{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T14:19:10Z","timestamp":1789395550781,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Extended-spectrum \u03b2-lactamase (ESBL)-producing Klebsiella pneumoniae causes difficult-to-treat bloodstream infections in patients with haematological malignancies, particularly after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Carbapenems remain reliable, but their anti-anaerobic activity may aggravate intestinal dysbiosis and increase selection pressure for carbapenem resistance. Cefepime\u2013enmetazobactam is a novel fourth-generation cephalosporin\/\u03b2-lactamase inhibitor combination active against many class A ESBL-producing Enterobacterales. We describe a profoundly immunocompromised patient with acute myeloid leukaemia after allo-HSCT, grade III steroid-refractory gastrointestinal graft-versus-host disease, and intestinal colonization by an ESBL-producing K. pneumoniae isolate resistant to ceftolozane\u2013tazobactam. The patient developed persistent bacteraemia and right pyelonephritis with small renal abscess-like lesions. Meropenem was rapidly de-escalated to cefepime\u2013enmetazobactam, with temporary adjunctive fosfomycin and subsequently tigecycline. Blood-culture time to positivity progressively lengthened from 1.18 h to 16 h before cultures became negative. Serial cefepime therapeutic drug monitoring permitted repeated assessment of exposure and neurological toxicity risk. Whole-genome sequencing identified K. pneumoniae ST307 carrying blaCTX-M-15, blaTEM-1, blaSHV-28, and blaOXA-1, together with multiple resistance determinants and a large conjugative plasmid. This case describes the use of cefepime\u2013enmetazobactam as part of a targeted carbapenem-sparing strategy for invasive ESBL-producing K. pneumoniae infection in a highly immunocompromised allo-HSCT recipient.<\/jats:p>","DOI":"10.3390\/pathogens15090976","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:05:26Z","timestamp":1789391126000},"page":"976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ESBL-Producing Klebsiella pneumoniae Bacteraemia with Renal Micro-Abscesses Treated with Cefepime\u2013Enmetazobactam in a Neutropenic Allogeneic Transplant Recipient"],"prefix":"10.3390","volume":"15","author":[{"given":"Carlo","family":"Tascini","sequence":"first","affiliation":[{"name":"Infectious Diseases Clinic, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"},{"name":"Department of Medicine (DMED), University of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Luca","family":"Montanari","sequence":"additional","affiliation":[{"name":"Infectious Diseases Clinic, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Francesca","family":"Patriarca","sequence":"additional","affiliation":[{"name":"Department of Medicine (DMED), University of Udine, 33100 Udine, Italy"},{"name":"Haematological Clinic and Transplant Centre, Azienda Sanitaria 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2475-8732","authenticated-orcid":false,"given":"Simone","family":"Giuliano","sequence":"additional","affiliation":[{"name":"Infectious Diseases Clinic, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8433-0394","authenticated-orcid":false,"given":"Jacopo","family":"Angelini","sequence":"additional","affiliation":[{"name":"Department of Medicine (DMED), University of Udine, 33100 Udine, Italy"},{"name":"Department of Laboratory Medicine, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"},{"name":"Clinical Pharmacology and Toxicology Institute, University Hospital Friuli Centrale, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3791-8635","authenticated-orcid":false,"given":"Paolo","family":"Gaibani","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Public Health, University of Verona, 37100 Verona, Italy"},{"name":"Microbiology and Virology Unit, Department of Pathology, Azienda Ospedaliera Universitaria Integrata di 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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":"101214","DOI":"10.1016\/j.lanepe.2025.101214","article-title":"2024 update of the AGIHO guideline on diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients with solid tumours and haematological malignancies","volume":"51","author":"Sandherr","year":"2025","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"339","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_4","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1182\/blood-2014-02-554725","article-title":"The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation","volume":"124","author":"Taur","year":"2014","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1016\/j.bbmt.2019.06.001","article-title":"Alteration of the intestinal microbiota by broad-spectrum antibiotic use correlates with the occurrence of intestinal graft-versus-host disease","volume":"25","author":"Lee","year":"2019","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1001\/jamainternmed.2024.0581","article-title":"Mortality of patients with sepsis administered piperacillin-tazobactam vs cefepime","volume":"184","author":"Chanderraj","year":"2024","journal-title":"JAMA Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e00180-20","DOI":"10.1128\/AAC.00180-20","article-title":"Pharmacodynamics