Endemic fungal infections in solid organ and hematopoietic cell transplant recipients enrolled in the Transplant-Associated Infection Surveillance Network (TRANSNET).

BACKGROUND: Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients, but few data have been reported on the epidemiology of endemic fungal infections in these populations. METHODS: Fifteen institutions belonging to the Transplant-Associated Infection Surveillance Network prospectively enrolled SOT and HCT recipients with histoplasmosis, blastomycosis, or coccidioidomycosis occurring between March 2001 and March 2006. RESULTS: A total of 70 patients (64 SOT recipients and 6 HCT recipients) had infection with an endemic mycosis, including 52 with histoplasmosis, 9 with blastomycosis, and 9 with coccidioidomycosis. The 12-month cumulative incidence rate among SOT recipients for histoplasmosis was 0.102%. Occurrence of infection was bimodal; 28 (40%) infections occurred in the first 6 months post transplantation, and 24 (34%) occurred between 2 and 11 years post transplantation. Three patients were documented to have acquired infection from the donor organ. Seven SOT recipients with histoplasmosis and 3 with coccidioidomycosis died (16%); no HCT recipient died. CONCLUSIONS: This 5-year multicenter prospective surveillance study found that endemic mycoses occur uncommonly in SOT and HCT recipients, and that the period at risk extends for years after transplantation.

Preemptive intravenous immunoglobulin allows safe and timely administration of antineoplastic therapies in patients with multiple myeloma and parvovirus B19 disease.

BACKGROUND: Parvovirus B19 (B19) disease is a rare cause of anemia in cancer patients and often goes unrecognized, causing delays in anticancer therapy. METHODS: A retrospective review was carried out of the records of patients with multiple myeloma who underwent melphalan-based autologous stem cell transplantation (MEL-ASCT) and developed B19 infection (January 2009-December 2011). Cases were defined by the presence of clinical and laboratory findings consistent with B19 disease in patients with repeatedly positive plasma quantitative polymerase chain reaction for parvovirus. RESULTS: Six patients qualified as cases; 5 presented with trilineage cytopenias (chronic in 1) and 1 with anemia later progressing to pancytopenia. Transfusion-dependent thrombocytopenia led to testing in 5 patients. Two of these patients also had manifestations of autoimmune disease. Therapy with intravenous immunoglobulin (IVIG) resulted in clinical and hematologic response in all; however, 1 patient, whose white blood cell counts and serum hemoglobin levels improved, required splenectomy for persistent thrombocytopenia. All patients required additional IVIG for recurrent B19 disease. Although viral load at diagnosis did not correlate with the severity of cytopenia, its decrease was associated with response during 17 of 20 evaluable episodes (P = 0.02). Preemptive IVIG allowed the safe administration of chemotherapy in 3 patients, including MEL-ASCT in 1. CONCLUSION: Parvovirus B19 can cause severe disease in myeloma patients including ASCT recipients. Thrombocytopenia - not anemia - was the leading presentation and may be associated with autoimmune conditions. Patients with unexplained cytopenias, particularly when prolonged, should undergo testing for circulating parvovirus. A reduction in viral load was associated with response to IVIG, although additional therapy was needed for recurrent disease. Most importantly, preemptive IVIG allowed for safe and timely administration of antineoplastic therapy in patients with ongoing B19 disease.

Risk factors, preemptive therapy, and antiperistaltic agents for Clostridium difficile infection in cancer patients.

