Amphotericin B lipid complex for neonatal invasive candidiasis.

This study describes the safety and efficacy of amphotericin B lipid complex (ABLC) in 11 neonates with systemic Candida infections. Nine of the 11 improved clinically, and eight of nine evaluable patients had a mycological cure with ABLC. Creatinine levels improved or did not significantly change in eight of the 11 patients.

Differentiation of central nervous system lesions in AIDS patients using positron emission tomography (PET).

To determine if positron emission tomography (PET) imaging using F-18 fluorodeoxyglucose (FDG) can accurately distinguish between malignant and infectious central nervous system (CNS) mass lesions in patients with human immunodeficiency virus (HIV) infection, a prospective case series of 18 patients with HIV infection and focal CNS lesions on computed tomography (CT) or magnetic resonance (MR) scans was analysed. The patients were divided into 3 groups based on biopsy results, serology and response to therapy. Group 1 consisted of 8 patients with infectious lesions (4 with toxoplasmosis, 2 with neurosyphilis, 2 with progressive multifocal leukoencephalopathy (PML)). Group 2 consisted of 5 patients with biopsy proven CNS lymphoma. Group 3 consisted of 5 patients with presumed CNS lymphoma. Patients underwent FDG-PET studies as an adjunctive diagnostic procedure. The metabolic activity of each patient's lesion was graded using both a qualitative visual score and a semi-quantitative count ratio comparing the lesion with contralateral brain. CNS lesions diagnosed as lymphomas had statistically higher visual scores (P = 0.001) and count ratios (P = 0.002) than CNS lesions diagnosed as infections. FDG-PET could accurately differentiate lymphoma from infections in 16 of 18 cases. Two cases of PML had high metabolic activity and could not be differentiated from lymphoma. FDG-PET shows great promise in differentiating lymphoma from infectious lesions in the CNS of patients with HIV infection. If larger prospective studies confirm this impression, more specific and rapid treatment of CNS lesions could be performed and perhaps obviate the need for brain biopsy in many cases.

Zygomycosis (mucormycosis) and HIV infection: report of three cases and review.

We report three cases of zygomycosis (mucormycosis) occurring in three individuals infected with the human immunodeficiency virus (HIV) and review 12 other published cases. We present the only two case reports of disseminated zygomycosis in AIDS patients, and the only AIDS patient with renal zygomycosis to survive without nephrectomy, receiving intravenous (i.v.) amphotericin alone. Coinfection with zygomycosis and HIV is rare, occurs primarily in patients with low CD4+ lymphocyte counts, does not always require the usual predisposing conditions for zygomycosis, and may be the presenting opportunistic infection among HIV-infected persons. Transient episodes of neutropenia occurring within 4 months before presentation may be a risk factor for this disease. Zygomycosis may arise in multiple sites including the basal ganglia, cutaneous tissue, kidney, respiratory tract, and may be disseminated. Occurring more commonly in, but not restricted to, injection drug users, it is significantly associated with sites other than basal ganglia in those patients with advanced HIV disease or AIDS. The presenting symptoms are related to the site of involvement, and the illness may develop insidiously or progress rapidly to a fulminant course. Successful therapy usually consists of surgical debridement and intravenous amphotericin B. Overall mortality in this review is 40%, and is significantly associated with sites of disease inaccessible to surgical debridement.

A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group.

