Microbiological factors associated with neonatal necrotizing enterocolitis: protective effect of early antibiotic treatment TG Krediet 1 , N van Lelyveld 1 , DC Vijlbrief 1 , HAA Brouwers 1 , WLM Kramer 2 , A Fleer 3 and LJ Gerards 1 Departments of Neonatology 1 and Pediatric Surgery 2 , Wilhelmina Children’s Hospital, and Eijkman-Winkler Institute for Microbiology, Infectious Diseases and Inflammation 3 , University Medical Center, Utrecht, The Netherlands Krediet TG, van Lelyveld N, Vijlbrief DC, Brouwers HAA, Kramer WLM, Fleer A, Gerards LJ. Microbiological factors associated with neonatal necrotizing enterocolitis: protective effect of early antibiotic treatment. Acta Pædiatr 2003; 92: 1180–1182. Stockholm. ISSN 0803-5253 Aim: The incidence of necrotizing enterocolitis (NEC) strongly increased in an neonatal intensive care unit (NICU) in 1997 and 1998 compared with previous years, which coincided with increased incidence of nosocomial sepsis. Specific risk factors related to this NICU and a possible relationship between NEC and nosocomial sepsis were studied retrospectively, including all patients with NEC since 1990 and matched controls. Methods: Clinical and bacteriological data from the period before the development of NEC and a similar period for the controls were collected retrospectively and corrected for birthweight and gestational age. Statistical analysis was performed by a stepwise regression model. Results: Data of 104 neonates with NEC and matched controls were analysed. The median day of onset of NEC was 12 d (range 1–63 d). Significant risk factors for NEC were: insertion of a peripheral artery catheter [odds ratio (OR) 2.3, 95% confidence interval (95% CI) 1.3–3.9] and a central venous catheter (OR 5.6, 95% CI 3.1–10.1), colonization with Klebsiella sp. (OR 3.4, 95% CI 1.5–7.5) and Escherichia coli (OR 2.1, 95% CI 1.0–4.5), and the occurrence of sepsis, in particular due to coagulase-negative staphylococci (OR 2.6, 95% CI 1.4–5.1). The risk for NEC was decreased after the early use (<48 h after birth) of amoxicillin–clavulanate and gentamicin (OR 0.3, 95% CI 0.2–0.6). Conclusion: Insertion of central venous and peripheral arterial catheters is positively associated with NEC, as is colonization with the Gram-negative bacilli Klebsiella and E. coli and the occurrence of sepsis, particularly due to coagulase-negative staphylococci. Early treatment with amoxicillin–clavulanate and gentamicin is negatively associated with NEC and may be protective against NEC. Key words: Necrotizing enterocolitis, neonate, risk factors TG Krediet, Department of Neonatology, Room KE.04.123.1, Wilhelmina Children’s Hospital, University Medical Center, PO Box 85090, NL-3508 AB Utrecht, The Netherlands (Tel. 31 30 2504545, fax. 31 30 2505320, e-mail. t.krediet@wkz.azu.nl) Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency among infants admitted to a neonatal intensive care unit (NICU) and predominantly affects premature infants (1, 2). The reported incidence varies between 1 and 8%. The incidence of NEC in the authors’ NICU was 1.5–2.5% until 1997, when there was a two-fold increase in incidence, to 5%. In the years following 1997 the higher incidence of NEC persisted. This increased incidence coincided with a strong increase in incidence of nosocomial sepsis in the unit, which was 7% in 1990 and 18% in 1998. In an attempt to find specific risk factors related to this NICU and to elucidate a possible relationship between the incidence of NEC and the increased incidence of nosocomial sepsis, a retrospective study was performed, including all patients with NEC admitted since 1990 with a matched control group. Methods All neonates with NEC admitted to the NICU during 1990–1998 were included in the study and compared with a control group of patients with matching gesta- tional age, birthweight and period of admission. This NICU is a large academic referral centre for sick neonates from the central region of The Netherlands. According to the local policy all premature infants admitted to the NICU are equipped with central venous and arterial catheters, using umbilical catheters during the first week of life and peripheral arterial catheters and percutaneous Silastic 1 catheters after the first week. Surveillance cultures (ear, throat, umbilicus, faeces or anal region) are performed on admission and subse- quently weekly. Blood cultures are collected when indicated. NEC was defined as the presence of clinical  2003 Taylor & Francis. ISSN 0803-5253 Acta Pñdiatr 92: 1180±1182. 2003 DOI 10.1080/08035250310005233