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Biomedical subjects

W G Powderly

Publications and source records attributed to W G Powderly.

At least 91 records · Page 5Linked to original sources
PubMed1994

Resistant candidiasis.

Mucosal (oropharyngeal, esophageal, and, in women, vaginal) candidiasis is a common infectious complication in HIV-infected patients. There is a wide range of drugs to treat or suppress Candida infections. However, with the increasingly common use of fluconazole as treatment or prophylaxis in patients with relatively advanced HIV disease, mucosal candidiasis that is clinically resistant to fluconazole is increasingly recognized. Susceptibility testing for fluconazole has not been well standardized, and laboratory and clinical correlations often have been difficult to demonstrate. However, the frequency with which Candida strains resistant to fluconazole can be isolated appears to be increasing, particularly in patients with advanced HIV disease. Anecdotal results suggest that patients who fail fluconazole therapy usually do not respond to higher doses of fluconazole, but may occasionally respond to itraconazole or ketoconazole. In vitro susceptibility to these agents does not necessarily ensure clinical efficacy. Amphotericin B is usually effective initially but requires parenteral administration. However, with any therapy, relapses tend to occur and progressively recalcitrant disease often occurs, with increasing morbidity for patients. There is a clear need for studies addressing the incidence of resistance, the risk factors for its development, and more effective therapy.

AIDS-Related Opportunistic Infections↗
PubMed1994

Measurement of cryptococcal antigen in serum and cerebrospinal fluid: value in the management of AIDS-associated cryptococcal meningitis.

The value of monitoring titers of cryptococcal antigen in serum and cerebrospinal fluid (CSF) during therapy for AIDS-associated cryptococcal meningitis was evaluated. Baseline and final titers of antigen in serum and CSF from participants in two studies of such therapy were categorized as increased (a rise of at least two dilutions), unchanged, or decreased (a fall of at least two dilutions). There was no correlation between outcome and changes in serum titers of cryptococcal antigen during treatment for acute meningitis or during suppressive therapy. During therapy for acute infection, an unchanged or increased titer of antigen in CSF was correlated with clinical and microbiological failure to respond to treatment; the correlation was especially strong among patients whose baseline titer of antigen was > or = 1:8 (P = .01). A rise in CSF antigen titer during suppressive therapy was associated with relapse of cryptococcal meningitis (P < .001). We conclude that serial monitoring of cryptococcal antigen, as conducted in these studies, has a limited role in the management of AIDS patients with cryptococcal meningitis.

AIDS-Related Opportunistic Infections↗
PubMed1994

Serious Pseudomonas aeruginosa infections in patients infected with human immunodeficiency virus: a case-control study.

We conducted a case-control study to determine the incidence and clinical features of and risk factors for Pseudomonas aeruginosa infections in patients infected with human immunodeficiency virus (HIV). Twenty-five patients who had 37 episodes of P. aeruginosa infection from 1990 through 1992 were identified. Most of the patients (92%) were homosexual men with low CD4+ lymphocyte counts and a history of AIDS. The annual incidence rates of P. aeruginosa infection were 3.5% (1990), 6.3% (1991), and 8.7% (1992). Most infections were community-acquired (68%) and involved the respiratory tract (73%). Patients were more likely than HIV-infected controls to have AIDS and had more AIDS-defining opportunistic illnesses. The overall mortality was 36%. Recurrent episodes were common (39%). We conclude that P. aeruginosa infections may be an increasing problem in patients with extremely advanced HIV infection. Clinicians should consider including antibiotics with activity against P. aeruginosa in the empirical treatment for suspected bacterial infection in patients with advanced HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1994

The safety and efficacy of combination N-butyl-deoxynojirimycin (SC-48334) and zidovudine in patients with HIV-1 infection and 200-500 CD4 cells/mm3.

We conducted a double-blind, randomized phase II study to evaluate the safety and activity of combination therapy with N-butyl-deoxynojirimycin (SC-48334) (an alpha-glucosidase I inhibitor) and zidovudine versus zidovudine alone. Patients with 200 to 500 CD4 cells/mm3 who tolerated < or = 12 weeks of prior zidovudine therapy received SC-48334 (1000 mg every 8 h) and zidovudine (100 mg every 8 h) or zidovudine and placebo. Sixty patients received combination therapy and 58, zidovudine and placebo. Twenty-three patients (38%) and 15 (26%), in the combination and zidovudine groups, respectively, discontinued therapy (p = 0.15). The mean SC-48334 steady-state trough level (4.04 +/- 0.99 micrograms/ml) was below the in vitro inhibitory concentration for human immunodeficiency virus (HIV). The mean increase in CD4 cells at week 4 was 73.8 cells/mm3 and 52.4 cells/mm3 for the combination and zidovudine groups, respectively (p > 0.36). For patients with prior zidovudine therapy, the mean change in CD4 cells in the combination and zidovudine groups was 63.7 cells/mm3 and 4.9 cells/mm3 at week 8 and 6.8 cells/mm3 and -45.1 cells/mm3 at week 16, respectively. The number of patients with suppression of HIV p24 antigenemia in the combination and zidovudine groups was six (40%) and two (11%) at week 4 (p = 0.10) and five (45%) and two (14%) at week 24 (p = 0.08), respectively. Diarrhea, flatulence, abdominal pain, and weight loss were common for combination recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Deoxynojirimycin↗
PubMed1994