BACKGROUND: Clostridium difficile infection (CDI) is a serious complication of chemotherapy including high-dose regimens with autologous stem cell transplantation (ASCT). Antiperistaltic agents are contraindicated in CDI and preemptive CDI therapy is not recommended. We assessed the incidence, risk factors, and outcomes of CDI in patients with newly diagnosed multiple myeloma (MM) receiving similar antineoplastic therapy and supportive care including antiperistaltic agents and preemptive CDI antibiotics for significant diarrhea. METHODS: A total of 303 consecutive MM patients (2004-2007) were enrolled in a protocol consisting of induction chemotherapy, tandem melphalan (MEL)-ASCT, and consolidation. Patients with grade 2-4 diarrhea were simultaneously tested for CDI, and initiated on antiperistaltic agents (loperamide) and preemptive anti-CDI therapy. Risk factors, including prior CDI and MM immunoglobulin (Ig) isotype, were evaluated. Multinomial logistic regression was used to compute the relative risk ratio (RRR) and 95% confidence intervals (CIs). RESULTS: There were 43 cases of CDI (14.2%) during 1529 chemotherapy courses (536 ASCT). IgA MM protected against CDI (RRR 0.35; 95% CI 0.13-0.93, P = 0.04) whereas CDI during first induction markedly increased the risk of recurrence during second induction (RRR = 10.94; 95% CI 1.90, 62.92, P = 0.01) and following MEL-ASCT (RRR = 6.63; 95% CI 1.51, 29.12, P = 0.01). No CDI-related surgical intervention or death ensued despite use of antiperistaltic agents. CONCLUSIONS: CDI was not uncommon in cancer patients receiving chemotherapy. IgA myeloma appears to be protective. Concurrent antiperistaltic (loperamide) and preemptive CDI therapies were associated with excellent outcomes. Prior CDI history increased the risk for recurrence during successive chemotherapy courses.

Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients.

Contemporary epidemiology and outcomes of invasive fungal infections (IFIs) in solid organ transplant (SOT) recipients are not well described. From March 2004 through September 2007, proven and probable IFIs were prospectively identified in 17 transplant centers in the United States. A total 429 adult SOT recipients with 515 IFIs were identified; 362 patients received a single and 67 patients received >or=2 organs. Most IFIs were caused by Candida species (59.0%), followed by Aspergillus species (24.8%), Cryptococcus species (7.0%), and other molds (5.8%). Invasive candidiasis (IC) was the most frequently observed IFI in all groups, except for lung recipients where invasive aspergillosis (IA) was the most common IFI (P<0.0001). Almost half of IC cases in liver, heart, and lung transplant recipients occurred during the first 100 days post transplant. Over half of IA cases in lung recipients occurred >1 year post transplant. Overall 12-week mortality was 29.6%; liver recipients had the highest mortality (P=0.05). Organ damage, neutropenia, and administration of corticosteroids were predictors of death. These results extend our knowledge on the epidemiology of IFI in SOT recipients, emphasizing the occurrence of IC early after non-lung transplant, and late complications with molds after lung transplant. Overall survival appears to have improved compared with historical reports.

Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance registry.

BACKGROUND: With use of data from the Prospective Antifungal Therapy (PATH) Alliance registry, we performed this multicenter, prospective, observational study to assess the epidemiologic characters and outcomes of invasive fungal infection (IFI) in hematopoietic stem cell transplant (HSCT) recipients. METHODS: Sixteen medical centers from North America reported data on adult HSCT recipients with proven or probable IFI during the period July 2004 through September 2007. The distribution of IFIs and rates of survival at 6 and 12 weeks after diagnosis were studied. We used logistic regression models to determine risk factors associated with 6-week mortality for allogeneic HSCT recipients with invasive aspergillosis (IA). RESULTS: Two hundred thirty-four adult HSCT recipients with a total of 250 IFIs were included in this study. IA (59.2%) was the most frequent IFI, followed by invasive candidiasis (24.8%), zygomycosis (7.2%), and IFI due to other molds (6.8%). Voriconazole was the most frequently administered agent (68.4%); amphotericin B deoxycholate was administered to a few patients (2.1%). Ninety-three (46.7%) of 199 HSCT recipients with known outcome had died by week 12. The 6-week survival rate was significantly greater for patients with IA than for those with invasive candidiasis and for those with IFI due to the Zygomycetes or other molds (P < .07). The 6-week mortality rate for HSCT recipients with IA was 21.5%. At 6 weeks, there was a trend toward a worse outcome among allogeneic HSCT recipients with IA who received myeloablative conditioning (P = .07); absence of mechanical ventilation or/and hemodialysis (P = .01) were associated with improved survival. CONCLUSIONS: IA remains the most commonly identified IFI among HSCT recipients, but rates of survival in persons with IA appear to have improved, compared with previously reported data. Invasive candidiasis and IFI due to molds other than Aspergillus species remain a significant problem in HSCT recipients.

