Infections In Haematological Patients Research Articles

Endemic viral infections in immunocompromised hosts: Dengue, Chikungunya, Zika.

Arbovirus infections are a challenge for immunocompromised hosts who travel to or live in endemic regions or who receive organs or tissues from donors who travel or live in such areas. This review addresses Dengue (DENV), Chikungunya (CHIKV), and Zika (ZIKV) infections in hematological patients, hematopoietic cell or solid organ transplant recipients, and people with HIV (PWH). Transmission is mainly due through Aedes mosquito bite. DENV and ZIKV may also be transmitted through blood, tissues or donor grafts. Clinical manifestations are quite similar and diagnosis requires laboratory confirmation to provide appropriate management. The best diagnostic method is PCR since serology may present false negative results in immunocompromised patients, or cross-reactivity as in the case of DENV and ZIKV. There is no specific treatment for any of these infections. Educational and preventive measures are the best strategy: vector control, knowledge of the vector's habits, protection against mosquito bites, avoiding travel to endemic areas or with a current epidemic, and avoiding nonvector transmission according to local recommendations for donor deferral. Vaccination, currently only available for DENV, has not yet been studied in immunocompromised patients and is not currently recommended.

Risk factors of Carbapenem-resistant Enterobacterales intestinal colonization for subsequent infections in hematological patients: a retrospective case-control study.

Infections caused by Carbapenem-resistant Enterobacterales (CRE) have high treatment costs, high mortality and few effective therapeutic agents. This study aimed to determine the risk factors for progression from intestinal colonization to infection in hematological patients and the risk factors for 30-day mortality in infected patients. A retrospective case-control study was conducted in the Department of Hematology at Shandong Provincial Hospital affiliated to Shandong First Medical University from April 2018 to April 2022. Patients who developed subsequent infections were identified as the case group by electronic medical record query of patients with a positive rectal screen for CRE colonization, and patients who did not develop subsequent infections were identified as the control group by stratified random sampling. Univariate analysis and logistic regression analysis determined risk factors for developing CRE infection and risk factors for mortality in CRE-infected patients. Eleven hematological patients in the study developed subsequent infections. The overall 30-day mortality rate for the 44 hematological patients in the case-control study was 11.4% (5/44). Mortality was higher in the case group than in the control group (36.5 vs. 3.0%, P = 0.0026), and septic shock was an independent risk factor for death (P = 0.024). Univariate analysis showed that risk factors for developing infections were non-steroidal immunosuppressants, serum albumin levels, and days of hospitalization. In multivariable logistic regression analysis, immunosuppressants [odds ratio (OR), 19.132; 95% confidence interval (CI), 1.349-271.420; P = 0.029] and serum albumin levels (OR, 0.817; 95% CI, 0.668-0.999; P = 0.049) were independent risk factors for developing infections. Our findings suggest that septic shock increases mortality in CRE-infected hematological patients. Hematological patients with CRE colonization using immunosuppressive agents and reduced serum albumin are more likely to progress to CRE infection. This study may help clinicians prevent the onset of infection early and take measures to reduce mortality rates.

Application of plasma metagenomic next-generation sequencing improves prognosis in hematology patients with neutropenia or hematopoietic stem cell transplantation for infection.

Metagenomic next-generation sequencing (mNGS) is a novel technique for detecting pathogens. This retrospective study evaluated the diagnostic value of mNGS using plasma for infections in hematology patients and its impact on clinical treatment and prognosis in different subgroups of hematology patients. A total of 153 hematology patients with suspected infection who underwent mNGS using plasma were enrolled in the study. Their clinical histories, conventional microbiological test (CMT) results, mNGS results, treatment and prognosis were retrospectively analyzed. In 153 plasma samples, mNGS yielded a higher positivity rate than CMT (total: 88.24% vs. 40.52%, P<0.001; bacteria: 35.95% vs. 21.57%, P < 0.01; virus: 69.93% vs. 21.57%, P<0.001; fungi: 20.26% vs. 7.84%, P<0.01). mNGS had a higher positivity rate for bacteria and fungi in the neutropenia group than in the non-neutropenia group (bacteria: 48.61% vs. 24.69%, P<0.01; fungi: 27.78% vs. 13.58%, P<0.05). mNGS demonstrated a greater advantage in the group of patients with hematopoietic stem cell transplantation (HSCT). Both the 3-day and 7-day efficacy rates in the HSCT group were higher than those in the non-HSCT group (3-day: 82.22% vs. 58.65%, P < 0.01; 7-day: 88.89% vs. 67.31%, P < 0.01), and the 28-day mortality rate was lower in the HSCT group than in the non-HSCT group (6.67% vs. 38.89%, P < 0.000). The neutropenia group achieved similar efficacy and mortality rates to the non-neutropenia group (7-day efficiency rate: 76.39% vs. 71.43%, P > 0.05; mortality rate: 29.17% vs. 29.63%, P > 0.05) with more aggressive antibiotic adjustments (45.83% vs. 22.22%, P < 0.01). mNGS can detect more microorganisms with higher positive rates, especially in patients with neutropenia. mNGS had better clinical value in patients with hematopoietic stem cell transplantation (HSCT) or neutropenia, which had a positive effect on treatment and prognosis.

