Pulmonary zygomycosis in solid organ transplant recipients in the current era.

Fifty-eight solid organ transplant recipients with zygomycosis were studied to assess the presentation, radiographic characteristics, risks for extra-pulmonary dissemination and mortality of pulmonary zygomycosis. Pulmonary zygomycosis was documented in 31 patients (53%) and developed a median of 5.5 months (interquartile range, 2-11 months) posttransplantation. In all, 74.2% (23/31) of the patients had zygomycosis limited to the lungs and 25.8% (8/31) had lung disease as part of disseminated zygomycosis; cutaneous/soft tissue (50%, 4/8) was the most common site of dissemination. Pulmonary disease presented most frequently as consolidation/mass lesions (29.0%), nodules (25.8%) and cavities (22.6%). Patients with disseminated disease were more likely to have Mycocladus corymbifer as the causative pathogen. The mortality rate at 90 days after the treatment was 45.2%. In summary, pulmonary zygomycosis is the most common manifestation in solid organ transplant recipients with zygomycosis, and disseminated disease often involves the cutaneous/soft tissue sites but not the brain.

Cunninghamella bertholletiae infection in a bone marrow transplant patient: amphotericin lung penetration, MIC determinations, and review of the literature.

Infections caused by Cunninghamella bertholletiae, an opportunistic fungal organism, have an extremely high mortality rate. A fatal case of C. bertholletiae fungal pneumonia occurred in a man who had received an allogeneic bone marrow transplant. Aggressive debridement and high-dose liposomal amphotericin B failed to eradicate the infection. Right lung tissue samples obtained during lobectomy were assayed for amphotericin B concentrations by high-performance liquid chromatography, and minimum inhibitory concentration (MIC) determinations of amphotericin B against C. bertholletiae were determined by the macrobroth dilution method. The MIC for the isolate of C. bertholletiae was 4 microg/ml. Amphotericin B lung concentrations averaged 9.5 microg/ml (range 3.7-13.8 microg/ml), with a corresponding serum trough concentration of 0.9 microg/ml. To our knowledge, this is the first reported case of amphotericin B concentrations measured at the site of infection in a patient with a pulmonary Cunninghamella infection, together with a corresponding MIC of the organism. The patient's death, which occurred despite aggressive debridement and high amphotericin B lung concentrations, highlights the need for novel strategies to treat infections caused by invasive molds such as C. bertholletiae.

Verbal working memory in HIV-seropositive drug users.

Recent evidence suggests that HIV-seropositive drug users are impaired on tasks of visuospatial working memory compared with drug users seronegative for HIV. In the current study we evaluated the performance of 30 HIV-seropositive male drug users and 30 risk-matched seronegative controls on two measures of verbal working memory, the Listening Span and the verbal Self Ordered Pointing Task. Impaired working memory performance was significantly more common among HIV-seropositive persons compared to controls, with the highest incidence of deficit among symptomatic participants. These findings indicate that working memory deficits in persons with HIV are not domain-specific and can be demonstrated reliably in drug users.

Reaction times are faster in HIV-seropositive patients on antiretroviral therapy: A preliminary report.

We evaluated subclinical mental and motor slowing in 142 HIV-seropositive patients without dementia, using computerized simple and choice reaction time tasks and self-report measures of psychological distress. Patients on antiretroviral therapy at the time of testing (n = 79) had significantly faster choice reaction times (p < 0.05), indicating faster mental processing speed, than untreated patients (n = 63). These faster RTs could not be attributed to differences in age, education, risk factors, degree of immunosuppression, substance abuse history, peripheral neuropathy, or psychological distress. Reaction time tasks should be investigated further as potential outcome measures in clinical trials, particularly for subjects with few or no overt cognitive deficits.

Information processing and antiretroviral therapy in HIV-1 infection.

Computerized reaction time (RT) tasks are sensitive measures of subclinical HIV-related mental slowing. We previously reported that nondemented HIV-seropositive patients on antiretroviral therapy at the time of testing had faster choice RTs compared to matched untreated seropositive participants. In the present study, we evaluated the performance of 163 nondemented HIV-seropositive participants on a reaction time version of the Stroop task as a function of antiretroviral status. Persons on antiretroviral therapy at the time of testing had significantly faster reaction times than untreated individuals, although treated asymptomatic participants showed significantly less Stroop interference than treated symptomatic participants. These effects could not be attributed to differences in demographic variables, disease status, substance abuse, or psychological distress. These data indicate that central information processing is faster for patients treated with antiretroviral compounds compared to untreated patients, and suggest that reaction time tasks may have significant potential utility in clinical trials of neuroprotective compounds.

Working memory deficits in HIV-seropositive drug users.

