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Introduction . The remarkable intrinsic resistance of Fusarium species to most antifungal agents results in high mortality rates in the immunocompromised population. Aims . This study aimed to investigate the epidemiology, clinical features and antifungal susceptibility of Fusarium isolates in patients with invasive fusariosis. Methodology . A total of 27 patients admitted to a referral hospital from January 2008 to June 2017 were evaluated. Antifungal susceptibility testing of isolates was performed by broth microdilution according to the Clinical and Laboratory Standards Institute guidelines. Results . Haematological malignancy was the predominant underlying condition, with an incidence of invasive fusariosis of 14.8 cases per 1000 patients with acute lymphoid leukaemia and 13.1 cases per 1000 patients with acute myeloid leukaemia. The Fusarium solani species complex (FSSC) was the most frequent agent group, followed by the Fusarium oxysporum species complex (FOSC). Voriconazole showed the best activity against Fusarium , followed by amphotericin B. Itraconazole showed high minimum inhibitory concentration values, indicating in vitro resistance. Clinical FSSC isolates were significantly ( P <0.05) more resistant to amphotericin B and voriconazole than FOSC isolates. Conclusion . The present antifungal susceptibility profiles indicate a high incidence of fusariosis in patients with haematological malignancy. Species- and strain-specific differences in antifungal susceptibility exist within Fusarium in this setting.

Background: Surveillance of current changes in the epidemiology of Invasive Fungal Diseases (IFDs) as an important component of the antifungal stewardship programs (ASP), requires careful regular monitoring, especially in high-risk settings such as oncology centers. This study aimed to examine Candida colonization status and corresponding current changes in children with malignancy during repeated admissions and also investigate the possible epidemiological shifts after the implementation of ASP., Methods: In this prospective observational study, all eligible patients younger than 18 years were recruited during 2016-2017 at Amir Medical Oncology Center (AMOC) in Shiraz, Iran. Totally, 136 patients were enrolled and 482 samples were collected from different sites (oral/nasal discharges, urine and stool). Weekly regular sampling was carried out during hospitalization. Candida colonization status and epidemiological changes were monitored during repeated admissions. Samples were cultivated on Sabouraud Dextrose agar medium and identified by Polymerase Chain Reaction -Restriction Fragment Length Polymorphism (PCR-RFLP)., Results: Estimated Candida colonization incidence was 59.9% (82/136) in our patients. Candida colonization was found to be higher in oral cavity and rectum than that in nasal cavity. Among those long-term follow ups and repetitive hospitalizations, a significant number of patients exhibited changes in their colonization patterns (37.7%). Candida colonization did not reveal any significant relationship with age, sex, oncologic diseases and degree of neutropenia. C. albicans (72.0%) was found as the most common Candida species in colonized patients, followed by C. krusei, C. kefyr, C. glabrata and C. parapsilosis., Conclusion: Given the high incidence of Candida infections in children with cancers, close monitoring of epidemiologic changes is essential for judicious management, based on local surveillance data and improvement of overall quality of care in high risk patients.

Background: Stenotrophomonas maltophilia is an important nosocomial pathogen. This pathogen has intrinsic or acquired resistance to a number of antibiotics classes. Furthermore, Stenotrophomonas infections have been associated with high mortality, mainly in immunocompromised patients. Accordingly, we conducted a retrospective cohort study on the clinical data, microbiological characteristics, and outcomes of patients with S. maltophilia (SM) bacteremia., Methods: A retrospective cohort study was conducted at two tertiary care referral hospitals in Seoul, South Korea. Data were collected between January 2006 and December 2015 from electric medical records. Our analysis aimed to identify the risk factors associated with crude mortality, as well as the predictive factors of quinolone-resistant strains in SM bacteremia patients., Results: A total of 126 bacteremia patients were enrolled in the study. The mortality rate was 65.1%. On multivariable analysis, hypoalbuminemia (odds ratio [OR], 5.090; 95% confidence interval [CI], 1.321-19.621; P = 0.018), hematologic malignancy (OR, 35.567; 95% CI, 2.517-502.515; P = 0.008) and quinolone-resistant strains (OR, 7.785; 95% CI, 1.278-47.432; P = 0.026) were independent risk factors for mortality. Alternatively, usage of an empirical regimen with quinolone (OR, 0.172; 95% CI, 0.034-0.875; P = 0.034) was an independent protective factor for mortality. The multivariable analysis of predictive factors revealed that high Charlson comorbidity index (OR, 1.190; 95% CI, 1.040-1.361; P = 0.011) and indwelling of a central venous catheter (CVC) (OR, 3.303; 95% CI, 1.194-9.139; P = 0.021) were independent predisposing factors associated with quinolone-resistant strains in SM bacteremia patients., Conclusions: Our findings suggest that a high Charlson comorbidity score and indwelling of a CVC were significantly independent predictors of quinolone-resistant strains in SM bacteremia patients. Therefore, we need to carefully consider the antibiotic use in SM bacteremia patients with these predictive factors.

Background: The outcomes of deep-seated abscesses attributed to chronic disseminated candidiasis (CDC) in patients with hematological malignancies have rarely been reported in recent years., Methods: We retrospectively reviewed and analyzed the data of patients with hematological malignancies who received a diagnosis of CDC at a medical center in Taiwan between 2008 and 2013., Results: Sixty-one patients (32 men and 29 women) were diagnosed with CDC. The median age was 51 years (range: 18-83). The overall incidence of CDC was 1.53 per 100 patient-years in patients with hematological malignancies between 2008 and 2013. The highest incidence of CDC was 4.3 per 100 patient-years for acute lymphoblastic leukemia, followed by 3.6 for acute myeloid leukemia. We detected 3 (4.9%) proven, 13 (21.3%) probable, and 45 (73.8%) possible cases of CDC. A total of 13 patients had positive blood cultures for Candida species: C. tropicalis (8), C. albicans (2), C. glabrata (2), and C. famata (1). The median duration of antifungal treatment was 96 days (range: 7-796 days). Serial imaging studies revealed that the resolution rate of CDC was 30.0% at 3 months and 54.3% at 6 months. Five patients (8.2%) had residual lesions that persisted beyond one year. A multivariate analysis of the 90-day outcome revealed that shock was the only independent prognostic factor of 90-day survival in patients with CDC., Conclusion: The incidence of CDC did not decrease between 2008 and 2013. Patients with acute leukemia had a higher risk of CDC than those with other hematological malignancies. Imaging studies conducted at 6 months after diagnosis revealed that only half of the patients showed complete resolution. CDC requires prolonged treatment, and serial imaging at 6 months interval is suggested. Shock is the only independent prognostic factor of 90-day survival in patients with CDC.

Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in children with cancer. An overview of studies on the frequency and determinants of IFI in pediatric oncology patients in nonallogeneic stem cell transplantation settings is lacking. We performed a literature review in Pubmed and Embase, and included 13 prospective and 23 retrospective studies. The IFI frequency (proven/probable based on EORTC criteria) in nonallogeneic stem cell transplantation pediatric cancer patients ranged between 1.0% and 38.0%, with the highest frequencies reported in hematologic malignancies. The most common fungal species seen in the studied population was Candida, followed by Aspergillus. IFI are not well investigated in solid tumor patients. Significant recurrent determinants from univariate analysis were the diagnosis acute myeloid leukemia, (prolonged) neutropenia and an older age (above 10 years). The only 2 significant determinants based on multivariate analysis were the preceding number of days of broad-spectrum antibiotics (odds ratio, 1.05; 95% confidence interval, 1.02-1.07; P=0.0006) and the number of days of corticosteroids (odds ratio, 1.05; 95% confidence interval, 1.02-1.09; P=0.005), that were both based on a group of acute myeloid leukemia patients only. Future studies are necessary to determine the frequency and determinants of IFI in pediatric oncology including a representative number of solid tumor patients.

