Clinical significance of non-Candida fungal blood isolation in patients undergoing high-risk allogeneic hematopoietic stem cell transplantation (1993-2001).

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Safdar A, Singhal S, Mehta J.

Cancer. 2004 Jun 1;100(11):2456-61.

Abstract

BACKGROUND:

The clinical relevance of mold isolated from blood cultures, even in severely immunosuppressed allogeneic hematopoietic stem cell transplantation (HSCT) recipients, remains uncertain. The authors hypothesized that isolation of non-Candida fungi from blood cultures in patients undergoing high-risk HSCT would have clinical significance.

METHODS:

The authors reviewed the records of 73 allogeneic HSCT recipients between January 1, 1993 and January 1, 2001 in whom fungal species were isolated from blood cultures.

RESULTS:

Fifty-two episodes of non-Candida fungemia occurred in 48 patients (66%) after a median of 10 days (range, 2-341) after transplantation. All 48 patients had indwelling intravascular catheters, and 23 patients (48%) had profound neutropenia. Thirty-five of 48 patients had received partially matched, related donor stem cell grafts (19 patients had 3-antigen-mismatched grafts); 35 patients had undergone T-cell depleted transplantation and 9 patients were receiving treatment for acute graft-versus-host disease. In 5 of 48 patients (10%), death was attributed to fungemia that occurred 8-11 days after the initial fungal blood culture was obtained; all 5 patients were age > 30 years. No deaths occurred in the younger age group (n = 22 patients; P = 0.05). In the 24 patients who did not receive systemic antifungal therapy, 4 deaths (17%) were attributed to infections with Penicillium (n = 2 patients), Epicoccum (n = 1 patient), or Penicillium plus Cladosporium species (n = 1 patient). Of the 24 patients who received amphotericin B, only 1 patient (4%) died as a result of a probable hematogenous Aspergillus species infection; this difference in outcome, however, was not significant (P = 0.2).

CONCLUSIONS:

Most of the non-Candida fungal blood culture isolates in recipients of high-risk, mismatched donor transplantation were clinically nonsignificant. However, because these low-virulence saprophytes occasionally may cause life-threatening disease, a reevaluation of the existing diagnostic paradigm is needed so that clinically significant fungemia may be differentiated from pseudofungemia.

The predictors of outcome in immunocompetent patients with hematogenous candidiasis.

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Safdar A, Bannister TW, Safdar Z.

Int J Infect Dis. 2004 May;8(3):180-6.

Abstract

OBJECTIVE:

Clinical parameters that predict outcome in non-immunosuppressed candidemic patients are not fully understood.

METHODS:

Eighty-one consecutive episodes of candidemia were retrospectively evaluated in 75 patients during 1998-2000.

RESULTS:

Infection due to Candida albicans was common (n = 30; 37%) followed by Candida glabrata (n = 25; 31%), Candida parapsilosis (n = 14; 17%), Candida tropicalis (n = 6; 7%), Candida krusei (n = 5; 6%), and Candida lusitaniae (n = 1; 1%). Among 70 evaluable patients, 31 (44%) had fungemia-associated mortality; advanced age (P < 0.004), underlying malignancy (P < 0.025), coronary artery disease (P < 0.01), and concurrent non-Candida species fungal infection (P < 0.047) were significant prognosticators of compromised short-term survival by multivariate analysis. Mortality was higher in patients with Candida glabrata (60%) and C. tropicalis (75%) infection compared to 44% deaths in individuals with C. albicans infection (P > 0.1). 11/25 (44%) of non-immunocompromised individuals died and 20/45 (44%) immunosuppressed patients succumbed to fungemia: persistent vs. non-persistent (< 3 days) Candida bloodstream invasion, neutropenia, diabetes mellitus, renal insufficiency, prior antimicrobial therapy, cirrhosis of liver, abdomino-pelvis surgery, and critical-care-unit vs. non critical-care-unit admission did not significantly impact outcome in either group. All 11 infants, including nine with prematurity, survived Candida species bloodstream infection (P < 0.025).

CONCLUSIONS:

Short-term mortality in candidemic non-immunocompromised patients was comparable to fungemia-associated deaths in immunosuppressed patients. Ischemic heart disease has appeared as a new predictor of unfavorable outcome in patients with hematogenous candidiasis.

Strongyloidiasis in patients at a comprehensive cancer center in the United States.

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Safdar A, Malathum K, Rodriguez SJ, Husni R, Rolston KV.

