{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T08:05:45Z","timestamp":1784189145063,"version":"3.55.0"},"reference-count":18,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"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>Background: Neonatal sepsis caused by multidrug-resistant (MDR) Gram-negative pathogens poses significant therapeutic challenges in neonatal intensive care units (NICUs), particularly in surgical neonates. Ceftazidime-avibactam (CAZ-AVI), a novel \u03b2-lactam\/\u03b2-lactamase inhibitor combination, offers activity against extended-spectrum \u03b2-lactamases (ESBLs), AmpC, and serine carbapenemases, but neonatal experience remains limited. Methods and Results: We present a 35-week preterm neonate with long-gap esophageal atresia who developed late-onset sepsis caused by MDR Enterobacter hormaechei, including a KPC-producing carbapenem-resistant isolate, during postoperative recovery. After a multidisciplinary review, the patient received off-label CAZ-AVI at 25 mg\/kg\/dose (20\/5 mg\/kg) every 8 h, infused over 2 h, informed by available neonatal pharmacokinetic evidence and weight-adjusted dosing recommendations. Amikacin was administered contextually. Consecutive blood cultures obtained 48\u201372 h after dual antibiotic therapy initiation became negative and remained sterile, with concordant decline in inflammatory biomarkers, confirming rapid microbiological clearance. Unfortunately, the newborn died in the hours immediately following the final surgery performed to repair the esophageal atresia via end-to-end anastomosis; the cause was complications (hemothorax) unrelated to infectious diseases, although the onset of such severe sepsis may have compromised an already impaired immunological status. Discussion: This case shows mechanism-concordant antimicrobial selection and the feasibility of neonatal dosing when MDR Enterobacterales drive invasive infection. Our experience supports prospective evaluation of CAZ-AVI in carefully selected septic newborns while emphasizing the importance of rapid carbapenemase genotyping, susceptibility testing, and multidisciplinary oversight.<\/jats:p>","DOI":"10.3390\/antibiotics15070690","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T06:49:36Z","timestamp":1784184576000},"page":"690","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Use of Ceftazidime\u2013Avibactam in a Late-Preterm Newborn with Multidrug-Resistant Enterobacter hormaechei Sepsis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8105-5139","authenticated-orcid":false,"given":"Marcello","family":"Trizzino","sequence":"first","affiliation":[{"name":"Infectious and Tropical Diseases Unit, Sicilian Regional Reference Center for the Fight Against AIDS, AOU Policlinico \u201cP. Giaccone\u201d, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Notarbartolo","sequence":"additional","affiliation":[{"name":"Neonatology and Neonatal Intensive Care Unit, AOU Policlinico \u201cP. Giaccone\u201d, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Pipit\u00f2","sequence":"additional","affiliation":[{"name":"Infectious and Tropical Diseases Unit, Sicilian Regional Reference Center for the Fight Against AIDS, AOU Policlinico \u201cP. Giaccone\u201d, 90133 Palermo, Italy"},{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2918-9826","authenticated-orcid":false,"given":"Gregorio","family":"Serra","sequence":"additional","affiliation":[{"name":"Neonatology and Neonatal Intensive Care Unit, AOU Policlinico \u201cP. Giaccone\u201d, 90127 Palermo, Italy"},{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6958-8605","authenticated-orcid":false,"given":"Bendetta","family":"Romanin","sequence":"additional","affiliation":[{"name":"Infectious and Tropical Diseases Unit, Sicilian Regional Reference Center for the Fight Against AIDS, AOU Policlinico \u201cP. Giaccone\u201d, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Carta","sequence":"additional","affiliation":[{"name":"Neonatology and Neonatal Intensive Care Unit, AOU Policlinico \u201cP. Giaccone\u201d, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0376-7468","authenticated-orcid":false,"given":"Vincenzo","family":"Insinga","sequence":"additional","affiliation":[{"name":"Neonatology and Neonatal Intensive Care Unit, AOU Policlinico \u201cP. Giaccone\u201d, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2170-8035","authenticated-orcid":false,"given":"Maria R.","family":"Di Pace","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90133 Palermo, Italy"},{"name":"Pediatric Surgery Unit, AOU Policlinico \u201cP. Giaccone\u201d, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa M. A.","family":"Fasciana","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1992-1796","authenticated-orcid":false,"given":"Antonio","family":"Cascio","sequence":"additional","affiliation":[{"name":"Infectious and Tropical Diseases Unit, Sicilian Regional Reference Center for the Fight Against AIDS, AOU Policlinico \u201cP. Giaccone\u201d, 90133 Palermo, Italy"},{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9576-1635","authenticated-orcid":false,"given":"Mario","family":"Giuffr\u00e8","sequence":"additional","affiliation":[{"name":"Neonatology and Neonatal Intensive Care Unit, AOU Policlinico \u201cP. Giaccone\u201d, 90127 Palermo, Italy"},{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1136\/archdischild-2020-320217","article-title":"Global incidence and mortality of neonatal sepsis: A systematic review and meta-analysis","volume":"106","author":"Fleischmann","year":"2021","journal-title":"Arch. Dis. Child."