Changes in plasma amino acid concentrations in response to HIV-1 infection.

Plasma concentrations of 21 amino acids were determined for 20 control subjects and 20 subjects infected with human immunodeficiency virus type 1 (HIV). Compared with the control subjects, the HIV-infected group had lower cystine, tryptophan, and methionine (decreased 67%, 52%, and 32%, respectively, P < 0.001 for each) and increased taurine (230%, P < 0.001) and lysine concentrations (30%, P < 0.001). Other amino acid concentrations changed modestly. Amounts of cystine, tryptophan, methionine, taurine, and lysine did not differ significantly between subgroups of HIV-infected subjects with > 200 (n = 6) or < 200 (n = 14) CD4+ lymphocytes per microliter, suggesting that the concentrations decrease soon after infection and change little thereafter. Activation of metabolism of cystine to taurine may explain reciprocal changes in these amino acids and known depletion of cystine and glutathione. The selective changes in amino acid profiles observed during HIV infection differ from those recognized for malnutrition or other pathological processes.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Alternating and intermittent regimens of zidovudine and dideoxycytidine in patients with AIDS or AIDS-related complex.

OBJECTIVE: To determine whether alternating regimens consisting of zidovudine and 2',3'-dideoxycytidine (ddC) reduce the toxicity and maintain or increase the antiretroviral effect associated with each drug alone. DESIGN: An unblinded, randomized (phase II) clinical trial in which seven treatment regimens were compared. SETTING: Outpatient clinics of 12 AIDS Clinical Trials Units. PATIENTS: One hundred thirty-one patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and serum p24 antigenemia (> or = 70 pg/mL). INTERVENTION: Treatments included weekly or monthly alternating zidovudine (200 mg every 4 hours) and ddC (0.01 or 0.03 mg/kg body weight every 4 hours); weekly intermittent zidovudine, 200 mg every 4 hours, or ddC, 0.03 mg/kg every 4 hours; and continuous zidovudine. MEASUREMENTS: Toxicity, CD4 cell counts, serum p24 antigen levels, and clinical end points. Data were analyzed for the first 48 weeks of therapy (median follow-up, 40 weeks). RESULTS: Hematologic toxicity was significantly less frequent in patients who received zidovudine therapy every other week (11% to 15%) or every other month (11% to 14%) than in those who received continuous zidovudine therapy (33%) (P < 0.02). Weekly alternating therapy with zidovudine and ddC, 0.03 mg/kg, or intermittent therapy with ddC, 0.03 mg/kg, produced high rates of peripheral neuropathy (41% and 50%, respectively). Neuropathy occurred in 10% to 21% of patients in the other three alternating-therapy limbs and in 17% of patients receiving zidovudine alone (intermittently or continuously). Initial increases in CD4 cell counts were sustained in three alternating-therapy limbs, but counts returned to baseline by week 28 in the remaining limbs. The median weight gain at week 48 was significantly greater in patients treated with alternating regimens (0.9 to 3.8 kg) compared with those treated with continuous zidovudine therapy (-0.7 kg) (P = 0.008). Patients treated with alternating regimens and those treated with continuous zidovudine had similarly sustained decreases in p24 antigen levels. CONCLUSIONS: These findings suggest that alternating therapy with zidovudine and ddC reduces the toxicity associated with each drug alone while maintaining strong antiretroviral activity.

AIDS-Related Complex↗
PubMed1993

Failure of high-dose oral acyclovir with or without immune globulin to prevent primary cytomegalovirus disease in recipients of solid organ transplants.