Infectious complications represent one of the most common causes of morbidity and mortality in allogeneic hematopoietic cell transplant (HCT) recipients. Prophylactic and preemptive treatment strategies against bacterial, fungal, viral, and parasitic pathogens are routinely implemented during high-risk post-HCT periods at most transplant centers. The basic concepts and review of current guidelines of antibiotic prophylaxis and empirical/preemptive antibiotic treatment in allogeneic HCT recipients are reviewed in this article., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Invasive fungal disease (IFD) has a poor prognosis in children with hematological disorders after hematopoietic stem cell transplantation (HSCT). We assessed if drug combinations with different targets may improve the outcome., Methods: Retrospective study to assess the outcome of combination antifungal therapy (CAT) for proven-probable IFD (PP-IFD) in children with hematological disorders after HSCT from January 2008 to June 2018., Results: Over the 10-year period, 95 PP-IFD were diagnosed in pediatric recipients, median age of 5.6 years. Twenty-seven patients received combinations of caspofungin and voriconazole, 28 patients received combinations of caspofungin and amphotericin B, and 40 patients received combinations of voriconazole and amphotericin B. The overall response rate of PP-IFD was 77.9%, while the 100-day overall survival rates were 66.8%. Univariate analysis showed that factors that significantly affected the response to combination treatments were type of combination (P = 0.02), the stem cell source (P = 0.04), the donor type (P = 0.03), HLA-match (P = 0.03), aGVHD (P = 0.02), period of treatment (P = 0.044), use of corticosteroids (0.036), CD4:CD8 ratio (P = 0.014), and CMV viremia (P = 0.033). In addition, multivariate analysis demonstrated that only the type of combination remained a significant factor (odds ratio = 0.335, 95% confidence interval: 0.071-0.812, P = 0.042). Forty-three children suffered from mild and reversible adverse reactions, no serious side effects during treatment., Conclusion: A variety of factors can affect the outcome of CAT. Combination of caspofungin with voriconazole is a safe and helpful treatment option for HSCT recipients with IFD., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Bacteremia (bloodstream infection) is frequent (20%-30% incidence) in the stem cell transplant and hematologic malignancy population and often occurs in the early post-transplant engraftment period. In most studies, Gram-positive bacteria occur at greater frequency than gram-negative bacteria, although some centers report that rates of gram-negative bloodstream infections have recently increased. In many centers, resistance rates among Enterococci and gram-negative bacteria, especially the Enterobacteriaceae, are extensive and associated with increased mortality. Better prediction tools, enhanced infection control, and new anti-infective agents hold promise for the treatment of highly resistant pathogens in this population., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Despite advances in chemotherapy and supportive care, morbidity and mortality remain high for patients with hematologic malignancies (HMs). Those who require hematopoietic stem cell transplantation (HSCT) often require significant immunosuppression and are subject to a variety of complications. These patients carry multiple risk factors for infectious complications, including the development of invasive fungal infections, compared with the general population. Because antifungal prophylaxis has been widely adopted, there has been a shift away from invasive candidiasis toward invasive mold infections, including breakthrough infections. For patients with HM and HSCT, we outline the epidemiology, manifestations, diagnosis, and treatment of invasive fungal infections., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Clostridioides difficile infection (CDI) is common in the stem cell transplant (SCT) and hematologic malignancy (HM) population and mostly occurs in the early posttransplant period. Treatment of CDI in SCT/HM is the same as for the general population, with the exception that fecal microbiota transplant (FMT) has not been widely adopted because of safety concerns. Several case reports, small series, and retrospective studies have shown that FMT is effective and safe. A randomized controlled trial of FMT for prophylaxis of CDI in SCT patients is underway. In addition, an abundance of novel therapeutics for CDI is currently in development., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Pulmonary computed tomography (CT) scans are commonly used as part of the clinical criteria in diagnostic workup of invasive fungal diseases like invasive aspergillosis, and may identify radiographic abnormalities, such as halo signs or air-crescent signs. We assessed the diagnostic utility of CT assessment in patients with hematologic malignancies or those who had undergone allogeneic hematopoietic stem cell transplantation in whom invasive aspergillosis was suspected., Methods: This post-hoc analysis assessed data from a prospective, multicenter, international trial of voriconazole (with and without anidulafungin) in patients with suspected invasive aspergillosis (IA; proven, probable, or possible, using 2008 European Organisation for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria) [NCT00531479]. Eligible patients received at least one baseline lung CT scan., Results: Of 395 patients included in this post-hoc analysis, 240 patients (60.8%) had 'confirmed' proven (9/240, 3.8%) or probable (231/240, 96.3%) invasive aspergillosis (cIA) and 155 patients (39.2%) had 'non-confirmed' invasive aspergillosis (all nIA; all possible IA (de Pauw et al., Clin Infect Dis 46:1813-21, 2008)). Mean age was 52.3 and 50.5 years, 56.3 and 60.0% of patients were male, and most patients were white (71.7 and 71.0%) in the cIA and nIA populations, respectively. Median baseline galactomannan was 1.4 (cIA) and 0.2 (nIA), mean Karnofsky score was 65.3 (cIA) and 66.8 (nIA), and mean baseline platelet count was 48.0 (cIA) and 314.1 (nIA). Pulmonary nodules (46.8% of all patients), bilateral lung lesions (37.5%), unilateral lung lesions (28.4%), and consolidation (24.8%) were the most common radiographic abnormalities. Ground-glass attenuation (cIA: 24.2%; nIA: 11.6%; P < 0.01) and pulmonary nodules (cIA: 52.5%; nIA: 38.1%; P < 0.01) were associated with cIA. Other chest CT scan abnormalities (including halo signs and air-crescent signs) at baseline in patients with hematologic malignancy or hematopoietic stem cell transplantation, and suspected IA, were not associated with cIA., Conclusions: These findings highlight the limitations in the sensitivity of chest CT scans for the diagnosis of IA, and reinforce the importance of incorporating other available clinical data to guide management decisions on individual patients, including whether empirical treatment is reasonable, pending full evaluation., Trial Registration: NCT00531479 (First posted on ClinicalTrials.gov on September 18, 2007).

Background: Bacterial bloodstream infections are one of the most common complications in cancer patients under treatment. Bacteremia in these patients is a medical crisis that needs antibiotic treatment. The aim of this study was to determine bacterial spectrum and antimicrobial resistance pattern in febrile neutropenic cancer patients. Methods: In this prospective study, 212 cancer patients with febrile neutropenia who were referred to Shahid Sadoughi hospital in Yazd from 2012 to 2015 were participated. Bacterial pathogens isolated by the BACTEC media and antimicrobial susceptibility tests performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: The mean age of patients was 43.5 ± 24.98 years old. Out of 212 participants, 62.3℅ (132/212) were suffering from hematologic malignancies, and 37.7℅ (80/212) had solid tumors. Gram-negative bacteria were the predominant microorganisms (84.9℅). E.coli was the most frequently isolated pathogen (38.68 %), followed by Klebsiella (14.15℅) and Acinetobacter species (11.32℅). In addition, Staphylococcus epidermidis was the most common isolated Gram-positive bacteria (8.5℅). Gram-negative bacteria were susceptible to ciprofloxacin with a response range of 53.7% to 100%. The majority of E.coli isolates were sensitive to ceftazidime (87.8℅) and were resistance to Co-trimoxazole (15.8℅). Klebsiella isolates were 100% susceptible to cephalosporins, meropenem and imipenem. Conclusion: The majority of bacterial pathogens were resistance to various antibiotics. Judicious use of antibiotic therapy can prevent the emergence and spread of antibiotic-resistant Gram-negative bacteria., (Creative Commons Attribution License)

Mucormycosis is an opportunistic infection occurring in immunocompromised hosts with hematological malignancies. Mortality due to mucormycosis in patients with hematological malignancies is high. However, the clinical symptoms of mucormycosis are poorly characterized, and diagnosis is difficult due to the lack of specific culture or serological markers or antigens. We present two cases in which nested polymerase chain reaction with specific primers was used in the serum of patients with hematological malignancies.

