Adult T-cell leukemia-lymphoma during pregnancy.

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Safdar A, Johnson N, Gonzalez F, Busowski JD.

N Engl J Med. 2002 Jun 20;346(25):2014-5.

Listeriosis in recipients of allogeneic blood and marrow transplantation: thirteen year review of disease characteristics, treatment outcomes and a new association with human cytomegalovirus infection.

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Safdar A, Papadopoulous EB, Armstrong D.

Bone Marrow Transplant. 2002 Jun;29(11):913-6.

Abstract

Listeriosis is uncommon in recipients of allogeneic blood, marrow and organ transplantation. Six patients with systemic Listeria monocytogenes infection during 1985-1997 at Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center are described. In two male and four female patients, the median duration from transplantation to isolation of L. monocytogenes was 62.5 (range 29 to 821) days. Among five allogeneic marrow transplant recipients, four (80%) received HLA antigen matched, T cell-depleted grafts from three unrelated and a single related donor. One patient underwent mismatched-related marrow graft transplant. Cord stem cell transplantation was performed in a single patient. Two required therapy for graft-versus-host disease (GVHD). The 13 year incidence of systemic Listeria infections was 0.47 percent. All six presented with fever (>39 degrees C), and L. monocytogenes bloodstream invasion. Mental status changes and meningioencephalitis were observed in two (33.3%). A concurrent primary opportunistic infection was present in five individuals (83.3%), and four (80%) were being treated for acute human cytomegalovirus (HCMV) viremia. Sixty-six percent responded to therapy and two died from unrelated, non-listeric causes. Systemic listeriosis was uncommon in our high-risk allogeneic blood and marrow transplantation population, and response to therapy with parenteral ampicillin and gentamicin was excellent. The association between primary HCMV reactivation and subsequent listeric infection emphasizes the significance of HCMV-related dysfunction in hosts’ cellular immune responses, especially in the setting of allogeneic transplantation.

Intracranial perineural extension of invasive mycosis: a novel mechanism of disease propagation by Aspergillus fumigatus.

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Safdar A, Dommers MP Jr, Talwani R, Thompson CR.

Clin Infect Dis. 2002 Sep 1;35(5):e50-3. Epub 2002 Aug 1.

Abstract

We describe an immunocompetent woman who had refractory, invasive sphenoid sinus Aspergillus fumigatus infection for which there was radiologic evidence of intracranial perineural spread. The patient responded to a combination of antifungal and adjuvant recombinant cytokine therapy.

Prolonged candidemia in patients with cancer.

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Safdar A, Cross EW, Chaturvedi V, Perlin DS, Armstrong D.

Clin Infect Dis. 2002 Sep 15;35(6):778-9.

Prospective, multicenter surveillance study of Candida glabrata: fluconazole and itraconazole susceptibility profiles in bloodstream, invasive, and colonizing strains and differences between isolates from three urban teaching hospitals in New York City (Candida Susceptibility Trends Study, 1998 to 1999).

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Safdar A, Chaturvedi V, Koll BS, Larone DH, Perlin DS, Armstrong D.

Antimicrob Agents Chemother. 2002 Oct;46(10):3268-72.

Abstract

Since the 1990s, the substantial increase in the rate of Candida glabrata infections has become a serious problem. As most C. glabrata infections arise from the host’s endogenous microflora, the present prospective, multicenter analysis included all clinical isolates associated with colonization and with systemic and hematogenous candidiasis. Among 347 C. glabrata isolates, the overall rates of resistance to fluconazole (MIC > or = 64 micro g/ml) and itraconazole (MIC > or = 1 micro g/ml) were 10.7 and 15.2%, respectively, although for half (n = 148) of the itraconazole-susceptible isolates the MICs (0.25 to 0.5 micro g/ml) were in the susceptible-dependent upon dose range. Fluconazole resistance was more common among C. glabrata isolates obtained from centers caring for patients with cancer (MICs at which 90% of isolates are inhibited [MIC(90)s] = 32 micro g/ml) or AIDS (MIC(90)s > 64 micro g/ml) than among C. glabrata isolates from a community-based university medical center (MIC(90)s = 16 micro g/ml) (P = 0.001). Thirty-three bloodstream isolates and those obtained from other body sites had similar in vitro susceptibility profiles. The fluconazole MIC(90)s (< or =16 micro g/ml) for C. glabrata yeast isolates from the gastrointestinal tract were lower than those (> or =64 micro g/ml) for C. glabrata isolates from respiratory and urinary tract samples (P = 0.01). A similar discrepancy for itraconazole was not significant (P > 0.5). We did not observe differences in fluconazole or itraconazole susceptibility profiles among C. glabrata isolates associated with either hematogenous dissemination or colonization. The significant discrepancy in antifungal susceptibility among C. glabrata organisms isolated from hospitals in the same geographic region emphasizes the significance of periodic susceptibility surveillance programs for individual institutions, especially those providing care to patients at risk.

Hematogenous infections due to Candida parapsilosis: changing trends in fungemic patients at a comprehensive cancer center during the last four decades.

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Safdar A, Perlin DS, Armstrong D.

Diagn Microbiol Infect Dis. 2002 Sep;44(1):11-6.