of cefepime combined with the novel Extended-Spectrum-\u03b2-lactamase (ESBL) inhibitor enmetazobactam for murine infections caused by ESBL-producing Klebsiella pneumoniae","volume":"64","author":"Johnson","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e00078-20","DOI":"10.1128\/AAC.00078-20","article-title":"Pharmacokinetics-pharmacodynamics of enmetazobactam combined with cefepime in a neutropenic murine thigh infection model","volume":"64","author":"Bernhard","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1001\/jama.2022.17034","article-title":"Effect of cefepime\u2013enmetazobactam vs piperacillin\u2013tazobactam on clinical cure and microbiological eradication in patients with complicated urinary tract infection or acute pyelonephritis: The ALLIUM randomized clinical trial","volume":"328","author":"Kaye","year":"2022","journal-title":"JAMA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e70181","DOI":"10.1002\/phar.70181","article-title":"Consensus Guidance for Beta-Lactam Antibiotic Dose Individualization in Acutely Ill Patients: Endorsed by the American College of Clinical Pharmacy, European Society of Clinical Microbiology and Infectious Diseases, European Society of Clinical Microbiology and Infectious Diseases PK\/PD of Anti-Infectives Study Group, Infectious Diseases Society of America, International Association of Therapeutic Drug Monitoring and Clinical Toxicology, Society of Critical Care Medicine, and the Society of Infectious Diseases Pharmacists","volume":"46","author":"Barreto","year":"2026","journal-title":"Pharmacotherapy"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1093\/jac\/dkx001","article-title":"Determining \u03b2-lactam exposure threshold to suppress resistance development in Gram-negative bacteria","volume":"72","author":"Tam","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"106727","DOI":"10.1016\/j.ijantimicag.2023.106727","article-title":"Beta-lactam target attainment and associated outcomes in patients with bloodstream infections","volume":"61","author":"Alshaer","year":"2023","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"107480","DOI":"10.1016\/j.ijantimicag.2025.107480","article-title":"In reply to the Letter to Editor regarding \u2019Renal function and its impact on the concentration of ceftazidime-avibactam: A cross-sectional study\u2019","volume":"65","author":"Angelini","year":"2025","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1007\/s40262-022-01137-y","article-title":"Clinical Pharmacokinetics and Pharmacodynamics of Cefepime","volume":"61","author":"Pais","year":"2022","journal-title":"Clin. Pharmacokinet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1186\/s13054-017-1856-1","article-title":"Cefepime-induced neurotoxicity: A systematic review","volume":"21","author":"Payne","year":"2017","journal-title":"Crit. Care."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.cmi.2017.01.005","article-title":"Cefepime plasma concentrations and clinical toxicity: A retrospective cohort study","volume":"23","author":"Huwyler","year":"2017","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.cmi.2019.06.028","article-title":"Cefepime neurotoxicity: Thresholds and risk factors. A retrospective cohort study","volume":"26","author":"Atkinson","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"dlac043","DOI":"10.1093\/jacamr\/dlac043","article-title":"Therapeutic drug monitoring of cefepime in a non-critically ill population: Retrospective assessment and potential role for model-based dosing","volume":"4","author":"Suttels","year":"2022","journal-title":"JAC Antimicrob. Resist."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"106472","DOI":"10.1016\/j.ijantimicag.2021.106472","article-title":"Prospective assessment of breakthrough infections and neurotoxicity and their association with cefepime trough concentrations in patients with febrile neutropenia","volume":"59","author":"Gijsen","year":"2022","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_20","first-page":"1127","article-title":"Infection Section of European Society of Intensive Care Medicine (ESICM); Pharmacokinetic\/pharmacodynamic and Critically Ill Patient Study Groups of European Society of Clinical Microbiology and Infectious Diseases (ESCMID); Infectious Diseases Group of International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT); Infections in the ICU and Sepsis Working Group of International Society of Antimicrobial Chemotherapy (ISAC). Antimicrobial therapeutic drug monitoring in critically ill adult patients: A position paper","volume":"46","author":"Alffenaar","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1007\/s40121-026-01360-1","article-title":"Ventilator-associated pneumonia due to ESBL-producing Escherichia coli successfully treated with cefepime\u2013enmetazobactam: A European case report","volume":"15","author":"Viaggi","year":"2026","journal-title":"Infect. Dis. Ther."},{"key":"ref_22","unstructured":"(2025, January 11\u201315). Cefepime\/enmetazobactam as treatment for extended-spectrum-\u03b2-lactamase Escherichia coli bloodstream infection in a septic patient with liver cirrhosis: A case report. Proceedings of the Annual Congress of the European Society of Clinical Microbiology and Infectious Diseases, Vienna, Austria."