{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:59:08Z","timestamp":1789664348358,"version":"4.0.1"},"reference-count":47,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIAID","award":["K01AI143881"],"award-info":[{"award-number":["K01AI143881"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Broad-spectrum antibiotics are often used for suspected infections in patients with hematologic malignancies due to the risk of severe infections. Although antibiotic use can lead to antimicrobial resistance and microbiome dysbiosis, the effects of antibiotics on the microbiome and resistome in patients with acute myeloid leukemia (AML) undergoing remission induction chemotherapy (RIC) are not well understood. Methods: Various statistical models were utilized to examine the effects of antibiotic administration on the microbiome and resistome over time, as well as differences in AR-infection (ARI) and colonization (ARC) by important CDC-threats in 119 AML patients. Results: A greater number of unique antibiotic classes administered correlated with a loss of unique antibiotic resistance genes (ARGs) (R = \u22120.39, p = 0.008). Specifically, although a greater number of oxazolidinone administrations was correlated with a greater loss of diversity (R = \u22120.58, p &lt; 0.001), each additional day of linezolid reduced the risk of ARC by ~30% (HR: 0.663, p = 0.047) and decreased the odds of acquiring genes predicted to confer macrolide (HR: 0.50, p = 0.026) resistance. Conclusions: The number of antibiotic administrations and the types of antibiotics used can influence the risk of antibiotic resistance gene (ARG) expansion and ARC events in AML patients undergoing RIC. While certain antibiotics may reduce microbial diversity, they are not always linked to an increase in ARGs or ARC events.<\/jats:p>","DOI":"10.3390\/antibiotics14080770","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:00:41Z","timestamp":1753884041000},"page":"770","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Characterization of Antibiotic Administration Factors Associated with Microbiome Disruption and Subsequent Antibiotic-Resistant Infection and Colonization Events in Acute Myeloid Leukemia Patients Receiving Chemotherapy"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2503-6838","authenticated-orcid":false,"given":"Samantha","family":"Franklin","sequence":"first","affiliation":[{"name":"Interdisciplinary Graduate Program in Genetics and Genomics, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corina","family":"Ramont","sequence":"additional","affiliation":[{"name":"Department of Statistics, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maliha","family":"Batool","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"McMahon","sequence":"additional","affiliation":[{"name":"Interdisciplinary Graduate Program in Genetics and Genomics, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranoti","family":"Sahasrabhojane","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Infection Control and Employee Health, The University of Texas MD, Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Blazier","sequence":"additional","affiliation":[{"name":"Texas A&M Institute for Genome Sciences & Society, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8051-2940","authenticated-orcid":false,"given":"Dimitrios P.","family":"Kontoyiannis","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Infection Control and Employee Health, The University of Texas MD, Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0636-2363","authenticated-orcid":false,"given":"Yang","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Statistics, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1081-254X","authenticated-orcid":false,"given":"Jessica","family":"Galloway-Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Interdisciplinary Graduate Program in Genetics and Genomics, Texas A&M University, College Station, TX 77843, USA"},{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024, August 30). Antimicrobial Resistance. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/antimicrobial-resistance."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Walsh, T.R., Gales, A.C., Laxminarayan, R., and Dodd, P.C. (2023). Antimicrobial resistance: Addressing a global threat to humanity. PLoS Med., 20.","DOI":"10.1371\/journal.pmed.1004264"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e24655","DOI":"10.1002\/jcla.24655","article-title":"Antibiotic resistance: The challenges and some emerging strategies for tackling a global menace","volume":"36","author":"Ugwu","year":"2022","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"743","DOI":"10.2147\/TCRM.S68450","article-title":"Bloodstream infections in patients with hematological malignancies: Which is more fatal\u2013cancer or resistant pathogens?","volume":"10","author":"Gedik","year":"2014","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"S206","DOI":"10.1093\/clind\/15.Supplement_1.S206","article-title":"Evaluation of new anti-infective drugs for the treatment of febrile episodes in neutropenic patients","volume":"15","author":"Hughes","year":"1992","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7486","DOI":"10.1038\/ncomms8486","article-title":"Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment","volume":"6","author":"Nobel","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.scitotenv.2016.01.044","article-title":"An assay for determining minimal concentrations of antibiotics that drive horizontal transfer of resistance","volume":"548","author":"Jutkina","year":"2016","journal-title":"Sci. Total Environ."