Rare Invasive Fungal Infections in Hematologic Patients: A Large Unicentric Series

Introduction: Invasive fungal infections (IFI) are a major cause of infectious mortality in immunocompromised hematologic patients. While Candida spp and Aspergillus spp account for most cases, IFI by so-called “rare” fungi (about 1% of all IFI) are clinically relevant, with challenging diagnoses (including difficult phenotypic identification and misinterpretation as contaminants) and insufficient data on antifungal susceptibility to guide treatment guidelines. International efforts to record the epidemiology of these rare IFIs are fundamental to help overcome the lack of data that hinders successful diagnosis and treatment. Methods: We reviewed all fungal infections diagnosed in our Hematology Department in adults (18 years and over) from 06.01.2006 to 03.31.2023, selecting cases with identification of rare fungi by mycologic methods. The date of “Diagnosis” (Dx) was that of collection of the first positive sample. Results: A total of 67 patients (pts, 52.2% male) with a median age of 63.6 years (mean: 59.2, range: 23.2-90.0) were included; 68.7% had acute leukemias - 89.4% of which myeloid (AML), 13.0% lymphoblastic, 4.4% promyelocytic and 2.2% of ambiguous lineage - and 4.5% had myelodysplastic syndromes; 20.9% had a chronic lymphoproliferative disease, 3.0% had aplastic anemia and 3.0% had plasma cell dyscrasias. There was an average of 4 cases of rare IFI per year (range: 0-9), with a peak in 2017 (13.4% of total); 50.8% of all infections diagnosed over the nearly 17 years of the study occurred in the 5 years between 2013-2017, a period of renovation work in our hospital. Time to Dx ranged from 0 (collection on the day of hospitalization) to 98 days (mean: 25.4; median: 22 days). Identification of the fungus took a median of 5 days (mean: 5.6, range: 2-16 days) from the time of collection. In 8 patients (12.9%), the lab report with a fungal identification was released post-mortem; in these pts, results were available a median of 3.5 days after exitus (mean: 5.4, range: 1-13 days). In 79.1% of pts, a yeast was isolated (68.7% Geotrichum-like), while in 20.9% a filamentous fungus was identified (3.0% Mucorales). The most frequent genera were Geotrichum (62.7%), Saprochaete (5.8%), Fusarium and Alternaria (4.5% each). Cryptococcus, Trichosporon and Penicillium accounted for 3% of infections each, with 9 additional species identified in single pts. Fungemia was found in 58.2% of pts (in peripheral blood in 52.2%; in central access blood in 38.8%; in both in 32.8%). Pulmonary isolates were obtained in 26.9% of pts (in sputum in 19.4%; in bronchial aspirate or lavage in 10.4%; in both in 3.0%). Urinary isolates were found in 6.0% of pts; 13.4% had fungi in other biologic samples. The median overall survival was 20 days; 32.6% of pts died within a week of Dx, 45.6% within the first fortnight and 60.9% within the first month; 26.1% died between 1 and 3 months from Dx; and 13.0% died over 3 months after Dx. At the time of the study, 5 pts (7.5% of the cohort) were still alive, all with yeast infections; survivors had evidence of fungemia in 20% of cases and pulmonary involvement in 60%. Discussion: In our large clinical series, AML was responsible for nearly 2/3 of cases of rare IFI, reflecting its overall increased risk for IFI. The rarity of these agents was highlighted by the fact that our tertiary hematology center, serving a population of 2.3 million, had an average of 4 cases of rare IFI per year; yearly variations were in part accounted for by construction work (which releases fungal spores). Dx varied from the day of admission to over 3 months into hospitalization, reflecting a range from community-acquired to nosocomial infections; the average pt had been in hospital for 3 weeks by the time they were diagnosed. There were 4-fold more yeast infections than filamentous fungi, with Geotrichum and related yeasts accounting for 2/3 of cases. Fungemia was present in over half of patients, and pulmonary infiltrates in 1/4, a proportion that was reversed in survivors. Fungal identification took up to a fortnight, and over 10% of patients were dead before a Dx was established, not benefiting from directed treatment. The high lethality of these infections was underlined by the fact that 1/3 died within a week of Dx, with a median OS of 3 weeks. About 1/10 of pts died more than 3 months from Dx, with progressive hematologic disease being the most likely cause of death in that pt subset; less than 10% of the cohort is currently alive, and in remission.

COVID-19 omicron variant outbreak in a hematopoietic stem cell transplant unit.

Recommendations and guidelines for management of SARS-COV-2 infection in hematologic patients were developed in the very difficult context of dealing with novel viral variants from one pandemic wave to another, with different susceptibility to available drugs and vaccines. Moreover, the largest SARS-COV-2 case series in patients treated for hematologic malignancies, including stem cell transplant recipients, was published before the Omicron surge, and refers mainly to Alpha and Delta viral variants. These infections had very high mortality, in a period when antivirals and monoclonal antibodies were mostly unavailable. Here, we report for the first time a SARS-COV-2 Omicron variant outbreak inside a Bone Marrow Transplant (BMT) Unit, describing the characteristics, clinical course, and infection outcomes shortly before and shortly after myeloablative transplantation. We detail how infections were treated off-label and managed inside the BMT ward, to guarantee the best possible outcomes while avoiding risks for non-infected inpatients. The positive outcomes observed suggest that it may not be absolutely necessary to obtain SARS-CoV-2 PCR negativity before BMT in hematologic patients after treated infection, in cases with long-term PCR positivity and high-risk hematologic disease.