18F-fluorodeoxyglucose positron emission tomography contributes to the diagnosis and management of infections in patients with multiple myeloma: a study of 165 infectious episodes.

PURPOSE: Correctly identifying infection in cancer patients can be challenging. Limited data suggest that positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) may be useful for diagnosing infection. To determine the role of FDG-PET in the diagnosis of infection in patients with multiple myeloma (MM). PATIENTS AND METHODS: The medical records of 248 patients who had FDG-PET performed for MM staging or infection work-up revealing increased uptake at extramedullary sites and/or bones and joints that would be atypical for MM between October 2001 and May 2004 were reviewed to identify infections and evaluate FDG-PET contribution to patient outcome. RESULTS: One hundred sixty-five infections were identified in 143 adults with MM. Infections involved the respiratory tract [99; pneumonia (93), sinusitis (six)], bone, joint and soft tissues [26; discitis (10), osteomyelitis (nine), septic arthritis (one), cellulitis (six)], vascular system [18; septic thrombophlebitis (nine), infection of implantable catheter (eight), septic emboli (one)], gastrointestinal tract [12; colitis (seven), abdominal abscess (three), and diverticulitis and esophagitis (one each)], and dentition [periodontal abscess (10)]. Infections were caused by bacteria, mycobacteria, fungi, and viruses. FDG-PET detected infection even in patients with severe neutropenia and lymphopenia (30 episodes). The FDG-PET findings identified infections not detectable by other methods (46 episodes), determined extent of infection (32 episodes), and led to modification of work-up and therapy (55 episodes). Twenty silent, but clinically relevant, infections were detected among patients undergoing staging FDG-PET. CONCLUSION: In patients with MM, FDG-PET is a useful tool for diagnosing and managing infections even in the setting of severe immunosuppression.

Oral mucositis in myeloma patients undergoing melphalan-based autologous stem cell transplantation: incidence, risk factors and a severity predictive model.

Melphalan-based autologous stem cell transplant (Mel-ASCT) is a standard therapy for multiple myeloma, but is associated with severe oral mucositis (OM). To identify predictors for severe OM, we studied 381 consecutive newly diagnosed myeloma patients who received Mel-ASCT. Melphalan was given at 200 mg/m2 body surface area (BSA), reduced to 140 mg/m2 for serum creatinine >3 mg/dl. Potential covariates included demographics, pre-transplant serum albumin and renal and liver function tests, and mg/kg melphalan dose received. The BSA dosing resulted in a wide range of melphalan doses given (2.4-6.2 mg/kg). OM developed in 75% of patients and was severe in 21%. Predictors of severe OM in multiple logistic regression analyses were high serum creatinine (odds ratio (OR)=1.581; 95% confidence interval (CI): 1.080-2.313; P=0.018) and high mg/kg melphalan (OR=1.595; 95% CI: 1.065-2.389; P=0.023). An OM prediction model was developed based on these variables. We concluded that BSA dosing of melphalan results in wide variations in the mg/kg dose, and that patients with renal dysfunction who are scheduled to receive a high mg/kg melphalan dose have the greatest risk for severe OM following Mel-ASCT. Pharmacogenomic and pharmacokinetic studies are needed to better understand interpatient variability of melphalan exposure and toxicity.

Iron overload is a major risk factor for severe infection after autologous stem cell transplantation: a study of 367 myeloma patients.

