{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T18:32:38Z","timestamp":1784140358617,"version":"3.55.0"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Victor Babe\u0219 University of Medicine and Pharmacy, Timi\u0219oara"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background\/Objectives: Perinatal infections caused by Gram-negative bacteria pose a significant risk to neonatal health, especially in low-resource settings. These infections often lead to severe complications due to diagnostic and therapeutic challenges. This study aimed to clinical characterize, early outcomes, and risk factors associated with Gram-negative infections in neonates admitted to the tertiary neonatal intensive care unit (NICU) at \u201cLouis Turcanu\u201d Children\u2019s Hospital, Timisoara. Methods: A retrospective, case\u2013control study was conducted at a tertiary neonatal care unit in Timi\u0219oara, Romania, including neonates with microbiologically confirmed Gram-negative infections (n = 44) and a matched control group without infection (n = 47). Clinical, laboratory, and microbiological data were analyzed. Statistical comparisons and logistic regression analyses were used to evaluate risk factors and outcomes. Results: Male sex (79.5% in infected vs. 57.4% in controls; p = 0.0418) and vaginal delivery (43.2% vs. 17.0%; p = 0.00001) were significantly associated with infection. Respiratory distress (72.7%) and digestive symptoms (75.0%) were common in infected neonates. C-reactive protein and procalcitonin levels were markedly elevated in infected infants. Escherichia coli was the most common pathogen, with multidrug-resistant strains observed in bloodstream infections. Mechanical ventilation was required in 75% of infected neonates compared with 16.2% in controls (p &lt; 0.0001). Mortality was higher among infected neonates (25% vs. 4.3% in the control group), although not statistically significant. Conclusions: Gram-negative perinatal infections are associated with considerable morbidity, particularly in male neonates and those delivered vaginally. Early identification, antimicrobial stewardship, and intensive respiratory support are essential to improving outcomes in this vulnerable population.<\/jats:p>","DOI":"10.3390\/children12121692","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T10:11:23Z","timestamp":1765793483000},"page":"1692","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical Characteristics and Early Evolution of Neonates with Perinatal Gram-Negative Bacterial Infections"],"prefix":"10.3390","volume":"12","author":[{"given":"Mihaela","family":"Zaharie","sequence":"first","affiliation":[{"name":"Ph.D. School, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, 2 E. Murgu Sq., 300041 Timisoara, Romania"},{"name":"Department of Neonatology and Puericulture, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania"},{"name":"Neonatology and Preterm Department, \u201cLouis \u0162urcanu\u201d Children Emergency Hospital, 300011 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniko Maria","family":"Manea","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Puericulture, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania"},{"name":"Neonatology and Preterm Department, \u201cLouis \u0162urcanu\u201d Children Emergency Hospital, 300011 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marioara","family":"Boia","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Puericulture, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania"},{"name":"Neonatology and Preterm Department, \u201cLouis \u0162urcanu\u201d Children Emergency Hospital, 300011 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana","family":"Costescu","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Puericulture, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania"},{"name":"Neonatology and Preterm Department, \u201cLouis \u0162urcanu\u201d Children Emergency Hospital, 300011 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Cioboata","sequence":"additional","affiliation":[{"name":"Neonatology and Preterm Department, \u201cLouis \u0162urcanu\u201d Children Emergency Hospital, 300011 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timea","family":"Brandibur","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Puericulture, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania"},{"name":"Neonatology and Preterm Department, \u201cLouis \u0162urcanu\u201d Children Emergency Hospital, 300011 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2468-6003","authenticated-orcid":false,"given":"Daniela","family":"Iacob","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Puericulture, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania"},{"name":"Clinic of Neonatology, \u201cPius Brinzeu\u201d County Clinical Emergency Hospital, 300723 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1136\/archdischild-2022-324047","article-title":"Incidence and Aetiology of Infant Gram-Negative Bacteraemia and Meningitis: Systematic Review and Meta-Analysis","volume":"107","author":"Andrews","year":"2022","journal-title":"Arch. Dis. Child."