Infections In Haematological Patients Research Articles

Editorial introductions

Current Opinion in Infectious Diseases was launched in 1988. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of infectious diseases is divided into 11 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Monica A. SlavinMonica A. SlavinMonica A. Slavin MBBS, FRACP, MD, is based in Melbourne, Australia, where she has been Head of the Department of Infectious Diseases at the Peter MacCallum Cancer Centre since 2000 and Head of the Immunocompromised Host Infection Service at Royal Melbourne Hospital, Australia, since 2013. She is a Professor in the Department of Medicine at the University of Melbourne, Australia. Professor Slavin received her medical degree from the University of Melbourne and trained in infectious diseases in Melbourne and in the Program in Infectious Diseases at the Fred Hutchison Cancer Research Center in Seattle, USA. She has been an infectious diseases physician since 1993 with a major interest in infections in immunocompromised patients, especially those with cancer and undergoing stem cell transplantation. Her current research focus is prevention diagnosis and early treatment of invasive fungal infections in hematology patients. She has served on national steering committees for the development of antifungal and fever and neutropenia treatment guidelines and for the conduct of Australia-wide studies of the epidemiology of fungal infection. She is currently chair of the Australian & New Zealand Mycoses Interest Group and leads the writing group for Australasian Society for Infectious Diseases (ASID) guidelines for the use of antifungal agents in the hematology and oncology setting. She is Vice-President of the International Immunocompromised Host Society. William IrvingWilliam IrvingProfessor Irving has been Professor and Honorary Consultant in Virology at the University of Nottingham, UK, and Nottingham University Hospitals NHS Trust, UK, since 2002, having previously been Senior Lecturer (1990–1996) and Reader (1997–2001). His particular interest is in the field of viral hepatitis and he has been a member of the Department of Health Advisory Group on Hepatitis (AGH) since 1998, becoming Chair in 2009. Professor Irving is co-chair for HCV Research UK, a multicenter, multidisciplinary effort to create a national cohort of 10,000 patients with HCV infection, together with a clinical database and biobank, to act as a resource for future research.

Human metapneumovirus pneumonia in patients with hematological malignancies

BackgroundHuman metapneumovirus (HMPV) has recently emerged as a cause of respiratory infections in hematological patients. Clinical data are lacking to guide the management of HMPV pneumonias. ObjectivesTo characterize the clinical and radiographic presentation and outcome of HMPV pneumonias diagnosed in hematological patients. Study designWe screened the patients with a positive HMPV respiratory test in two French teaching hospitals between 2007 and 2011. Among them, the medical charts from the hematological patients who presented with HMPV pneumonia were reviewed. ResultsAmong the 54 patients with several underlying hematological conditions who were positive for HMPV, we found 13 cases of HMPV pneumonias. HMPV could be the cause of pneumonia as a single pathogen without associated upper respiratory infection. Centrilobular nodules were constant on lung computed tomography scans. No patients died despite the absence of administration of antiviral treatments. ConclusionsOur data provide further insights in the diagnosis and management of HMPV pneumonias in this setting.

The risk of infections in hematologic patients treated with rituximab is not influenced by cumulative rituximab dosage - a single center experience.

BackgroundRituximab, a monoclonal antibody directed against CD20, is approved for the treatment of CD20-positive B-cell Non-Hodgkin’s lymphoma and rheumatologic disorders. Due to its potent activity in depleting CD20-positive lymphocytes, the influence on opportunistic infections is still under discussion. Thus, we analyzed the impact of rituximab either as monotherapy or in combination with other chemotherapeutic regimens to elucidate its role in contributing to infectious complications.MethodsThe records of consecutive patients (n = 125, 141 treatment episodes) treated with rituximab alone or in combination with chemotherapy and corticosteroids were analyzed retrospectively for the incidence, spectrum and outcome of infections during treatment and 6 months after the last course of rituximab. Univariate analysis of cofactors such as steroid medication, antiinfective prophylaxis, underlying disease and remission status were performed.ResultsAltogether 80 therapy episodes were associated with infections, the median number of infections per patient being 1 (range 1–7). The number of infectious complications was significantly higher in patients receiving a combination of rituximab and chemotherapy compared to rituximab monotherapy (p < 0.001). There was no statistically significant difference regarding number of rituximab courses or cumulative rituximab dosage between episodes with and without infections, respectively.Mean cumulative prednisone dosage between the cohort with infections and the one without infections showed a trend towards higher dosage of prednisone in the patients with infections (mean difference 441 mg, p > 0.14).ConclusionsRituximab in induction treatment, either as monotherapy or combined with chemotherapy by itself does not increase the incidence or change the spectrum of infections in hematologic patients. However the possible influence of higher dosages of concomitant steroid medication on frequency of infections suggests that a heightened awareness of the potential for infectious complications should be applied to patients receiving higher doses of glucocorticoids in combination with other therapeutic regimens.