BACKGROUND: Cryptococcal meningitis and other serious fungal infections are common complications in patients infected with the human immunodeficiency virus (HIV). Fluconazole is effective for long-term suppression of many fungal infections, but its effectiveness as primary prophylaxis had not been adequately evaluated. METHODS: We conducted a prospective, randomized trial that compared fluconazole (200 mg per day) with clotrimazole troches (10 mg taken five times daily) in patients who were also participating in a randomized trial of primary prophylaxis for Pneumocystis carinii pneumonia. RESULTS: After a median follow-up of 35 months, invasive fungal infections had developed in 4.1 percent of the patients in the fluconazole group (9 of 217) and in 10.9 percent of those in the clotrimazole group (23 of 211; relative hazard, as adjusted for the CD4+ count, 3.3; 95 percent confidence interval, 1.5 to 7.6). Of the 32 invasive fungal infections, 17 were cryptococcosis (2 in the fluconazole group and 15 in the clotrimazole group; adjusted relative hazard, 8.5; 95 percent confidence interval, 1.9 to 37.6). The benefit of fluconazole was greater for the patients with 50 or fewer CD4+ cells per cubic millimeter than for the patients with higher counts. Fluconazole was also effective in preventing esophageal candidiasis (adjusted relative hazard, 5.8; 95 percent confidence interval, 1.7 to 20.0; P = 0.004) and confirmed and presumed oropharyngeal candidiasis (5.7 and 38.1 cases per 100 years of follow-up in the fluconazole and clotrimazole groups, respectively; P < 0.001). Survival was similar in the two groups. CONCLUSIONS: Fluconazole taken prophylactically reduces the frequency of cryptococcosis, esophageal candidiasis, and superficial fungal infections in HIV-infected patients, especially those with 50 or fewer CD4+ lymphocytes per cubic millimeter, but the drug does not reduce overall mortality.

Correlation of in vitro fluconazole resistance of Candida isolates in relation to therapy and symptoms of individuals seropositive for human immunodeficiency virus type 1.

Yeast strains isolated from the oropharynx of 87 consecutive patients infected with human immunodeficiency virus type 1 were examined for in vitro susceptibility to fluconazole. Candida albicans was isolated from 73 patients. Fifty-one patients had received antifungal therapy in the month preceding the yeast infection. Thirty-two patients had symptomatic oropharyngeal candidiasis. The MICs were correlated with azole use and with clinical symptoms and signs. Although there is overlap between groups, in vitro testing identified a large group of patients for whose yeast isolates the fluconazole MICs were high and who remained symptomatic while receiving azole therapy. This study supports the ability of in vitro testing to predict the clinical outcome of mucosal fungal infections. The study also demonstrates that azole resistance of oropharyngeal yeasts is a common problem in patients infected with human immunodeficiency virus type 1 and that this azole resistance has clinical relevance.

Differences between men and women with HIV-related Pneumocystis carinii pneumonia: experience from 3,070 cases in New York City in 1987.

Although women make up the fastest growing group of persons with AIDS, studies of human immunodeficiency virus (HIV)-infected persons reported to date have included predominantly or exclusively men. We evaluated sex differences in sociodemographic characteristics, hospital characteristics, in-hospital resource use, and short-term mortality rates for 2,526 men and 544 women admitted for their first-episode of HIV-related Pneumocystis carinii pneumonia (PCP) in New York City in 1987. Compared with men, women were significantly less likely to be white (81% vs. 54%, p < or = 0.001) or have private health insurance (80% vs. 58%, p < or = 0.001), and more likely to be admitted through an emergency room (79% vs. 71%, p < or = 0.001) and receive care at hospitals that had less experience treating PCP (p < or = 0.001). Women were more likely than men to die in the hospital [33% vs. 24%; crude odds ratio = 1.56, confidence interval (CI) = 1.28-1.91, p < or = 0.001]. In a logistic regression model, the risk of death in the hospital was associated with age 60-65 years [adjusted odds ratio (AOR) = 4.19, CI = 2.13-8.21], not having private health insurance (AOR = 1.37, CI = 1.08-1.75), admission through the emergency room (AOR = 1.54, CI = 1.21-1.96), and receiving care at hospitals with less experience treating PCP (AOR = 1.63, CI = 1.15-2.30), but women were not significantly more likely to die in the hospital than men (AOR = 1.18, CI = 0.93-1.50). Poorer access to medical care as well as higher use of hospitals with less experience treating AIDS may account for the difference in mortality rates observed in women with HIV-related PCP.

FDG-PET in differentiating lymphoma from nonmalignant central nervous system lesions in patients with AIDS.

Structural imaging studies such as CT or MRI are not able to accurately differentiate infectious from malignant cerebral lesions in patients with AIDS. We studied 11 individuals with AIDS and central nervous system (CNS) lesions with 18F-fluoro-2-deoxyglucose (FDG) and positron emission tomography (PET). FDG-PET was able to accurately differentiate between a malignant (lymphoma) and nonmalignant etiology for the CNS lesions. Both qualitative visual inspection of the images as well as semiquantitative analysis using count ratios was performed and revealed similar results. FDG-PET may be useful in the management of AIDS patients with CNS lesions since high FDG uptake most likely represents a malignant process which should be biopsied for confirmation rather than treated presumptively as infectious.

