The Impact of Share 35 Policy on Patient Survival in Patients Undergoing Liver Transplantation With Gender- and Race-Mismatched Donors: An Analysis of the United Network for Organ Sharing Registry.

INTRODUCTION: The United Network for Organ Sharing (UNOS) instituted the Share 35 policy in June 2013 in order to reduce death on liver transplant waitlist. The effect of this policy on patient survival among patients with gender- and race-mismatched donors has not been examined. RESEARCH QUESTION: To assess the impact of Share 35 policy on posttransplantation patient survival among patients with end-stage liver disease (ESLD) transplanted with gender- and race-mismatched donors. DESIGN: A total of 16 467 adult patients with ESLD who underwent liver transplantation between 2012 and 2015 were identified from UNOS. An overall Cox proportional hazards model adjusting for demographic, clinical, and geographic factors and separate models with a dummy variable of pre- and post-Share 35 periods as well as its interaction with other factors were performed to model the effect of gender and race mismatch on posttransplantation patient survival and to compare the patient survival differences between the first 18 months of Share 35 policy to an equivalent time period before. RESULTS: Comparison of the pre- and post-Share 35 periods did not show significant changes in the numbers of gender- and race-mismatched transplants, or the risk of death for gender-mismatched recipients. However, black recipients with Hispanic donors (hazard ratio: 0.51, 95% confidence interval, 0.29-0.90) had significantly increased patient survival after Share 35 policy took effect. CONCLUSION: The Share 35 policy had a moderate impact on posttransplantation patient survival among recipients with racially mismatched donors according to the first 18-month experience. Future research is recommended to explore long-term transplantation.

Efficacy and cost-effectiveness of voriconazole prophylaxis for prevention of invasive aspergillosis in high-risk liver transplant recipients.

Aspergillus infection remains a significant and deadly complication after liver transplantation (LT). We sought to determine whether the antifungal prophylactic use of voriconazole reduces the incidence of invasive aspergillosis (IA) in high-risk LT recipients without prohibitively increasing cost. During the study era (April 2008 to April 2014), 339 deceased donor LTs were performed. Of those patients, 174 high-risk recipients were administered antifungal prophylaxis with voriconazole. The median biological Model for End-Stage Liver Disease score at the time of LT was 33 (range, 18-49) with 56% requiring continuous renal replacement therapy and 50% requiring ventilatory support immediately before transplantation. Diagnosis of IA was stratified as proven, probable, or possible according to previously published definitions. No IA was documented in patients receiving voriconazole prophylaxis. At 90 days after LT, the institutional cost of prophylaxis was $5324 or 5.6% of the predicted cost associated with post-LT aspergillosis. There was no documentation of resistant strains isolated from any recipient who received voriconazole. In conclusion, these data suggest that voriconazole prophylaxis is safe, clinically effective, and cost-effective in high-risk LT recipients.

Combined lung and liver transplantation: analysis of a single-center experience.

Patients with end-stage lung disease complicated by cirrhosis are not expected to survive lung transplantation alone. Such patients are potential candidates for combined lung-liver transplantation (CLLT), however few reports document the indications and outcomes after CLLT. This is a review of a large single-center CLLT series. Eight consecutive CLLT performed during 2009-2012 were retrospectively reviewed. One patient received a third simultaneous heart transplant. Mean age was 42.5 ± 11.5 years. Pulmonary indications included cystic fibrosis (CF) (n = 3), idiopathic pulmonary fibrosis (n = 2), α1-antitrypsin deficiency (AATD) (n = 1) and pulmonary hypertension (n = 2). Liver indications were CF (n = 3), hepatitis C (n = 2), AATD (n = 1), cryptogenic (n = 1), and cardiac/congestive (n = 1). Urgency was reflected by median lung allocation score (LAS) of 41 (36.0-89.0) and median predicted FEV1 of 25.7%. Median donor age was 25 (20-58) years with median cold ischemia times of 147 minutes and 6.1 hours for lung and liver, respectively. Overall patient survival at 30 days, 90 days and 1 year was 87.5%, 75.0% and 71.4% respectively. One patient had evidence of acute lung rejection, and no patients had liver allograft rejection. Early postoperative mortalities (90 days) were caused by sepsis in 2 recipients who exhibited the highest LAS of 69.9 and 89.0. The remaining recipients had a median LAS of 39.5 and 100% survival at 1-year. Median length of stay was 25 days (7-181). Complications requiring operative intervention included bile duct ischemia (n = 1) and bile leak (n = 1), ischemia of the bronchial anastomosis (n = 1), and necrotizing pancreatitis with duodenal perforation (n = 1). This series reflects a large single-center CLLT experience. Sepsis is the most common cause of death. The procedure should be considered for candidates with LAS < 50.