Background: Fungal infections are still a relevant challenge for clinicians involved in the cure of patients with cancer. We retrospectively reviewed charts of hospitalized patients with haematological malignancies (HMs), in which a documented fungaemia was diagnosed between January 2011 and December 2015 at 28 adult and 6 paediatric Italian Hematology Departments., Methods: During the study period, we recorded 215 fungal bloodstream infections (BSI). Microbiological analyses documented that BSI was due to moulds in 17 patients (8%) and yeasts in 198 patients (92%), being Candida spp identified in 174 patients (81%)., Results: Mortality rates were 70% and 39% for mould and yeast infections, respectively. Infection was the main cause of death in 53% of the mould and 18% of the yeast groups. At the multivariate analysis, ECOG ≥ 2 and septic shock were significantly associated with increased mortality, and removal of central venous catheter (CVC) survival was found to be protective. When considering patients with candidemia only, ECOG ≥ 2 and removal of CVC were statistically associated with overall mortality., Conclusions: Although candidemia represents a group of BSI with a good prognosis, its risk factors largely overlap with those identified for all fungaemias, even though the candidemia-related mortality is lower when compared to other fungal BSI. Management of fungal BSI is still a complex issue, in which both patients and disease characteristics should be focused to address a personalized approach., (© 2019 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Triazole resistance is an increasing problem in invasive aspergillosis (IA). Small case series show mortality rates of 50%-100% in patients infected with a triazole-resistant Aspergillus fumigatus, but a direct comparison with triazole-susceptible IA is lacking., Methods: A 5-year retrospective cohort study (2011-2015) was conducted to compare mortality in patients with voriconazole-susceptible and voriconazole-resistant IA. Aspergillus fumigatus culture-positive patients were investigated to identify patients with proven, probable, and putative IA. Clinical characteristics, day 42 and day 90 mortality, triazole-resistance profiles, and antifungal treatments were investigated., Results: Of 196 patients with IA, 37 (19%) harbored a voriconazole-resistant infection. Hematological malignancy was the underlying disease in 103 (53%) patients, and 154 (79%) patients were started on voriconazole. Compared with voriconazole-susceptible cases, voriconazole resistance was associated with an increase in overall mortality of 21% on day 42 (49% vs 28%; P = .017) and 25% on day 90 (62% vs 37%; P = .0038). In non-intensive care unit patients, a 19% lower survival rate was observed in voriconazole-resistant cases at day 42 (P = .045). The mortality in patients who received appropriate initial voriconazole therapy was 24% compared with 47% in those who received inappropriate therapy (P = .016), despite switching to appropriate antifungal therapy after a median of 10 days., Conclusions: Voriconazole resistance was associated with an excess overall mortality of 21% at day 42 and 25% at day 90 in patients with IA. A delay in the initiation of appropriate antifungal therapy was associated with increased overall mortality., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The correct management of immunocompromised patients with pneumonia is debated. We evaluated the prevalence, risk factors, and characteristics of immunocompromised patients coming from the community with pneumonia., Methods: We conducted a secondary analysis of an international, multicenter study enrolling adult patients coming from the community with pneumonia and hospitalized in 222 hospitals in 54 countries worldwide. Risk factors for immunocompromise included AIDS, aplastic anemia, asplenia, hematological cancer, chemotherapy, neutropenia, biological drug use, lung transplantation, chronic steroid use, and solid tumor., Results: At least 1 risk factor for immunocompromise was recorded in 18% of the 3702 patients enrolled. The prevalences of risk factors significantly differed across continents and countries, with chronic steroid use (45%), hematological cancer (25%), and chemotherapy (22%) the most common. Among immunocompromised patients, community-acquired pneumonia (CAP) pathogens were the most frequently identified, and prevalences did not differ from those in immunocompetent patients. Risk factors for immunocompromise were independently associated with neither Pseudomonas aeruginosa nor non-community-acquired bacteria. Specific risk factors were independently associated with fungal infections (odds ratio for AIDS and hematological cancer, 15.10 and 4.65, respectively; both P = .001), mycobacterial infections (AIDS; P = .006), and viral infections other than influenza (hematological cancer, 5.49; P < .001)., Conclusions: Our findings could be considered by clinicians in prescribing empiric antibiotic therapy for CAP in immunocompromised patients. Patients with AIDS and hematological cancer admitted with CAP may have higher prevalences of fungi, mycobacteria, and noninfluenza viruses., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: Large-scale clinical studies investigating associations between intestinal microbiota signatures and human diseases usually rely on stool samples. However, the timing of repeated stool sample collection cannot be predefined in longitudinal settings. Rectal swabs, being straightforward to obtain, have the potential to overcome this drawback. Therefore, we assessed the usability of rectal swabs for microbiome sampling in a cohort of hematological and oncological patients., Study Design: We used a pipeline for intestinal microbiota analysis from deep rectal swabs which was established and validated with test samples and negative controls. Consecutively, a cohort of patients from hematology and oncology wards was established and weekly deep rectal swabs taken during their admissions and re-admissions., Results: Validation of our newly developed pipeline for intestinal microbiota analysis from rectal swabs revealed consistent and reproducible results. Over a period of nine months, 418 rectal swabs were collected longitudinally from 41 patients. Adherence to the intended sampling protocol was 97%. After DNA extraction, sequencing, read pre-processing and filtering of chimeric sequences, 405 of 418 samples (96.9%) were eligible for further analyses. Follow-up samples and those taken under current antibiotic exposure showed a significant decrease in alpha diversity as compared to baseline samples. Microbial domination occurred most frequently by Enterococcaceae (99 samples, 24.4%) on family level and Enterococcus (90 samples, 22.2%) on genus level. Furthermore, we noticed a high abundance of potential skin commensals in 99 samples (24.4%)., Summary: Deep rectal swabs were shown to be reliable for microbiome sampling and analysis, with practical advantages related to high sampling adherence, easy timing, transport and storage. The relatively high abundance of putative skin commensals in this patient cohort may be of potential interest and should be further investigated. Generally, previous findings on alpha diversity dynamics obtained from stool samples were confirmed., Competing Interests: LMB has received lecture honoraria from Astellas Pharma and MSD and travel grants from 3M and Gilead. MJGTV has served at the speakers’ bureau of Pfizer, Merck, Gilead Sciences and Astellas Pharma, received research funding from 3M, DaVolterra, Astellas Pharma, Gilead Sciences and Merck and is a consultant to Berlin Chemie, Astellas Pharma and Merck. All other authors: none to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: There is a paucity of data regarding the utility of routine urine cultures in adults with febrile neutropenia (FN) without urinary symptoms receiving protocolised antibiotics. This is reflected by inconsistent recommendations in international and regional FN guidelines. We addressed this issue by retrospectively reviewing the impact of routine urine cultures on antibiotic management in haematology cancer inpatients at a tertiary hospital., Methods: All haematology inpatients over a 5-year period (2011-2015) were retrospectively reviewed for episodes of FN (neutrophil count < 0.5 × 10 9 /L and fever > 37.5 °C). For each episode, demographic data, urinary tract symptoms and signs (absence of which was termed 'asymptomatic'), urinalysis and urine culture results, antibiotic therapy and duration, and patient outcomes were collected. A urine culture was considered positive if > 10 5 colony forming units (CFU)/L were detected. Empiric antibiotic therapy for FN consisted of intravenous piperacillin/tazobactam in stable patients, with the addition of vancomycin and a single dose of gentamicin if systemically compromised., Results: Four hundred and thirty-three episodes of FN were identified in 317 patients. Urine cultures were performed in 362 (84%) episodes. Cultures were positive in 9 of 48 (19%) symptomatic episodes versus 8 of 314 (2.5%) asymptomatic episodes (RR = 7.4, p < 0.0001). A change in antibiotic management due a positive urine culture occurred in only 5 episodes (1.4%): 3 of 48 (6.3%) symptomatic and 2 of 314 (0.6%) asymptomatic episodes respectively (RR = 9.8, p = 0.01)., Conclusion: Routine urine cultures in FN patients without urinary symptoms who are already receiving protocolised broad spectrum antibiotics rarely impact subsequent antibiotic management.