A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. AIDS Clinical Trials Group Protocol 021.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) continues to be the most common index diagnosis in the acquired immunodeficiency syndrome (AIDS), but it is not clear which of several available agents is the most effective in preventing a recurrence of PCP. METHODS: We conducted a comparative, open-label trial in 310 adults with AIDS who had recently recovered from an initial episode of PCP and had no treatment-limiting toxic effects of trimethoprim-sulfamethoxazole or pentamidine. All the patients were treated with zidovudine and were randomly assigned to receive either 800 mg of sulfamethoxazole and 160 mg of trimethoprim once daily or 300 mg of aerosolized pentamidine administered every four weeks by jet nebulizer. The participants were followed for a median of 17.4 months. RESULTS: In the trimethoprim-sulfamethoxazole group (n = 154) there were 14 recurrences of PCP, as compared with 36 recurrences (including 1 extrapulmonary recurrence) in the aerosolized-pentamidine group (n = 156). The estimated recurrence rates at 18 months were 11.4 percent with trimethoprim-sulfamethoxazole and 27.6 percent with pentamidine (P < 0.001). The risk of a recurrence (adjusted for initial CD4 cell count) was 3.25 times higher in the pentamidine group (P < 0.001, 95 percent confidence interval, 1.72 to 6.16). There were no significant differences between the groups in survival or in hematologic or hepatic toxicity. Crossovers from trimethoprim-sulfamethoxazole to aerosolized pentamidine were more common than the reverse (27 vs. 4 percent), partly because of the study protocols for the management of leukopenia. There were 19 serious bacterial infections in the trimethoprim-sulfamethoxazole group and 38 in the pentamidine group. The time to a first bacterial infection was significantly greater for those assigned to trimethoprim-sulfamethoxazole (P = 0.017). CONCLUSIONS: In patients with AIDS who are receiving zidovudine, trimethoprim-sulfamethoxazole is more effective than aerosolized pentamidine in conventional doses for the prevention of recurrent pneumocystis infection.

Syphilitic cerebral gumma with HIV infection.

We describe two human immunodeficiency virus (HIV)-infected patients with syphilitic cerebral gummas. Both patients presented with a seizure disorder associated with an isolated, peripherally located, contrast-enhancing lesion of the brain on CT. Cranial MRI performed on one patient revealed dural thickening in the region of the lesion. A brain biopsy in that patient revealed a lymphoplasmacytic infiltrate with extensive perivascular inflammation. Clinical manifestations, radiographic resolution of the lesions, and a decline in nontreponemal serologic tests for syphilis followed high-dose aqueous penicillin therapy in both patients. These patients illustrate that (1) cerebral mass lesions occurring with HIV infection may result from syphilis; (2) seizures may be the presenting manifestation of this form of neurosyphilis; and (3) high-dose, intravenous, aqueous penicillin is effective in treating these lesions.

Prevalence of antibody to Trypanosoma cruzi among blood donors in Los Angeles, California.

Transfusion-associated Chagas' disease is a serious public health problem in Central and South America. With the recent influx of immigrants from Chagas' disease-endemic areas, concern about the risk of disease from blood transfusion has increased in the United States. To assess the prevalence of Trypanosoma cruzi infection in one area, 1024 consecutive blood donations from 988 voluntary blood donors at a medical center in Los Angeles County were screened serologically. The median age of donors screened was 32.5 years; 53.4 percent were male, and 38.4 percent were born in Chagas' disease-endemic countries. All donor sera were tested by complement fixation (CF) and indirect immunofluorescence (IIF) tests. A radioimmunoprecipitation assay (RIPA) was also done on all sera from CF- or IIF-reactive donors and an equal number of sera from nonreactive donors. A second serum specimen was obtained, and interviews were completed for 18 (67%) of 27 donors with an initial CF titer greater than or equal to 8 or an IIF titer greater than or equal to 64. The overall seroreactivity (by CF and IIF) was 1.1 percent (11/988). One donor (0.1%) had antibody specific to the 72- and 90-kDa antigens of T. cruzi on RIPA. Seven recipients of blood components from the seroreactive donors were located and were seronegative at 3 to 6 months. Seroreactive donors were 3.6 times more likely to have been born or to have resided in Mexico or Central America, 8.7 times more likely to have donated blood in the past, and 11.8 times more likely to have a history of malaria prophylaxis or treatment.