Hema e-Chart Registry of invasive fungal infections in haematological patients: improved outcome in recent years in mould infections

The electronic surveillance system Hema e-Chart allowed us to prospectively collect data and to perform an analysis of invasive fungal infections (IFI) diagnosed in febrile patients as well as the procedures allowing their diagnosis and outcome according to the treatment given. Every patient admitted to 26 Italian Haematology Units with a new diagnosis of haematological malignancy and who was a candidate for chemotherapy was consecutively registered between March 2007 and March 2009. In all, 147 haematological patients with mycoses were identified. Yeasts were found in 23 infections; moulds were diagnosed in 17 proven, 35 probable and 72 possible mycoses. Galactomannan (GM) antigen was the most important test to diagnose probable mould infection; it was positive (cut-off >0.5) in 27 (77%) probable and in nine (53%) proven mould infections. Among patients with probable/proven mould infection who received no prophylaxis or non-mould-active prophylaxis with fluconazole, more patients (n = 26, 78.8%) had GM antigen positivity compared with patients (n = 10, 52.6%) given prophylaxis with mould-active drugs (p <0.05). First-line antifungal therapy was effective in 11/23 (48%) yeast infections and in 37/52 (71.2%) proven/probable mould infections. Twenty patients (14%) died within 12 weeks. The fungal attributable mortality was 30.4% and 17.3% in yeast and proven/probable mould infections, respectively. Among risk factors only age was independently associated (p 0.013) with mortality; sex, underlying haematological malignancy, previous prophylaxis and presence of neutropenia at diagnosis were not significant. A diagnosis of mould infection seemed to have a trend for a better outcome than the diagnosis of yeast infection (p 0.064).

Second- versus first-generation azoles for antifungal prophylaxis in hematology patients: a systematic review and meta-analysis

Second-generation azoles may be more effective than first-generation azoles in the prevention of fungal infections in hematology patients. We performed a systematic review with meta-analysis of randomized controlled trials comparing second- with first-generation azoles in hematology patients with respect to proven or probable invasive fungal infections, invasive aspergillosis, receipt of empirical antifungal therapy, overall mortality, and withdrawal from the studies due to the development of adverse effects. We searched the Medline, Embase, and Cochrane Registry of Controlled Trials electronic databases as well as conference proceedings from 2002 to 2012 for randomized controlled trials comparing second-generation azoles (voriconazole, posaconazole) versus first-generation azoles (fluconazole, itraconazole). Treatment effect measures for all outcomes were expressed as odds ratio with 95 % confidence interval. Meta-analysis was performed using Review Manager, version 5.1. Data from four randomized clinical trials representing a large population of patients demonstrated that antifungal prophylaxis with second-generation azoles reduces proven or probable invasive fungal infections, invasive aspergillosis, and receipt of empirical antifungal therapy in high-risk hematology patients, while there were no differences between second- and first-generation azoles with regard to overall mortality and patients or withdrawal from the studies due to the development of adverse effects. In conclusion, antifungal prophylaxis with second-generation azoles can significantly reduce the incidence of invasive fungal infections and invasive aspergillosis but with no risk of an increase in adverse events.