Invasive mold infections are life-threatening complications in patients with hematological malignancies. Conventional microbiological methods for diagnosing invasive pulmonary mold infections have low sensitivity, and molecular methods are being developed. Detection of molds using PCR with a narrow spectrum has been reported, but data with broad-spectrum PCR are lacking. In this study, the diagnostic performance and utility of a broad-spectrum PCR (broad-spectrum PCR with subsequent electrospray ionization-mass spectrometry, PCR/ESI-MS) for detection of molds in bronchoalveolar lavage (BAL) in 27 hematological patients with a new pulmonary infiltrate was analyzed. Using the revised EORTC/MSG criteria, PCR/ESI-MS was the only positive microbiological test in patients with proven invasive mold infection (n = 2) and correctly identified all cases of probable invasive pulmonary aspergillosis (n = 5). In patients with a possible invasive mold infection (n = 5), PCR/ESI-MS was positive in three patients. Mucorales was identified with PCR/ESI-MS in four patients that were all culture negative. The PCR/ESI-MS results had a clinical impact on antifungal therapy in 12 (44%) of the patients: modification of treatment in 6 (22%) patients and discontinuation in 6 (22%) patients. This study provides proof of concept that routine use of a broad-spectrum PCR for molds in bronchoalveolar lavage in immunocompromised patients is sensitive, fast, and has an impact on clinical decision-making., Competing Interests: The authors have declared that no competing interests exist.

Hemorrhagic pneumonia (HP) is known as the clinical manifestation of Stenotrophomonas maltophilia infection, while catheter-related blood stream infection (CRBSI) is the common clinical presentation of S. maltophilia bacteremia (SMB). The purpose of this study is to evaluate the risk factors for mortality in hematologic malignancy patients with SMB and to analyze clinical and microbiological characteristics of HP associated with SMB and CRBSI. SMB cases of patients with a hematologic malignancy were collected from 2006 through 2016. The overall 30-day mortality rate and mortality risk factors were assessed. The expression of major virulence-associated genes from S. maltophilia isolates, which included genes encoding type-1 fimbriae (smf-1), proteases (StmPr1 and StmPr2), and esterase (Smlt3773), from the blood of patients with HP and CRBSI was investigated. The phenotypic and genotypic traits were also compared. A total of 118 cases of SMB were included. The overall 30-day mortality rate was 61.0%. A multivariable analysis showed that HP was the most important risk factor for mortality (adjusted OR = 106.41; 95% CI = 5.18-2184.55). Although no statistical significance was observed in microbiological analysis, isolates from HP have a trend toward a higher protease activity (93.8% vs. 73.3%, P = 0.172). Clinical analysis showed that thrombocytopenia (P = 0.037) and prolonged neutropenia (P = 0.043) were significant factors associated with HP. Our data, which includes hematologic malignancy patients with SMB, suggest that HP is the significant risk factor for mortality and that the unique characteristics of patients and microbes contribute to the pathogenesis.

Human beings are inhabited by innumerable microorganisms that interrelate with the host in a reciprocal way, establishing a combined and efficient ecosystem - the microbiota - that can affect healthiness as well as disease. There is evidence that the conformation of the microbiota may influence, and is controlled by, the human immune system. Microbes existing in human tissues offer a multiplicity of advantages that participate in functional actions in the host through the adjustment of essential processes such as immunity, signal transduction, and metabolism. The imbalance of this microbial structure has been connected with the pathogenesis and progression of cancer. We reviewed the present knowledge of the diverse microbial ecosystems and we investigated their potential link to carcinogenesis, and the possibility of using advantageous microbes in controlling and preventing hematologic malignancies.

Objectives: Early diagnosis of invasive aspergillosis (IA) remains challenging, with available diagnostics being limited by inadequate sensitivities and specificities. Triacetylfusarinine C, a fungal siderophore that has been shown to accumulate in urine in animal models, is a potential new biomarker for diagnosis of IA., Methods: We developed a method allowing absolute and matrix-independent mass spectrometric quantification of TAFC. Urine TAFC, normalized to creatinine, was determined in 44 samples from 24 patients with underlying hematologic malignancies and probable, possible or no IA according to current EORTC/MSG criteria and compared to other established biomarkers measured in urine and same-day blood samples., Results: TAFC/creatinine sensitivity, specificity, positive and negative likelihood ratio for probable versus no IA (cut-off ≥ 3) were 0.86, 0.88, 6.86, 0.16 per patient., Conclusion: For the first time, we provide proof for the occurrence of TAFC in human urine. TAFC/creatinine index determination in urine showed promising results for diagnosis of IA offering the advantages of non-invasive sampling. Sensitivity and specificity were similar as reported for GM determination in serum and bronchoalveolar lavage, the gold standard mycological criterion for IA diagnosis., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aspergillosis, which is saprophytic in nature, is known to cause massive destruction of paranasal sinuses in immunocompromised hosts, but in immunocompetent individuals invasive aspergillosis is rare. Diagnosis is posed from history, physical examination including anterior and posterior rhinoscopy, endoscopy of the nose and paranasal sinuses, radiological findings (CT and/or MRI), fungus cultures and histopathological examination. Non-specific presenting symptoms provide time for infection to extent from sinuses to vital surroundings such as bony, vascular and central nervous system structures, thereby increasing morbidity and mortality. Mass lesions involving the sinuses are initially misdiagnosed as tumors, inflammatory pseudotumors or pituitary adenomas. Therefore, diagnosis should be always confirmed by histopathology. Aspergillus sinusitis is a potentially fatal complication of immunosupression or of chemotherapy-induced leucopenia. Concerning patients with hematologic malignancies, it seems that its incidence is progressively increased. A combination of early diagnosis and application of specific antifungals provides the perfect management and prognosis in the corresponding patients. In the current special review, we present new data regarding the infection in patients with hematologic malignancies.

Objectives: The '3-day rule' for stool culture ordering suggests that only selected inpatients with nosocomial diarrhoea should have stool cultures for enteropathogenic bacteria (EPBs). Patients with haematological malignancies are not included in this group. We have analysed the ordering of stool cultures at Laikon Hospital to investigate whether all patients with haematological malignancies should be excluded from the 3-day rule., Methods: We have retrospectively analysed all inpatient stool specimens sent to the microbiology laboratory for enteropathogenic bacteria culture at Laikon Hospital, Athens, Greece, between January 1, 2014 and December 31, 2014. We classified stool cultures sent after the third day as 'appropriate', 'excluded' with standard rule, 'excluded' with haematological malignancies, and 'inappropriate'., Results: During the study period, 1101/1593 inpatient stool cultures (69.1%) had been ordered after the third day of hospitalization. The total yield for inpatient EPB stool cultures was 0.7% (11/1593). The yield for 'appropriate' cultures was significantly higher than the yield of all 'excluded' specimens (3.7% (3/81) versus 0.3% (2/585), p 0.018) and to 'inappropriate' orders (3.7% (3/81) versus 0.0% (0/485), p 0.0028). There was no difference in the yield between specimens 'excluded' with the standard rule and 'excluded' with haematological malignancies., Conclusions: In our hospital, the yield of stool cultures from patients with haematological malignancies is similar to that of patients 'excluded' from the standard 3-day rule. If patients with haematological malignancies were not excluded from the rule, we would reduce the inpatient stool cultures by 13.6% (217/1593) at the cost of missing one positive stool culture., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: This study was performed to explore the characteristics and outcomes of patients with sepsis accompanied by active cancer who were admitted to the intensive care unit (ICU)., Methods: The baseline characteristics, infection profiles, and outcomes of patients with sepsis were retrospectively analyzed according to the presence of concomitant active cancer. The association between concomitant active cancer and 28-day mortality was explored., Results: Of 23,956 patients with sepsis, 1574 (6.6%) had concomitant active cancer. The most common type was digestive (30.7%). The 28-day mortality ranged from 41.9% to 81.5%. Patients with active cancer had a significantly higher Simplified Acute Physiology Score II and significantly shorter length of ICU stay. Respiratory (32.9%), genitourinary (31.0%), and bloodstream (17.0%) infections were most common. Escherichia coli was the most frequent gram-negative pathogenic bacteria. The 28-day mortality rate was significantly higher in patients with than without active cancer. Concomitant active cancer was associated with increased 28-day mortality in patients with sepsis. Hematological malignancy was associated with a significantly higher risk of death than solid tumors., Conclusions: Concomitant active cancer was associated with higher 28-day mortality in patients with sepsis requiring ICU admission. Hematological malignancy was associated with a higher risk of death than solid tumors.