Molecular epidemiology and disease severity of influenza virus infection in patients with haematological disorders.

Influenza virus infection is a common cause of self-limiting respiratory tract infection (RTI), however immunocompromised patients are at an increased risk for a severe course of disease or fatal outcome. We therefore aimed to gain a better understanding of the molecular epidemiology of influenza viruses from patients with haematological disorders and their impact on the clinical course of disease. Molecular analysis using polymerase chain reaction (PCR) of nasopharyngeal swabs was performed for influenza virus in haematological patients at the Heidelberg University Hospital. Clinical data was evaluated to identify associated risk factors. For phylogenetic analysis, the hemagglutinin (HA) gene was sequenced. Out of 159 influenza positive patients, 117 patients developed upper RTI (influenza A: n = 73; influenza B: n = 44). Lower RTI was observed in n = 42 patients (26%), n = 22/42 patients developed severe disease and n = 16/159 (10.1%) patients died. Risk factors for lower RTI were nosocomial infection (p = 0.02), viral shedding for ≥14 days (p = 0.018), IgG levels <6 g/dL (p = 0.046), bacterial/fungal co-infections (p < 0.001). Risk factors for fatal outcome were age ≥65 years (p = 0.032), bacterial/fungal (p≤0.001) co-infections and high viral load (p = 0.026). Sequencing of the HA gene (n = 115) revealed subtype A(H3N2) (n = 46), A(H1N1)pdm09 (n = 24), B/Victoria (n = 34), B/Yamagata (n = 11). There was no correlation between influenza (sub)type and lower RTI. Influenza infection in haematological patients is associated with significant morbidity and mortality, the risk for aggravating co-infections, prolonged viral shedding and nosocomial transmission emphasizing the need for infection control.

Risk factors and outcomes for carbapenem-resistant klebsiella pneumoniae in hematological patients

Background Prolonged hospitalization, prolonged neutropenia, and immunosuppressive treatments increase bloodstream infections in hematological patients. Identifying risk factors for carbapenem-resistant Klebsiella pneumonia (CRKP) infection will shed light on controlling the spread of CRKP. Our retrospective study aimed to determine the clinical features, antimicrobial susceptibility, and mortality risk factors of patients who developed CRKP in patients followed up for hematological cancer in the Izmir University of Economics Haematology Department.&#x0D; Material and Methods 19,170 blood-urine-sputum cultures were delivered from the patients, 1,595 (8.31%) of which presented growth. CRKP comprised 302 (1.57%) of such growth cases. The study included 72 patients with hematological malignancy who presented CRKP growth in 302 cultures obtained during the neutropenic fever period.&#x0D; Results The mean age of patients was 51 (18-75 years). Acute myeloid leukemia was the most common disease (n: 26, 36.11%). As to the antibiotic sensitivity of CRKP, 44 patients (61.1%) were colistin sensitive, 28 patients (38.9%) were colistin-resistant, 47 patients (65.3%) were tigecycline sensitive/medium sensitivity, 25 patients (34.7%) were tigecycline resistant, there was no statistically significant difference between antibiotic sensitivities and survival.&#x0D; Conclusions Today, early detection of CRKP colonization in high-risk hematological patients, taking rectal culture, and if the patient presents rectal colonization of CRKP or had CRKP bacteremia during prior hospitalizations, early initiation of treatment with antibiotics acting against CRKP during NPF would significantly reduce mortality.

A case report of 3 saprochaete clavate disseminated infections in hematological patients at irccs ospedale policlinico san martino, genoa, liguria, north-west italy

A case report of 3 saprochaete clavate disseminated infections in hematological patients at irccs ospedale policlinico san martino, genoa, liguria, north-west italy

Fungal infections in pediatric patients with acute myeloid leukemia in a tertiary hospital.

Acute leukemia accounts for more than 30% of all pediatric cancer cases, and of these, 15-20% are acute myeloid leukemia (AML). Children who super from AML are more likely to develop infections due to the humoral and cellular immune deficits generated by the disease and its treatment. The incidence of fungal infections is underestimated; reports show that up to 75% of fungal infections go undiagnosed until autopsy. In only 30 years, the incidence of invasive candidiasis has increased by 40-fold. Thus, the high morbidity and mortality associated with fungal infections in hematological patients make it necessary to adopt preventive measures. This work aimed to retrospectively identify pediatric patients with acute myeloid leukemia and invasive fungal diseases (IFDs) in a Latin American tertiary care hospital. A retrospective analysis of 36 clinical records of pediatric patients diagnosed with AML from 2007 to 2017 was carried out. One hundred and twenty-nine hospitalizations were associated with infectious events. Thirteen patients in our study presented 15 infectious events associated with IFDs (11.6%). Two patients died because of complications related to IFDs (15.3%). The most frequent IFD type was aspergillosis, which was observed in 7 cases, followed by Candidemia, which was observed in 4 cases. The most frequent clinical manifestations were fever and respiratory distress. Mortality due to IFD can be prevented with effective pharmacotherapy. An appropriate antifungal prophylaxis strategy still needs to be developed through larger prospective studies in Latin America.