Longitudinal surveillance of bacteraemia in haematology and oncology patients at a UK cancer centre and the impact of ciprofloxacin use on antimicrobial resistance

To assess and compare the current trends in bacteraemia and antimicrobial resistance and analyse the impact of ciprofloxacin prescribing on Gram-negative bacterial resistance in haematology and oncology patients. Information on bacteraemia episodes, causative pathogens, antimicrobial resistance and consumption was compared between haematology and oncology patients at a UK cancer centre in a 14 year longitudinal surveillance study. Haematology patients had a 3-fold higher incidence of bacteraemia compared with oncology patients (10.9/1000 versus 3.6/1000 admissions, respectively). Coagulase-negative staphylococci were the most common Gram-positive cause of bacteraemia for both cancer groups, whereas the overall rate of methicillin-resistant Staphylococcus aureus bacteraemia was low (0.16/1000 admissions). Escherichia coli was the most common Gram-negative cause of bacteraemia for both groups, but with a higher incidence in haematology patients (0.92/1000 admissions) compared with oncology patients (0.5/1000 admissions). Pseudomonas spp. formed the second most common Gram-negative infection in haematology patients, with a 4-fold higher bacteraemia incidence compared with oncology patients (0.76 versus 0.16/1000 admissions). Ciprofloxacin resistance of Gram-negative isolates was 22% in haematology and 5% in oncology patients. The rate of ciprofloxacin use measured showed high ciprofloxacin consumption in haematology patients compared with oncology patients (3.6 versus 1.5 defined daily doses/10 admissions, respectively), suggesting that ciprofloxacin may drive resistance. Our longitudinal surveillance highlights the continued importance of Gram-negative bacteraemia, in particular that due to Pseudomonas, in the cancer population and raises concerns regarding increasing ciprofloxacin use and resistance.

Prophylaxis and treatment of invasive fungal infections in hematological patients

The evidence from the literature strongly support antifungal prophylaxis in high risk haematological patients, such as patients with AML during remission induction chemotherapy and alloHSCT patients. Current antifungal prophylaxis guidelines for high risk patients recommend azoles (fluconazole, posaconazole, voriconazole) and echinocandins (micafungin) with the strongest level of evidence. In terms of treatment, the choice between empiric therapy (or fever driven) and pre-emptive therapy (or diagnostic driven) is still debated. Not a single therapeutic strategy is appropriate in every patients, in particular empirical antifungal therapy may be recommended in patients at very high risk, while a pre-emptive approach may be advised for those at standard risk. In order to exploit the synergistic and/or additive effect of two antifungal drugs it’s possible to combine two agents that work with different mechanisms of action (e.g. echinocandins + azoles or polyenes). Once the treatment has been initiated we should consider the therapeutic drug monitoring (TDM) of the drugs, especially when the pharmacokinetic variability is high and the dose-concentration effect relationships is not predictable (e.g. for itraconazole, voriconazole and posaconazole).

Prophylaxis and treatment of invasive fungal infections in hematological patients

The evidence from the literature strongly support antifungal prophylaxis in high risk haematological patients, such as patients with AML during remission induction chemotherapy and alloHSCT patients. Current antifungal prophylaxis guidelines for high risk patients recommend azoles (fluconazole, posaconazole, voriconazole) and echinocandins (micafungin) with the strongest level of evidence. In terms of treatment, the choice between empiric therapy (or fever driven) and pre-emptive therapy (or diagnostic driven) is still debated. Not a single therapeutic strategy is appropriate in every patients, in particular empirical antifungal therapy may be recommended in patients at very high risk, while a pre-emptive approach may be advised for those at standard risk. In order to exploit the synergistic and/or additive effect of two antifungal drugs it’s possible to combine two agents that work with different mechanisms of action (e.g. echinocandins + azoles or polyenes). Once the treatment has been initiated we should consider the therapeutic drug monitoring (TDM) of the drugs, especially when the pharmacokinetic variability is high and the dose-concentration effect relationships is not predictable (e.g. for itraconazole, voriconazole and posaconazole).

Pulmonary Mucormycosis

Mucormycosis (formerly zygomycosis) is a life-threatening opportunistic mycosis that infects a broad range of hosts with qualitative or quantitative defects in innate immunity, including patients with severe neutropenia, recipients of corticosteroids or other immunosuppressive medications, poorly controlled diabetes mellitus, and those with iron overload states. Mucormycosis has recently emerged as breakthrough sinopulmonary infection in hematologic patients and recipients of transplantation being on antifungal prophylaxis with Aspergillus-active antifungals that lack activity against Mucorales. Unlike pulmonary aspergillosis, the prognosis and outcome of pulmonary mucormycosis have not improved significantly over the last decade, mainly because of difficulties in early diagnosis and the limited activity of current antifungal agents against Mucorales. Recent evidence suggests a critical role for iron metabolism and fungal-endothelial cell interactions in pathogenesis of mucormycosis, and holds promise for development of novel therapeutic strategies. Currently, prompt initiation of antifungal therapy with a lipid amphotericin B-based regimen, reversal of underlying host factors, and aggressive surgical approach offers the best chances for survival of patients infected with this devastating mycosis.