We studied the integrity of working memory operations in 38 HIV-seropositive and 20 seronegative drug users, using a modified version of the Tower of London task. This new task, the Tower of London-Working Memory version (TOL-WM), includes a delayed-response component in addition to the planning required for successful performance of the standard TOL. Symptomatic HIV-seropositive participants solved significantly fewer TOL-WM problems compared to matched seronegative controls. However, seropositive and seronegative subjects showed similar overall levels of planning efficiency, suggesting that the TOL-WM deficit may be associated primarily with failure to encode or maintain an adequate online memory representation. The results of this study confirm our previous report of a possible working memory deficit in HIV-1 infection and suggest that measures of working memory have particular utility in the evaluation of HIV-related cognitive deficits.

Active immunization in HIV-infected patients.

Patients infected with human immunodeficiency virus (HIV) are at risk for various viral and bacterial infections. Active immunization with currently available vaccines may reduce the risk of some vaccine-preventable diseases in this population. Based on available data, most vaccines used in the United States are safe in HIV-infected adults and children. Their clinical efficacy in these individuals is not well defined, although it appears that patients in the earlier stages of infection are more likely to mount a protective antibody response than those in the later stages. Current guidelines for vaccination in HIV-infected children and adults in the United States have been recommended by the Advisory Committee on Immunization Practices.

Delayed recognition memory span in HIV-1 infection.

We administered a spatial version of the Delayed Recognition Span Test (DRST), a working memory task performed abnormally by patients with basal ganglia disease, to a group of 96 HIV-seropositive and 83 seronegative subjects with a high prevalence of substance abuse. For comparison purposes, we also administered the Symbol-Digit Modalities Test (SDMT) and the Trail Making Test (TMT), measures which detect HIV-related mental slowing efficiently in gay men but are nonspecifically impaired in subjects with a history of substance abuse. As predicted, scores on the TMT and the SDMT did not discriminate the groups, but HIV-seropositive subjects had significantly shorter spatial spans (p < .007) and DRST total scores (p < .005). These effects could not be attributed to differences in age, education, estimated intelligence, or psychological distress, because the groups were well matched on these variables. The DRST is a promising measure of HIV-related cognitive dysfunction in substance abusers, who are often nonspecifically impaired on psychomotor tasks. These preliminary data also indicate that working memory function should be studied further in HIV-seropositive subjects.

A cluster of four cases of Mycobacterium haemophilum infection.

Four cases of infection with Mycobacterium haemophilum occurred at a single hospital in a seven-month period. Only 22 cases have been reported since 1976. All four patients were immunocompromised; two had AIDS and two were the first known recipients of allogeneic bone marrow transplants (BMT) to develop the infection. One BMT recipient died of Mycobacterium haemophilum pneumonia. The organism requires hemin or ferric ammonium citrate and incubation of media at 30 degrees C for optimum growth. Clinicians and microbiologists should consider infection with Mycobacterium haemophilum, particularly when specimens are from immunocompromised patients with unexplained illness and/or when acid-fast bacilli are seen on smear.

Invasive pulmonary aspergillosis complicating neoplastic disease.

Invasive pulmonary aspergillosis is a necrotizing pneumonia that is most frequently seen in association with profound granulocytopenia as a consequence of cytotoxic chemotherapy that is used to treat hematologic neoplasms. There is considerable evidence that the incidence of this infection is increasing over the past decade as a result of improved medical support used in the management of "at risk" patients. Heightened clinical awareness coupled with advances in diagnostic techniques have led to earlier treatment and improved outcomes of this once uniformly fatal infection. Amphotericin B remains the treatment of choice; however, newer therapeutics (azoles) and strategies (combination chemotherapy, biological response modifiers) show promise as alternative regimens. Novel approaches in preventing the acquisition of pulmonary aspergillosis in the "at risk" patient are being explored.

Aspergillus species colonization and invasive disease in patients with AIDS.

Invasive aspergillosis is an uncommon infectious complication in patients with AIDS. Of the 972 patients with AIDS who were observed at our institution over a 10-year period, Aspergillus species were isolated from the respiratory sites of 45 patients before death. Invasive aspergillosis was documented at autopsy in four of these patients and was strongly suspected in an additional patient on whom an autopsy was not performed. A fifth case was documented at autopsy (no antemortem respiratory sample was obtained from this patient). Traditional risk factors for the development of invasive disease (neutropenia, hematologic malignancy, and/or corticosteroid use) were present in all of our patients with invasive aspergillosis. A review of the literature revealed reports of an additional 13 cases of invasive aspergillosis in patients with AIDS. Therapy with amphotericin B should be considered for neutropenic patients with AIDS who have pneumonia of uncertain etiology and from whom Aspergillus species have been isolated from a respiratory specimen.