The Role of Metagenomics Next-Generation Sequencing (mNGS) in Early Diagnosis of Bloodstream Infection in Hematologic Patients with Febrile Neutropenia: A Multicenter Prospective Study

Background: Bloodstream infection (BSI) is a lethal complication in hematologic patients with febrile neutropenia (FN). The delayed diagnosis and intervention will lead to significant mortality. Unfortunately, the traditional golden standard diagnostic method using blood culture (BC) can only identify pathogens in 20-30% patients with BSI, and usually needs more than 48 hours. Therefore, novel methods with fast turnover, improved sensitivity and specificity are needed. Metagenomics next-generation sequencing (mNGS) shows promise as diagnostic testing for difficult and critical infectious diseases in immunodeficient hosts, but its significance in BSI of hematological patients remains unclear, and has not been evaluated in prospective study. Aims: To evaluate the ability of mNGS to identify infectious etiologies in FN patients with BSI. Method: This study was prospective performed in four Chinese hematologic centers since October 2021. For patients≥15 years with hematologic diseases, patients were screened at the onset of neutropenia. At the onset of FN, Peripheral blood specimens were collected per subject for simultaneous BC and mNGS (separate sequencing for plasma and blood cells). All patients will be followed for 14 days, or until death before 14 days. The intervention was per the attending physician. The primary endpoints of this study is the sensitivity and specificity of mNGS. Thepositive agreement was defined as mNGS identified at least one same pathogen as initial BC. The negative agreement was defined as both mNGS and BC were negative. And the adjudication of the result of BC, mNGS, and clinical diagnosis was evaluated by 4 independent specialists in hematology. Clinical adjudication categorized mNGS results as: Definite, mNGS identified at least one pathogen also found by BC or SMT with in 7 days; Probable, mNGS result was concordant with a clinical diagnosis of BSI in FN; Possible, mNGS result was consistent with BSI but not considered a common cause of FN; Unlikely, mNGS result was not a plausible cause of BSI in FN. This study was registered on ClinicalTrials.gov ID: NCT05149547. This is an interim analysis of 134 patients enrolled in this multicenter, prospective observational study. Results: Te basic information of the patients was summarized in table 1. Clinical adjudication categorized mNGS results as: Definite (N=24); Probable (N=21); Possible (N=7); Unlikely (N=49). Definite, probable and possible cases were regarded as true positives. The positive percent agreement (PPA) and negative percent agreement (NPA) with BC were 80.0% (20/25) and 25.7% (28/109) respectively; 44% of mNGS results were polymicrobial (except viruses). According to the clinical adjudication, mNGS sensitivity and specificity were 94.6% (52/55) and 38.0% (30/79) respectively (table 2 and table 3). Compared with BC, the reporting time of mNGS was significant shorter (24.8±4.0 vs. 72.3±21.2 h, p < 0.05). Conclusions: Compared with conventional BC, mNGS might provide an early and rapid microbiological diagnosis of BSI in hematologic patients with FN. However, the clinical application needs pending further study. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Risk Factors and Outcome of COVID-19 Infection in Haematological Patients : A Multicenter Retrospective Analysis in Malaysia

Introduction: Hematological patients as immunocompromised hosts are vulnerable to severe COVID-19 infection. Given the significant risk of heightened morbidity and mortality from COVID-19, there is an urgent and critical need to establish its impact in these population. A better understanding of adverse prognostic factors could assist hematologist to tailor appropriate treatment. With this background, our aims were to analyse the outcome of COVID-19 infection and to identify risk factors associated with severity and mortality. Methods: This is a multicenter retrospective observational study with data collected from 6 Malaysian hematological centers. This cohort included patients age ≧ 15 years with hematological diseases who developed PCR-documented SARS-CoV-2 infection from 1st January 2021 to 31st December 2021. Data were collected locally from the 6 participating centers. Anonymized data were centrally processed by a coordinating team in Penang General Hospital. The variables assessed included baseline characteristics, type of hematological diseases, anti-neoplastic therapies, COVID-19 treatments and outcomes. Analyses were generated using R statistical software version 4.1.2. Prognostic factors were analysed using Cox proportional hazard regression analysis. Results: A total of 300 patients (168 males, 132 females) were evaluated. The median age was 51 years (range: 15-85 years). 52% were 50 years old and above. 44% had at least one comorbidity. There were 153 (51%) lymphoid malignancies, 94 (31%) myeloid malignancies and 53 (18%) benign hematological disorders. Non hodgkin lymphoma (26.6%) was the commonest hematological disease followed by acute myeloid leukaemia (16.3 %), acute lymphoblastic leukaemia (9.0%), autoimmune diseases (8.0%) and multiple myeloma (7.0%). Of the 247 patients with malignancy, 55% patients had refractory disease. 104 (42.1%) patients were receiving intensive chemotherapy, 40 (16.2%) low intensity chemotherapy, 25 (10.1%) hypomethylating agent, 22 (8.9%) molecular targeted therapy, 36 (14.6%) supportive care and the remaining 20 (8.1%) were not on active therapy. 19.0% of patients were treated with B cell depleting monoclonal antibody including Rituximab (15.3%), Daratumomab (2.7%) or Blinatumomab (1.0%). Only 24 (8%) patients had prior hematopoietic stem cell transplantation. 34.7% were fully vaccinated prior to COVID-19 infection. 45% of patients developed severe or critical COVID-19 infection based on WHO criteria. Cytokine release syndrome (37%) and organising pneumonia (33%) were the two commonest complications. The median follow up was 158 days (range: 4 - 345 days). The overall mortality rate was 31.7% with survival rate at 90 days of 68.3% (95% CI: 62.6 to 73.2). Poor prognostic factors identified in the multivariable cox regression included age ≥ 50 (HR 1.66; 95 CI 1.05 - 2.64; p = 0.029), ECOG 2-4 (HR 2.34; 95 CI 1.51 - 3.63; p < 0.001), vaccine naive (HR 3.06; 95 CI 1.85 - 5.06; p < 0.001) and absolute lymphocyte count (ALC) < 0.5 (HR 1.51; 95 CI 0.96 -2.38; p = 0.080). Age ≥ 50 (OR 2.43; 95 CI 1.41- 4.24; P = 0.001), ECOG 2-4 (OR 2.72; 95 CI 1.51 - 4.99; p <0.001), refractory hematological disease (OR 2.15; 95 CI 1.19 - 3.91; p = 0.011) and usage of B cell depleting monoclonal antibody (OR 8.25; 2.80 - 30.74; p <0.001) were significantly associated with severe Covid-19 infection. Conclusion: 45% of hematological patients with COVID-19 had severe or critical infection with mortality rate of 31.7%. Poor survival was correlated with older age (≥ 50 years old), poor performance status, severe lymphopenia and vaccine naive. Vaccination is effective in preventing mortality but not severe infection. Hence, antiviral drugs and anti-SARS COV-2 monoclonal antibodies for early treatment and prophylaxis should also be considered for high risk patients and potential vaccine non-responders. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Neutralizing monoclonal antibodies for early treatment of hospital-acquired SARS-CoV-2 infection in hematologic patients.