PURPOSE: To assess the efficacy of acyclovir and intravenous immune globulin (IVIG) for cytomegalovirus (CMV) prophylaxis in high-risk recipients of solid organ transplants. PATIENTS AND METHODS: We randomized 21 CMV-seronegative organ transplant recipients with seropositive donors (D+R-) to receive oral acyclovir, 800 mg four times daily, or, in addition to acyclovir, IVIG, 300 mg/kg, every 2 weeks for six doses. Patients were followed closely for the development of CMV infection and disease. RESULTS: All but one prophylactically treated patient (95%) developed CMV infection. Fifteen of 21 patients (71%) who received prophylaxis fulfilled criteria for CMV disease. Disease onset was delayed in those who received IVIG, but this did not reach statistical significance. Ganciclovir was used for treatment in 15 of the 21 patients (71%). CONCLUSIONS: Acyclovir, with or without IVIG, did not prevent primary CMV infection or disease in D+R- solid organ transplant recipients at our institution. Moreover, most patients were treated with ganciclovir despite the use of prophylaxis. Given the ready availability of ganciclovir to treat CMV disease, we recommend a reappraisal of the role of CMV prophylaxis by these means in the solid organ transplant population.

Acyclovir↗
PubMed1993

Symptomatic cytomegalovirus infection in renal transplant recipients given either Minnesota antilymphoblast globulin (MALG) or OKT3 for rejection prophylaxis.

To compare the impact of using Minnesota antilymphoblast globulin (MALG) versus the monoclonal antibody, OKT3, on the development of symptomatic cytomegalovirus (CMV) infection, we reviewed a cohort of 130 cadaveric renal transplant recipients enrolled in a prospective comparison of MALG versus OKT3 for rejection prophylaxis. Among the 112 patients at risk for CMV, prophylactic MALG was associated with an increased risk of symptomatic infection (relative hazard [rh] = 3.31; 95% confidence interval CI], 1.50 to 7.30; P = 0.003). Transplantation of kidneys from CMV-seropositive donors into CMV-seronegative recipients (rh = 5.22; 95% CI, 2.34 to 11.63; P = 0.00004), first transplantation (rh = 4.76; 95% CI, 1.06 to 21.3; P = 0.039), and acute rejection therapy (rh = 2.03; 95% CI, 0.98 to 4.21; P = 0.055) were also associated with an increased risk. Prophylactic MALG followed by treatment with any agent for acute rejection was strongly correlated with symptomatic CMV infection (rh = 4.46; 95% CI, 3.71 to 5.21; P = 0.00006). Symptomatic CMV infection was not only more frequent, but more severe in recipients of prophylactic MALG, and more MALG recipients were treated with ganciclovir. There was no difference in rejection rate for the two rejection prophylaxis regimens (P = 0.625). Prophylactic OKT3 results in less risk of symptomatic CMV infection than prophylactic MALG in cadaveric renal transplant recipients who are seropositive for CMV or whose donors are seropositive for CMV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Alterations in spliced and unspliced HIV-1-specific RNA detection in peripheral blood mononuclear cells of individuals with varying CD4-positive lymphocyte counts.

Reverse transcriptase-polymerase chain amplification reactions (RT-PCR) were used to identify transcripts for HIV-1 structural and regulatory proteins in peripheral blood mononuclear cells of a cohort of 48 patients. At least one set of PCR primers was capable of detecting HIV-1 transcripts in 94% of patients. Unspliced gag-pol transcripts were detected with gag or pol primer sets in 60 and 63% of samples, respectively. A significant inverse correlation was noted between transcript identification with the gag primer set and the number of CD4-positive lymphocytes in the blood sample and the clinical stage of infection. Single-spliced env transcripts were identified in 44% of individuals. Multiple-spliced tat or nef transcripts were detected in 6.2 and 53% of individuals, respectively. These findings indicate that viral transcripts are expressed throughout the course of HIV-1 infection.

Base Sequence↗
PubMed1993

Use of paromomycin for treatment of cryptosporidiosis in patients with AIDS.

Cryptosporidiosis in patients with AIDS often leads to a severe wasting illness that is difficult to treat. Recent reports suggest that paromomycin may be useful in the treatment of intestinal cryptosporidiosis. We reviewed our experience using paromomycin for the treatment of cryptosporidiosis in seven patients with AIDS. All patients received paromomycin (500 mg orally every 6 hours) for an average of 11.7 days. The mean follow-up period was 3.2 months. All patients had an initial response to paromomycin that was characterized by a decrease in frequency of diarrheal episodes, stabilization of body weight, and/or eradication of cryptosporidia from the stool. The mean number of diarrheal episodes decreased from 10.9 to 1.7 daily. Stabilization or increase in body weight was noted for five of seven patients, and eradication of oocysts was documented for three patients. Relapses or recurrences were noted for three patients. Treatment with paromomycin was well tolerated by all patients with the exception of two, who experienced nausea and abdominal discomfort. Thus, paromomycin appears to be a promising agent for treatment of acute cryptosporidiosis.

