Extrapulmonary tuberculosis active infection misdiagnosed as cancer: Mycobacterium tuberculosis disease in patients at a Comprehensive Cancer Center (2001-2005).

Aisenberg GM, Jacobson K, Chemaly RF, Rolston KV, Raad II, Safdar A.

Cancer. 2005 Dec 15;104(12):2882-7.

Abstract

BACKGROUND:

Extrapulmonary tuberculosis is an uncommon disease in the U.S., even in immunosuppressed cancer patients. This study evaluated characteristics and frequency of extrapulmonary tuberculosis in patients at a tertiary care referral cancer center.

METHODS:

The records of all consecutive patients with Mycobacterium tuberculosis diagnosed during January 2001 through April 2005 at the M. D. Anderson Cancer Center were reviewed after obtaining institutional review board approval.

RESULTS:

There were 26 patients with active tuberculosis during the period studied; 18 of them were cancer patients and the others had been referred for a presumed cancer but did not have cancer. The overall rate of active tuberculosis during this period was 0.2 in 1000 new cancer diagnoses. There were 18 men (69%), the median age was 54 years (range, 3-84 yrs), and 16 patients (62%) were born in the U.S. Thirteen (72%) of the 18 cancer patients had solid-organ tumors; 3 of the 5 patients with a hematologic malignancy had non-Hodgkin lymphoma. Three patients (12%) had diabetes mellitus, and 2 patients (8%) had received high-dose (>1 mg/kg of prednisone daily) corticosteroids in the previous week. No patient had a recent history (within the past 4 wks) of chemotherapy; 4 patients had neutropenia. Cough was a prominent symptom (31%), followed by bone pain (19%), dyspnea (15%), and fever (12%). Fifteen patients (58%) had extrapulmonary infection, including 5 patients with concurrent pulmonary involvement; 7 noncancer patients (88%) and 8 cancer patients (44%, P = 0.22) had extrapulmonary disease. In 11 patients (42%), the lungs were the only site of active tuberculosis. Cavitary pneumonia was seen radiographically in 3 of 16 patients (19%) with pulmonary tuberculosis. All M. tuberculosis isolates were susceptible to isoniazid, rifampin, ethambutol, and pyrazinamide; streptomycin resistance was noted in 1 of 22 (5%) isolates tested. Twenty-two patients (85%) received appropriate antituberculosis treatment; all had a clinical and radiographic response. In 3 patients (12%) the cause of death was attributed to M. tuberculosis disease; 2 of 18 cancer patients (11%) died of progressive M. tuberculosis, and they had advanced solid-organ cancer, whereas 1 of 8 patients (13%) without cancer died and the tuberculosis diagnosis was made only on postmortem examination. Univariate analysis showed no significant differences in patients or disease characteristics between non-U.S.-born and U.S.-born patients, whereas noncancer patients (age 52 yrs) and those with extrapulmonary tuberculosis (age 53 yrs) were younger compared with cancer patients (63 yrs; P < 0.007) and those with pulmonary disease (age 60 yrs; P = 0.09).

CONCLUSIONS:

Extrapulmonary tuberculosis was relatively common in younger patients with active M. tuberculosis infection, and was often initially misdiagnosed as cancer.

Inactive pulmonary tuberculosis mimicking metastasis from papillary thyroid carcinoma in diagnostic radioiodine whole-body scintigraphy.

Picolos MK, Habra M, Safdar A, Sarlis NJ.

Thyroid. 2005 Sep;15(9):1105-6.

Streptococcus pneumoniae bacteremia in patients with cancer: disease characteristics and outcomes in the era of escalating drug resistance (1998-2002).

Kumashi P, Girgawy E, Tarrand JJ, Rolston KV, Raad II, Safdar A.

Medicine (Baltimore). 2005 Sep;84(5):303-12.