Efficacy of early treatment with anti‐SARS‐CoV‐2 spike protein monoclonal antibodies (mAbs) for nosocomial SARS‐CoV‐2 infection in hematologic patients is unknown. Retrospective, cohort study conducted in four Italian teaching hospitals. We included adult patients with hematologic malignancies and hospital‐acquired SARS‐CoV‐2 infection diagnosed between November 2020 and December 2021. The principal exposure variable was administration of mAbs. The primary endpoint was clinical failure dea composite outcome of mortality and/or invasive and noninvasive ventilation within 90 days from infection onset. We included 52 patients with hospital‐acquired SARS‐CoV‐2 infection. Males were 29 (60%), median age was 62 (interquartile range [IQR] 48–70). Forty‐five (86%) patients were on chemotherapy or had received chemotherapy within 30 days. MAbs were administered in 19/52 (36%) patients. Clinical failure occurred in 22 (42%) patients; 21% (4/19) in mAbs group versus 54% (18/33) in non‐mAbs group (p = 0.03). Other predictors of clinical failure were older age (median [IQR] 69 [61–72] versus 58 [46–66], p = 0.001), and higher Charlson comorbidity index (median [IQR], 5 [3.25‐5] versus 3 [2–5], p = 0.002). At multivariable Cox regression model, mAbs were independently associated with a significantly lower rate of clinical failure (HR 0.11, 95% CI 0.01–0.85, p = 0.01), after adjusting for confounders. In conclusion, mAbs are promising for early treatment of hematologic patients with healthcare‐related SARS‐CoV‐2 infection.

Management of Invasive Infections due to a Rare Arthroconidial Yeast, Saprochaete capitata, in Two Patients with Acute Hematological Malignancies.

Saprochaete capitata is an arthroconidial yeast, found principally in the environment, even if it belongs also to the normal microbial flora that colonize human subjects. This yeast is increasingly associated with invasive infections in hematological patients, in particular in those affected by acute leukemia. An important risk factor that predisposes to this infection is the profound neutropenia present in such immunocompromised patients. Saprochaete spp. were found resistant to both echinocandins and fluconazole so the treatment is often difficult. Here, we report two cases of sepsis in two patients with acute leukemia. All of them had fatal events, due to the worsening of their clinical condition. An early diagnosis and appropriate management of these pathogens is important in consideration of the poor prognosis associated to these fungal invasive infections.

Clinical characteristics and outcome of 125 polymicrobial bloodstream infections in hematological patients: an 11-year epidemiologic survey.

Polymicrobial bloodstream infections (pBSI) occurring in hematological patients are still poorly understood, and specific information are very limited. In this epidemiologic survey, we describe clinical characteristics and outcome of 125 consecutive pBSI occurred in oncohematological patients. Polymicrobial bloodstream infections (pBSI) were defined with the isolation of 2 or more bacteria from blood culture specimens obtained within 72h. Over an 11-year period, we documented 500 bacterial bloodstream infections (BSI) in 4542 hospital admissions and 25% (125) of these were pBSI. Most common underlying hematological disease was acute myeloid leukemia and 89% of patients had severe neutropenia. Fifty pBSI (40%) occurred in patients undergoing a stem cell transplantation (SCT), mostly within 30days from transplant (42/50-84%). Principal bacterial association was Gram-positive plus Gram-negative (57%). Resolution rate of pBSI was 82%, without differences between SCT and non-SCT cases. pBSI-related mortality was 15% (6% in SCT cases). Septic shock occurred in 16% of cases and septic shock-related mortality was 65% (75% in SCT cases and 63% in non-SCT cases; p = 0.6). Multidrug-resistant (MDR) bacteria were involved in 22% of pBSI and the MDR-pBSI-related mortality was significantly higher in SCT patients (p = 0.007). This observational study highlights that pBSI is not a rare bloodstream infectious complication in oncohematological patients. pBSI-related mortality is lower than 20%, but, if septic shock occurs, mortality reaches 65%. MDR bacteria were involved in 22% of cases and pBSI-MDR-related mortality was significantly higher in SCT patients.