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1056\/NEJMoa2002606","article-title":"Macrolide and nonmacrolide resistance with mass azithromycin distribution","volume":"383","author":"Doan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Van Vliet, M.J., Harmsen, H.J., de Bont, E.S., and Tissing, W.J. (2010). The role of intestinal microbiota in the development and severity of chemotherapy-induced mucositis. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000879"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wong, M., Barqasho, B., \u00d6hrmalm, L., Tolfvenstam, T., and Nowak, P. (2013). Microbial translocation contribute to febrile episodes in adults with chemotherapy-induced neutropenia. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068056"},{"key":"ref_12","unstructured":"Craig, M. (2019). CDC\u2019s Antibiotic Resistance Threats Report, 2019, Extended Spectrum \u03b2-Lactamase (ESBL)-Producing Enterobacteriaceae."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e2020009","DOI":"10.4084\/mjhid.2020.009","article-title":"Febrile neutropenia in acute leukemia. Epidemiology, etiology, pathophysiology and treatment","volume":"12","author":"Hansen","year":"2019","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"106919","DOI":"10.1016\/j.ijantimicag.2023.106919","article-title":"Prospective analysis of febrile neutropenia patients with bacteraemia: The results of an international ID\u2013IRI study","volume":"62","author":"Erdem","year":"2023","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"ofac240","DOI":"10.1093\/ofid\/ofac240","article-title":"Bloodstream infections in hematologic malignancy patients with fever and neutropenia: Are empirical antibiotic therapies in the United States still effective?","volume":"9","author":"Zimmer","year":"2022","journal-title":"Open Forum Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1080\/21505594.2016.1156821","article-title":"Bloodstream infections in neutropenic cancer patients: A practical update","volume":"7","author":"Gustinetti","year":"2016","journal-title":"Virulence"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.idh.2019.08.006","article-title":"Bloodstream infections in neutropenic patients with haematological malignancies","volume":"25","author":"Carvalho","year":"2020","journal-title":"Infect. Dis. Health"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3866","DOI":"10.1016\/j.jmb.2014.05.029","article-title":"The yin and yang of bacterial resilience in the human gut microbiota","volume":"426","author":"Gibson","year":"2014","journal-title":"J. Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"339ra71","DOI":"10.1126\/scitranslmed.aaf2311","article-title":"Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice","volume":"8","author":"Shono","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_20","unstructured":"Tibayrenc, M. (2024). Genetics and Evolution of Infectious Diseases, Elsevier."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/ismej.2014.106","article-title":"Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology","volume":"9","author":"Gibson","year":"2015","journal-title":"ISME J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1101\/gr.155465.113","article-title":"Country-specific antibiotic use practices impact the human gut resistome","volume":"23","author":"Forslund","year":"2013","journal-title":"Genome Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Pehrsson, E.C., Forsberg, K.J., Gibson, M.K., Ahmadi, S., and Dantas, G. (2013). Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs. Front. Microbiol., 4.","DOI":"10.3389\/fmicb.2013.00145"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1093\/nar\/gkac163","article-title":"Landscape of mobile genetic elements and their antibiotic resistance cargo in prokaryotic genomes","volume":"50","author":"Khedkar","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Nielsen, K.L., Olsen, M.H., Pallej\u00e1, A., Ebdrup, S.R., S\u00f8rensen, N., Lukjancenko, O., Marvig, R.L., M\u00f8ller, K., Frimodt-M\u00f8ller, N., and Hertz, F.B. (2021). Microbiome compositions and resistome levels after antibiotic treatment of critically ill patients: An observational cohort study. Microorganisms, 9.","DOI":"10.3390\/microorganisms9122542"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1086\/383050","article-title":"Management of fever in neutropenic patients with different risks of complications","volume":"39","author":"Klastersky","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1002\/cncr.30039","article-title":"The role of the gastrointestinal microbiome in infectious complications during induction chemotherapy for acute myeloid leukemia","volume":"122","author":"Smith","year":"2016","journal-title":"Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13073-017-0409-1","article-title":"Characterization of oral and gut microbiome temporal variability in hospitalized cancer patients","volume":"9","author":"Smith","year":"2017","journal-title":"Genome Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.3324\/haematol.2013.091025","article-title":"European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: Summary of the 2011 4th European Conference on Infections in Leukemia","volume":"98","author":"Averbuch","year":"2013","journal-title":"Haematologica"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1093\/cid\/ciy339","article-title":"The effect of antibiotic selection pressure on the nasopharyngeal macrolide resistome: A cluster-randomized trial","volume":"67","author":"Keenan","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_31","first-page":"CD003543","article-title":"Interventions to improve antibiotic prescribing practices for hospital inpatients","volume":"2","author":"Davey","year":"2017","journal-title":"Cochrane Database Syst Rev."