We evaluated the risk factors for infection of 367 consecutive myeloma patients who underwent high-dose melphalan and autologous stem cell transplantation (ASCT). Examination of bone marrow iron stores (BMIS) prior to ASCT was used to evaluate body iron stores. Other variables included age, sex, active smoking, myeloma remission status, severity of mucositis and duration of severe neutropenia post-ASCT (<100 absolute neutrophils counts (ANC)/microl). Median age was 56 years; 61% of patients were males. 140 episodes of severe infections occurred in 116 patients, including bacteremia (73), pneumonia (40), severe colitis (25) and bacteremia with septic shock (two). The infection incidence per 1,000 days at risk was 45.2. Pre-ASCT risk factors for severe infection by univariate analysis were increased BMIS (OR=2.686; 95% CI 1.707-4.226; P<0.0001), smoking (OR=1.565; 95% CI 1.005-2.437; P=0.0474) and male gender (OR=1.624; 95% CI 1.019-2.589; P=0.0414). Increased BMIS (OR=2.716; 95% CI 1.720-4.287; P<0.0001) and smoking (OR=1.714; 95% CI 1.081-2.718; P=0.022) remained significant by multivariate analysis. Duration of ANC <100 micro/l (OR=1.129; 95% CI 1.039-1.226; P=0.0069 and OR=1.127; 95% CI 1.038-1.224; P=0.0045 by both univariate and multivariate analysis, respectively) was the only post-ASCT risk factor for infection. Increased pre-transplant BMIS and smoking are significant predictors of severe infection after myeloablative chemotherapy followed by ASCT in myeloma patients.

Recovery from neutropenia can be predicted by the immature reticulocyte fraction several days before neutrophil recovery in autologous stem cell transplant recipients.

The duration of neutropenia (absolute neutrophil count (ANC) < or = 100/microl) identifies cancer patients at risk for infection. A test that precedes ANC > or = 100/microl would be of clinical value. The immature reticulocyte fraction (IRF) reflects erythroid engraftment and hence a recovering marrow. We evaluated the IRF as predictor of marrow recovery among 90 myeloma patients undergoing their first and second (75 patients) melphalan-based autologous stem cell transplantation (Mel-ASCT). The time to IRF doubling (IRF-D) preceded ANC > or = 100/microl in 99% of patients after the first Mel-ASCT by (mean+/-s.d.) 4.23+/-1.96 days and in 97% of the patients after the second Mel-ASCT by 4.11+/-1.95 days. We validated these findings in a group of 117 myeloma patients and 99 patients with various disorders undergoing ASCT with different conditioning regimens. We also compared the time to hypophosphatemia and to absolute monocyte count > or = 100/microl to the time to ANC > or = 100/microl. These markers were reached prior to this ANC end point in 55 and 25% of patients but were almost always preceded by IRF-D. We conclude that the IRF-D is a simple, inexpensive and widely available test that can predict marrow recovery several days before ANC> or = 100/microl.

Serial measurement of serum C-reactive protein levels can identify patients at risk for severe complications following autologous stem cell transplantation.

The value of serum C-reactive protein (CRP) levels as a predictor of complications in neutropenic patients needs to be further defined. We sought to identify an association between severe complications and daily CRP levels measured in 104 multiple myeloma patients during the 3 week period following high-dose melphalan and autologous transplant. Significantly higher mean CRP levels and CRP velocity of increase were observed among patients with severe complications. A cut-off point of 100 mg/l (CRP levels) and 15 mg/l/day (CRP velocity) identified patients likely to suffer severe complications with 86 and 75% sensitivity, respectively. Prospective validation of this model is currently underway.

Malignant pleural effusion of multiple myeloma: prognostic factors and outcome.

Malignant pleural effusion (MPE) in multiple myeloma (MM) is rare. Approximately 80 cases have been reported. To delineate optimal treatment and prognostic variables in these patients, we reviewed 11 MM patients with MPE. MPE developed at median of 12 months from diagnosis of MM. All the patients had high-risk disease based on complex karyotypic abnormalities including deletions of chromosome-13 (n=9), elevated beta-2 microglobulin (B2M) (n=9), high C-reactive protein (CRP) (n=8), high plasma cell labeling index (n=5) or high LDH (n=5). A significant increase in B2M, LDH, and CRP was observed at the onset of MPE. The initial diagnosis of MPE was based on positive cytology (n=9), pleural fluid cIg/DNA (n=9) or pleural fluid cytogenetics (n=4). Pleural tissue infiltration was found on pleural biopsy and autopsy in one patient each. Systemic chemotherapy comprising dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP) (n=7) and pleurodesis (n=7) were effective in resolving MPE but survival was short. High dose chemotherapy with peripheral blood stem cell support for MPE in six patients conferred no clear survival advantage. These patients died at median of four months from onset of MPE. Patients with bone marrow complex karyotypic abnormalities including deletion-13 (n=9) had a shorter (median--18 months) overall survival compared to patients with normal cytogenetics (median--38 months). MPE in patients with MM is often associated with high-risk disease including deletion 13 chromosomal abnormality and heralds a poor prognosis despite aggressive local and systemic treatment.