Real-world assessment of the effectiveness of posaconazole for the prophylaxis and treatment of invasive fungal infections in hematological patients: A retrospective observational study.

The aim of the study was to analyze the efficacy of posaconazole for the prophylaxis and treatment of invasive fungal diseases (IFDs) in patients with hematological malignancies.In this retrospective observational multi-center study, 762 patients from 25 Chinese hematological centers were enrolled. Inclusion criteria were patients with hematological malignancy or they had undergone hematopoietic stem cell transplantation and received at least 1 dose of posaconazole. The primary endpoints were the observation of breakthrough rates and the clinical efficacy of posaconazole prophylaxis. The secondary endpoint was the efficacy of posaconazole for the treatment of IFDs.Of the 762 enrolled patients, 456 (59.8%) were prescribed posaconazole prophylactically while 243 (31.9%) received posaconazole as an IFD treatment (12 proven, 61 probable, 109 possible, and 61 unclassified IFD cases) for ≥7 days. The overall IFD breakthrough rate (probable cases) for the ≥4 days prophylactic treatment (n = 445) group was 1.6% (95% Cl: 0.6%–3.2%), with breakthrough rates of 2.6% for acute myeloid leukemia/myelodysplastic syndrome patients undergoing chemotherapy and 2.2% for hematopoietic stem cell transplantation patients. For primary antifungal prophylaxis, the breakthrough rate was 1.9% and for secondary antifungal prophylaxis 0%. The overall effective IFD remission rate of patients treated for ≥7 days with posaconazole was 56.0% and the effective remission rate of proven/probable/possible IFD cases was 59.3%. The effective remission rate of posaconazole as salvage therapy was 50% (95% CI: 32.4%–67.6%) including 75% (CI: 19.4%–99.4%) for Aspergillus infections.The present retrospective study confirmed posaconazole as IFD prophylaxis and medication for hematological malignancy patients undergoing various treatments in China.

Urine Cultures at the Onset of Febrile Neutropenia (FN) in Patients with Haematological Malignancies Rarely Impact Antibiotic Management in the Absence of Urinary Symptoms

IntroductionThe Choosing Wisely initiative aims to reduce wasteful testing. Our institution is participating in this initiative and hence has a focus on evidence-based approaches to the investigation of FN. We have previously shown that routine chest x-rays are not generally useful in this scenario. Urine cultures are also commonly performed in this context. However, specimen collection may delay the administration of antibiotics, laboratory costs are not inexpensive and the impact of culture results on subsequent antibiotic management is not well documented in patients receiving protocol specified broad spectrum antibiotics. We assessed this latter issue by evaluating the impact of urine cultures on the management of FN in haematology inpatients at a major tertiary hospital.Methods:A retrospective single-centre analysis of adult (≥16years) patients with haematological malignancy undergoing recent chemotherapy admitted to a large cancer centre with FN was performed over a 5-year period (2011-2015). FN was defined as fever ≥37.5°C and a neutrophil count <0.5 x 109/L or <1.5 x 109/L and predicted decline to <0.5 x 109/L over the next 48 hours. Local protocolised investigations for newly diagnosed FN included a urine culture. Empiric antibiotic therapy for FN consisted of IV tazocin in stable patients or, if systemically compromised, IV meropenem, gentamicin and vancomycin. Patients were identified from electronic hospital records. For each episode, baseline demographic data, urinary tract symptoms and signs (absence of which was termed ‘asymptomatic‘), beside urinalysis results (nitrites and leucocytes), urine culture results (chemistry, microscopy, culture and sensitivity) and any consequent change in antibiotic management were collected. A urine culture was considered positive if >108 organisms/L of a predominant organism were detected. Cultures were considered contaminated if mixed growth was present. Each positive culture and impact on antibiotic therapy was reviewed by an infectious disease physician.Results:Four hundred and thirty-three episodes of FN were identified in 317 patients, the baseline characteristics of which are summarized in Table 1. A urine culture was performed in 365 (84%) cases of which 16 (4.4%) were positive, 77 were contaminated (21%), and 272 (75%) had no growth. Cultures were positive in 7 of 317 (2.2%) asymptomatic patients; all were gram-negative bacteria of which 2 were extended spectrum beta-lactamase (ESBL) E. coli. Nine of 48 (19%) symptomatic patients had positive cultures of which 8 were non-ESBL E. coli. Four patients had a catheter, all of whom were asymptomatic with a negative culture. Bedside urinalysis was documented in 186 (43) patients who had urine cultures. Nitrites were detected in 5 of 12 evaluable patients with positive cultures compared with 4 of 174 patients with negative cultures; the positive and negative predictive values were 56%and 96%respectively. Only 5 patients (1.4%) had a change in antibiotic management due a positive urine culture: 3 of 48 (6.3%) symptomatic and 2 of 317 (0.6%) asymptomatic patients.Conclusion:Urinary tract infections are a rare source of infection in haematology patients with FN in the absence of focal urinary symptoms. Urine cultures rarely impact on antibiotic management in this context without urinary tract symptoms. As a result of this study we no longer perform urine cultures routinely in FN, restricting this investigation to symptomatic or catheterised patients without another clear source of infection, and those with nitrite positivity. [Display omitted] DisclosuresHawkes:Roche: Other: Travel expenses, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Other: Travel expenses; Celgene: Research Funding; Bristol-Myers Squibb: Research Funding; Roche: Other: Travel expenses; Merck Serono: Research Funding; Merck Sharpe Dohme: Research Funding. Grigg:Merck Sharpe Dohme: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses.