Aerosol pentamidine prophylaxis following Pneumocystis carinii pneumonia in AIDS patients: results of a blinded dose-comparison study using an ultrasonic nebulizer.

PURPOSE: To compare the efficacy and safety of three different doses of prophylactic aerosol pentamidine in patients with one prior episode of Pneumocystis carinii pneumonia (PCP) and the acquired immunodeficiency syndrome. PATIENTS AND METHODS: The design of the study was a double-blind, randomized, dose-comparison clinical trial conducted at 13 medical centers within the United States. In stage I of the trial, patients were randomized to receive either 5 mg, 60 mg, or 120 mg of aerosol pentamidine delivered biweekly with the Fisoneb (Fisons, Inc., Rochester, New York) ultrasonic nebulizer. After 24 weeks of therapy, patients entered stage II of the trial, where the 5-mg group was re-randomized to either the 60-mg or 120-mg group. RESULTS: One hundred seventy-five patients entered stage I of the trial and received prophylaxis for a mean of 123.6 days. Seven assigned to the 5-mg biweekly dosing schedule had a confirmed recurrence of PCP, compared with none in the 60-mg group (p = 0.007) and three in the 120-mg group (p = 0.304). During stage II of the trial, eight patients in the 60-mg group and one additional patient in the 120-mg group had recurrent PCP. After 52 weeks of observation, the likelihood of being PCP-free was 88.0% in the 60-mg group and 93% in the 120-mg group (p = 0.712). Minor adverse events related to aerosol pentamidine administration included cough, taste perversion, chest pain, bronchospasm, and dyspnea. These side effects were more common in the 60-mg and 120-mg treatment groups and resulted in withdrawal from the study by one patient. Serious events were more common after 24 weeks of therapy and included asymptomatic hypoglycemia (five), pancreatitis (two), pneumothorax (one), and extrapulmonary pneumocystosis (one). CONCLUSIONS: These results demonstrate that biweekly administration of 60 mg or 120 mg of aerosol pentamidine significantly decreases PCP recurrence when compared with a 5-mg regimen or findings in historic controls and is generally well tolerated. There is no significant difference in effect or safety between these two dosing regimens in patients followed for at least 52 weeks of therapy.

Treatment of systemic sporotrichosis with ketoconazole.

Infections of deep soft tissues with the dimorphic fungus Sporothrix schenckii are uncommon in humans, and therapy has often required toxic drugs. We report our experience in treating 11 patients who had deep-seated sporotrichosis with ketoconazole, a well-tolerated, orally absorbed antifungal agent. Eight infections involved one or more joints, and three involved thoracic, cervical, and widespread cutaneous sites, respectively. For eight patients all evidence of infection resolved during therapy. Sustained remissions (6 months to 5 years) were noted for six patients after the discontinuation of all therapy and for an additional patient 4 years after the initiation of ketoconazole treatment. Durable responses were associated with prolonged treatment with 400-800 mg of ketoconazole daily. Our favorable experience suggests that oral therapy with ketoconazole may benefit other patients with systemic sporotrichosis.

Manifestations of pulmonary cryptococcosis in patients with acquired immunodeficiency syndrome.

Cryptococcosis is a common opportunistic infection in patients with AIDS. Meningitis is the most frequent manifestation of infection with Cryptococcus neoformans; pneumonia due to this organism, though less frequently recognized, is also a significant entity. A retrospective review was performed of all patients seen at Duke University Medical Center between January 1981 and July 1989 who were infected with both human immunodeficiency virus type 1 and C. neoformans. Of 31 patients with these concomitant infections, 12 had cryptococcal pneumonia (10 definite and two presumptive cases). Eleven of these 12 patients had evidence of extrapulmonary cryptococcal disease as well. Chest radiography showed interstitial infiltrates in 11 instances. For ten of the 12 patients, pulmonary cultures were positive for C. neoformans. Bronchoalveolar lavage fluid from all five patients who underwent bronchoscopy yielded the organism. Acute-phase mortality from cryptococcosis was 42% among patients with pneumonia. Cryptococcal pneumonia in patients with AIDS is probably more common than has previously been recognized and typically presents as interstitial disease that may mimic other opportunistic infections.