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chan, G.J., Lee, A.C., Baqui, A.H., Tan, J., and Black, R.E. (2015). Prevalence of Early-Onset Neonatal Infection among Newborns of Mothers with Bacterial Infection or Colonization: A Systematic Review and Meta-Analysis. BMC Infect. Dis., 15.","DOI":"10.1186\/s12879-015-0813-3"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Yu, X., Chen, H., and Chen, G. (2024). Analysis of Risk Factors and Complications of Neonatal Infection in 500 Pregnant Women with Premature Rupture of Membranes. Research Square.","DOI":"10.21203\/rs.3.rs-5280140\/v1"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Siefker, D.T., and Adkins, B. (2017). Rapid CD8+ Function Is Critical for Protection of Neonatal Mice from an Extracellular Bacterial Enteropathogen. Front. Pediatr., 4.","DOI":"10.3389\/fped.2016.00141"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/s41390-021-01696-z","article-title":"Mohan Pammi Diagnosis of Neonatal Sepsis: The Past, Present and Future","volume":"91","author":"Celik","year":"2022","journal-title":"Pediatr. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Morris, S., and Cerceo, E. (2020). Trends, Epidemiology, and Management of Multi-Drug Resistant Gram-Negative Bacterial Infections in the Hospitalized Setting. Antibiotics, 9.","DOI":"10.3390\/antibiotics9040196"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e00077-17","DOI":"10.1128\/CMR.00077-17","article-title":"Antibiotic Hybrids: The Next Generation of Agents and Adjuvants against Gram-Negative Pathogens?","volume":"31","author":"Domalaon","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.2217\/fmb-2018-0189","article-title":"Re-Evaluating the Potential of Immunoprophylaxis and\/or Immunotherapy for Infections Caused by Multidrug Resistant Klebsiella pneumoniae","volume":"13","author":"Kobayashi","year":"2018","journal-title":"Future Microbiol."},{"key":"ref_9","first-page":"e67084","article-title":"Antibiotic Treatment Practices and Microbial Profile in Diabetic Foot Ulcers: A Retrospective Cohort Study","volume":"16","author":"Daniel","year":"2024","journal-title":"Cureus"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Daoud, Z., and Dropa, M. (2023). Editorial: The Global Threat of Carbapenem-Resistant Gram-Negative Bacteria, Volume II. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1196488"},{"key":"ref_11","first-page":"9","article-title":"Toll Like Receptor Type Four Gene Polymorphism in Neonatal Sepsis in Zagazig University Children\u2019s Hospital","volume":"27","author":"Nafea","year":"2019","journal-title":"Zagazig Univ. Med. J."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wen, S.C.H., Ezure, Y., Rolley, L., Spurling, G., Lau, C.L., Riaz, S., Paterson, D.L., and Irwin, A.D. (2021). Gram-Negative Neonatal Sepsis in Low- and Lower-Middle-Income Countries and WHO Empirical Antibiotic Recommendations: A Systematic Review and Meta-Analysis. PLoS Med., 18.","DOI":"10.2139\/ssrn.3777180"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Al Abdullatif, M. (2019). Microbiology of Neonatal Gram-Negative Sepsis in A Level III Neonatal Intensive Care Unit (NICU). A Single Center Experience. GJPNC, 1.","DOI":"10.33552\/GJPNC.2019.01.000519"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1136\/archdischild-2023-325569","article-title":"Incidence of Infant Gram-Negative Invasive Bacterial Infections in England, 2011\u20132019: An Observational Study Using Population-Wide Surveillance Data","volume":"108","author":"Andrews","year":"2023","journal-title":"Arch. Dis. Child."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lee, P., Sin, E., Yip, K.-T., and Ng, K. (2025). A 10-Year Study of Neonatal Sepsis from Tuen Mun Hospital, Hong Kong. Pathogens, 14.","DOI":"10.3390\/pathogens14030276"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/s41564-021-00870-7","article-title":"Characterization of Antimicrobial-Resistant Gram-Negative Bacteria That Cause Neonatal Sepsis in Seven Low- and Middle-Income Countries","volume":"6","author":"Sands","year":"2021","journal-title":"Nat. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Negrini, R., Da Silva Ferreira, R.D., and Guimar\u00e3es, D.Z. (2021). Value-Based Care in Obstetrics: Comparison between Vaginal Birth and Caesarean Section. BMC Pregnancy Childbirth, 21.","DOI":"10.1186\/s12884-021-03798-2"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/nm.4272","article-title":"Maturation of the Infant Microbiome Community Structure and Function across Multiple Body Sites and in Relation to Mode of Delivery","volume":"23","author":"Chu","year":"2017","journal-title":"Nat. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"36666","DOI":"10.1038\/srep36666","article-title":"Composition of Gut Microbiota in Infants in China and Global Comparison","volume":"6","author":"Kuang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_20","first-page":"5","article-title":"Comparing Maternal and Neonatal Side Effects of Natural Vaginal Delivery under Neuro-Axial Analgesia with Usual Vaginal Delivery and Cesarean Section: A Primary Single Center Study","volume":"2","author":"Darvish","year":"2017","journal-title":"J. Obstet. Gynecol. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9681","DOI":"10.2147\/IJGM.S335893","article-title":"Effects of Modes and Timings of Delivery on Feto-Maternal Outcomes in Women with Severe Preeclampsia: A Multi-Center Survey in Mainland China","volume":"14","author":"Wu","year":"2021","journal-title":"Int. J. Gen. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Chiusaroli, L., Liberati, C., Caseti, M., Rulli, L., Barbieri, E., Giaquinto, C., and Don\u00e0, D. (2022). Therapeutic Options and Outcomes for the Treatment of Neonates and Preterms with Gram-Negative Multidrug-Resistant Bacteria: A Systematic Review. Antibiotics, 11.","DOI":"10.3390\/antibiotics11081088"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/s41390-021-01745-7","article-title":"Neonatal Multidrug-Resistant Gram-Negative Infection: Epidemiology, Mechanisms of Resistance, and Management","volume":"91","author":"Flannery","year":"2022","journal-title":"Pediatr. Res."