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ballo, O., Tarazzit, I., Stratmann, J., Reinheimer, C., Hogardt, M., Wichelhaus, T.A., Kempf, V., Serve, H., Finkelmeier, F., and Brandts, C. (2019). Colonization with multidrug resistant organisms determines the clinical course of patients with acute myeloid leukemia undergoing intensive induction chemotherapy. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0210991"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/imr.12563","article-title":"The intestinal microbiota: Antibiotics, colonization resistance, and enteric pathogens","volume":"279","author":"Kim","year":"2017","journal-title":"Immunol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2333748","DOI":"10.1080\/19490976.2024.2333748","article-title":"The effects of antibiotic exposures on the gut resistome during hematopoietic cell transplantation in children","volume":"16","author":"Heston","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1093\/cid\/ciz319","article-title":"Inappropriate empirical antibiotic treatment in high-risk neutropenic patients with bacteremia in the era of multidrug resistance","volume":"70","author":"Gudiol","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"102538","DOI":"10.1016\/j.jiac.2024.10.006","article-title":"Association between inappropriate empirical antimicrobial therapy and mortality in gram-negative bloodstream infections in patients with febrile neutropenia and hematological malignancy","volume":"31","author":"Castro","year":"2025","journal-title":"J. Infect. Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1093\/cid\/ciz777","article-title":"Gut microbiome signatures are predictive of infectious risk following induction therapy for acute myeloid leukemia","volume":"71","author":"Shi","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41375-019-0547-0","article-title":"Specific gut microbiota changes heralding bloodstream infection and neutropenic fever during intensive chemotherapy","volume":"34","author":"Rashidi","year":"2020","journal-title":"Leukemia"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Rattanathammethee, T., Tuitemwong, P., Thiennimitr, P., Sarichai, P., Na Pombejra, S., Piriyakhuntorn, P., Hantrakool, S., Chai-Adisaksopha, C., Rattarittamrong, E., and Tantiworawit, A. (2020). Gut microbiota profiles of treatment-na\u00efve adult acute myeloid leukemia patients with neutropenic fever during intensive chemotherapy. PLoS ONE, 15.","DOI":"10.1101\/2020.07.09.194910"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.cmi.2021.10.022","article-title":"Estimating daily antibiotic harms: An umbrella review with individual study meta-analysis","volume":"28","author":"Curran","year":"2022","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Li, G., Walker, M.J., and De Oliveira, D.M. (2022). Vancomycin resistance in Enterococcus and Staphylococcus aureus. Microorganisms, 11.","DOI":"10.3390\/microorganisms11010024"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"572","DOI":"10.3390\/antibiotics3040572","article-title":"Old and new glycopeptide antibiotics: Action and resistance","volume":"3","author":"Binda","year":"2014","journal-title":"Antibiotics"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Navidifar, T., Zare Banadkouki, A., Parvizi, E., Mofid, M., Golab, N., Beig, M., and Sholeh, M. (2025). Global prevalence of macrolide-resistant Staphylococcus spp.: A comprehensive systematic review and meta-analysis. Front. Microbiol., 16.","DOI":"10.3389\/fmicb.2025.1524452"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1093\/infdis\/jiad033","article-title":"Impact of antibiotic treatment on the gut microbiome and its resistome in hematopoietic stem cell transplant recipients","volume":"228","author":"Moestrup","year":"2023","journal-title":"J. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Willmann, M., Vehreschild, M.J., Biehl, L.M., Vogel, W., D\u00f6rfel, D., Hamprecht, A., Seifert, H., Autenrieth, I.B., and Peter, S. (2019). Distinct impact of antibiotics on the gut microbiome and resistome: A longitudinal multicenter cohort study. BMC Biol., 17.","DOI":"10.1186\/s12915-019-0692-y"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1038\/s41564-018-0257-9","article-title":"Recovery of gut microbiota of healthy adults following antibiotic exposure","volume":"3","author":"Palleja","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e159","DOI":"10.1016\/S2666-5247(20)30202-0","article-title":"Antibiotic prophylaxis and the gastrointestinal resistome in paediatric patients with acute lymphoblastic leukaemia: A cohort study with metagenomic sequencing analysis","volume":"2","author":"Margolis","year":"2021","journal-title":"Lancet Microbe"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/8\/770\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:18:55Z","timestamp":1760033935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/8\/770"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,30]]},"references-count":47,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["antibiotics14080770"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14080770","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,30]]}}}