AIDS-Related Opportunistic Infections↗
PubMed1993

Cryptococcal meningitis and AIDS.

Dr. William G. Powderly provides a comprehensive review of the state of our knowledge regarding cryptococcal infection in persons with infection due to human immunodeficiency virus type 1. The introduction of fluconazole and itraconazole increased insight into prognostic factors affecting these patients. The need to suppress this fungal infection in individuals with impaired immunity has greatly altered the management of cryptococcal meningitis; therapy for this condition was established by the landmark study conducted by the Mycosis Study Group in 1979 (Bennett JE, Dismukes WE, Duma RJ, et al. A comparison of amphotericin B alone and combined with flucytosine in treatment of cryptococcal meningitis. N Engl J Med 1979;301:126-31). In this AIDS commentary Dr. Powderly clearly outlines the progress made through clinical investigations and the problems that remain to be resolved.

AIDS-Related Opportunistic Infections↗
PubMed1993

Molecular epidemiology of recurrent oral candidiasis in human immunodeficiency virus-positive patients: evidence for two patterns of recurrence.

The causative strains in 22 patients with recurrent oral candidiasis were examined using two DNA probes (a Histoplasma capsulatum DNA probe that cross-hybridizes with Candida albicans and a C. albicans strain-specific probe derived from repetitive sequence DNA). C. albicans was the causative organism in all 22 initial episodes of infection and was also obtained from 17 patients with recurrent oral disease. Molecular analysis showed that in 11 cases, the same isolate was identified in each episode. Six patients had a clearly different isolate of C. albicans causing a later episode of candidiasis. Five patients had different Candida species causing recurrent disease: 4, Torulopsis glabrata; 1, Candida parapsilosis. Patients with a new isolate (either new species or a new C. albicans strain) were more immunosuppressed and were significantly more likely (P < .001) than patients with the same recurrent strain to have received suppressive azole antifungal agents. These data indicate that the epidemiology of recurrent candidiasis in individual patients seropositive for the human immunodeficiency virus is complex and that both failure of eradication of Candida from the oral cavity and new infection occur.

AIDS-Related Opportunistic Infections↗
PubMed1992

Blastomycosis in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To describe the clinical, demographic, radiographic, diagnostic, and therapeutic aspects of blastomycosis in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective survey. SETTING: Ten university medical centers and community hospitals, six in geographic areas endemic for Blastomyces dermatitidis, and four outside the endemic area. PATIENTS: We identified 15 patients with blastomycosis and positive serologic test results for human immunodeficiency virus (HIV). MEASUREMENTS: A diagnosis of blastomycosis was based on a positive culture (14 patients) or typical histopathologic features (one patient) for B. dermatitidis in clinical specimens. RESULTS: Twelve of 15 patients had a previous or concomitant AIDS-defining illness at the time of diagnosis of blastomycosis, and only one patient had a CD4 lymphocyte count of greater than 200 cells/mm3. Two patterns of disease emerged: localized pulmonary involvement (seven patients), and disseminated or extrapulmonary blastomycosis (eight patients). Central nervous system involvement was common (40%). Six patients died within 21 days of presentation with blastomycosis, including four patients with disseminated and two with fulminant pulmonary disease. Among the nine patients who survived longer than 1 month, all received amphotericin B as initial antifungal therapy, and most received subsequent therapy with ketoconazole. Only two of these nine patients died with evidence of progressive blastomycosis. CONCLUSIONS: Blastomycosis is a late and frequently fatal infectious complication in a few patients with AIDS. In these patients, overwhelming disseminated disease including involvement of the central nervous system is common, and it is associated with a high early mortality. Initial therapy with amphotericin B is appropriate in patients with AIDS and presumptive blastomycosis.

Acquired Immunodeficiency Syndrome↗
PubMed1992

A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. The NIAID AIDS Clinical Trials Group and Mycoses Study Group.