Cancer. 2004 Apr 1;100(7):1531-6.

Abstract

BACKGROUND:

The frequency of Strongyloides stercoralis infestation and complication in patients with cancer in the United States is unknown.

METHODS:

The authors performed a retrospective analysis of S. stercoralis infection in patients who were undergoing cancer treatment at The University of Texas M. D. Anderson Cancer Center (Houston, TX).

RESULTS:

The overall S. stercoralis infection frequency was approximately 1.0 per 10,000 new cancer cases between 1971 and 2003. Twenty-two of 25 patients (88%) were U.S. residents (19 from Texas; 1 each from Mississippi, Tennessee, and Puerto Rico), and the remaining 3 (13%) were from Latin America. Thirteen (52%) had solid-organ malignancies, whereas 12 (48%) had hematologic malignancies (lymphoma or multiple myeloma, n=8; leukemia, n=3; aplastic anemia, n=1). Twelve patients (48%) received systemic corticosteroids, 9 (36%) received antineoplastic therapy, and 2 underwent hematopoietic stem cell transplantation (HSCT). Diarrhea was reported in 13 patients (57%), and eosinophilia was observed in 11 patients (48%); 4 patients (16%) had probable hyperinfection syndrome (in 3 cases of polymicrobial gram-negative bacteremia, 1 patient had Klebsiella pneumoniae pneumonia, whereas 1 patient presented with K. pneumoniae lung infection alone). Evidence of definite pulmonary hyperinfection syndrome was observed in 2 HSCT recipients (8%). Fourteen (74%) of 19 patients responded to thiabendazole therapy. Two patients with definite pulmonary hyperinfection syndrome developed fatal S. stercoralis hemorrhagic alveolitis despite receiving high-dose thiabendazole plus ivermectin therapy.

CONCLUSIONS:

In the current study, strongyloidiasis was uncommon in patients with cancer and remained localized in individuals with solid-organ malignancies. Definite pulmonary accelerated autoinfections were observed only in HSCT recipients. Therefore, pre-HSCT S. stercoralis screening in individuals from endemic regions of the United States warrants further study.

Role of quantitative human cytomegalovirus PCR in predicting antiviral treatment response among high-risk hematopoietic stem-cell transplant recipients.

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Safdar A, Bruorton M, Henslee-Downey JP, van Rhee F.

Bone Marrow Transplant. 2004 Feb;33(4):463-4.

Curvularia–favorable response to oral itraconazole therapy in two patients with locally invasive phaeohyphomycosis.

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Safdar A.

Clin Microbiol Infect. 2003 Dec;9(12):1219-23.

Abstract

Curvularia species are ubiquitous and occasionally lead to infections in humans. In immunosuppressed patients, infections are often serious, and systemic dissemination is not uncommon. The optimal antifungal therapy is unclear. I here present two cases, a healthy man with locally invasive, mulicentric paranasal fungal sinusitis, and a case of progressive verrucal distal onychomycosis that developed while the patient was undergoing accelerated chemotherapy for non-Hodgkin’s lymphoma. Both patients showed excellent responses to treatment with itraconazole suspension. Oral itraconazole may provide a safe and effective alternative for patients with locally invasive non-disseminated mycoses due to Curvularia species.

Hospitalization of an oncology patient suspected of having severe acute respiratory syndrome: a setup for an infection control quagmire at a comprehensive cancer center.

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Safdar A, Chemaly RF, Perego CA, Gonzalez VR, Rolston KV, Raad II, Tarrand JJ, Callender DL.

Cancer. 2003 Dec 15;98(12):2738-9.

Efficacy of vancomycin plus levofloxacin combination therapy for refractory pericarditis due to multiresistant Streptococcus pneumoniae.

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Safdar A.

Int J Infect Dis. 2003 Dec;7(4):287.

Candidemia in a tertiary care cancer center: in vitro susceptibility and its association with outcome of initial antifungal therapy.

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Antoniadou A, Torres HA, Lewis RE, Thornby J, Bodey GP, Tarrand JP, Han XY, Rolston KV, Safdar A, Raad II, Kontoyiannis DP.

Medicine (Baltimore). 2003 Sep;82(5):309-21.