Abstract

In the current era of multidrug-resistant organisms, the clinical spectrum of Streptococcus pneumoniae infection remains unclear, especially in immunosuppressed patients with cancer. We sought to define the characteristics of pneumococcal bacteremia in patients who were receiving care at a comprehensive cancer center. All consecutive episodes of S. pneumoniae bacteremia between January 1998 and December 2002 were evaluated retrospectively. One hundred thirty-five episodes of pneumococcal bacteremia occurred in 122 patients. Sixty-three (52%) of 122 patients had hematologic malignancies; the others had solid tumors. The median Acute Physiology and Chronic Health Evaluation II score was 14 +/- 5. Twenty-four episodes (18%) occurred during neutropenia (<500 cells/microL). Sixty-five patients (53%) were receiving antineoplastic therapy, and 36 (30%) were receiving systemic corticosteroids. Twelve (41%) of 29 hematopoietic stem cell transplant (HSCT) recipients had received transplantation within 12 months of the infection diagnosis; 11 patients had graft-versus-host disease (chronic in 10). In 27 episodes (22%), S. pneumoniae bacteremia was considered as a breakthrough infection. Nine (56%) of 16 hospital-acquired episodes of S. pneumoniae bloodstream infection occurred in patients with profound neutropenia, whereas 15 (13%) of 119 episodes of community-acquired infection occurred during neutropenia (p < 0.0002). In 91 episodes (67%), patients had radiographic evidence of pneumonia. Infected catheters were associated with 21 episodes (16%). Forty-eight (36%) of 135 isolates were not susceptible to penicillin (minimum inhibitory concentration [MIC] > or = 2 microg/mL); 9 (7%) showed intermediate susceptibility to ceftriaxone (MIC >0.5 and <2.0 microg/mL). Nineteen patients (16%) died within 2 weeks of diagnosis; 18 deaths were attributed to systemic pneumococcal infection. Univariate analysis showed no significant increase in the risk of short-term death in patients with infection due to penicillin non-susceptible organisms (OR [odds ratio], 1.47; 95% confidence intervals [CI], 0.53-4.05; p < 0.46), initially discordant treatment (OR, 1.0; 95% CI, 0.62-665.4; p < 0.16), presence of pneumonia (OR, 1.19; 95% CI, 0.39-3.62; p < 0.76), neutropenia (OR, 1.0; 95% CI, 0.28-4.09; p < 0.92), systemic corticosteroid use (OR, 1.96; 95% CI, 0.69-5.60; p < 0.21), or antineoplastic therapy (OR, 1.45; 95% CI, 1.52-4.05; p < 0.47). Similarly, patients with hematologic cancers compared to those with solid cancers (OR, 1.0; 95% CI, 0.49-3.70; p < 0.56) and recipients of HSCT compared to those with no history of transplantation (OR, 1.0; 95% CI 0.59-12.71; p < 0.20) did not have a less favorable outcome. In conclusion, most pneumococcal bloodstream infections were community acquired, although hospital-acquired infections were common in neutropenic patients. It is noteworthy that initially discordant therapy, penicillin non-susceptible S. pneumoniae, and other conventional predictors of unfavorable outcome were not associated with increased mortality rates in these high-risk patients with cancer.

Mycobacterium lentiflavum, a recently identified slow-growing mycobacterial species: clinical significance in immunosuppressed cancer patients and summary of reported cases of infection.

Safdar A, Han XY.

Eur J Clin Microbiol Infect Dis. 2005 Aug;24(8):554-8.

Abstract

The clinical significance of Mycobacterium lentiflavum, a recently identified nontuberculous mycobacterium, remains uncertain, especially in immunosuppressed cancer patients. The records of all patients in whom M. lentiflavum was identified using a gene sequencing technique between January 2001 and December 2003 were reviewed. The mean age among 12 patients was 51+/-20 years, and 11 (92%) patients had a hematologic malignancy. Six of seven (86%) hematopoietic stem cell transplant recipients had received allogeneic donor grafts. Nine (75%) patients had predisposing risk factors for infection, seven (58%) had severe lymphocytopenia (<400 cells/microl), five (42%) were receiving systemic corticosteroid therapy, and three (25%) had acute graft-versus-host disease. Only 1 of the 12 (8%) patients had evidence of probable pulmonary M. lentiflavum infection. Six M. lentiflavum strains were initially misidentified as Mycobacterium simiae and Mycobacterium avium-intracellulare complex using traditional biochemical tests. Four M. lentiflavum isolates were tested for antimicrobial susceptibility; they were susceptible to isoniazid, ethambutol, clarithromycin, and amikacin, and resistant to rifampin. M. lentiflavum was not clinically significant, even in these severely immunosuppressed cancer patients.