Uncommon yeast infections in hematological patients: from diagnosis to treatment

Invasive fungal diseases have been recognized with increasing frequency as major pathogens in patients with cancer over the past few decades, as a result of new and more aggressive anticancer treatments and supportive care, and this has been especially reported for patients suffering from hematological malignancies. In these settings, typically uncommon yeasts and filamentous fungi have recently emerged as significant human pathogens, frequently as breakthrough infections in patients receiving empirical antifungal therapy or antifungal prophylaxis and with reported high crude mortality rates. The aim of this article is to discuss certain aspects of the approach to invasive fungal diseases due to uncommon yeasts (e.g., Trichosporon spp., Blastomyces spp. and Cryptococcus spp.) in patients with hematological malignancies, focusing on epidemiology, diagnosis, treatment outcomes and the role of novel antifungal drugs (i.e., new triazoles and echinocandins).

A cluster of mucormycosis infections in hematology patients: challenges in investigation and control of invasive mold infections in high-risk patient populations

Mucormycosis has been reported to be occurring more frequently in hematopoietic stem cell transplant (HSCT) recipients in recent years. We investigated a hospital cluster of mucormycosis cases among patients with hematologic disorders. Case-patients were identified through hospital microbiology and pathology database searches and compared to randomly selected controls matched on underlying disease and hospital discharge date using conditional logistic regression. Environmental assessments, including collection of samples for fungal cultures, were performed. Of 11 case-patients, 6 (55%) had acute myelogenous leukemia and 3 (27%) were allogeneic HSCT recipients. Five case-patients (45%) died. In univariate analysis, case-patients were more likely than controls to have refractory hematologic disease (odds ratio [OR], 13.75; 95% confidence interval [CI], 1.31–689); neutropenia >14 days (OR, 11.50; 95% CI, 1.27–558) or to have received voriconazole prophylaxis (OR, 11.26; 95% CI, 1.11–infinity). A point source was not identified. Factors such as underlying disease state and antifungal prophylaxis type may identify hematology patients at highest risk for mucormycosis. Our investigation highlighted critical knowledge gaps, including strain typing methods, the role of the hospital environment in mucormycosis outbreaks, and hospital environmental infection control measures most likely to reduce exposure of immunosuppressed persons to mucormycetes.

Uncommon mold infections in hematological patients: epidemiology, diagnosis and treatment

Invasive fungal diseases continue to be an important cause of morbidity and mortality in immunosuppressed patients. This is of particular interest, since the progress we made in the treatment of underlying malignancies has led to an increase of the number of persons ‘at high risk’. During the last few years, several changes in clinical practice in hematology (new immunosuppressants, hematopoietic stem cell transplants) have influenced the epidemiology of invasive fungal diseases; in particular, cases due to some uncommon etiologic agents are being increasingly reported, making it even more urgent to reconsider differential diagnoses in high-risk patients. A better understanding of epidemiology, risk factors and prognosis appears to be crucial to analyze prevention and diagnostic strategies, as well as to guarantee an early and adequate treatment.

Incidence of cytomegalovirus infection and disease in patients with lymphoproliferative disorders treated with alemtuzumab

The aim of this study was to assess the incidence of cytomegalovirus (CMV) infection and disease in patients with hematologic malignancies treated with alemtuzumab. The outcome of CMV infection in hematologic patients treated with alemtuzumab in 19 hospitals throughout Spain was assessed retrospectively. Data were collected from the medical records of patients over a period of 6 months following initiation of alemtuzumab therapy. We studied 102 patients (89 with B-cell chronic lymphocytic leukemia and 13 with other lymphoproliferative diseases, with a median age of 63 years [range 29–81 years]). Alemtuzumab was administered for a mean of 11.2 (standard deviation: 13.8) weeks, with a median total dose of 423 mg (range: 59–1440 mg). Alemtuzumab as a single agent was administered in 92.2% of patients and was associated with chemotherapy in 7.8% of cases. Prophylactic antivirals included famcyclovir (47%), acyclovir (34%), valacyclovir (14%) and valgancyclovir (5%). CMV viremia testing was performed a mean of 6.3 times (range: 1–19). The incidence of CMV infection was 38.9% (46% in patients treated with steroids and 75% in patients receiving ≥1000 mg of alemtuzumab). Treatment of CMV infection included gancyclovir or valgancyclovir in 94% of cases. Viremia became negative after a median of 20 days (95% CI: 13.4–26.6). CMV disease occurred in five patients. The incidence of CMV infection in alemtuzumab-treated patients was 38.9%. The incidence increased in patients treated concomitantly with steroids and in those treated with high doses of alemtuzumab, although only eight patients received 1000 mg or more, systematic monitoring of CMV viremia and early treatment of infection resulted in a favorable outcome of CMV reactivation.