Abstract

This study was performed to evaluate trends in species distribution in patients’ with hematogenous candidiasis at a comprehensive cancer center. The results of a retrospective analysis from January 1, 1993 to December 31, 1998 were compared with prior reports from Memorial Sloan-Kettering Cancer Center in the last forty years. In 570 total episodes since 1974, 43.9% were due to Candida albicans. During 1990’s, C. parapsilosis emerged as the most frequent yeast species in the non-C. albicans group (36.1% during 1993-1998 from 20.9% 1974-1982; p < 0.01). An increase in C. krusei from 5.9% (1974-1982) to 10.5% during the recent six years (1993-1998) was also noticed. The proportion of C. tropicalis among non-albicans fungemia during 1974-1982 was 42.8%, whereas in 1993 to 1998 a marked decline in C. tropicalis hematogenous infection was observed (27.8%; p < 0.01). During 1998, the incidence of candidemia declined from 7.1% (1972-1973) and 6.5% (1982) to 3.4% (p < 0.01), and improved survival among fungemic patients (33% mortality in 1998; 77.3% during 1974-1982; p < 0.001) was encouraging. The increase in C. parapsilosis bloodstream invasion during 1990’s was associated with a significant reduction in the endogenous non-albicans Candida tropicalis infection that probably resulted in part due to the common prophylaxis, and/or preemptive fluconazole given routinely in high-risk patients undergoing treatment for cancer. The widespread use of extraneous implantable and/or semi-implantable indwelling intra-vascular devices may also have played an important role in promoting (exogenous) C. parapsilosis infection. This study emphasizes the importance of periodic evaluation of candidemia, especially at centers caring for patients at risk.

Fatal immune restoration disease in human immunodeficiency virus type 1-infected patients with progressive multifocal leukoencephalopathy: impact of antiretroviral therapy-associated immune reconstitution.

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Safdar A, Rubocki RJ, Horvath JA, Narayan KK, Waldron RL.

Clin Infect Dis. 2002 Nov 15;35(10):1250-7. Epub 2002 Oct 28.

Abstract

Immune reconstitution resulting from use of highly active antiretroviral therapy in patients infected with human immunodeficiency virus type 1 (HIV-1) has been associated with a significant decrease in infectious morbidity and with improved survival. Occasionally, patients with quiescent disease due to human cytomegalovirus or nontuberculous mycobacteria may experience paradoxical worsening due to “dysregulated” restitution of the immune system (that is, immune restoration disease [IRD]). Acquired immunodeficiency syndrome-related progressive multifocal leukoencephalopathy (PML) is uncommon and often improves with immune recovery. We describe 2 HIV-1-infected patients with PML that presented with paradoxical worsening after the patients had commenced active antiretroviral therapy. After they had a transient response to high-dose corticosteroid therapy, both patients died of progressive neurological deterioration. IRD in these patients with PML was unexpected and occurred soon after they had started receiving active antiretroviral therapy, during the period of improved antigen-specific T-helper cell function. Predictors of patients’ proclivity for these adverse events are uncertain. Evaluation of targeted immunomodulatory therapy directed towards disease-specific IRD is critical and may play an important role in improved survival for patients who are at risk.

Acute foreign body reaction to synthetic dural graft.

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Safdar A, Kohn LF, Narayan KK.

Am J Med. 2002 Oct 15;113(6):529.

Urban trench fever in a healthy man from the southeastern United States.

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Safdar A.

Clin Infect Dis. 2002 Dec 15;35(12):1577.

Prospective evaluation of Candida species colonization in hospitalized cancer patients: impact on short-term survival in recipients of marrow transplantation and patients with hematological malignancies.

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Safdar A, Armstrong D.

Bone Marrow Transplant. 2002 Dec;30(12):931-5.

Abstract

Most hematogenous candidiasis originates from endogenous host flora. The impact of clinically prominent Candida colonization on short-term mortality (<or=14 weeks) was prospectively studied in 193 hospitalized patients from 1998 to 1999. Clinically prominent colonization included yeasts isolated from all sterile body sites and >50 colonies of Candida from non-sterile sites. Fourteen (7.1%) patients were granulocytopenic (ANC <or=100/microl). Nineteen (9.8%) had undergone marrow transplantation, 26 (13.5%) had a hematologic malignancy and 129 (66.5) had non-hematologic cancer. Candida isolates (216) were collected form 210 specimens. Fifty-three (27.5%) patients died; 25 (19.4%) with solid tumors, compared to 16 (61.5%) with hematological malignancy, and 11 (57.9%) BMT recipients (P < 0.001). No deaths were seen in patients with AIDS, and one (7.7%) in a patient with a benign condition (P < 0.001). Twenty-six (29.2%) patients with respiratory tract, 13 (23.2%) with gastrointestinal tract, and three (14.3%) with genitourinary tract colonization died. In patients with multiple-site colonization, mortality was significantly higher (45.5%) (P < 0.05). Mortality was higher in patients with C. glabrata (52.9%) and C. krusei (75%) colonization than with C. albicans (24.1%) (P < 0.025). This study shows that patients with hematologic cancer and recipients of marrow transplant with Candida colonization of multiple body sites, and colonization with C. glabata or C. krusei have poor survival.