BACKGROUND: After primary treatment for cryptococcal meningitis, patients with the acquired immunodeficiency syndrome (AIDS) require some form of continued suppressive therapy to prevent relapse. METHODS: We conducted a multicenter, randomized trial that compared fluconazole (200 mg per day given orally) with amphotericin B (1 mg per kilogram of body weight per week given intravenously) in patients with AIDS who had completed primary therapy for cryptococcal meningitis with amphotericin B (greater than or equal to 15 mg per kilogram). To be eligible, patients had to have at least two negative cultures of cerebrospinal fluid immediately before randomization. The primary end point was relapse of cryptococcal disease as confirmed by biopsy or culture. RESULTS: Of 218 patients initially enrolled, 119 were assigned to fluconazole and 99 to amphotericin B. Twenty-three patients were found not to have met the entry criteria; six other patients assigned to amphotericin B did not receive it and were lost to follow-up. Of the remaining 189 patients, after a median follow-up of 286 days 14 of 78 receiving amphotericin B (18 percent) and 2 of 111 assigned to fluconazole (2 percent) had relapses of symptomatic cryptococcal disease (P less than 0.001 by Fisher's exact test). There was a difference of 19 percent in the estimated probability of remaining relapse-free at one year between the fluconazole group (97 percent) and the amphotericin B group (78 percent) (95 percent confidence interval, 7 percent to 31 percent; P less than 0.001). Serious drug-related toxicity was more frequent in the amphotericin B group (P = 0.02), as were bacterial infections (P = 0.004) and bacteremia (P = 0.002). CONCLUSIONS: Fluconazole taken by mouth is superior to weekly intravenous therapy with amphotericin B to prevent relapse in patients with AIDS-associated cryptococcal meningitis after primary treatment with amphotericin B.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. The NIAID Mycoses Study Group and the AIDS Clinical Trials Group.

BACKGROUND: Intravenous amphotericin B, with or without flucytosine, is usually standard therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS). Fluconazole, an oral triazole agent, represents a promising new approach to the treatment of cryptococcal disease. METHODS: In a randomized multicenter trial, we compared intravenous amphotericin B with oral fluconazole as primary therapy for AIDS-associated acute cryptococcal meningitis. Eligible patients, in all of whom the diagnosis had been confirmed by culture, were randomly assigned in a 2:1 ratio to receive either fluconazole (200 mg per day) or amphotericin B. Treatment was considered successful if the patient had had two consecutive negative cerebrospinal fluid cultures by the end of the 10-week treatment period. RESULTS: Of the 194 eligible patients, 131 received fluconazole and 63 received amphotericin B (mean daily dose, 0.4 mg per kilogram of body weight in patients with successful treatment and 0.5 mg per kilogram in patients with treatment failure; P = 0.34). Treatment was successful in 25 of the 63 amphotericin B recipients (40 percent; 95 percent confidence interval, 26 percent to 53 percent) and in 44 of the 131 fluconazole recipients (34 percent; 95 percent confidence interval, 25 percent to 42 percent) (P = 0.40). There was no significant difference between the groups in overall mortality due to cryptococcosis (amphotericin vs. fluconazole, 9 of 63 [14 percent] vs. 24 of 131 [18 percent]; P = 0.48); however, mortality during the first two weeks of therapy was higher in the fluconazole group (15 percent vs. 8 percent; P = 0.25). The median length of time to the first negative cerebrospinal fluid culture was 42 days (95 percent confidence interval, 28 to 71) in the amphotericin B group and 64 days (95 percent confidence interval, 53 to 67) in the fluconazole group (P = 0.25). Multivariate analyses identified abnormal mental status (lethargy, somnolence, or obtundation) as the most important predictive factor of a high risk of death during therapy (P less than 0.0001). CONCLUSIONS: Fluconazole is an effective alternative to amphotericin B as primary treatment of cryptococcal meningitis in patients with AIDS. Single-drug therapy with either drug is most effective in patients who are at low risk for treatment failure. The optimal therapy for patients at high risk remains to be determined.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Therapy for cryptococcal meningitis in patients with AIDS.

Treatment of cryptococcal meningitis in patients with AIDS with amphotericin B plus flucytosine is associated with a failure rate of 20%-30%. In the absence of chronic suppressive therapy, 40%-60% of patients develop recurrent disease. Recent comparative studies have evaluated fluconazole, a new triazole antifungal agent. In primary therapy, fluconazole is associated with response rates of 35%-60%, which are equivalent to those seen with amphotericin B alone. However, a smaller study suggested that amphotericin B plus flucytosine was superior to fluconazole alone. Both studies identified risk factors associated with a poor outcome; these factors include lethargy or obtundation at presentation, a high titer of cryptococcal antigen titer in the cerebrospinal fluid, and a low leukocyte count in the cerebrospinal fluid. Fluconazole is highly effective in suppressing relapses of cryptococcal meningitis. Itraconazole has been investigated less extensively in the treatment of cryptococcosis but offers promise. Future studies need to address alternative approaches to the management of acute cryptococcal disease and primary prophylaxis for cryptococcal infection in patients with AIDS.

Acquired Immunodeficiency Syndrome↗