administration's recent approval of foscarnet, this discussion is very timely; it is particularly relevant for clinicians to be made aware of current lines of thought regarding induction versus maintenance therapy, the benefits of efficacy versus adverse effects of drug-related toxicity, and the interactions between antiretroviral drugs and ganciclovir or foscarnet. Dr. W. Lawrence Drew's career in this area has been long-standing and productive, and he is one of the leading experts in the field. In this update he addresses these perplexing issues.     

Candida colonization in patients with esophageal disease: a prospective clinical study

The incidence of Candida infection has significantly increased over the recent years, becoming the fourth most common pathogens isolated in patients admitted to intensive care units (ICU). Mortality rates ranging between 6 and 38% have been reported to be associated with candidemia. Esophageal surgery may increase the risk of systemic Candida infection in critical patients requiring postoperative ICU admission. The aim of the present study was to assess the prevalence of Candida colonization in patients with esophageal disease undergoing surgery. Between April 1999 and April 2001, 131 patients with esophageal disease and 40 healthy volunteers were prospectively tested for Candida colonization by oral and pharyngeal swab. Candida colonization was significantly more frequent in patients with esophageal disease than in control subjects (38.9 vs 7.5%, P < 0.01); the prevalence was higher in individuals with carcinoma than in those with benign disease (51.8 vs 24%, P < 0.02), and in patients undergoing neoadjuvant chemoradiation therapy compared to those having primary surgery (55.5 vs 34.4%, P < 0.01). These data suggest that Candida colonization of the gastrointestinal tract is common in patients with esophageal disease. Pharmacological attempts to prevent or reduce the magnitude of this event may be worthwhile before surgery. However, the hypothesis that antifungal oral prophylaxis with nonabsorbable drugs may lower the incidence of candidemia in patients with gastrointestinal Candida colonization, especially in those candidates to postoperative ICU admission, should be tested by randomized double-blinded studies.     

Splenic tuberculosis in patients with AIDS.

Splenic tuberculosis is an uncommonly considered diagnosis in clinical practice. We report splenic tuberculosis in three patients with AIDS who were admitted to the hospital because of fever and constitutional syndrome. In all of the patients, abdominal sonography and abdominal computed tomography revealed multiple hypoechoic and hypodense lesions, respectively. In two patients needle aspiration of the spleen with sonographic control was the diagnostic procedure. In the third patient the diagnosis was confirmed after splenectomy. In AIDS patients tuberculosis must be included in the differential diagnosis of hypoechoic and hypodense lesions by means of sonography and computed tomography, respectively, especially in those patients with active tuberculosis.