{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T16:56:16Z","timestamp":1789232176984,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>As antibiotic resistance has become a global problem, the intervention of an antimicrobial stewardship team (AST) is warranted. In hematological disorders, infectious complications are crucial owing to abnormal neutrophil function and decreased cell-mediated immunity. Despite the widespread implementation of AST intervention, the effectiveness of stewardship practices for immunocompromised patients remains uncertain. We determined the effect of AST interventions on carbapenem therapy in the department of hematology. Patients admitted to the department and undergoing carbapenem therapy were enrolled. We compared carbapenem use between the pre-AST (April 2016\u2013March 2018) and post-AST (April 2018\u2013March 2021) periods. Factors associated with long-term carbapenem therapy were investigated. Overall, 515 episodes of carbapenem therapy in 264 patients in the department were evaluated. According to the interrupted time series analysis, the number of days of therapy decreased with AST intervention (\u03b2 = \u22120.263, p = 0.011). In multivariate analysis, predictive factors associated with long-term carbapenem therapy (&gt;8 days) were outpatient onset, chronic obstructive pulmonary disease, acute myeloid leukemia, multiple myeloma, and infection with resistant bacteria (such as extended spectrum \u03b2-lactamases and AmpC) (95% confidence interval, 1.030\u20132.818, 1.067\u201366.667, 1.057\u20132.782, 0.168\u20130.742, and 1.382\u20135.750, respectively). The AST intervention reduced carbapenem use in patients with hematological disorders.<\/jats:p>","DOI":"10.3390\/antibiotics12020302","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T02:57:24Z","timestamp":1675306644000},"page":"302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Antimicrobial Stewardship Program for Patients in the Hematological Department Receiving Carbapenem Therapy: A Single-Center and Interrupted Time Series Analysis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6150-7700","authenticated-orcid":false,"given":"Ayako","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"},{"name":"Antimicrobial Stewardship Team, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1611-6991","authenticated-orcid":false,"given":"Fumihiro","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Antimicrobial Stewardship Team, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"},{"name":"Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5917-668X","authenticated-orcid":false,"given":"Masayuki","family":"Maeda","sequence":"additional","affiliation":[{"name":"Division of Infection Control Sciences, Department of Clinical Pharmacy, Showa University School of Pharmacy, Tokyo 142-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyuki","family":"Hashiguchi","sequence":"additional","affiliation":[{"name":"Antimicrobial Stewardship Team, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"},{"name":"Department of Nursing, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Kabasawa","sequence":"additional","affiliation":[{"name":"Antimicrobial Stewardship Team, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"},{"name":"Department of Hematology, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Antimicrobial Stewardship Team, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"},{"name":"Department of Emergency and Critical Care Medicine, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tokutada","family":"Sato","sequence":"additional","affiliation":[{"name":"Antimicrobial Stewardship Team, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"},{"name":"Department of Cardiology, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Fuyama","sequence":"additional","affiliation":[{"name":"Antimicrobial Stewardship Team, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"},{"name":"Department of Pediatrics, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Antimicrobial Stewardship Team, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"},{"name":"Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Endo","sequence":"additional","affiliation":[{"name":"Antimicrobial Stewardship Team, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"},{"name":"Department of Diabetes Metabolism and Endocrinology, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kae","family":"Iwata","sequence":"additional","affiliation":[{"name":"Antimicrobial Stewardship Team, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"},{"name":"Department of Inspection, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sei","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Antimicrobial Stewardship Team, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"},{"name":"Department of Otorhinolaryngology, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisato","family":"Fujihara","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan"},{"name":"Department of Hospital Pharmaceutics School of Pharmaceutical Sciences, Showa University, Tokyo 142-8666, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1093\/cid\/cir073","article-title":"Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of America","volume":"52","author":"Freifeld","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1002\/cncr.21847","article-title":"Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients","volume":"106","author":"Kuderer","year":"2006","journal-title":"Cancer"},{"key":"ref_3","first-page":"1826","article-title":"ECIL4, a joint venture of EBMT, EORTC, ICHS, ESGICH\/ESCMID and ELN. