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.

Clinical microbiological case: infection imitating lymphocutaneous sporotrichosis during pregnancy in a healthy woman from the south-eastern USA.

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Safdar A.

Clin Microbiol Infect. 2003 Mar;9(3):221, 244-6.

A novel defect in interferon-gamma secretion in patients with refractory nontuberculous pulmonary mycobacteriosis.

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Safdar A, Armstrong D, Murray HW.

Ann Intern Med. 2003 Mar 18;138(6):521.

Infectious diarrhea in the southeastern United States, 1998-2000.

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Safdar A.

Clin Infect Dis. 2003 Feb 15;36(4):533-4.

Breakthrough Scedosporium apiospermum (Pseudallescheria boydii) brain abscess during therapy for invasive pulmonary aspergillosis following high-risk allogeneic hematopoietic stem cell transplantation. Scedosporiasis and recent advances in antifungal therapy.

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Safdar A, Papadopoulos EB, Young JW.

Transpl Infect Dis. 2002 Dec;4(4):212-7.

Abstract

Systemic scedosporiasis due to the anamorph or asexual form Scedosporium apiospermum (Pseudallescheria boydii) has become an important cause of opportunistic mycosis, especially in patients undergoing high-risk hematopoietic stem cell transplantation. We report a case of rapidly progressive cerebellar hyalohyphomycosis due to Scedosporium apiospermum in an allogeneic marrow graft recipient receiving treatment for severe graft-versus-host disease. This fatal breakthrough intracranial abscess, due to amphotericin B-resistant (minimum inhibitory concentration > 16 micro g/ml) mold, developed during the course of systemic antifungal therapy given for multicentric pulmonary aspergillosis. Despite treatment with high-dose Abelcet (10 mg/kg daily), free amphotericin B was not detected in postmortem cerebellar tissue. A broad-spectrum triazole-based agent (voriconazole/UK-109, 496–Vfend), and a novel fungal cell wall inhibitor, an echinocandin/pneumocandin analog (caspofungin/MK-0991–Cancidas), which exhibit excellent in vitro activity against most clinical Pseudallescheria boydii-Scedosporium apiospermum isolates, have recently become available in the United States and may provide much needed treatment options for patients at risk.

Clinical microbiological case: severe relapsing septal panniculitis in a healthy man from the south-eastern USA.

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Safdar A, McEvoy PL, Burns RG, Perfect JR.

Clin Microbiol Infect. 2002 Dec;8(12):801-2; 830-2.

Antimicrobial activities against 84 Listeria monocytogenes isolates from patients with systemic listeriosis at a comprehensive cancer center (1955-1997).

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Safdar A, Armstrong D.

J Clin Microbiol. 2003 Jan;41(1):483-5.

Abstract

Listeriosis is a serious complication in patients undergoing treatment for cancer. We present antimicrobial susceptibility profiles of 84 clinical Listeria monocytogenes isolates. During 1955 to 1997, in vitro susceptibility for penicillin (97.6%), ampicillin (90.7%), erythromycin (98.8%), tetracycline (96.9%), and gentamicin (98.0%) remained unchanged. All isolates were susceptible to amikacin, ciprofloxacin, imipenem, rifampin, trimethoprim-sulfamethoxazole (TMP-SMX), and vancomycin. High prevalence of clindamycin resistance (96.2%) was unexpected. Ampicillin plus gentamicin is standard therapy for systemic listerosis, and TMP-SMX may be used for patients with beta-lactam intolerance. In vitro susceptibility profiles for carbapenem and fluoronated quinolone are promising, although clinical validation is critically needed before routine use is advocated, especially for listeric patients with severe cellular immune defects.

Profound interferon gamma deficiency in patients with chronic pulmonary nontuberculous mycobacteriosis.

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Safdar A, White DA, Stover D, Armstrong D, Murray HW.

Am J Med. 2002 Dec 15;113(9):756-9.