Pre-transplant utilization of sorafenib is not associated with increased complications after liver transplantation.

Hepatocellular carcinoma (HCC) is increasing in incidence, resulting in approximately 35% of orthotopic liver transplantation (OLT) performed each year. Sorafenib (SOR) is a multi-kinase inhibitor that is approved for the treatment of unresectable HCC. Concerns have been raised regarding the safety of SOR in patients undergoing major surgery. We retrospectively reviewed 79 consecutive patients with HCC receiving OLT. Patient data were compared for those who received SOR pre-OLT with those who did not. SOR was continued until time of transplant. During this time period, 15 patients received SOR pre-OLT and 64 did not. The two groups were similar with regards to demographic and clinical data. SOR patients were more likely to have larger tumors, more tumor nodules, and be outside of Milan criteria. The rate of recurrence of HCC was not different between the groups (13% in SOR group, 11% in no-SOR group). Surgical complications were not increased in patients receiving SOR prior to OLT. Survival rate was also similar between the two groups (median follow-up 19.7 months). In this small cohort of patients, use of SOR prior to liver transplantation does not confer an increased risk of surgical complications, even when continued until the day of surgery.

Outcomes of Liver Transplantation for Hepatocellular Carcinoma Beyond the University of California San Francisco Criteria: A Single-center Experience.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor. Currently, liver transplantation may be the optimal treatment for HCC in cirrhotic patients. Patient selection is currently based on tumor size. We developed a program to offer liver transplantation to selected patients with HCC outside of traditional criteria. METHODS: Retrospective review for patients transplanted with HCC between April 2008 and June 2017. Patients were grouped by tumor size according to Milan, University of California San Francisco (UCSF), and outside UCSF criteria. Patient demographics, laboratory values, and outcomes were compared. Patients radiographically outside Milan criteria were selected based on tumor control with locoregional therapy (LRT) and 9 months of stability from LRT. α-fetoprotein values were not exclusionary. RESULTS: Two hundred twenty HCC patients were transplanted, 138 inside Milan, 23 inside UCSF, and 59 beyond UCSF criteria. Patient survival was equivalent at 1, 3, or 5 years despite pathologic tumor size. Waiting time to transplantation was not significantly different at an average of 344 days. In patients outside UCSF, tumor recurrence was equivalent to Milan and UCSF criteria recipients who waited >9 months from LRT. Although tumor recurrence was more likely in outside of UCSF patients (3% versus 9% versus 15%; P = 0.02), recurrence-free survival only trended toward significance among the groups (P = 0.053). CONCLUSIONS: Selective patients outside of traditional size criteria can be effectively transplanted with equivalent survival to patients with smaller tumors, even when pathologic tumor burden is considered. Tumor stability over time can be used to help select patients for transplantation.

Effects of Share 35 Policy on Liver Transplantation Outcomes for Patients With Nonalcoholic Steatohepatitis.

BACKGROUND: To examine the temporal variation and outcomes of liver transplantation between pre- and post-Share 35 eras for patients with nonalcoholic steatohepatitis. METHODS: A retrospective analysis was performed among 4380 patients with end-stage liver disease from the United Network for Organ Sharing database from 2009 to 2017 due to primary diagnosis of nonalcoholic steatohepatitis or cryptogenic cirrhosis with body mass index greater than 30. Cox regressions were used to model the effect of Share 35 policy on patient and graft survival comparing the first 3 years of Share 35 policy to an equivalent time period before. RESULTS: The number of nonalcoholic steatohepatitis-related transplants increased from 232 (14.1%) in 2009 to 266 (20.5%) in 2017. In post-Share 35 era, average waitlist time and cold ischemic time decreased, while Model for End-Stage Liver Disease (MELD) scores increased with higher proportion of recipients having MELD ≥35. No significant difference in average length of hospitalization or survival was found after Share 35. CONCLUSIONS: The Share 35 policy benefits patients with nonalcoholic steatohepatitis from reduced liver transplantation waiting time. It is also associated with comparable outcomes in 2 eras without increasing cold ischemic time or posttransplant length of hospitalization.