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1080\/14767058.2020.1732342","article-title":"Literature review on the distribution characteristics and antimicrobial resistance of bacterial pathogens in neonatal sepsis","volume":"35","author":"Wang","year":"2022","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1007\/s11908-014-0400-6","article-title":"Antimicrobial treatment of serious gram-negative infections in newborns","volume":"16","author":"Gray","year":"2014","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e322","DOI":"10.1542\/peds.2013-1248","article-title":"Risk factors and outcomes for multidrug-resistant Gram-negative bacteremia in the NICU","volume":"133","author":"Tsai","year":"2014","journal-title":"Pediatrics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s40272-021-00465-z","article-title":"Potential Antibiotics for the Treatment of Neonatal Sepsis Caused by Multidrug-Resistant Bacteria","volume":"23","author":"Darlow","year":"2021","journal-title":"Paediatr. Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"iv23","DOI":"10.1093\/jac\/dkab352","article-title":"Current and future perspectives in the treatment of multidrug-resistant Gram-negative infections","volume":"76","author":"Bassetti","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1080\/20469047.2017.1408738","article-title":"Reviewing the WHO guidelines for antibiotic use for sepsis in neonates and children","volume":"38","author":"Fuchs","year":"2018","journal-title":"Paediatr. Int. Child Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1093\/jac\/dkad280","article-title":"Efficacy and safety of ceftazidime\/avibactam in patients with infections caused by \u03b2-lactamase-producing Gram-negative pathogens: A pooled analysis from the Phase 3 clinical trial programme","volume":"78","author":"Torres","year":"2023","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1007\/s40121-024-00999-y","article-title":"Ceftazidime-Avibactam in the Treatment of Patients with Bacteremia or Nosocomial Pneumonia: A Systematic Review and Meta-analysis","volume":"13","author":"Shields","year":"2024","journal-title":"Infect. Dis. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1097\/INF.0000000000002392","article-title":"Safety and Efficacy of Ceftazidime-Avibactam Plus Metronidazole in the Treatment of Children \u2265 3 Months to <18 Years with Complicated Intra-Abdominal Infection: Results from a Phase 2, Randomized, Controlled Trial","volume":"38","author":"Bradley","year":"2019","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"piaf028","DOI":"10.1093\/jpids\/piaf028","article-title":"Pharmacokinetics and Safety of Ceftazidime-Avibactam in Neonates and Young Infants: A Phase 2a, Multicenter Prospective Trial","volume":"14","author":"Bradley","year":"2025","journal-title":"J. Pediatr. Infect. Dis. Soc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e149","DOI":"10.1097\/INF.0000000000004247","article-title":"Off-label Use of Ceftazidime\/Avibactam in Neonatal Intensive Care Unit: A Real-life Experience and Literature Review","volume":"43","author":"Ftergioti","year":"2024","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s00134-021-06506-y","article-title":"Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021","volume":"47","author":"Evans","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Aslan, A.T., Ezure, Y., Horcajada, J.P., Harris, P.N.A., and Paterson, D.L. (2023). In vitro, in vivo and clinical studies comparing the efficacy of ceftazidime-avibactam monotherapy with ceftazidime-avibactam-containing combination regimens against carbapenem-resistant Enterobacterales and multidrug-resistant Pseudomonas aeruginosa isolates or infections: A scoping review. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1249030"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1177\/08971900221087131","article-title":"Off-Label Use of Ceftazidime-Avibactam in a Premature Infant with Multidrug-Resistant Klebsiella pneumoniae Infection: A Case Report","volume":"36","author":"Nascimento","year":"2023","journal-title":"J. Pharm. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1097\/INF.0000000000002344","article-title":"Use of Ceftazidime-avibactam for the Treatment of Extensively drug-resistant or Pan drug-resistant Klebsiella pneumoniae in Neonates and Children <\u00a05 Years of Age","volume":"38","author":"Iosifidis","year":"2019","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1097\/INF.0000000000002807","article-title":"Successful Treatment of Pandrug-resistant Klebsiella pneumoniae Infection with Ceftazidime-avibactam in a Preterm Infant: A Case Report","volume":"39","author":"Coskun","year":"2020","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Notarbartolo, V., Bacile, D., Badiane, B.A., Lo Leggio, A., Angileri, V.M., Duca, V., and Giuffr\u00e8, M. (2026). Use of RESERVE-Antibiotics in Newborns: Clinical Experience of Two NICUs in the Metropolitan Area of Palermo. Antibiotics, 15.","DOI":"10.3390\/antibiotics15020231"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/7\/690\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T07:27:27Z","timestamp":1784186847000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/7\/690"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,16]]},"references-count":18,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["antibiotics15070690"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics15070690","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,16]]}}}