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1080\/17460913.2025.2468112","article-title":"Cefepime-enmetazobactam: First approved cefepime-\u03b2-lactamase inhibitor combination for multidrug-resistant Enterobacterales","volume":"20","author":"Bhowmick","year":"2025","journal-title":"Future Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1177\/10600280241279904","article-title":"Cefepime-enmetazobactam: A drug review of a novel \u03b2-lactam\/\u03b2-lactamase inhibitor","volume":"59","author":"Lanier","year":"2025","journal-title":"Ann. Pharmacother."},{"key":"ref_25","unstructured":"European Medicines Agency (2024). Exblifep (Cefepime\u2013Enmetazobactam): European Public Assessment Report and Product Information, EMA."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/ki.2011.322","article-title":"Drug dosing consideration in patients with acute and chronic kidney disease\u2014A clinical update from Kidney Disease: Improving Global Outcomes","volume":"80","author":"Matzke","year":"2011","journal-title":"Kidney Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1093\/jac\/dky492","article-title":"Emergence and rapid global dissemination of CTX-M-15-associated Klebsiella pneumoniae strain ST307","volume":"74","author":"Wyres","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e00213-16","DOI":"10.1128\/genomeA.00213-16","article-title":"Complete genome sequence of KPC-3- and CTX-M-15-producing Klebsiella pneumoniae sequence type 307","volume":"4","author":"Villa","year":"2016","journal-title":"Genome Announc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e01148-20","DOI":"10.1128\/AAC.01148-20","article-title":"Emerging antimicrobial-resistant high-risk Klebsiella pneumoniae clones ST307 and ST147","volume":"64","author":"Peirano","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s12941-020-00366-y","article-title":"Emerging high-risk ST101 and ST307 carbapenem-resistant Klebsiella pneumoniae clones from bloodstream infections in southern Italy","volume":"19","author":"Loconsole","year":"2020","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1093\/jac\/dky453","article-title":"OXA-1 \u03b2-lactamase and non-susceptibility to penicillin\/\u03b2-lactamase inhibitor combinations among ESBL-producing Enterobacterales","volume":"74","author":"Livermore","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e3842","DOI":"10.1093\/cid\/ciaa1479","article-title":"MERINO Trial Investigators and the Australasian Society for Infectious Disease Clinical Research Network (ASID-CRN). Association between minimum inhibitory concentration, \u03b2-lactamase genes and mortality for patients treated with piperacillin\u2013tazobactam or meropenem from the MERINO study","volume":"73","author":"Henderson","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"116993","DOI":"10.1016\/j.diagmicrobio.2025.116993","article-title":"In-vitro activity of cefepime\/enmetazobactam against extended spectrum beta-lactamases and\/or ampC producing Enterobacterales and Pseudomonas aeruginosa collected across India","volume":"113","author":"Bakthavatchalam","year":"2025","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lamy, B., Darg\u00e8re, S., Arendrup, M.C., Parienti, J.J., and Tattevin, P. (2016). How to optimize the use of blood cultures for the diagnosis of bloodstream infections? A state-of-the art. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.00697"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1111\/j.1469-0691.2007.01736.x","article-title":"Microbial and clinical determinants of time-to-positivity in patients with bacteraemia","volume":"13","author":"Pozo","year":"2007","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_36","first-page":"322","article-title":"In vitro activity of Cefepime\/Enmetazobactam and Cefepime\/Zidebactam against OXA-48-producing Klebsiella pneumoniae clinical strains","volume":"48","author":"Bulfoni","year":"2025","journal-title":"New Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101679","DOI":"10.1016\/j.nmni.2025.101679","article-title":"Case report of a bloodstream infection due by Salmonella strathcona ST2559 in northeast Italy, 2025","volume":"68","author":"Bulfoni","year":"2025","journal-title":"New Microbes New Infect."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e0234524","DOI":"10.1128\/spectrum.02345-24","article-title":"In vivo efficacy of enmetazobactam combined with cefepime in a murine pneumonia model induced by OXA-48-producing Klebsiella pneumoniae","volume":"12","author":"Albac","year":"2024","journal-title":"Microbiol. Spectr."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/9\/976\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:26:00Z","timestamp":1789392360000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/9\/976"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,14]]},"references-count":38,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["pathogens15090976"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15090976","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,14]]}}}