Influenza A (H1N1) Virus Infection in Hematologic patients In The South And West Of Spain

AbstractAbstract 1740 Background:Patients with hematologic malignancies are likely to be at an increased risk for influenza infection. A few small series have documented seasonal influenza outbreaks among such patients, demonstrating the susceptibility of immunocompromised populations. These limited reports suggest that cancer patients are at a high risk for acquisition of influenza in both the community and health care settings. In April 2009, Mexico reported Influenza A virus outbreak. The virus was recognized as a novel known as Influenza A/pandemic 2009/H1N1 or 2009 H1N1 Influenza A. At present, there is scarce information on the clinical course of influenza A virus infection in hematologic patients. Objectives:To analyze the clinical course and laboratory characteristics of a cohort of hematologic patients diagnosed with influenza virus H1N1. Patients and Methods:Prospective study in five centers in Andalucia and Extremadura (Spain), in hematologic patients who developed an influenza H1N1 virus infection in the winter of 2009. Clinical characteristics, laboratory, radiological findings and clinical course were collected and analyzed. Diagnosis of the infection was made by viral isolation determined by PCR in pharyngal or nasal samples or both. Patients were followed during at least one month after diagnosis of infection. Non-normal distribution data were expressed as median values (range). Chi-square test or Fisher exact test were used to compare differences between groups of categorical data. Differences were considered statistically significant for p-values <0.05. All statistical analyses were performed using SPSS 17.0 software (Chicago, IL). Results:A total of twenty-nine patients entered the study between September and December 2009. One patient had been vaccinated against influenza H1N1 virus. Fifty per cent were female, with a median age of 40 years (3-78). Hematolgic diseases were: acute leukemia (24.1%), multiple myeloma 13.8%, non-hodgkin lymphomas 17.2%, Hodgkin lymphoma 20.7%, chronic lymphocytic leukemia 10.3%, myelodysplastic syndrome 3.4%, hemoglobinopathies 6.9% and other hematologic diseases 3.4%. Twelve (41.4%) patients were hematopoietic stem cell recipients: allogeneic (58.3%), most of them from identical sibling (85.7%) and peripheral blood source (91.7%) and autologous (41.7%). Lymphopenia was observed in 72.4% cases and neutropenia in 27.6% cases. The median days between the initial symptoms and diagnosis was 2 days (0-7). Most patients were in an outpatient basis (82.2%) and only 8 patients (27.6%) were hospitalized for these reason. Thirteen patients (44.8%) presented radiologic findings: interstitial changes (54.5%) and alveolar condensation (45.5%). 28 patients received treatment with oseltamivir, most of them at 75 mg/12 h, during a median of 5 days (1-21) and 21 patients received simultaneously another antimicrobial therapy. Six patients (20.7%) needed mechanical ventilation. At the end of the follow up the global mortality was 20.7% (6 cases) being three death (10.3) caused by influenza A H1N1 virus infection. There was an increase risk of mortality in patients who had pneumonia at the beginning of the infection (9.5% vs 50%, p=0.033), suffered a respiratory co-infection (8% vs 60%, p=0.008), developed respiratory complications (0 vs 46.1%, p=0.005), progressed to pneumonia during the infection (4.7% vs 71.4%, p=0.001) or required mechanical ventilation (8% vs 66.7%, p=0.008). There were no differences in the evolution of HSCT recipients. Conclusions:Respiratory co-infection, pneumonia at the beginning or during the infection and mechanical ventilation showed a relationship with fatal clinical course of influenza A/H1N1 virus infection in haematologic patients. Disclosures:No relevant conflicts of interest to declare.