Catheter-related Staphylococcus aureus bacteremia in cancer patients: high rate of complications with therapeutic implications.

Risk factors for complications of catheter-related Staphylococcus aureus bacteremia (CRSAB) have been studied in the general patient population but have not been well defined in cancer patients. We investigated potential risk factors for intravascular and extravascular complications in these patients. We retrospectively reviewed the records of patients with CRSAB hospitalized at our institution between January 2001 and December 2004. Demographic, clinical, laboratory, and microbiologic characteristics were extracted for the period of hospitalization and up to 3 months thereafter. Intravascular complications were defined as infective endocarditis and/or septic thrombosis. Extravascular complications included septic arthritis, deep tissue abscess, osteomyelitis, septic pulmonary emboli, septic shock, and CRSAB-related death. Ninety-one patients were included in the current study; 63% had solid tumors and the remainder had hematologic malignancies. The incidence of overall complications was 40% (n = 36); 19% (n = 17) were intravascular. On multivariate analysis, renal failure was associated with an increased risk of overall complications (odds ratio [OR], 12.78; 95% confidence interval [CI], 1.43-114.29; p = 0.0226). Patients with solid tumors were more likely to have intravascular complications (OR, 5.47; 95% CI, 1.11-27.01; p = 0.04369). Risk factors for extravascular complications included hematologic malignancy (OR, 9.56; 95% CI, 2.36-38.77; p = 0.0016) and female sex (OR, 5.25; 95% CI, 1.2-22.99; p = 0.0279). Renal failure is a risk factor for CRSAB complications in patients with cancer. Patients with solid tumors and CRSAB tend to develop intravascular complications, while patients with hematologic malignancies are prone to develop extravascular complications. Hence consideration should be given to extending the duration of therapy beyond 2 weeks.

Hepatocellular carcinoma: a review.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. In the United States, HCC is the ninth leading cause of cancer deaths. Despite advances in prevention techniques, screening, and new technologies in both diagnosis and treatment, incidence and mortality continue to rise. Cirrhosis remains the most important risk factor for the development of HCC regardless of etiology. Hepatitis B and C are independent risk factors for the development of cirrhosis. Alcohol consumption remains an important additional risk factor in the United States as alcohol abuse is five times higher than hepatitis C. Diagnosis is confirmed without pathologic confirmation. Screening includes both radiologic tests, such as ultrasound, computerized tomography, and magnetic resonance imaging, and serological markers such as α-fetoprotein at 6-month intervals. Multiple treatment modalities exist; however, only orthotopic liver transplantation (OLT) or surgical resection is curative. OLT is available for patients who meet or are downstaged into the Milan or University of San Francisco criteria. Additional treatment modalities include transarterial chemoembolization, radiofrequency ablation, microwave ablation, percutaneous ethanol injection, cryoablation, radiation therapy, systemic chemotherapy, and molecularly targeted therapies. Selection of a treatment modality is based on tumor size, location, extrahepatic spread, and underlying liver function. HCC is an aggressive cancer that occurs in the setting of cirrhosis and commonly presents in advanced stages. HCC can be prevented if there are appropriate measures taken, including hepatitis B virus vaccination, universal screening of blood products, use of safe injection practices, treatment and education of alcoholics and intravenous drug users, and initiation of antiviral therapy. Continued improvement in both surgical and nonsurgical approaches has demonstrated significant benefits in overall survival. While OLT remains the only curative surgical procedure, the shortage of available organs precludes this therapy for many patients with HCC.

Catheter-related vancomycin-resistant Enterococcus faecium bacteremia: clinical and molecular epidemiology.

