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      A practical update on the epidemiology and risk factors for the emergence and mortality of bloodstream infections from real-world data of 3014 hematological malignancy patients receiving chemotherapy

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          Abstract

          Background: Bloodstream infection (BSI) is a common and serious complication after patients with hematologic malignancies (HM) receiving chemotherapy. This study examined real-world data seeking to characterize HM BSI and identify risk factors for BSI emergence and mortality.

          Methods: We retrospectively analyzed the pathogenic epidemiology, antibiotic resistance, and BSI risk factors in a single-center cohort including 3014 consecutive patients with HM receiving chemotherapy between 2013 and 2016. Results of the pathogenic epidemiology were validated via comparison to available reported data.

          Results: We found that 725 patients (24.1%) had BSIs. Gram-negative (G-) bacteria represented 64.7% of the 744 isolated pathogenic strains, while Gram-positive (G+) bacteria and fungi accounted for 27.7% and 7.7% of the BSIs, respectively. The most common isolates were Klebsiella pneumoniae (19.2%), and 95.1% of the multidrug-resistant strains (MDR) were extended-spectrum beta-lactamase producing strains. G- bacteria were the main microflora responsible for BSI in our cohort of Chinese HM patients compared to studies in developed countries or in neutropenic children with HM or solid tumors. Multivariate analysis revealed that male sex, age ≥ 45 and < 65 yr, hospital length of stay ≥ 9d, neutropenia ≥ 7d before cultures, ≥ 2 antibiotics, and infections (gastrointestinal, perirectal, or urinary tract) independently predicted BSI emergence. Furthermore, age ≥ 65 yr, neutropenia ≥ 7d before blood cultures, no HM remission, lower white blood cell count, ≥ 3 antibiotics, respiratory infections, and Acinetobacter baumannii and Stenotrophomonas maltophilia BSI were independent predictors of 30-day mortality.

          Conclusions: G- bacteria were the predominant microflora during the study period and antibiotic resistance levels of the pathogens detected were high, especially for MDR strains. The mortality of BSI patients was high in this large cohort. Close attention should be paid to the risk factors identified here to facilitate timely and effective clinical management of such patients.

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          Extended-Spectrum β-Lactamases: a Clinical Update

          Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamases which share the ability to hydrolyze third-generation cephalosporins and aztreonam yet are inhibited by clavulanic acid. Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these β-lactamases. This extends the spectrum of β-lactam antibiotics susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described. The presence of ESBLs carries tremendous clinical significance. The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. There is substantial debate as to the optimal method to prevent this occurrence. It has been proposed that cephalosporin breakpoints for the Enterobacteriaceae should be altered so that the need for ESBL detection would be obviated. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in klebsiellae and Escherichia coli . In common to all ESBL detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.
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            Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management.

            Cytotoxic chemotherapy suppresses the hematopoietic system, impairing host protective mechanisms and limiting the doses of chemotherapy that can be tolerated. Neutropenia, the most serious hematologic toxicity, is associated with the risk of life-threatening infections as well as chemotherapy dose reductions and delays that may compromise treatment outcomes. The authors reviewed the recent literature to provide an update on research in chemotherapy-induced neutropenia and its complications and impact, and they discuss the implications of this work for improving the management of patients with cancer who are treated with myelosuppressive chemotherapy. Despite its importance as the primary dose-limiting toxicity of chemotherapy, much concerning neutropenia and its consequences and impact remains unknown. Recent surveys indicate that neutropenia remains a prevalent problem associated with substantial morbidity, mortality, and costs. Much research has sought to identify risk factors that may predispose patients to neutropenic complications, including febrile neutropenia, in an effort to predict better which patients are at risk and to use preventive strategies, such as prophylactic colony-stimulating factors, more cost-effectively. Neutropenic complications associated with myelosuppressive chemotherapy are a significant cause of morbidity and mortality, possibly compromised treatment outcomes, and excess healthcare costs. Research in quantifying the risk of neutropenic complications may make it possible in the near future to target patients at greater risk with appropriate preventive strategies, thereby maximizing the benefits and minimizing the costs. Copyright 2003 American Cancer Society.
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              Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States.

              A total of 2340 patients with underlying malignancy were identified among 22,631 episodes of nosocomial bloodstream infections (BSIs) in a prospectively collected database for 49 hospitals in the United States (Surveillance and Control of Pathogens of Epidemiologic Importance [SCOPE] Project). Data were obtained for the period of March 1995 through February 2001. Gram-positive organisms accounted for 62% of all BSIs in 1995 and for 76% in 2000 (P<.001), and gram-negative organisms accounted for 22% and 14% of all BSIs for these years, respectively. Neutropenia was observed in 30% of patients, so neutropenic and nonneutropenic patients were compared. In both, the predominant pathogens were coagulase-negative staphylococci (32% of isolates recovered from neutropenic patients and 30% of isolates recovered from nonneutropenic patients). The source of BSI was not determined for 57% of patients. The crude mortality rate was 36% for neutropenic patients and 31% for nonneutropenic patients.
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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2021
                25 July 2021
                : 12
                : 18
                : 5494-5505
                Affiliations
                [1 ]Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China
                [2 ]Department of Cancer, Fujian Provincial Cancer Hospital, Fuzhou 350014, Fujian, P. R. China
                [3 ]Department of Hematology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen 361021, Fujian, P. R. China
                [4 ]Department of Hematology, Affiliated Nanping First Hospital of Fujian Medical University, Nanping 353000, Fujian, P.R. China
                [5 ]Department of Hematology, Zhongshan Hospital, Fudan University (Xiamen Branch), Xiamen 361015, Fujian, P.R. China
                Author notes
                ✉ Corresponding authors: Ting Yang, Department of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Rd, 350001, Fuzhou, Fujian, China. Tel: 86-591-83357896; Fax: 86-591-83300181; E-mail: yang.hopeting@ 123456gmail.com . Jianda Hu, Department of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Rd, 350001, Fuzhou, Fujian, China. Tel:86-591-83357896; Fax: 86-591-83324116; E-mail: drjiandahu@ 123456163.com

                * These authors contributed equally to this work as co-authors.

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                jcav12p5494
                10.7150/jca.50802
                8364636
                34405012
                b603c75c-6f50-4d36-842a-007d929ba25e
                © The author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 18 July 2020
                : 15 June 2021
                Categories
                Research Paper

                Oncology & Radiotherapy
                bloodstream infections,hematological malignancy,pathogen,resistance,risk factor

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