Viral and bacterial infections cause chronic inflammation and produce bacterial metabolites that may lead to carcinogenesis. Ehrlichiosis is an intracellular infection that primarily infects white blood cells. Given that infections can lead to cancer, and that Ehrlichia has tropism for white blood cells, it can be deduced that Ehrlichia may cause hematologic malignancies, such as acute leukemia. A prospective study was performed that tested the blood of ten patients with acute leukemia for prior exposure to Ehrlichia. The RT-PCR that was performed did not detect Ehrlichia DNA in any of the ten samples. Therefore, based on this small study, one cannot conclude that Ehrlichia can lead to hematologic malignancies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

There is a paucity of data regarding mixed mold pulmonary infections (MMPIs) in patients with haematological malignancies with or without haematopoietic stem cell transplantation (HSCT). We retrospectively studied 27 such patients (2005-2015) and compared them to patients with invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus. Factors associated with the diagnosis of MMPIs were significant corticosteroid use [20 (74%) vs 6 (22%), P < 0.001], sputum as the source specimen [13 (48%) vs 3 (11%), P = 0.003], younger age (median age: 58 vs 66 years, P = 0.006), and male sex [22 (81%) vs 13 (48%), P = 0.01]. Haematological cancers other than acute myeloid leukaemia (AML)/myelodysplastic syndromes (MDS) were less common in MMPIs than in IPA patients [AML/MDS: 6 (22%) vs 14 (52%), P = 0.04]. Only significant corticosteroid use [95% CI (2.7-42.7), P < 0.001], and sputum as the source specimen [95% (1.6-41.6), P = 0.012] were statistically significant as independently associated with increased risk of MMPIs diagnosis in multivariate analysis. Total mortality rate at day 42 postdiagnosis was comparable in both groups., (© 2018 Blackwell Verlag GmbH.)

Infections and especially blood stream infections (BSI) with gram-negative bacteria (GNB) represent a major threat for patients with hematological diseases undergoing chemotherapy and mainly contribute to morbidity and mortality. In this retrospective single-center study, we analyzed the impact of BSI with different gram-negative multidrug-resistant bacteria (MDRGN) compared to BSI with antibiotic susceptible gram-negative bacteria. Data of 109 patients with hematological malignancies and GNB BSI were analyzed with overall survival (OS) 30 days after BSI being the primary endpoint. BSI with non-fermentative gram-negative bacteria were found in 26.6% of all patients and 73.4% suffered from a BSI with an Enterobacteriaceae. Thirty-two of 109 patients suffered from BSI with MDRGN. Characteristics of MDRGN and non-MDRGN BSI patients did not differ besides the fact that significantly more patients received an immunosuppressive therapy in the MDRGN BSI group. OS (30 days after BSI) of patients with MDRGN BSI was significantly lower (85.6 vs. 55.9%; p < 0.001) compared to patients with non-MDRGN BSI. Patients with MDRGN BSI with non-fermentative pathogens had a worse OS after 30 days compared to MDRGN BSI with Enterobacteriaceae and the same holds true for non-MDRGN BSI. In multivariate analysis of MDRGN BSI, non-fermenters and ICU admission were independently associated with increased 30-day mortality. Our data demonstrate the negative impact of non-fermentative gram-negative pathogens causing BSI compared to Enterobacteriaceae in hematological patients and thereby underlining the heterogeneity of gram-negative BSI.

Although the widespread use of mold-active agents (especially the new generation of triazoles) has resulted in reductions of documented invasive mold infections (IMIs) in patients with hematological malignancies and allogeneic hematopoietic stem cell transplantation (HSCT), a subset of such patients still develop breakthrough IMIs (bIMIs). There are no data from prospective randomized clinical trials to guide therapeutic decisions in the different scenarios of bIMIs. In this viewpoint, we present the current status of our understanding of the clinical, diagnostic, and treatment challenges of bIMIs in high-risk adult patients with hematological cancer and/or HSCT receiving mold-active antifungals and outline common clinical scenarios. As a rule, managing bIMIs demands an individualized treatment plan that takes into account the host, including comorbidities, certainty of diagnosis and site of bIMIs, local epidemiology, considerations for fungal resistance, and antifungal pharmacological properties. Finally, we highlight areas that require future investigation in this complex area of clinical mycology.

There is a paucity of studies on the yield of Gomori-methenamine-silver (GMS) staining in bronchoalveolar lavage (BAL) fluid cytology and its comparison with fluorescent dye staining for the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with hematologic malignancies. To that end, we analyzed the yield of direct fungal visualization in BAL fluid cytology with GMS staining, in a series of culture-positive IPA cases in 67 patients with hematologic malignancies, and we compared the results with those of direct examination with calcofluor white staining and BAL fluid galactomannan assays, when available. GMS staining in BAL fluid cytology was positive in 42% of the 67 cases and revealed coinfections in 7 cases. In contrast, only 2/67 (3.6%) BAL fluid samples were positive in direct smears stained with the fluorescent dye calcofluor white. Positive GMS staining results were significantly more frequent in IPA cases with cavitary lesions and IPA cases caused by >1 Aspergillus species, but the proportions of positive cytology results among Aspergillus species were not different., (Copyright © 2018 American Society for Microbiology.)

Infections by multidrug-resistant (MDR) bacteria are a worrisome phenomenon in hematological patients. Data on the incidence of MDR colonization and related bloodstream infections (BSIs) in haematological patients are scarce. A multicentric prospective observational study was planned in 18 haematological institutions during a 6-month period. All patients showing MDR rectal colonization as well as occurrence of BSI at admission were recorded. One-hundred forty-four patients with MDR colonization were observed (6.5% of 2226 admissions). Extended spectrum beta-lactamase (ESBL)-producing (ESBL-P) enterobacteria were observed in 64/144 patients, carbapenem-resistant (CR) Gram-negative bacteria in 85/144 and vancomycin-resistant enterococci (VREs) in 9/144. Overall, 37 MDR-colonized patients (25.7%) developed at least one BSI; 23 of them (62.2%, 16% of the whole series) developed BSI by the same pathogen (MDRrel BSI), with a rate of 15.6% (10/64) for ESBL-P enterobacteria, 14.1% (12/85) for CR Gram-negative bacteria and 11.1% (1/9) for VRE. In 20/23 cases, MDRrel BSI occurred during neutropenia. After a median follow-up of 80 days, 18 patients died (12.5%). The 3-month overall survival was significantly lower for patients colonized with CR Gram-negative bacteria (83.6%) and VRE (77.8%) in comparison with those colonized with ESBL-P enterobacteria (96.8%). CR-rel BSI and the presence of a urinary catheter were independent predictors of mortality. MDR rectal colonization occurs in 6.5% of haematological inpatients and predicts a 16% probability of MDRrel BSI, particularly during neutropenia, as well as a higher probability of unfavourable outcomes in CR-rel BSIs. Tailored empiric antibiotic treatment should be decided on the basis of colonization.

Objectives: To determine effective risk factors on mortality in febrile neutropenic cases with hematologic malignancy. Patients with hematologic diseases are more prone to infections and those are frequent causes of mortality., Methods: This retrospective study was performed using data of 164 febrile neutropenic cases with hematologic malignancies who were followed up in a hematology clinic of a tertiary health care center between 2011-2015. The relationship between descriptive and clinical parameters rates and rates of mortality on the 7th and the 21st days were investigated., Results: Patients with absolute neutrophil count less than 100/mm3, duration of neutropenia longer than 7 days, pneumonia or gastrointestinal foci of infection, central catheterization (p=0.025), isolation of Gram (-) bacteria in culture, carbapenem resistance, septic shock, and bacterial growth during intravenous administration of antibiotic treatment were under more risk for mortality on both the 7th and the 21st days. The final multivariate logistic regression results showed that pneumonia (p less than 0.0001), septic shock (p=0.004) and isolation of Gram-negative bacteria (p=0.032) were statistically significant risk factors., Conclusion: Early diagnosis and appropriate treatment of serious infections, which are important causes of morbidity and mortality, are crucial in patients with febrile neutropenia. Thus, each center should closely follow up causes of infection and establish their empirical antibiotherapy protocols to accomplish better results in the management of febrile neutropenia.