OBJECTIVE: To study the clinical and molecular epidemiology of vancomycin-resistant Enterococcus faecium organisms causing catheter-related bacteremia in patients with cancer. DESIGN: Retrospective case-control study. SETTING: University of Texas M. D. Anderson Cancer Center, a tertiary-care hospital in Houston, Texas. PATIENTS: Case-patients were patients with cancer who had catheter-related vancomycin-resistant E. faecium bacteremia and control-patients were patients with cancer and vancomycin-resistant E. faecium gastrointestinal colonization without infection. RESULTS: Ten case-patients with catheter-related vancomycin-resistant E. faecium bacteremia were compared with 30 control-patients with gastrointestinal colonization by vancomycin-resistant E. faecium. Patients with catheter-related vancomycin-resistant E. faecium bacteremia were more likely to have required mechanical ventilation (P < .01), received total parenteral nutrition (P < .01), and had polyurethane catheters (P < .01) inserted in the femoral vein (P = .01). With the use of pulsed-field gel electrophoresis, 4 of the 10 catheter-related vancomycin-resistant E. faecium bacteremia isolates were genetically indistinguishable, whereas only 2 of the 30 control vancomycin-resistant E. faecium isolates displayed this same DNA pattern (P = .03). CONCLUSION: This study suggests that catheter-related vancomycin-resistant E. faecium bacteremia occurs more frequently in patients who receive total parenteral nutrition, mechanical ventilation, and femoral catheters.

Spectrum of bacille Calmette-Guérin (BCG) infection after intravesical BCG immunotherapy.

Intravesical instillation of bacille Calmette-Guérin (BCG) effectively treats transitional cell carcinoma of the bladder. Occasionally, BCG infection complicates such treatment. In some patients, infection appears early (within 3 months after instillation) and is characterized by generalized symptoms, with pneumonitis and hepatitis. Late-presentation disease occurs >1 year after the first BCG treatment and usually involves focal infection of the genitourinary tract (the site at which bacteria were introduced) and/or other sites that are typical for reactivation of mycobacterial disease, such as the vertebral spine or the retroperitoneal tissues. Noncaseating granulomas are found in the majority of cases, whether early or late. Most patients respond to treatment with antituberculous drugs; in early-presentation disease, when features of hypersensitivity predominate, glucocorticosteroids are sometimes added. Late localized infection often requires surgical resection.

Management of central venous catheters in patients with cancer and candidemia.

To determine the need and appropriate timing of catheter removal in patients with candidemia, the records for 404 patients with cancer and central venous catheters (CVCs) who developed candidemia during the period of 1993-1998 were retrospectively reviewed. Of the total 404 cases of candidemia, 241 (60%) were due to a primary source, 111 (27%) were catheter related, and 52 (13%) were secondary cases of candidemia caused by a source other than the catheter. Multivariate analysis showed that catheter removal < or =72 h after onset improved response to antifungal therapy exclusively in patients with catheter-related candidemia (P=.04). Clinical characteristics that suggested a noncatheter source for the candidemia were disseminated infection (P<.01), previous chemotherapy (P<.01), previous corticosteroid therapy (P=.02), and poor response to antifungal therapy (P<.03). CVC removal < or =72 h after onset should be considered in patients with suspected catheter-related candidemia who have no evidence of dissemination, recent corticosteroid therapy, or chemotherapy.

Antibiotic-coated hemodialysis catheters for the prevention of vascular catheter-related infections: a prospective, randomized study.

PURPOSE: To determine the efficacy of minocycline-rifampin-coated hemodialysis catheters in reducing catheter-related infections in patients requiring hemodialysis for acute renal failure. METHODS: Between May 2000 and March 2002, 66 patients were randomly assigned to receive a minocycline-rifampin-impregnated central venous catheter and 64 were randomly assigned to receive an unimpregnated catheter. Patients were followed prospectively until the catheter was removed. Catheter-related infection was determined through quantitative catheter cultures, quantitative blood cultures, or both. RESULTS: Both groups of patients were similar in age, sex, underlying disease, type of dialysis (continuous vs. intermittent), neutropenia during catheterization and its duration, catheter insertion difficulties, and administration of blood products or medication. The mean (+/- SD) catheter dwell time was the same in both groups (8 +/- 6 days, P = 0.7). There were seven catheter-related infections (11%), all associated with the use of unimpregnated catheters. Kaplan-Meier estimates for the risk of catheter-related infection showed that coated catheters were less likely to be associated with infection (P = 0.006). CONCLUSION: The use of polyurethane hemodialysis catheters impregnated with minocycline and rifampin decreases the risk of catheter-related infection in patients with acute renal failure.

The epidemiology of Candida glabrata and Candida albicans fungemia in immunocompromised patients with cancer.