Invasive aspergillosis: epidemiology and environmental study in haematology patients (Sfax, Tunisia)

Invasive aspergillosis (IA) is a major opportunistic infection in haematology patients. Preventive measures are important to control IA because diagnosis is difficult and the outcome of treatment is poor. We prospectively examined the environmental contamination by Aspergillus and other fungal species and evaluated the prevalence of invasive aspergillosis in the protect unit of haematology. A three-year prospective study (December 2004-September 2007) was carried out in the department of haematology of Hedi Chaker Hospital. Suspected invasive aspergillosis cases were reviewed and classified as proven, probable and possible invasive aspergillosis using the EORTC criteria. During the study period, we collected weekly environmental samples (patient's rooms, tables and acclimatisers) and clinical samples from each patient (nasal, expectoration and auricular). Among 105 neutropenic patients, 16 had probable and 13 had possible IA. A total of 1680 clinical samples were collected and A. flavus was most frequently isolated (79.2%). Analysis of 690 environmental samples revealed that Penicillium (44%) was the most frequent followed by Cladosporium (20%), Aspergillus spp. (18%) and Alternaria (13%). The PCR-sequencing of 30 A. flavus isolates detected from clinical and environmental samples confirmed the mycological identification. Our findings underline the importance of environmental surveillance and strict application of preventive measures.

Epidemiology and outcome of Rhodotorula infection in haematological patients

Rhodotorula spp. are emergent opportunistic pathogens, particularly in haematological patients. However, no systematic review of this infection has been undertaken in this high-risk patient group. The aim of this study was to review all reported cases of Rhodotorula infection to determine the epidemiology and outcome of this infection in this high-risk population. The 29 reported cases were fungaemias. The most common underlying haematological disorder was the presence of acute leukaemia (65.5%). Rhodotorula mucilaginosa was the species found more frequently (79.3%). Most cases (58.6%) had several risk factors (≥ 3) simultaneously. The most common predisposing factors were the presence of central venous catheter (CVC, 100%) and neutropenia (62.1%). A substantial number of patients (81.5%) received antifungal treatment with amphotericin B. The overall mortality was higher (13.8%) than that described in non-haematological patients (5.8% in solid-organ neoplasms and 9% in AIDS or other chronic diseases). Patients with acute leukaemia had a higher mortality rate (15.7%) than patients with non-Hodgkin's lymphoma (0%). Our data suggest that patients with acute leukaemia might be managed as high-risk patients and intensive measures might be taken. In addition, it appears that the subgroup of patients without acute leukaemia have a good outcome and might be managed as low-risk patients with a less intensive approach.

Current therapeutic approaches to fungal infections in immunocompromised hematological patients

Invasive fungal infections are significant causes of morbidity and mortality in patients with hematological malignancies. Patients with acute myeloid leukemia and those who have undergone allogeneic hematopoietic stem cell transplantation are at especially high risk. Various fungal agents are responsible for this complication, but Aspergillus spp. and Candida spp. are the most frequently isolated micro-organisms; less commonly, infections could be caused by Zygomycetes or other rare molds or yeasts. Several new systemically-administered antifungal agents have been approved for clinical use since 2001; these agents include liposomal amphotericin B, voriconazole, caspofungin, and posaconazole, and they represent a major advance in antifungal therapy and have improved the prognosis of patients with hematological malignancies. This review focuses on therapeutic aspects of the management of fungal infections in hematological patients.

Rhodotorula mucilaginosa catheter-related fungaemia in a patient with multiple myeloma

To date, there have been several case reports of Rhodotorula infection in haematological patients, but none affecting patients with multiple myeloma (MM). We describe a 54-year-old man with MM receiving prophylaxis with fluconazole who was using a subclavian Port-A-Cath and presented two episodes of fungaemia caused by Rhodotorula mucilaginosa. The first episode was resolved with oral itraconazole and neutropenia recovery. During the second episode, caspofungin was administered without success; however, liposomal amphotericin B and catheter withdrawal resolved the fungaemia. As far as we know, this is the first case reported of R.mucilaginosa fungaemia in a patient with MM.