Clostridium difficile infection (CDI) is one of the most common causes of nosocomial infectious diarrhea in children during anticancer therapy or undergoing hematopoietic stem cell transplantation (HSCT) in Europe. Immunosuppression in these patients is a risk factor for CDI. Malignant diseases, age, acute graft-versus-host disease (aGVHD), HLA mismatch, or use of total body irradiation may play an important role in CDI course. The aim of this study was to evaluate the incidence, course, and outcome of CDI in children treated for malignancy or undergoing HSCT. Between 2012 and 2015, a total number of 1846 patients were treated for malignancy in Polish pediatric oncological centers (PHO group) and 342 underwent transplantation (HSCT group). In PHO group, episodes of CDI occurred in 210 patients (14%). The incidence of CDI was higher in patients with hematological malignancies in comparison to that with solid tumors. Patients with acute myeloblastic leukemia had shorter time to episode of CDI than those with acute lymphoblastic leukemia. Patients over 5 years and treated for acute leukemia had more severe clinical course of disease in PHO group. In HSCT group, CDI occurred in 29 (8%) patients. The incidence of CDI was higher in patients transplanted for acute leukemia. The recurrence rate was 14.7% in PHO and 20.7% in HSCT patients. CDI incidence was highest in patients with hematological malignancies. Most of patients experienced mild CDI. Age < 5 years and diagnosis other than acute leukemia were the positive prognostic factors influencing clinical CDI course.

The management of long-term central venous catheter (LTCVC) infections by multidrug-resistant (MDR) bacteria in cancer patient is a challenge. The objectives of this study were to analyze outcomes in cancer patients with LTCVC-associated infection, identify risks for unfavorable outcomes, and determine the impact of MDR bacteria and antibiotic lock therapy (ALT) in managing such infections. We evaluated all LTCVC-associated infections treated between January 2009 and December 2016. Infections were reported in accordance with international guidelines for catheter-related infections. The outcome measures were 30-day mortality and treatment failure. We analyzed risk factors by Cox forward-stepwise regression. We identified 296 LTCVC-associated infections; 212 (71.6%) were classified as bloodstream infections (BSIs). The most common agent was Staphylococcus aureus Forty-six (21.7%) infections were due to MDR Gram-negative bacteria. ALT was used in 62 (29.2%) patients, with a 75.9% success rate. Risk factors identified for failure of the initial treatment were having a high sequential organ failure assessment (SOFA) score at diagnosis of infection and being in palliative care; introduction of ALT at the start of treatment was identified as a protective factor. Risk factors identified for 30-day mortality after LTCVC-associated infection were a high SOFA score at diagnosis, infection with MDR bacteria, and palliative care; introduction of ALT at the start of treatment, hematological malignancies, and adherence to an institutional protocol for the management of LTCVC-associated infection were identified as protective factors. Despite the high incidence of infection with MDR bacteria, ALT improves the outcome of LTCVC-associated infection in cancer patients., (Copyright © 2018 American Society for Microbiology.)

Purpose: Patients with hematological malignancies (HMs) are at a higher risk for bloodstream infections (BSIs), which pose significant burden on morbidity and mortality. Better risk stratification helps in medical decision making, increasing efficiency and reducing economic burden. The aim of this study was to develop and validate a reliable prediction model which can be used to identify HM patients at higher risk for BSIs., Methods: We conducted a retrospective cohort study in three university-affiliated hospitals in Hunan Province, China, from January 2010 to April 2015. A total of 521 HMs patients with BSIs were finally included in this study and were divided into the derivation set and validation set. Survivors and non-survivors were compared to identify the predictors of 30-day mortality., Results: The multivariate analysis yielded the following significant mortality-related risk factors: age > 60 years (95% CI 1.047-5.474), relapsed or uncontrolled malignancy (95% CI 2.043-14.029), Pitt bacteremia score > 3 (95% CI 1.614-6.35), prolonged neutropenia (95% CI 1.181-5.824), use of vasopressors (95% CI 3.009-12.210), acute respiratory failure (95% CI 3.061-14.911), fungemia (95% CI 1.334-12.121), inadequate antibiotic treatment (95% CI 1.682-7.591), albumin < 30 g/L (95% CI 1.030-3.446), TBil > 34.2 µmol/L (95% CI 1.109-5.438). In both derivation and validation sets, our model showed reliable prediction value with areas under the receiver operating curve of 0.876 and 0.873., Conclusions: The risk factors in this study have the ability to identify patients with HMs and BSIs at high risk for mortality. Our model provides an excellent foundation for predicting 30-day morality in HM patients suffering from BSI and helps target high-risk patients for management decision making.

In a cohort of inpatients with hematologic malignancy and positive enzyme immunoassay (EIA) or polymerase chain reaction (PCR) Clostridium difficile tests, we found that clinical characteristics and outcomes were similar between these groups. The method of testing is unlikely to predict infection in this population, and PCR-positive results should be treated with concern.Infect Control Hosp Epidemiol 2018;863-866.

Bloodstream and venous catheter-related corynebacterial infections in paediatric patients with haematological cancer were investigated from January 2003 to December 2014 at the Brazilian National Cancer Institute in Rio de Janeiro, Brazil. We observed that during cancer treatment, invasive corynebacterial infections occurred independent of certain factors, such as age and gender, underlying diseases and neutropenia. These infections were ssscaused by Corynebacterium amycolatum and other non-diphtherial corynebacteria. All cases presented a variable profile of susceptibility to antimicrobial agents, except to vancomycin. Targeted antibiotic therapy may contribute to catheters maintenance and support quality of treatment. Non-diphtherial corynebacteria must be recognized as agents associated with venous access infections. Our data highlight the need for the accurate identification of corynebacteria species, as well as antimicrobial susceptibility testing., (Copyright © 2018. Published by Elsevier Editora Ltda.)

Background: Patients hospitalized with hematologic malignancy are particularly vulnerable to infection. The impact of reported beta-lactam (BL) allergy in this population remains unknown., Methods: This was a retrospective cohort study of adult inpatients with hematologic malignancy admitted at 2 tertiary care hospitals from 2010 through 2015. The primary outcome was hospital length of stay (LOS) after administration of the first antibiotic. Secondary outcomes included readmission, mortality, complications, hospital charges, and antibiotic usage. Our goal was to define the impact of BL-only allergy (BLOA) label on clinical outcomes compared to those with no BL allergy (NBLA) in hematologic malignancy inpatients who required systemic antibiotics., Results: In our cohort (n = 4671), 38.3% had leukemia, 4.9% had Hodgkin lymphoma, 36.1% had non-Hodgkin lymphoma, and 20.7% had multiple myeloma. Among patients, 35.1% reported antibiotic allergy, and 14.1% (n = 660) had BLOA (including 9.3% with penicillin-only allergy and 3.3% cephalosporin-only allergy). Patients with BLOA had longer median LOS compared to patients with NBLA (11.3 vs 7.6 days, P < .001), which remained significant after multivariable adjustment. Patients with BLOA also had significantly worse outcomes in terms of mortality rate at 30 days (7.6% vs 5.3%, P = .017) and 180 days (15.8% vs 12.2%, P = .013), 30-day readmission rate, Clostridium difficile rate, hospital charges ($223 046 vs $173 256, P < .001), antibiotic classes used, and antibiotic duration., Conclusions: In hospitalized patients with hematologic malignancy, patients with reported BL allergy had worse clinical outcomes and higher healthcare cost than those without BL allergy label.