PURPOSE: Candida glabrata is an increasing cause of candidemia, especially at cancer and bone marrow transplant centers where fluconazole is used for antifungal prophylaxis. This yeast is less susceptible to fluconazole in vitro than is Candida albicans. We compared the characteristics of patients who had C. glabrata and C. albicans candidemia at a large cancer center. SUBJECTS AND METHODS: We searched the microbiological laboratory reports and identified 116 cases of C. glabrata candidemia between 1993 and 1999. The 116 cases of C. albicans candidemia that occurred most closely in time (before or after each case of C. glabrata candidemia) served as the control group. Data were collected from patients' medical records. RESULTS: When compared with patients who had C. albicans infection, patients with C. glabrata candidemia more often had an underlying hematologic malignancy (68 [59%] vs. 26 [22%], P = 0.0001), had an Acute Physiology and Chronic Health Evaluation (APACHE) II score > or =16 (55 [48%] vs. 28 [25%], P = 0.0002), and received fluconazole prophylaxis (57 [49%] vs. 8 [7%], P = 0.0001). Patients with C. albicans candidemia more often had concomitant infections (101 [87%] vs. 78 [67%], P = 0.0003) and septic thrombophlebitis (11 [10%] vs. 2 [2%], P = 0.01). Among patients treated with antifungal therapy, those with C. albicans candidemia had a significantly greater overall response to therapy (83/104 [80%] vs. 60/97 [62%], P = 0.005) and to primary therapy (74/104 [71%] vs. 45/97 [46%], P = 0.0003). Amphotericin B preparations were not more effective than fluconazole (19/45 [42%] vs. 20/38 [53%], P = 0.5) in patients with C. glabrata candidemia. Fluconazole was less effective against C. glabrata than against C. albicans (20/38 [53%] vs. 57/74 [77%], P = 0.008). CONCLUSION: C. glabrata has emerged as an important cause of candidemia, especially among neutropenic patients who receive fluconazole prophylaxis.

Central venous catheter-related bacteremia due to gram-negative bacilli: significance of catheter removal in preventing relapse.

OBJECTIVE: To study the characteristics of catheter-related, gram-negative bacteremia (GNB) and the role of central venous catheter (CVC) removal. DESIGN: This retrospective study involved a search of the microbiological department records of CVC and blood cultures and patients' medical records. SETTING: University of Texas M. D. Anderson Cancer Center, a tertiary-care hospital in Houston, Texas. PATIENTS: Patients with cancer who had catheter-related GNB, defined as (1) a positive catheter tip culture with at least 15 colony-forming units semiquantitatively, (2) isolation of the same organism from the tip and peripheral blood cultures, (3) no other source for bacteremia except the CVC, and (4) clinical manifestations of infection (fever or chills). RESULTS: Between January 1990 and December 1996, 72 cases of catheter-related GNB were available for review. Most of the patients (67; 93%) had their CVCs removed in response to the bacteremia. Few patients (5; 7%) retained their CVCs and were treated with appropriate antibiotics. When CVCs were removed, only 1 patient (1%) relapsed with the same organism, whereas all 5 patients with retained CVCs relapsed after having responded (P < .001). The most commonly isolated organisms were Enterobacter, Klebsiella, Stenotrophomonas, Pseudomonas, and Acinetobacter species. Catheter removal within 72 hours of the onset of the catheter-related GNB was the only independent protective factor against relapse of the infection (odds ratio, 0.13; 95% confidence interval, 0.02-0.75; P = .02). CONCLUSION: In patients with documented catheter-related GNB, CVCs should be removed within 48 to 72 hours to prevent relapse.

Epidemiology, molecular mycology, and environmental sources of Fusarium infection in patients with cancer.