Cutaneous toxoplasmosis: a case of confounding diagnosis.

Lee SA, Diwan AH, Cohn M, Champlin R, Safdar A.

Bone Marrow Transplant. 2005 Sep;36(5):465-6.

 

Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases.

Kontoyiannis DP, Lionakis MS, Lewis RE, Chamilos G, Healy M, Perego C, Safdar A, Kantarjian H, Champlin R, Walsh TJ, Raad II.

J Infect Dis. 2005 Apr 15;191(8):1350-60. Epub 2005 Mar 16.

Abstract

BACKGROUND:

Anecdotal evidence suggests a rise in zygomycosis in association with voriconazole (VRC) use in immunosuppressed patients.

METHODS:

We performed prospective surveillance of patients with zygomycosis (group A; n = 27) and compared them with contemporaneous patients with invasive aspergillosis (group B; n = 54) and with matched contemporaneous high-risk patients without fungal infection (group C; n = 54). We also performed molecular typing and in vitro susceptibility testing of Zygomycetes isolates.

RESULTS:

Nearly all patients with zygomycosis either had leukemia (n = 14) or were allogeneic bone marrow transplant recipients (n = 13). The Zygomycetes isolates (74% of which were of the genus Rhizopus) had different molecular fingerprinting profiles, and all were VRC resistant. In multivariate analysis of groups A and C, VRC prophylaxis (odds ratio [OR], 10.37 [95% confidence interval [CI]], 2.76-38.97]; P = .001), diabetes (OR, 8.39 [95% CI, 2.04-34.35]; P = .003), and malnutrition (OR, 3.70 [95% CI, 1.03-13.27]; P = .045) were found to be independent risk factors for zygomycosis. Between patients with zygomycosis (after excluding 6 patients with mixed mold infections) and patients with aspergillosis, VRC prophylaxis (OR, 20.30 [95% CI, 3.85-108.15]; P = .0001) and sinusitis (OR, 76.72 [95% CI, 6.48-908.15]; P = .001) were the only factors that favored the diagnosis of zygomycosis.

CONCLUSIONS:

Zygomycosis should be considered in immunosuppressed patients who develop sinusitis while receiving VRC prophylaxis, especially those with diabetes and malnutrition.

Francisella tularensis peritonitis in stomach cancer patient.

Han XY, Ho LX, Safdar A.

Emerg Infect Dis. 2004 Dec;10(12):2238-40.

Abstract

Tularemia with peritonitis developed in a 50-year-old man soon after diagnosis of stomach cancer with metastasis. The ascites grew Francisella tularensis subsp. holarctica, which was identified by sequencing analysis of the 16S rDNA. The infection resolved with antimicrobial treatment. Antibodies detected 4 weeks after onset disappeared after chemotherapy-associated lymphopenia.

The safety of interferon-gamma-1b therapy for invasive fungal infections after hematopoietic stem cell transplantation.

Safdar A, Rodriguez G, Ohmagari N, Kontoyiannis DP, Rolston KV, Raad II, Champlin RE.

Cancer. 2005 Feb 15;103(4):731-9.

Abstract

BACKGROUND:

The restoration of normal immune responses, especially of the T-helper type 1 immune response, is an important predictor of fungal infection outcome in patients with malignant disease who undergo hematopoietic stem cell transplantation (HSCT). The authors sought to evaluate the safety of adjuvant recombinant interferon-gamma-1b as an immune-modulatory therapy HSCT recipients.