Introduction: Successful treatment of haematological malignancies is frequently complicated by Invasive Aspergillosis (IA), a life-threatening fungal infection that occurs in at least 10% of haemato-oncological patients. Case fatality rates (CFR) may fluctuate over time, depending on host pathogen interactions as well as on treatment and quality of patient care. We conducted a systematic review and metaanalysis of current - i.e. 2008-revised EORTC-MSG criteria era - incidence and case fatality rates (CFR) of IA in patients with haematological malignancy., Methods: A systematic search according to PRISMA guidelines was performed to identify all literature reporting populations with a haematological malignancy and the incidence of IA, defined according to the EORTC/MSG 2008 criteria. Pooled cumulative incidences and CFR within 100 days were estimated using a random effects model for predefined patient populations and stratified by use of prophylaxis., Results: The systematic literature search yielded 1285 publications of which n = 49 met the inclusion criteria. Overall, 16.815 patients were involved of which 1056 (6.3%) developed IA. IA risk ranged from 4% (during remission-induction, with prophylaxis) to 11% (during remission-induction, without prophylaxis). Antifungal prophylaxis was associated with a lower rate of IA, especially in the pre-HSCT population. The pooled CFR within 100 days was 29% (95% CI: 20-38%)., Discussion: This study confirms that IA is a relevant threat in the treatment of haematological cancer despite the universal use of antifungal prophylaxis. These outcomes inform scientists and other stakeholders about the current burden of IA and may be used to direct, implement and improve antifungal stewardship programs., (Copyright © 2018. Published by Elsevier Ltd.)

Invasive aspergillosis (IA) is a life-threatening infection affecting haematological cancer patients with chemotherapy-induced neutropenia. The diagnosis of IA often relies on the detection of galactomannan (GM) in serum or bronchoalveolar lavage fluid (BAL). Bi-weekly serum GM screening has been proposed for a pre-emptive therapeutic approach of IA in patients not receiving mold-active prophylaxis. We have analysed all IA cases among patients with haematological malignancies and prolonged chemotherapy-induced neutropenia (>14 days) in our institution over a 10-year period (2007-2017). Serum GM was measured twice weekly and mold-active prophylaxis was not routinely administered. Thirty IA cases were observed and a positive serum GM was the first indicator of IA in 10 (33%) of them, which represents a need of approximately 500 GM tests for the detection of a single IA case. In the other 20 (67%) cases, suggestive chest CT lesion was the first sign of IA and bronchoscopy was required in 15 (50%) cases with negative serum GM for establishing the diagnosis of probable/proven IA. A positive serum GM was associated with a worse prognosis (57% 12-week survival vs 100% among serum GM-negative patients, P = .006), irrespective of the timing of GM positivity compared to CT. We concluded that bi-weekly serum GM screening demonstrated limited benefit in this population., (© 2018 Blackwell Verlag GmbH.)

Objectives: Exhaled breath condensate (EBC) is a noninvasive means of sampling the airways that has shown significant promise in the diagnosis of many disorders. There have been no reports of its usefulness in the detection of galactomannan (GM), a component of the cell wall of Aspergillus. The suitability of EBC for the detection of GM for the diagnosis of invasive aspergillosis (IA) using the Platelia Aspergillus enzyme-linked immunosorbent assay was investigated., Methods: Prospective, cross-sectional study of lung transplant recipient and haemotologic malignancy patients at a university centre. EBC samples were compared to concomitant bronchoalveolar lavage (BAL) samples among lung transplant recipients and healthy controls. EBC was collected over 10 minutes using a refrigerated condenser according to the European Respiratory Society/American Thoracic Society recommendations, with the BAL performed immediately thereafter., Results: A total of 476 EBC specimens with 444 matched BAL specimens collected from lung transplant recipients (n = 197) or haemotologic malignancy patients (n = 133) were examined. Both diluted and untreated EBC optical density (OD) values (0.0830, interquartile range (IQR) 0.0680-0.1040; and 0.1130, IQR 0.0940-0.1383), respectively, from all patients regardless of clinical syndrome were significantly higher than OD values in healthy control EBCs (0.0508, IQR 0.0597-0.0652; p < 0.0001). However, the OD index values did not correlate with the diagnosis of IA (44 samples were associated with IA). Furthermore, no significant correlation was found between EBC GM and the matched BAL specimen., Conclusions: GM is detectable in EBC; however, no correlation between OD index values and IA was noted in lung transplant recipients., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Posaconazole is superior to fluconazole or itraconazole in preventing invasive fungal diseases (IFDs) in patients with haematological malignancies; however, there have been reports of the comparing posaconazole and voriconazole., Methods: This single-centre, retrospective study in China enrolled AML, ALL and MDS patients, among others. Prophylaxis with posaconazole or voriconazole was administered for patients recovering from neutropenia or who had achieved complete remission. The primary emphasis was proven, probable, or possible IFDs during treatment. The cost-effectiveness, the proportion of adverse events and systemic antifungal treatment were the secondary emphasis., Results: A total of 164 patients were recruited to receive posaconazole (n=81) or voriconazole (n=83). The incidence rates of proven, probable or possible IFD were 2.46% (2/81) and 4.82% (4/83) in the posaconazole group and voriconazole groups, respectively (P>0.05). Only one patients experienced adverse events on posaconazole, while eleven patients experienced such events on voriconazole (P=0.003). Patients receiving posaconazole or voriconazole had similar proportions of systemic antifungal treatment: 18.52% (15/81) in the posaconazole group and 16.87% (14/83) in the voriconazole group (P>0.05). In the cost-effectiveness analysis, the prognosis of the two groups was close, but the drug acquisition costs of posaconazole were higher than those of voriconazole (P=0.021)., Conclusion: Posaconazole and voriconazole have the same prophylactic effect against IFDs in high-risk neutropenic Chinese patients. However, the safety of posaconazole is superior to that of voriconazole, while in terms of cost-effectiveness, voriconazole has an advantage over posaconazole., (Copyright © 2017. Published by Elsevier Masson SAS.)

Objectives: Definitive diagnosis of invasive candidiasis (IC) may be difficult to achieve in patients with haematological malignancy (PHM). We aimed to evaluate the performance of BDG for the diagnosis and the follow-up of IC in PHM., Patients and Methods: We retrospectively reviewed the serological data of BDG assay in adult and paediatric PHM, who developed candidemia or chronic disseminated candidiasis (CDC) through a 4-year period. Sensitivity and kinetics of BDG were determined for both clinical forms., Results: In a panel of 3027 PHM, incidence rates of candidemia and CDC ranged between 0.74 and 0.77 and 0.30 and 0.44 according to the group of patients. At the time of diagnosis, 43.5% and 73% of cases of candidemia and CDC had a positive BDG assay, respectively. We found a significant correlation between the level of BDG at diagnosis and the outcome of candidemia (p = 0.022). In all cases of CDC, BDG negative results were obtained 2 to 6 months before recovery of the CT-scan lesions., Conclusions: BDG exhibits a low sensitivity to detect IC in PHM, but its kinetics correlates the clinical outcome. Additional studies are warranted in patients with CDC to evaluate the interest of monitoring BDG levels to anticipate the discontinuation of antifungal maintenance therapy., (Copyright © 2018 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To describe the trend of multidrug resistant (MDR) strains isolated from blood in patients with cancer from 2005 to 2015., Material and Methods: 33 127 blood cultures were processed by retrospective analysis. Identification and antimicrobial sensitivity were performed through automated methods: WaLK away (Siemens Labora- tory Diagnostics) and BD Phoenix (Becton, Dickinson and Company). Resistant strains were determined according to the minimum inhibitory concentration, following the parameters of the Clinical and Laboratory Standards Institute (CLSI)., Results: Of 6 397 isolates, 5 604 (16.9%) were positive; 3 732 (58.4%) Gram- bacilli; 2 355 (36.9%) Gram+ cocci; 179 (2.7%) yeasts, and 126 (1.9%) Gram+ bacilli. Escherichia coli (n=1 591, 24.5%) was the most frequent bacteria, with 652 (41%) strains being extended-spectrum beta-lactamases producers (ESBL); of Enterococcus faecium (n=143, 2.1%), 45 (31.5%) were vancomycin resistant; of Staphylococcus aureus (n=571, 8.7%), 121 (21.2%) methicillin resistant (MRSA); of Klebsiella pneumoniae (n=367, 5.6%), 41 (11.2%) ESBL; of Acinetobacter baumanii (n=96, 1.4%), 23 (24%) MDR, and of Pseudomonas aeruginosa (n=384, 5.6%), 43 (11.2%) MDR. MDR strains were significantly more frequent in patients with hematological malignancies, compared to those with solid tumors: MRSA (OR=4.48, 95%CI 2.9-6.8), ESBL E. coli(OR=1.3, 95%CI 1.10-1.65) and MDR Acinetobacter baumanii (OR=3.2, 95%CI 1.2-8.3)., Conclusions: We observed significantly higher isolations of E-ESPAKE MDR strains in patients with hematological malignancies., Competing Interests: Declaration of conflict of interests. The authors declare that they have no conflict of interests.