OBJECTIVE: To investigate the epidemiology and environmental sources of Fusarium infections in patients with cancer. DESIGN: Retrospective case-control study conducted following surveillance environmental cultures and DNA analysis of isolated organisms. SETTING: A tertiary-care, university cancer center. METHODS: In 1996 and 1997, environmental cultures were performed on air samples and water systems. A retrospective chart review was performed for 70 patients with cancer identified with fusariosis between 1987 and 1997. Patients with fusariosis were compared with 49 uninfected control patients who occupied hospital rooms with positive environmental cultures for Fusarium. With the use of random amplification of polymorphic DNA, organisms isolated from infected patients were compared with environmental organisms. RESULTS: Most of the patients with Fusarium (40, 57%) were infected on or within 3 days of admission, indicating community rather than nosocomial acquisition. Patients were comparable in terms of underlying immunocompromised status to 49 uninfected control patients. However, the duration from admission to infection in the patients with fusariosis tended to be shorter than the duration from admission to discharge in the exposed control patients (P = .06). Water cultured from the hospital tanks and from sinks and water fountains was negative for Fusarium. With the use of polymerase chain reaction, environmental isolates did not match clinical ones. Quantitative air sampling showed that the quantitative outdoor Fusarium levels were eightfold higher than the indoor levels. During the rainy summer season, outdoor air concentrations of Fusarium were at their highest, coinciding with the peak incidence of fusariosis at our center. CONCLUSION: The most likely source of fusariosis was the external environment rather than nosocomial sources, such as water.

Conventional TACE and drug-eluting bead TACE as locoregional therapy before orthotopic liver transplantation: comparison of explant pathologic response.

BACKGROUND: Hepatocellular carcinoma (HCC) is responsible for significant morbidity and mortality worldwide. Despite its increasing incidence, significant progress has been made in the clinical management of HCC. Transarterial chemoembolization (cTACE) has been shown to improve survival in patients with unresectable HCC; it has also been successfully used as bridging therapy before orthotopic liver transplantation (OLT) in efforts to delay tumor growth or to downstage HCC. TACE with drug-eluting beads (DEB-TACE), a novel drug delivery system that produces a slow and sustained release of chemotherapeutic agent, has recently been shown to have similar efficacy to conventional TACE (cTACE); it also exhibits fewer adverse effects resulting from reduced systemic drug concentrations. To date, the pathologic response rate to cTACE compared with DEB-TACE in patients undergoing OLT has not been well described. METHODS: A total of 111 consecutive patients with HCC who underwent cTACE (n=76) or DEB-TACE (n=35) before OLT at a single center between January 2005 and December 2010 were evaluated. RESULTS: Complete necrosis was achieved in 50.9% and 57.1% of cTACE and DEB-TACE patients, respectively; at least 50% necrosis was evident in approximately three fourths of patients in both groups. Rates of necrosis and tumor recurrence did not differ between groups. Dropout from the transplant list was equal in both groups. CONCLUSIONS: Either modality is an acceptable treatment to achieve tumor control for patients awaiting OLT and can be expected to result in excellent necrosis rates in the majority of patients.

Liver transplantation for hepatocellular carcinoma: past, present, and future.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death globally. HCC is an aggressive disease with high fatality as reflected by the close numbers of annual deaths per year from HCC and annual incidence worldwide. In the United States, HCC incidence has increased substantially during the past two decades and is projected to continue to rise. Surgical resection remains the best treatment option for anatomically resectable tumors in patients with well-preserved liver function. For patients who are not resection candidates, liver transplantation offers treatment not only for HCC, but also for the cirrhotic liver. Liver transplantation for HCC is a rapidly evolving field. The results have dramatically improved with implementation of surveillance, careful selection of patients for transplantation, and pre-transplant tumor ablation. New promising tumor biomarkers, therapies for hepatitis C virus, molecular targeted therapies for HCC, and immunosuppression will ensure even better outcomes moving forward. This review discusses how liver transplant for HCC has changed over the many years, is currently improving, and how future research will shape better results.

Amphotericin B lipid complex versus liposomal amphotericin B monotherapy for invasive aspergillosis in patients with hematologic malignancy.