Clinical activity of arsenic trioxide for the treatment of multiple myeloma.

Arsenic has been used since ancient times as a therapeutic agent. However, until recently its use in modern medicine has been restricted to the treatment of a limited number of parasitic infections. In the early 1990s, reports from China described impressive results with arsenic trioxide in patients with de novo, relapsed, and refractory acute promyelocytic leukemia (APL). Other investigators subsequently confirmed these results leading to approval of its use for relapsed or refractory APL in the United States. Investigations of this agent have demonstrated that its efficacy in APL and preclinical tumor models is dependent upon a number of mechanisms, including induction of apoptosis, effects on cellular differentiation, cell cycling, and tumor angiogenesis. Subsequent preclinical studies showed significant activity of arsenic trioxide in multiple myeloma (MM). Based on this, in a phase II trial, we have evaluated the activity of arsenic trioxide in 14 patients with relapsed MM, refractory to conventional salvage therapy. With the dose and schedule used, treatment with arsenic trioxide produced responses in three patients and prolonged stable disease in a fourth patient, with the longest response lasting 6 weeks. Although treatment was reasonably well tolerated, in these patients with extensive prior therapy, 11 developed cytopenia, five associated with infectious complications and three developed deep vein thromboses. The results of this small trial support further investigation of this novel drug for the treatment of patients with relapsed or refractory MM.

Treatment of neutropenia-related fungal infections with granulocyte colony-stimulating factor-elicited white blood cell transfusions: a pilot study.

Neutropenia-related fungal infections can be life-threatening despite antifungal therapy. We evaluated the role of recombinant granulocyte colony-stimulating factor (rG-CSF)-elicited white blood cell (WBC) transfusions in patients with neutropenia-related fungal infections. Adult patients with hematologic malignancies, absolute neutrophil counts (ANC) <500/microl and fungal infections refractory to amphotericin B, received daily transfusions of rG-CSF-elicited and irradiated WBC transfusions from related donors. Donors received 5 microg/kg/day of rG-CSF subcutaneously. Donors achieved a mean ANC of 29.4 x 10(3) per microliter. The mean yield of neutrophils per transfusion was 41 x 10(9) (range, 10-116). Fifteen patients received a median of eight transfusions (range, 3-16). Fourteen patients had received rG-CSF for a median of 12 days. The median ANC baseline was 20/microl. Eleven patients had favorable responses and eight of them remained free of infection 3 weeks after therapy. Favorable responses occurred among patients with better Zubrod performance status (median, 3 vs 4) and shorter duration of both profound neutropenia (median, 15 vs 25 days) and active infection (median, 8 vs 17 days). The mean 1- and 24-h post-transfusion ANCs were 594/microl (range, 98-1472/microl) and 396/microl (range, 50-1475/microl), respectively. Adverse reactions were observed in nine of 35 donors and in the recipients of six of 130 transfusions. rG-CSF-elicited WBC transfusions may be a safe and promising approach for treating neutropenia-related fungal infections.

Reserpine in propranolol-resistant thyroid storm.

beta-Adrenergic blockers are considered the drugs of choice in the management of the hyperadrenergic state in hyperthyroidism. However, we observed a patient in thyroid storm and coma who failed to respond to large doses of oral and intravenous propranolol hydrochloride but who responded promptly to intramuscular reserpine. Reserpine may have been lifesaving and should be considered in propranolol-resistant hyperthyroidism and in hyperthyroid patients in whom propranolol is contraindicated.

Stenotrophomonas (Xanthomonas) maltophilia urinary tract infection. A disease that is usually severe and complicated.