},{"key":"ref_24","first-page":"F1","article-title":"Neonatal Sepsis: Clinical Spectrum, Bacteriological Profile and Antibiotic Sensitivity Patterns in Neonatal Intensive Care Unit in a Tertiary Care Hospital","volume":"6","author":"Kurma","year":"2019","journal-title":"Int. J. Contemp. Med. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/tropej\/fmz062","article-title":"Predictors of Early Onset Neonatal Sepsis among Neonates in Dodoma, Tanzania: A Case Control Study","volume":"66","author":"Masanja","year":"2020","journal-title":"J. Trop. Pediatr."},{"key":"ref_26","first-page":"147","article-title":"Thrombocytopenia Is More Frequent in Gram Negative Neonatal Septicemia","volume":"2","author":"Zaky","year":"2022","journal-title":"Pediatr. Sci. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"52","DOI":"10.4103\/aam.aam_34_16","article-title":"Neonatal Sepsis in a Nigerian Private Tertiary Hospital: Bacterial Isolates, Risk Factors, and Antibiotic Susceptibility Patterns","volume":"16","author":"Shobowale","year":"2017","journal-title":"Ann. Afr. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Salahi, M., Moghadam, A.G., Mousavizadeh, A., Marashifard, M., Taghavi, S.J., Rezanejad, M., Moradi, S., and Khoramrooz, S.S. (2020). Neonatal Sepsis in Southwest of Iran; Prevalence of Microbial Pathogens, Risk Factors, Clinical Manifestations and Laboratory Findings. Research Square.","DOI":"10.21203\/rs.3.rs-122635\/v1"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tang, S., Li, M., Chen, H., Ping, G., Zhang, C., and Wang, S. (2017). A Chronological Study of the Bacterial Pathogen Changes in Acute Neonatal Bacterial Conjunctivitis in Southern China. BMC Ophthalmol., 17.","DOI":"10.1186\/s12886-017-0570-8"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.32553\/ijmbs.v3i1.609","article-title":"Neonatal Sepsis and Identification of Risk Factors: Study in Kmmc and Hospital Mathura","volume":"3","author":"Singh","year":"2019","journal-title":"Int. J. Med. Biomed. Stud."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"F507","DOI":"10.1136\/archdischild-2015-309554","article-title":"Neonatal Gram-Negative Infections, Antibiotic Susceptibility and Clinical Outcome: An Observational Study","volume":"101","author":"Kent","year":"2016","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e92212","DOI":"10.5812\/pedinfect.92212","article-title":"Bacterial Causative Agents of Neonatal Sepsis and Their Antibiotic Susceptibility in Neonatal Intensive Care Units (NICUs) and Neonatal Wards in Iran: A Systematic Review","volume":"8","author":"Akya","year":"2020","journal-title":"Arch. Pediatr. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Thomas, R., Ondongo-Ezhet, C., Motsoaledi, N., Sharland, M., Clements, M., and Velaphi, S. (2022). Incidence and All-Cause Mortality Rates in Neonates Infected With Carbapenem Resistant Organisms. Front. Trop. Dis., 3.","DOI":"10.3389\/fitd.2022.832011"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"721","DOI":"10.4236\/health.2019.116060","article-title":"Measurements of C-Reactive Protein for Successful Management and Follow-Up Treatment of Neonatal Sepsis and Nosocomial Infection","volume":"11","author":"Alagha","year":"2019","journal-title":"Health"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"150","DOI":"10.14235\/bs.2016.1037","article-title":"Retrospective Evaluation of Culture Proven Neonatal Sepsis Cases in Neonatal Intensive Care Unit","volume":"5","author":"Karacanoglu","year":"2018","journal-title":"Bezmialem Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6","DOI":"10.37185\/248","article-title":"Neonatal Sepsis; Incidence and Microbiological Profile along with Antibiotic Sensitivity of Causative Microorganisms","volume":"4","author":"Hussain","year":"2023","journal-title":"Life Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Solomon, S., Akeju, O., Odumade, O.A., Ambachew, R., Gebreyohannes, Z., Van Wickle, K., Abayneh, M., Metaferia, G., Carvalho, M.J., and Thomson, K. (2021). Prevalence and Risk Factors for Antimicrobial Resistance among Newborns with Gram-Negative Sepsis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0255410"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e134278","DOI":"10.5812\/jjm-134278","article-title":"Frequency, Bacteriological Profile, and Outcome of Neonatal Sepsis with Carbapenem-Resistant Gram-Negative Bacteria at the Tertiary Neonatal Intensive Care Unit, Ahvaz, Iran","volume":"16","author":"Aletayeb","year":"2023","journal-title":"Jundishapur J. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"11795565231189595","DOI":"10.1177\/11795565231189595","article-title":"Gram-Negative Late Onset Neonatal Sepsis in a Tertiary Care Center From Central India: A Retrospective Analysis","volume":"17","author":"Pataskar","year":"2023","journal-title":"Clin. Med. Insights Pediatr."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/12\/1692\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T10:46:03Z","timestamp":1765795563000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/12\/1692"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,13]]},"references-count":39,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["children12121692"],"URL":"https:\/\/doi.org\/10.3390\/children12121692","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,13]]}}}