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: Summary of the 2011","volume":"98","author":"Averbuch","year":"2013","journal-title":"Haematol. 4th Eur Conf. Infect. Leuk."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S105","DOI":"10.1007\/s00277-003-0764-4","article-title":"Antimicrobial therapy of unexplained fever in neutropenic patients\u2014Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO), Study Group Interventional Therapy of Unexplained Fever, Arbeitsgemeinschaft Supportivmassnahmen in der Onkologie (ASO) of the Deutsche Krebsgesellschaft (DKG-German Cancer Society)","volume":"82","author":"Link","year":"2003","journal-title":"Ann. Hematol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Villafuerte-Gutierrez, P., Villalon, L., Losa, J.E., and Henriquez-Camacho, C. (2014). Treatment of febrile neutropenia and prophylaxis in hematologic malignancies: A critical review and update. Adv. Hematol., 2014.","DOI":"10.1155\/2014\/986938"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1086\/510393","article-title":"Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship","volume":"44","author":"Dellit","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1093\/jac\/dkx181","article-title":"Sparing carbapenem usage","volume":"72","author":"Wilson","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1001\/jama.2018.12565","article-title":"Carbapenem-sparing therapy for extended-Spectrum \u03b2-lactamase-producing E coli and Klebsiella pneumoniae bloodstream infection: The search continues","volume":"320","author":"Hayden","year":"2018","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1017\/ice.2016.149","article-title":"Current state of antimicrobial stewardship at Solid Organ and Hematopoietic Cell Transplant Centers in The United States","volume":"37","author":"Seo","year":"2016","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1093\/cid\/ciz900","article-title":"Antimicrobial stewardship in a hematological malignancy unit: Carbapenem reduction and decreased vancomycin-resistant enterococcus infection","volume":"71","author":"Webb","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1007\/s10096-018-3328-1","article-title":"De-escalation and discontinuation strategies in high-risk neutropenic patients: An interrupted time series analyses of antimicrobial consumption and impact on outcome","volume":"37","author":"Robin","year":"2018","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_12","first-page":"276","article-title":"Antibiotic resistance status and its costs in hematological patients: A two-year analysis","volume":"8","author":"Gedik","year":"2017","journal-title":"Casp. J. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e843","DOI":"10.1200\/JOP.18.00775","article-title":"Standardizing febrile neutropenia management: Antimicrobial stewardship in the hematologic malignancy population","volume":"15","author":"Marcelin","year":"2019","journal-title":"J. Oncol. Pr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1469-0691.2005.01298.x","article-title":"Risk of bacteraemia and mortality in patients with haematological malignancies","volume":"12","author":"Larsson","year":"2006","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Guisado-Gil, A.B., Aguilar-Guisado, M., Pe\u00f1alva, G., Lepe, J.A., Espigado, I., Rodr\u00edguez-Arbol\u00ed, E., Gonz\u00e1lez-Campos, J., Rodr\u00edguez-Torres, N., Montero-Cuadrado, M.I., and Falantes-Gonz\u00e1lez, J.F. (2021). Long-term impact of an educational antimicrobial stewardship program on management of patients with hematological diseases. Antibiotics, 10.","DOI":"10.3390\/antibiotics10020136"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.ajic.2017.09.030","article-title":"Implementation of an antimicrobial stewardship program for patients with febrile neutropenia","volume":"46","author":"Madran","year":"2018","journal-title":"Am. J. Infect. Control"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mardani, M., Abolghasemi, S., and Shabani, S. (2020). Impact of an antimicrobial stewardship program in the antimicrobial-resistant and prevalence of Clostridioides difficile infection and amount of antimicrobial consumed in cancer patients. BMC Res. Notes, 13.","DOI":"10.1186\/s13104-020-05085-3"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.cmi.2018.07.026","article-title":"Current time-to-positivity of blood cultures in febrile neutropenia: A tool to be used in stewardship de-escalation strategies","volume":"25","author":"Cardozo","year":"2019","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1080\/23744235.2018.1438649","article-title":"Early