Abstract

Since the 1990s, changing trends have been documented in species distribution and susceptibility to bloodstream infections caused by Candida species in cancer patients. However, few data are available regarding the association between in vitro antifungal susceptibility and outcome of candidemia in this patient population. We therefore evaluated the association of in vitro antifungal susceptibility and other risk factors with failure of initial antifungal therapy in cancer patients with candidemia. Candidemia cases in cancer patients from 1998 to 2001 (n = 144) were analyzed retrospectively along with their in vitro susceptibility to amphotericin B, fluconazole, and itraconazole (National Committee for Clinical and Laboratory Standards M27-A method). Patients were evaluable for outcome analysis if they received continuous unchanged therapy with either fluconazole or amphotericin B for >/=5 days. We excluded cases of mixed candidemia. In vitro susceptibility testing data of the first Candida bloodstream isolate were analyzed. Appropriate therapy was defined as that using an active in vitro antifungal for >/=5 days. For fluconazole susceptible-dose dependent Candida species, we defined appropriate therapy as a fluconazole dose of >/=600 mg/day. The Candida species distribution was 30% Candida albicans, 24% Candida glabrata, 23% Candida parapsilosis, 10% Candida krusei, 9% Candida tropicalis, and 3% other. Overall, amphotericin B was the most active agent in vitro, with only 3% of the isolates exhibiting resistance to it (>1 mg/L). Dose-dependent susceptibility to fluconazole and itraconazole was seen in 13% and 21% of the isolates, respectively, while resistance to fluconazole and itraconazole was seen in 13% and 26%, respectively.Eighty patients were evaluable for outcome analysis. In multivariate analysis, the following factors emerged as independent predictors of failure of initial antifungal therapy: leukemia (p = 0.01), bone marrow transplantation (p = 0.006), and intensive care unit stay at onset of infection (p = 0.02). Inappropriate antifungal therapy, as defined by daily dose and in vitro susceptibility, was not shown consistently to be a significant factor (it was significant in multivariate analysis, p = 0.04, but not in univariate analysis), indicating the complexity of the variables that influence the response to antifungal treatment in cancer patients with candidemia.

Listeriosis in patients at a comprehensive cancer center, 1955-1997.

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Safdar A, Armstrong D.

Clin Infect Dis. 2003 Aug 1;37(3):359-64. Epub 2003 Jul 22.

Abstract

Listeria monocytogenes infection occurred in 94 patients during 1955-1997 at Memorial Sloan-Kettering Cancer Center. The incidence was 0.5 (1955-1966), 0.96 (1970-1979), and 0.14 (1985-1997) cases per 1000 new admissions. Eighty-five patients (90%) were bacteremic, and 34 (36%) had evidence of intracranial infection. In 91 patients with cancer, 70 (77%) received chemotherapy for advanced or relapsed malignancy (n=51; 56%); 64 (68%) received corticosteroids. Breast cancer was the most common solid-organ cancer (n=14; 45%), and 34 (36%) had preexisting advanced liver disease. In 14 (39%) of 37 patients who died of listeriosis, death occurred within 48 h of L. monocytogenes isolation. Four (80%) of 5 patients with extracranial foci of infection died of their infection, compared with 33 (37%) of 89 patients with isolated bacteremia and/or intracranial infection (odds ratio, 2.34; P=.05). Most infections (60%) were due to L. monocytogenes serotype 1/2, and the remainder (40%) were due to serovar 4b. Listeriosis in these patients with cancer occurred most often in individuals receiving antineoplastic therapy for advanced or relapsed malignancy and systemic corticosteroids. The presence of advanced liver disease may have increased the risk of systemic listeriosis in susceptible patients with underlying cancer.

Prospective epidemiologic analysis of triazole-resistant nosocomial Candida glabrata isolated from patients at a comprehensive cancer center.

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

Int J Infect Dis. 2002 Sep;6(3):198-201.

Abstract

OBJECTIVE:

The emergence of Candida glabrata infections among patients with compromised immunity has become a serious concern, especially at centers caring for individuals with cancer.

METHODS:

During a prospective evaluation of Candida species associated with either clinically significant colonization or infection, 26.9% of C. glabrata isolates showed in vitro resistance to fluconazole (MIC of > or = 64 microg/ml).

RESULTS:

Antifungal susceptibility profiles and genetic fingerprinting analysis performed by randomly amplified polymorphic DNA (RAPD) techniques confirmed low-probability of phenotypic and genotypic relatedness among nosocomial C. glabrata isolates.

CONCLUSIONS:

Presence of polyclonal strains of C. glabrata in patients at our hospital was probably related to selection of resistant yeasts from environmental pool rather than monoclonal expansion or clustering of multi-drug resistant C. glabrata in high-risk patients.