Healthcare-associated blood stream infections in hematological patients in Finland during the years 2006-2016.

The aim was to identify the clinical characteristics, outcome, and antimicrobial susceptibility of healthcare-associated bloodstream infections (BSIs) in hematological patients. This retrospectively collected laboratory-based surveillance data include 3404 healthcare-associated BSIs in 2296 patients with a hematological malignancy in hospitals participating in the Finnish Hospital Infection Program from January 1, 2006, to December 31, 2016. The most common underlying diseases were acute myelogenous leukemia (35%) and non-Hodgkin lymphoma (22%). Gram-positive organisms accounted for 60%-46% and gram-negative organisms for 24%-36% of BSIs in 2006-2016. The most common causative organism was coagulase-negative staphylococci (CoNS) (n=731). The 7- and 28-day case fatality rates were 5.2% and 11.4%, respectively, and was highest in BSIs caused by Candida species (10.8% and 30.8%). The median age of patients increased from 59years in 2006-2008 to 62years in 2015-2016 (P<.01). Five percent of Saureus isolates were resistant to methicillin and five percent of Pseudomonas aeruginosa isolates were multidrug-resistant. Four percent of Klebsiella and seven percent of E coli isolates were resistant to ceftazidime. The proportion of gram-positive bacteria decreased and gram-negative bacteria increased over time. The case fatality rate was low and the median age of patients increased during the study.

1095. Investigation of Risk Factors Associated with Serious Bacterial, Viral and Invasive Fungal Infections in Hematologic Patients on Ibrutinib

BackgroundIbrutinib is a tyrosine kinase inhibitor used to treat hematologic malignancies that may increase the risk of serious infection including invasive fungal infections (IFI). In a study of 378 patients with hematologic malignancy on ibrutinib, serious infection and IFI occurred in 11% and 4% respectively (Varughese et al. Clin Infect Dis). The primary aims of our study were to determine the incidence of serious infection and associated risk factors in patients on ibrutinib.MethodsWe performed a retrospective analysis of patients with hematologic malignancy prescribed ibrutinib for ≥ 1 week at Yale New Haven Hospital from 2014 to 2019 to identify serious infections defined as those requiring inpatient management. We collected demographic, clinical and oncologic data. Chi-squared tests were used to determine factors associated with an increased risk of infection.ResultsA total of 254 patients received ibrutinib including 156 with CLL, 89 with NHL and 9 with other leukemias. Among these, 21 underwent HSCT, 9 complicated by GVHD. There were 51 (20%) patients with serious infections including 45 (17.7%) bacterial, 9 (3.5%) viral and 5 (2%) IFI (1 pulmonary cryptococcosis, 4 pulmonary aspergillosis). Anti-mold prophylaxis was prescribed to 7 (2.8%) patients, none of whom developed IFI. Risk factors associated with serious infection included ECOG score ≥ 2 (OR 4.6, p < 0.001), concurrent steroid use (≥ 10 mg prednisone daily for ≥ 2 weeks; OR 3.0, p < 0.001), neutropenia (OR 3.6, p < 0.01), lymphopenia (OR 2.4, p < 0.05) and maximum ibrutinib dose of 560 mg (OR 2, p < 0.05). There was a dose dependent increase in infections based on number of chemotherapy regimens prior to ibrutinib initiation: 14.3% with 0, 19.7% with 1-2 and 28.7% with ≥ 3 prior treatments.ConclusionThe incidence of serious infection in hematologic patients on ibrutinib was higher than previously reported (20% versus 11%) but the rate of IFI was lower (2% versus 4%). High ECOG score, leukopenia, steroids, and higher ibrutinib doses were associated with an increased risk for serious infection. Targeted antimicrobial prophylaxis should be considered for patients on ibrutinib with these risk factors. Improving functional status may also reduce the risk of infection in patients on ibrutinib.Disclosures All Authors: No reported disclosures

Clinical Characteristics and Outcomes of Breakthrough Candidemia in 71 Hematologic Malignancy Patients and/or Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Single-center Retrospective Study From China, 2011-2018.