Occupational exposure to aerosolized pentamidine.

Occupational exposure to aerosolized pentamidine has raised questions regarding transmission of tuberculosis and the effect of the drug itself. To estimate the exposure of a health care worker, we measured the ambient concentration of aerosolized pentamidine in field conditions in 36 m3 unventilated treatment room. The amount of pentamidine averaged in three different environmental air samples over a four-hour period was 4.5 +/- 3.6 x 10(-5) mg/m3. This amount is very small compared to the doses received by the patients in whom long-term adverse effects are few. The greater risk to health care workers is probably transmission of tuberculosis from undiagnosed cases, especially in populations with an increased incidence of tuberculosis. Tuberculosis control measures such as improved ventilation and masks should also decrease exposure to ambient air pentamidine until toxicity studies determine long-term adverse effects, if any, of aerosolized pentamidine.

Risk factors for hypoglycemia associated with pentamidine therapy for Pneumocystis pneumonia.

In 1984, three patients died of severe hypoglycemia after receiving pentamidine isethionate to treat Pneumocystis pneumonia. These deaths occurred on days 8, 12, and 19 of treatment, respectively. To assess risk factors associated with pentamidine treatment and hypoglycemia, we reviewed records of patients treated with pentamidine in New York City in 1984; ninety-seven percent of these patients had a diagnosis of acquired immunodeficiency syndrome. Hypoglycemia occurred in 23 (14%) of 164 patients. Hypoglycemia was more likely to occur in patients who received therapy of longer duration and an increasing dosage of pentamidine. Patients at greater risk for hypoglycemia also included those who had received pentamidine previously and those who experienced azotemia during treatment. This serious, potentially fatal, reaction should be considered in all patients who are treated with pentamidine, particularly those receiving prolonged or recurrent therapy.

Giardia transmission in a swimming pool.

In the fall of 1985, an outbreak of giardiasis occurred among several swimming groups at an indoor pool in northeast New Jersey. Nine clinical cases were identified, eight of whom had Giardia positive stool specimens. All were female; seven were adults (greater than 18 years) and two were children. The attack rate was highest (39 per cent, 5/13) for the ladies lap group who had exposure on one day. These cases had no direct contact with children or other risk factors for acquiring Giardia. Infection most likely occurred following the ingestion of swimming pool water contaminated with Giardia cysts. The source of Giardia contamination was a handicapped child who had a fecal accident in the pool. He was a member of a group that swam at the same time as the ladies lap group. A stool survey of the handicapped group showed that of the 20 persons tested, nine were positive for Giardia, including the specimen from this child. Examination of the pool records showed that no chlorine levels had been taken on the day of the fecal accident and that on the following day the chlorine level was zero. This is the second report of Giardia transmission among swimming pool attendees. It emphasizes the need to maintain appropriate chlorine levels in swimming pools and to institute measures to clear pools after a fecal accident.

Epidemic giardiasis caused by a contaminated public water supply.

In the period November 1, 1985 to January 31, 1986, 703 cases of giardiasis were reported in Pittsfield, Massachusetts (population 50,265). The community obtained its water from two main reservoirs (A and B) and an auxiliary reservoir (C). Potable water was chlorinated but not filtered. The incidence of illness peaked approximately two weeks after the city began obtaining a major portion of its water from reservoir C, which had not been used for three years. The attack rate of giardiasis for residents of areas supplied by reservoir C was 14.3/1000, compared with 7.0/1000 in areas that received no water from reservoir C. A case-control study showed that persons with giardiasis were more likely to be older and to have drunk more municipal water than household controls. A community telephone survey indicated that over 3,800 people could have had diarrhea that might have been caused by Giardia, and 95 per cent of households were either using alternate sources of drinking water or boiling municipal water. Environmental studies identified Giardia cysts in the water of reservoir C. Cysts were also detected in the two other reservoirs supplying the city, but at lower concentrations. This investigation highlights the risk of giardiasis associated with unfiltered surface water systems.