Risk factors for infection in haematology patients treated with rituximab

Although rituximab therapy is not considered to be closely associated with infection, there have been reports of serious infections in patients treated with rituximab. We performed a statistical retrospective analysis to clarify the risk factors for infection in patients receiving rituximab therapy. A retrospective study of data from clinical records was performed that targeted haematology patients treated at our university hospital between April 2003 and October 2006. We selected 63 patients with CD20-positive lymphoma whose peripheral blood immunoglobulin levels had been measured within 6 months before and after rituximab therapy. Logistic regression analysis was used to investigate the risk factors for serious infection in these patients. The three risk factors identified were: 1) reduction in IgM after administration of rituximab [odds ratio (OR) = 1.032, confidence interval (CI) = 1.007-1.057; P = 0.009], 2) duration of rituximab therapy [OR = 0.962, CI = 0.932-0.994; P = 0.021] and 3) G-CSF administration [OR = 4.825, CI = 1.411-16.495; P = 0.012]. Rituximab therapy may be associated with infection, indicating the need for sequential monitoring of IgM levels and identification of the optimal interval between rituximab cycles.

Catheter Related Bloodstream Infection in Haematological Patients: A Prospective, Randomized Study Comparing Heparin-Coated with Chlorhexidine and Silver Sulfadiazine Impregnated Central Venous Catheters

Central venous catheters (CVCs) are widely used in patients with hemato-oncological disease for indications such as administration of chemotherapy, parenteral nutrition, blood products and monitoring of hemodynamics. CVCs are a major source of hospital-acquired infection. The National Nosocomial Infections Surveillance System reported a rate of catheter-related bloodstream infection (CRBI) of five per 1000 central catheter-days. This study was a randomized trial in which patients with nontunneled catheters were randomly assigned to heparin-coated (7 French, polyurethane, double lumen; Arrow®, USA) or chlorhexidine and silver sulfadiazine impregnated CVCs (7 French, polyurethane, double lumen; Arrow®, USA). All CVCs were placed in the subclavian vein in the operating room. CRBI was defined according to Infectious Disease Society of America guidelines. The principal investigator determined whether infections were catheter related and had no knowledge of “the assigned arm” at the time of adjudication of the reference standard definition. Before catheter insertion, laboratory prothrombotic markers included factor V Leiden, the prothrombin gene Gly20210A mutation, plasma antithrombin levels, and protein C and S activity. In our study, all patients were systematically examined by ultrasonography just before, or less than 24 hours after, catheter removal and in case of clinical signs of thrombosis. Two radiologists performed the ultrasonography and were unaware of the allocation of the patients. Two hundred and twenty patients were randomly assigned. Eight patients were excluded after assignment. Ultimately, 212 patients were analyzed [median age: 28 years (7–60); 97 female and 115 male]. CRBI occurred in 6.7% (7/104) of those in the heparin-coated group (2.7 events per 1000 days) and in 4.6% (5/108) in the chlorhexidine and silver sulfadiazine group (2 events per 1000 days) (P=0.5). The microorganisms involved in CRBIs were coagulase-negative Staphylococcus (five cases in the heparin group and 3 cases in the antiseptic group), Staphylococcus aureus (one case in the heparin group), Candida parapsilosis (one case in the antiseptic group), Pseudomonas aeruginosa (one case in the heparin group and one case in the antiseptic group). We observed a CVC-related thrombosis in 11 patients (5.2%; 5 in the heparin group and 6 in the antiseptic group P=0.8). Catheter-related thrombosis and CRBI coincided in two patients and were not significantly correlated (P=0.6). Four (1.9%) and three (1.4%) patients had evidence of protein C and protein S deficiency, respectively. Only one patient had an antithrombin deficiency (0.5%). In total, 9 patients (4.2%) were heterozygous for the factor V Leiden mutation. Thrombosis was diagnosed in three out of 17 patients (17.6%) with a inherited prothrombotic abnormality compared to 8 out of 195 patients (4.1%) who did not have a thrombophilic marker (relative risk 4.3 CI 95% 1.2–14.7). Six and five patients experienced severe bleeding in the heparin and antiseptic groups, respectively. We did not observe heparin-induced thrombocytopenia and anaphylaxis to chlorhexidine was not reported. To our knowledge, this is the first randomized study comparing in haematological patients heparin-coated with antiseptic impregnated CVCs. Furthermore, our results suggest that inherited prothrombotic abnormalities contribute substantially to CVC-related thrombosis in hemato-oncological patients. Presently, the best options for reducing CRBI are heparin-coated and antibiotic-impregnated CVCs. A large, well designed randomized controlled trial is required to determine which of these is most effective.