Antifungal prophylaxis may result in breakthrough infections in hematology patients with severe agranulocytosis, with few studies assessing risk factors and clinical outcomes of breakthrough candidemia. We described the distribution of Candida species, assessed risk factors for mortality in such patients, and determined differences in the incidence and mortality of breakthrough candidemia between patients who did or did not receive an allogeneic hematopoietic stem cell transplant. We collected clinical and microbiological data of patients with hematologic malignancies and breakthrough candidemia from a single center. Seven-day and 30-day follow-up outcomes were recorded; the incidence and mortality of breakthrough candidemia between patients who did or did not undergo an allogeneic transplant were compared. Kaplan-Meier survival estimates were used to generate survival curves, and predictors were identified using Cox regression analyses. Of 71 enrolled patients, 17 received allogeneic transplants. Incidences of breakthrough candidemia were 17 of 2924 (0.58%) and 54 of 12 015 (0.45%) in the transplant and nontransplant groups, respectively (P = .35). The most common isolate was Candida tropicalis, and antifungal agent combinations were the most common first-line treatment. Cumulative mortality rates of patients were 21.1% and 31.0% at days 7 and 30, respectively, and they significantly differed between both groups. Septic shock, central venous catheter removal, and granulocyte recovery were significantly associated with 7-day mortality; the latter 2 remained independent predictors of 30-day mortality. Breakthrough candidemia-related mortality was higher in the allogeneic transplant group, although the incidence was not significantly different between the groups. Prompt and adequate antifungal treatment with catheter removal may reduce mortality.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Hematologic Patients: Experience at the Hospital Attending More Patients in Spain

INTRODUCTIONThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic raises many questions about the management of patients with significant comorbidities. Hematologic patients are usually fragile due to an important immunosuppression, so the impact of coronavirus disease (COVID-19) is yet to be determined.MATERIALS AND METHODSWe conducted a single-center retrospective observational study of patients with hematologic malignancies diagnosed with SARS-CoV-2 at Vall d´Hebron University Hospital (HUVH) between March 1st and May 31st 2020 to analyze their clinical characteristics and evolution. Patient’s demographic data, underlying pathology, signs and symptoms of COVID-19, treatment received and clinical course were collected. A statistical analysis was performed to identify the possible variables associated with COVID-19 mortality. For this purpose, we used univariate and multivariable logistic regression models.RESULTSWe identified 70 patients with PCR confirmed SARS-CoV-2 infection and hematologic malignancy. The median age was 75 years (range 22-91), and 44% were female. The majority (74%) had evidence of active malignancy and 53% were receiving active therapy. Lymphoid pathology (73%) predominated over myeloid. The median number of previous lines of treatment was 0 (range 0-6), 23% had received at least 2 lines, whereas 10% underwent hematopoietic stem cell transplantation (HSCT) (5 patients allo-HSCT, 2 auto-HSCT). Half of the patients had more than one pre-existing comorbidity (17% obstructive pulmonary disease).At diagnosis the most common symptoms were fever (76%), cough (60%) and dyspnea (31%). We observed that 58% of patients presented a chest X-ray compatible with COVID-19. Regarding laboratory parameters, stood out lymphopenia (65% of patients presented <1200 lymphocytes/mm3) and elevation of inflammation parameters, such as D-dimer (median 365 ng/mL, range 50-5860), ferritin (median 1063 ng/mL, range 73-14191), IL-6 (median 59,6 pg/mL, range 3-4079) and PCR (median 11,2 mg/dL, range 0,3-79,9). Empirical therapy for COVID-19 included antibiotics (78%), anti-virals (50%, 3% remdesivir), and hydroxychloroquine (88%). Only 24% received tocilizumab, 50% heparin (33% prophylactic dose), 12% G-CSF, 9% norepinephrine, 4% corticosteroids and 1% ß-IFN. Most of patients (73%) required oxygen therapy: 36% high-flow, 29% low flow and 8% endotracheal intubation. There were 6 patients who did not receive any treatment.COVID-19 was acquired via nosocomial infection in 23% of patients, 91% of them requiring hospitalization, 14% in the Intensive Care Unit (ICU). The median days of hospitalization since diagnosis was 17 (range 3-55). The case fatality rate (CFR) from COVID-19 was higher in hematologic patients than the one observed in non-hematologic patients at the HUVH (figure 1), being of 41% at 11 days from diagnosis. CFR was higher in patients older than 75 years old (61%), while the mortality among patients receiving active therapy was 42%. The main cause of death was acute respiratory failure (93%). In the univariate logistic regression model, age >75 years (OR 1.07; p=0.008), active malignancy (OR 5; p=0,02), >1 comorbidity (OR 5.3; p=0,049) and high levels of IL-6 (OR 8.2; p= 0.005) were statistically significant. In the multivariable logistic regression model, age ≥75 years (OR 4.4; p=0.01) and IL-6 levels at baseline > 59.6 pg/mL (OR 7.2; p=0.01) were associated with a higher mortality (table 1). The presence of an active malignancy was not a significant variable in the multivariable logistic regression model.CONCLUSIONSPatients with hematologic malignancies and COVID-19 presented similar symptoms, signs and radiological characteristics to those described in the general population at diagnosis. In our cohort, advanced age and high IL-6 values were associated with higher mortality. Furthermore, it was observed that active hematologic disease is a factor of poor prognosis of COVID-19.DisclosuresSalamero:Daichii Sankyo:Honoraria;Celgene:Consultancy, Honoraria;Novartis:Consultancy, Honoraria;Jazz Pharmaceuticals:Consultancy, Honoraria;Pfizer:Consultancy.Abrisqueta:Janssen:Consultancy, Honoraria, Speakers Bureau;AbbVie:Consultancy, Honoraria, Speakers Bureau;Roche:Consultancy, Honoraria, Speakers Bureau;Celgene:Consultancy, Honoraria.Bosch:Hoffmann-La Roche:Research Funding.