BACKGROUND: Stenotrophomonas (Xanthomonas) maltophilia has emerged as a causative agent of serious nosocomial infections. However, well-documented cases of urinary tract infection with this organism have rarely been reported. METHODS: review of the medical records of patients admitted to a large cancer center with cultures yielding S maltophilia from urinary sources during a 15-month period. RESULTS: All urinary tract infections were serious: 13 were complicated and two were acute uncomplicated pyelonephritis. The urinary tracts of 13 other patients were colonized with S maltophilia. Most of the colonized and infected patients were hospitalized with genitourinary malignancy, underwent urinary catheterization, and were receiving antibiotics inactive against S maltophilia. Neutropenia and urinary structural abnormalities were significantly associated with infection. The clinical course of infection was usually severe: fever (100%), sepsis disorder (47%), neutrophilia (70% of patients without neutropenia), bacteremia (13%) and death (7%). Still, response to treatment was prompt. CONCLUSIONS: Stenotrophomonas maltophilia urinary tract infection is usually associated with a severe clinical course. Risk factors for urinary colonization by this organism include hospitalization, urinary catheterization, and administration of inactive antibiotics. Risk factors for urinary tract infection include neutropenia and urinary structural abnormalities. In the presence of these risk factors, treatment of S maltophilia should be considered in patients with urinary colonization by the organism or in those with nosocomial urinary tract infection caused by an unknown pathogen and that is unresponsive to therapy with the antibiotics that are used to treat the common uropathogens.

A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients.

BACKGROUND: Neutropenic patients with cancer are traditionally treated with empiric antibiotic combinations when they become febrile. The availability of broad-spectrum antibiotics such as ceftazidime and imipenem has made it possible to initiate therapy with a single agent (monotherapy). The objectives of this trial were to compare ceftazidime and imipenem as single agents for the therapy of febrile episodes in neutropenic patients and to ascertain whether the addition of an aminoglycoside (amikacin) to either of these agents would provide an advantage. METHODS: A prospective clinical trial was conducted in which eligible neutropenic patients with cancer were randomized to one of four treatment arms: ceftazidime alone; imipenem alone; ceftazidime plus amikacin; and imipenem plus amikacin. Efficacy analysis was done for 750 assessable episodes. A multivariate logistic-regression analysis was also performed to examine the unique contribution of various prognostic factors. RESULTS: The overall response rates were 76% with imipenem plus amikacin, 72% with imipenem, 71% with ceftazidime plus amikacin, and 59% with ceftazidime alone. Single-organism gram-positive infections occurred in 101 of 750 episodes. Without a change in antibiotics, the response rates were 50% with imipenem, 40% with imipenem plus amikacin, 39% with ceftazidime plus amikacin, and 38% with ceftazidime. Most responded to vancomycin or other antibiotics, and the mortality associated with gram-positive infections was only 5%. Regardless of the antibiotic regimen, the majority of uncomplicated gram-negative infections responded to therapy and the majority of complicated gram-negative infections failed to respond. Multivariate logistic-regression analysis showed that recovery of the neutrophil count was the most favorable prognostic factor in a patient's response to infection, whereas the presence of gram-positive infection, acute leukemia, pulmonary or enteric infection, and therapy with ceftazidime were unfavorable factors. CONCLUSIONS: Single-agent therapy with imipenem is as effective as more conventional combination antibiotic therapy for the empirical treatment of febrile episodes in neutropenic patients with cancer.

Revisiting the source of candidemia: skin or gut?

The source of candidemia has been the subject of considerable debate, with some suggesting a origin in the gastrointestinal tract and others suggesting a skin origin. To evaluate the potential sources of candidemia, we performed a computerized search of the MEDLINE database for studies published from January 1966 through September 2000 and we identified relevant abstracts presented at national meetings. We reviewed the literature with special emphasis on studies that used appropriate definitions, evaluated both gut and skin as sources, and conducted molecular-relatedness studies. Among 203 candidemia studies published, we identified 21 that evaluated a specific source for candidemia and only 5 that performed molecular typing. Those studies and additional experimental, epidemiologic, and molecular-relatedness studies strongly suggested that the gut is an important source of candidemia, and studies that supported the skin as a source for this infection were surprisingly incomplete.