discontinuation of empirical antibacterial therapy in febrile neutropenia: The ANTIBIOSTOP study","volume":"50","author":"Talarmin","year":"2018","journal-title":"Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Haynes, R.B., Devereaux, P.J., and Guyatt, G.H. (2002). Physicians\u2019 and patients\u2019 choices in evidence based practice. BMJ, 324.","DOI":"10.1136\/bmj.324.7350.1350"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/S0140-6736(16)31592-6","article-title":"Progress in evidence-based medicine: A quarter century on","volume":"390","author":"Djulbegovic","year":"2017","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1159\/000486228","article-title":"Incidence, survival, and risk factors for adults with acute myeloid leukemia not otherwise specified and acute myeloid leukemia with recurrent genetic abnormalities: Analysis of the surveillance, epidemiology, and end results (SEER) Database, 2001\u20132013","volume":"139","author":"Song","year":"2018","journal-title":"Acta Haematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.jped.2015.08.008","article-title":"Acute myeloid leukemia: Analysis of epidemiological profile and survival rate","volume":"92","author":"Freund","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/leu.2013.313","article-title":"Continued improvement in survival in multiple myeloma: Changes in early mortality and outcomes in older patients","volume":"28","author":"Kumar","year":"2014","journal-title":"Leukemia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/joim.12590","article-title":"Modern multiple myeloma therapy: Deep, sustained treatment response and good clinical outcomes","volume":"281","author":"Landgren","year":"2017","journal-title":"J. Intern. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Niessen, F.A., van Mourik, M.S.M., Bruns, A.H.W., Raijmakers, R.A.P., de Groot, M.C.H., and van der Bruggen, T. (2020). Early discontinuation of empirical antibiotic treatment in neutropenic patients with acute myeloid leukaemia and high-risk myelodysplastic syndrome. Antimicrob. Resist. Infect. Control, 9.","DOI":"10.1186\/s13756-020-00729-2"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1200\/JCO.2000.18.16.3038","article-title":"The Multinational Association for Supportive Care in Cancer Risk Index: A Multinational Scoring System for Identifying Low-Risk Febrile Neutropenic Cancer Patients","volume":"18","author":"Klastersky","year":"2000","journal-title":"J. Clin. Oncol."},{"key":"ref_28","unstructured":"Alberta Provincial Tumour Teams (2014). Management of febrile neutropenia in adult cancer patients. Albertha. Health Serv., 3, 2\u201319."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1056\/NEJMra0800353","article-title":"Infection in the pathogenesis and course of chronic obstructive pulmonary disease","volume":"359","author":"Sethi","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"R267","DOI":"10.1186\/cc10545","article-title":"Duration of antibiotic therapy for bacteremia: A systematic review and meta-analysis","volume":"15","author":"Havey","year":"2011","journal-title":"Crit. Care"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/cid\/ciac268","article-title":"Infectious Diseases Society of America Guidance on the Treatment of Extended-Spectrum \u03b2-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance","volume":"25","author":"Tamma","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Komagamine, J., Yabuki, T., and Hiraiwa, T. (2019). A trend in prevalence of antimicrobial use and appropriateness of antimicrobial therapy in an acute care hospital from 2018 to 2019: Repeated prevalence surveys in Japan. BMC Res. Notes, 12.","DOI":"10.1186\/s13104-019-4849-0"},{"key":"ref_33","unstructured":"(2022, November 11). ATC\/DDD Index 2022. Available online: https:\/\/www.whocc.no\/atc_ddd_index\/."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1053\/j.ajkd.2008.12.034","article-title":"Comparative Study Revised Equations for Estimated GFR from Serum Creatinine in Japan","volume":"53","author":"Matsuo","year":"2009","journal-title":"Am. J. Kidney Dis."},{"key":"ref_35","unstructured":"Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group (2021). KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int., 100, S1\u2013S276."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Suzuki, A., Maeda, M., Yokoe, T., Hashiguchi, M., Togashi, M., and Ishino, K. (2021). Impact of the multidisciplinary antimicrobial stewardship team intervention focusing on carbapenem de-escalation: A single-centre and interrupted time series analysis. Int. J. Clin. Pract., 75.","DOI":"10.1111\/ijcp.13693"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/2\/302\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:21:55Z","timestamp":1760120515000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/2\/302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,2]]},"references-count":36,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["antibiotics12020302"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics12020302","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,2]]}}}