BACKGROUND: Invasive aspergillosis (IA) is a major cause of morbidity and mortality in patients with hematologic malignancy (HM). There are 2 lipid formulations of amphotericin B (AMB) currently in widespread use: AMB lipid complex (ABLC) and liposomal AMB (L-AMB). There are limited data comparing the efficacy and safety of these 2 agents in the treatment of IA in patients with cancer. METHODS: The authors retrospectively studied 381 consecutive patients with HM who had proven or probable IA (according to European Organization for Research and Treatment of Cancer/Mycosis Study Group of the National Institute of Allergy and Infectious Diseases criteria) between June 1993 and December 2005. Of these patients, 158 received primary antifungal therapy with either L-AMB (n=106) or ABLC (n=52). The number of salvage antifungal regimens given were 51 L-AMB regimens and 30 ABLC regimens. It should be noted that the population described in this report was not typical of the hematologic cancer population with IA because of the advanced stage and the severity of the underlying diseases. RESULTS: Risk factors for IA, such as underlying malignancy, neutropenia, steroid use, admission to an intensive care unit, and the presence of graft-versus-host disease, were comparable among the study drug group in the primary or salvage setting. Likewise, comparable distribution of types of Aspergillus species and the presence of disseminated IA were observed. Response to primary or salvage therapy was equally poor in both drug study groups regardless of treatment modality (range, 7.7-15.8% response). In the primary therapy group, ABLC was associated with significantly higher nephrotoxicity than L-AMB (P<.001). CONCLUSIONS: Among patients with HM, primary therapy and salvage therapy for IA with either ABLC or L-AMB as single agent were associated equally with poor outcome. L-AMB appeared to be less nephrotoxic in the primary therapy setting.

Colistin is effective in treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa in cancer patients.

The increasing incidence of infections caused by multidrug-resistant Pseudomonas aeruginosa is a worldwide health problem. Because no new antipseudomonal agents are expected to be available in the near future, we evaluated the safety and efficacy of colistin, an old drug with bactericidal activity against this organism. We collected clinical and demographic data on 95 cancer patients diagnosed with infections caused by multidrug-resistant P. aeruginosa between January 2001 and January 2004 and treated with either colistin (colistin group) or at least one active antipseudomonal agent (a beta-lactam antibiotic or a quinolone) (control group). We compared the results obtained for both groups. Thirty-one patients had been treated with colistin and 64 had been treated with an antipseudomonal non-colistin-containing regimen. Compared with the control group, patients in the colistin group had a lower median age (52 and 62 years, respectively; P = 0.012) but were more likely to have had nosocomial infections (87% and 64%, respectively; P = 0.02). Twenty-five patients (81%) in the colistin group and 40 patients (63%) in the control group had an APACHE II score of >15 (P = 0.074). The overall clinical response rates were 52% in the colistin group and 31% in the control group (P = 0.055). Multiple logistic regression analysis showed that those patients treated with colistin were 2.9 times (95% confidence interval, 1.1 to 7.6 times) more likely than those in the control group to experience a clinical response to therapy (P = 0.026). Colistin therapy was at least as effective and as safe a beta-lactam antibiotic or a quinolone in the treatment of infections caused by multidrug-resistant P. aeruginosa and, hence, may be a useful or preferred alternative therapy for this infection in cancer patients.

Central venous catheter and Stenotrophomonas maltophilia bacteremia in cancer patients.

BACKGROUND: Stenotrophomonas maltophilia bacteremia is frequently found in cancer patients. This study attempted to determine how often the catheters were the source of this infection and the risk factors associated with catheter-related bacteremias. METHODS: The microbiology records were retrospectively reviewed of all cancer patients having S. maltophilia bacteremia and indwelling central venous catheters seen between January 1998 and January 2004. In a multivariate analysis the patients' clinical characteristics, antimicrobial therapy, outcome, and source of bacteremia that were significantly associated with definite catheter-related S. maltophilia bacteremia as opposed to secondary bacteremia were identified. RESULTS: A total of 217 bacteremias were identified in 207 patients: 159 (73%) were primary catheter-related (53 definite, 89 probable, and 17 possible), 11 (5%) were primary noncatheter-related, and 47 (22%) were secondary. Multivariate analysis showed the following factors to be independently associated with definite catheter-related bacteremias: 1) polymicrobial bacteremia (odds ratio [OR], 7.6; 95% confidence interval [95% CI], 1.3-45.5); 2) no prior intensive care unit admission (OR, 0.06; 95% CI, 0.005-0.578); and 3) nonneutropenic status at onset (OR, 0.07; 95% CI, 0.013-0.419). The response rate to appropriate antibiotics and catheter removal was 95% in the patients with definite catheter-related bloodstream infections, compared with only 56% in the patients with secondary bacteremias (P = .001). CONCLUSIONS: The majority of the S. maltophilia bacteremias occurring in cancer patients with indwelling central venous catheters appear to be catheter-related and are often polymicrobial. Catheter-related S. maltophilia bacteremias occurred more frequently in noncritically ill, nonneutropenic patients, and prompt removal of the catheter was found to be associated with a better prognosis.