Fusariosis associated with pathogenic fusarium species colonization of a hospital water system: a new paradigm for the epidemiology of opportunistic mold infections.

We sought the reservoir of Fusarium species in a hospital with cases of known fusarial infections. Cultures of samples from patients and the environment were performed and evaluated for relatedness by use of molecular methods. Fusarium species was recovered from 162 (57%) of 283 water system samples. Of 92 sink drains tested, 72 (88%) yielded Fusarium solani; 12 (16%) of 71 sink faucet aerators and 2 (8%) of 26 shower heads yielded Fusarium oxysporum. Fusarium solani was isolated from the hospital water tank. Aerosolization of Fusarium species was documented after running the showers. Molecular biotyping revealed multiple distinct genotypes among the isolates from the environment and patients. Eight of 20 patients with F. solani infections had isolates with a molecular match with either an environmental isolate (n=2) or another patient isolate (n=6). The time interval between the 2 matched patient-environment isolates pairs was 5 and 11 months, and 2, 4, and 5.5 years for the 3 patient-patient isolate pairs. The water distribution system of a hospital was identified as a reservoir of Fusarium species.

Thalidomide in the management of multiple myeloma.

Thalidomide has recently been shown to have significant activity in refractory multiple myeloma (MM). A follow-up of the original phase II trial, expanded to 169 patients, shows 2-year survival of 60%; patients receiving > or =42 g over 3 months had a higher response rate and superior survival than those receiving lower doses. The addition of thalidomide to dexamethasone and chemotherapy for the management of post-transplant relapses results in higher response rates. The early results of the Total Therapy II trial for newly diagnosed MM patients show an unprecedented complete remission (CR) and near-CR rate of 69% after two melphalan-based transplants (whether or not receiving thalidomide). In addition, available clinical trial information involving at least 20 patients confirms that thalidomide is active in one third of patients in single-agent trials for refractory disease, with response rates increasing to 50% to 60% in combination with dexamethasone and to as high as 80% in combination with dexamethasone and chemotherapy. When applied as primary therapy in smoldering myeloma, one third of patients experienced 50% paraprotein reduction (PPR); in combination with dexamethasone pulsing, 70% to 80% of symptomatic patients responded. Thus, thalidomide is a major new tool in the treatment armamentarium of MM. The virtual lack of myelosuppression makes it an ideal agent for combination with cytotoxic chemotherapy. Newer, more potent, and less toxic derivatives of thalidomide are being evaluated.

Primary Candida pneumonia. Experience at a large cancer center and review of the literature.

We reviewed the experience over 20 years with primary Candida pneumonia among fatal cancer cases at our hospital. Unequivocal evidence of primary Candida pneumonia has been reported in only 55 cases. We report here 31 such cases. Unlike patients with disseminated candidiasis, and contrary to previous studies concentrating on cancer patients, only 9 of our 31 patients had severe neutropenia. In this report, the lack of organ involvement other than the lungs at complete autopsy examination, the exclusion of patients with candidemia, the very high percentage of intrabronchial and intra-alveolar fungal involvement without vascular invasion, and the concomitant presence of candidal esophagitis in some patients suggest that the mechanism of entry of the infectious particles may have been aspiration of oropharyngeal contents. The major clinical manifestations of primary Candida pneumonia are fever and tachypnea. Radiologically, nonspecific patchy infiltrates can be seen. Histopathologically, there is prevalence of bronchopneumonia, hemorrhage, and necrosis. The only accepted criterion for the definitive diagnosis of Candida pneumonia is histologic demonstration of the fungus in lung tissue. In contrast to previous reports, we demonstrated that primary Candida pneumonia can be life-threatening in patients with cancer since it directly contributed to the death of 84% of the patients in the present series. Very little data are available on the therapy and outcome of patients with Candida pneumonia. However, primary Candida pneumonia in the compromised host should be treated as a life-threatening infection with systemic antifungal therapy.