METHODS:

Thirty-two patients received interferon-gamma-1b after undergoing HSCT at the author’s institution between 1998 and 2003. A retrospective analysis was undertaken after obtaining permission from the Institutional Review Board.

RESULTS:

Twenty-six of 32 patients (81%) received allogeneic stem cell grafts. All but 1 patient received interferon-gamma-1b and antifungals to treat infections; the other patients received interferon-gamma-1b to promote autologous graft-versus-tumor effect. Interferon-gamma-1b usually was administered at a dose of 50 mug subcutaneously every other day. The median duration (+/- standard deviation) of interferon-gamma-1b therapy was 6+/-6.5 doses (range, 1-29 doses), and the median cumulative dose was 487+/-453 mug (range, 35-2175 microg). During therapy with interferon-gamma-1b, fever was common (n=9 patients; 28%). In 1 patient (3%), new-onset lymphocytopenia occurred but resolved after cytokine therapy was discontinued; there were no interferon- gamma-1b-related episodes of neutropenia, thrombocytopenia, anemia, or liver dysfunction. Interferon-gamma-1b therapy did not precipitate or exacerbate acute or chronic graft-versus-host disease (GVHD). In fact, in 2 of 7 patients (29%) with acute GVHD and in 3 of 10 patients (30%) with chronic GVHD, significant improvements in GVHD were noted during therapy with interferon-gamma-1b. Among the 26 patients with aspergillosis, 14 patients (54%) died. However, 5 of 10 patients (50%) with presumed pulmonary aspergillosis, 3 of 9 patients (33%) with probable pulmonary aspergillosis, 1 of 2 patients (50%) with definite pulmonary aspergillosis, and 3 of 5 patients (60%) with disseminated aspergillosis responded to antifungals and adjuvant interferon-gamma-1b.

CONCLUSIONS:

Recombinant interferon-gamma-1b was tolerated without serious adverse reactions in HSCT recipients. A large, prospective, randomized study will be needed to evaluate the efficacy of this cytokine in high-risk HSCT recipients who have invasive mycoses.

Impact of high-dose granulocyte transfusions in patients with cancer with candidemia: retrospective case-control analysis of 491 episodes of Candida species bloodstream infections.

Safdar A, Hanna HA, Boktour M, Kontoyiannis DP, Hachem R, Lichtiger B, Freireich EJ, Raad II.

Cancer. 2004 Dec 15;101(12):2859-65.

Abstract

BACKGROUND:

The efficacy and feasibility of donor granulocyte transfusion therapy (GTX) have changed considerably over the past four decades. The authors sought to determine the impact of high-dose (approximately 5.5 x 10(10) cells) GTX in patients with candidemia.

METHODS:

The authors’ case-control retrospective analysis comprised 491 consecutive patients treated at The University of Texas M. D. Anderson Cancer Center (Houston,TX) from 1993 to 2000. The cohort included 29 patients with Candida species bloodstream infection who had received GTX and 462 who had not.

RESULTS:

Both groups were comparable in age, gender, APACHE II score, recent chemotherapy received, broad-spectrum antibiotics, systemic corticosteroids, radiotherapy, intravascular catheter, and concordant antifungal therapy (P > or = 0.1). The patients who received GTX compared with those who did not had a higher incidence of underlying leukemia (86% vs. 29%, P <0.001), persistent neutropenia (59% vs. 18%, P <0.001), non-Candida albicans candidemia (Candida glabrata, 35%; Candida krusei, 31%: 90% vs. 67%, P=0.01), and breakthrough invasive mycosis (62% vs. 23%, P <0.001). Neutropenia was more prolonged in patients who received GTX (28 vs. 10 days, P <0.001). Also, more of the patients who received GTX had received hematopoietic stem cell transplantations (28% vs. 13%, P = 0.03), exposure (within 4 weeks) to antifungals (79% vs. 38%, P <0.001), and stays in critical care units (62% vs. 40%, P=0.02). The overall attributable mortality rate for 25 evaluable recipients of GTX was 48% (n=12), compared with 45% (n=115) of 254 evaluable patients in the control group (P=0.5). Of the 158 patients with leukemia, 25 (16%) had received GTX. In patients with leukemia, more of those who had received GTX experienced disseminated candidiasis (44% vs. 26%; P <0.07) and persistent neutropenia (68% vs. 43%, P <0.02), had candidemia that was more prolonged (> 72 hours, P <0.02), and had more stays in critical care units (68% vs. 44%, P <0.03). On the bases of a reduced multivariate model, a significantly increased risk of death was found for patients with hematopoietic stem cell transplantation (odds ratio [OR]=2.51; 95% confidence interval [95% CI], 0.99-6.31; P <0.05), for patients with persistent neutropenia (OR=4.57; 95% CI, 1.99-10.47; P <0.0003), and for patients with leukemia who also had prolonged candidemia (OR=3.59; 95% CI, 1.61-7.98; P <0.002), disseminated candidiasis (OR=5.19; 95% CI, 2.17-12.42; P <0.0002), or non-C. albicans candidemia (OR=5.02; 95% CI, 1.07-23.64; P <0.04). In patients with leukemia, death was attributable to candidemia in 50% of the GTX recipients, compared with 59% of the non-GTX patients who had received antifungal therapy alone (P=0.4).

CONCLUSIONS:

Despite the presence of multiple predictors of increased mortality, high-dose GTX therapy in these high-risk patients with cancer was associated with better than expected survival rates.

Bacteremia caused by Achromobacter and Alcaligenes species in 46 patients with cancer (1989-2003).

Aisenberg G, Rolston KV, Safdar A.

Cancer. 2004 Nov 1;101(9):2134-40.

Abstract

BACKGROUND:

Achromobacter and Alcaligenes are emerging infectious gram-negative bacterial species that can affect immunosuppressed patients. The authors sought to determine the incidence and characteristics of bloodstream infections caused by these organisms in patients with underlying malignancies.

METHODS:

All consecutive episodes of hematogenous Achromobacter and Alcaligenes infections recorded from December 26, 1989, to July 27, 2003, were studied retrospectively.

RESULTS:

Fifty-two episodes occurred in 46 patients; 31 patients (67%) had hematologic malignancies, and 24 (52%) experienced neutropenia (< 500 cells/microL). Diabetes mellitus was present in 12 patients (26%), and high-dose corticosteroids were administered to 12 patients (26%). Seventeen of the 52 infectious episodes (33%) were nosocomial in origin, and 10 patients (22%) had sepsis syndrome. Achromobacter xylosoxidans was the most common cause of infection (47 of 52 episodes [94%]), followed by Ach. denitrificans (2 of 52 episodes [4%]) and Alcaligenes faecalis (1 of 52 episodes [2%]). Twenty-seven episodes (52%) were polymicrobial, and 3 patients (7%) had concurrent fungemia. Infected intravascular catheters were present in 13 of 52 cases (25%), pneumonia was encountered in 6 of 52 cases (12%), and urinary tract infections were present in 5 of 52 cases (10%). Most isolates exhibited in vitro susceptibility to carbapenems, antipseudomonal penicillins, and trimethoprim-sulfamethoxazole. Resistance to ciprofloxacin, levofloxacin, aminoglycosides, and monobactam was common. Seven deaths (15%) were attributable to Achromobacter species. Incidence rates for sepsis syndrome, multiorgan dysfunction (Acute Physiology and Chronic Health Evaluation [APACHE] II score > 16), and use of mechanical ventilation and pressor support were significantly higher in patients who died (P < 0.001). Logistic regression analysis revealed that sepsis syndrome and high APACHE II scores were predictors of increased 30-day mortality.

CONCLUSIONS:

Most infections caused by this group of nonfermentative gram-negative bacteria were attributable to Ach. xylosoxidans, and only one-third were acquired during hospitalization. The presence of sepsis syndrome has evolved as an independent predictor of poor outcome in patients with high-risk malignancies accompanied by Achromobacter bloodstream infections.