Viridans group streptococci bloodstream infections (VGS BSI) remain a significant cause of mortality and morbidity in patients with severe neutropenia. The goal of our study was to evaluate clinical course and microbiological susceptibility of VGS BSI at our center. Retrospective analysis of all microbiologically documented bloodstream infections caused by VGS during the 9-year time period (from January 2006 until December 2014) was carried out. Only patients with severe neutropenia (< 500/μL) were included in the study. Clinical outcome and microbiological susceptibility pattern of isolates were recorded. Fifty-one individual patients with episode of VGS BSI were identified. The most frequent agent was Streptococcus mitis (23/51 cases, 45.1%). 88.2% (45/51) of patients were on recommended ciprofloxacin prophylaxis. 20/51 (39.2%) of patients suffered from mucositis at the time of diagnosis (10 patients had oral mucositis, 2 patients had bowel mucositis, and 8 patients both). Twenty-six patients (51.0%) had clinically relevant lung damage caused by VGS BSI (i.e., acute lung injury or acute respiratory distress syndrome). Twenty-four (47.0%) patients presented with bilateral lung infiltrated upon chest imaging, and two (4.0%) patients had unilateral lung infiltrates. Three patients (5.9%) died due to VGS BSI until day 28 of observation. No difference in signs of shock syndrome was observed in the patients during transplantation procedures compared to patients without transplantation as well as in a group received previous high-dose chemotherapy with cytosinarabinoside or in patients with mucositis. Only 3/51 of isolates (5.9%) were resistant to penicillin. All isolates were susceptible to empirical treatment. While the penicillin resistance of VGS remains low in middle Europe, initial antibiotic therapy of febrile neutropenia are still effective in most cases. The mortality and complication rates of VGS BSI were comparable to other studies, and no specific risk factor of shock presence could be identified.

Background: Posaconazole is a triazole with limited pharmacokinetic information in children. This study assessed the correlation between posaconazole oral solution daily dosage/kg/body weight and trough plasma level., Methods: A total of 97 hematology-oncology pediatric patients with ≥1 posaconazole plasma concentration level (PPC) assessment in the first 6 weeks after the start of posaconazole treatment were included., Results: Posaconazole was used as prophylaxis in 84 of 97 (87%) patients and as therapy in 13 of 97 (13%). The median daily dose/kg/bw ranged from 10 to 12 mg in the prophylaxis group and 12.5 to 16.5 mg in the therapy group. The median value of PPC for the prophylaxis group was 0.9 and 0.8 μg/mL at the first and second/third determinations, respectively. Posaconazole prophylaxis failed in 4 of 84 patients (5%). The median value of PPC for the therapy group was 1.5 and 1.4 μg/mL at the first/second and the third determination, respectively. Posaconazole-related side effects were reported in 6 patients and all regressed with the suspension of the drug. In the prophylaxis group, the use of proton-pump inhibitors was significantly associated with a lower PPC, P = 0.04., Conclusions: Posaconazole may be a valuable antifungal agent in children despite the incomplete knowledge of its pharmacokinetic characteristics., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Stenotrophomonas maltophilia (SM) has emerged as an important nosocomial pathogen with high morbidity and mortality. Because of its unique antimicrobial susceptibility pattern, appropriate antimicrobial therapy for SM bacteremia is still challenging, especially in immunocompromised patients. The present study was performed to assess clinical predictors of SM bacteremia in adult patients with hematologic malignancy. From 2006 through 2016, a case-control study was performed at a tertiary-care hospital. Case patients were defined as SM bacteremia in patients with hematologic malignancy. Date- and location-matched controls were selected from among patients with gram-negative bacteremia (GNB) other than SM. A total of 118 cases of SM bacteremia were identified and compared to 118 controls. While pneumonia was the most common source of SM bacteremia, centralline-associated infection was most common in the controls. The overall 30-day mortality rate of cases with SM bacteremia was significantly higher than that of the controls (61.0 and 32.2%, respectively; P < 0.001). A multivariable analysis showed that polymicrobial infection, previous SM isolation, the number of antibiotics previously used ≥ 3, and breakthrough bacteremia during carbapenem therapy were significantly associated with SM bacteremia (all P < 0.01). Previous use of trimethoprim/sulfamethoxazole (TMP/SMX) was negatively association with SM bacteremia (P = 0.002). Our data suggest that SM is becoming a significant pathogen in patients with hematologic malignancy. Several clinical predictors of SM bacteremia can be used for appropriate antimicrobial therapy in hematologic patients with suspected GNB.

Posaconazole is an antifungal drug used in both prophylaxis and treatment of invasive fungal infections. Its oral formulation requires therapeutic drug monitoring. To overcome gastric acidity, a gastro-resistant posaconazole tablet has recently been developed. POSANANTES was a prospective noninterventional study that aimed to monitor plasma concentration trough level ( C min ) of posaconazole tablets used prophylactically in patients with hematological malignancies. Fifty patients were included. Group A ( n = 31) included patients receiving induction chemotherapy for myeloid malignancies, and group B ( n = 19) included patients treated for graft-versus-host disease after allogeneic hematopoietic stem cells transplantation. In multivariate analysis, female sex, group B assignment, and evaluation of C min at day 8 (versus any other day planned by the analysis) were associated with a higher C min , while diarrhea was associated with a lower C min ( P < 0.05). Thirty-four percent ( n = 17) of all included patients had to prematurely stop treatment, mainly in group A. In conclusion, this real-life prospective study showed good absorption of posaconazole tablets used for prophylaxis in patients with hematological malignancies, even though this strategy was somewhat limited due to the high number of patients in group A who had to stop their treatment in an untimely fashion., (Copyright © 2018 American Society for Microbiology.)

Objective: To analyze the risk factors for mortality of blood stream infections (BSIs) caused by Escherichia coli in the patients with hematological malignancies., Methods: There were 110 Escherichia coli BSIs patients with hematological malignancies included in recent five years. Among them,77 cases had BSIs caused by extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli (ESBL-EC group),while 33 cases had BSIs with non-ESBL-producing Escherichia coli (non-ESBL-EC group). The antibiotic resistance and clinical features were compared between the two groups,and the risk factors for death within 30 d were analyzed., Results: Less than 10% of the isolates were resistant to carbapenems and amikacin. Between ESBL-EC group and non-ESBL-EC group,the clinical symptoms,prior use of antibiotics or antifungal agents,risk factors for infection,30 d mortality rates were not significantly different ( P >0.05). A logistic regression analysis confirmed that non remission of hematologic malignancies (odds ratio=9.575,95% confidence interval 1.546-59.312, P =0.015) and inappropriate initial antibiotic therapy (odds ratio=8.806,95% confidence interval 1.527-50.772, P =0.015) were independent risk factors for 30 d mortality., Conclusion: The use of effective antimicrobial treatment as early as possible could reduce the risk of death for hematological malignancies patients suffering Escherichia coli BSIs., (CopyrightCopyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Infections remain a threat for patients with haematological malignancies. In accordance with the European Hematology Association roadmap we provide a concise overview regarding the most relevant current challenges in infectious diseases for haematologists. These include bacterial infections and the need for antibiotic stewardship as well as infections with community-acquired respiratory viruses, infections in patients receiving targeted therapies, re-activations of latent infections and vaccination strategies. The following review intends to summarise the most relevant information for clinicians currently caring for patients with haematological malignancies. Recommendations given are based on the guidelines published by the Infectious Diseases Working Party of the German Society of Haematology and Medical Oncology., (© 2018 S. Karger GmbH, Freiburg.)