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Rates of sepsis exceeding 50% in a neonatal intensive care unit (NICU) in Cairo, Egypt, were not controlled by routine antimicrobial therapy. We investigated these conditions in September 2001.Case series and retrospective cohort studies were conducted on 2 groups of NICU infants admitted to an academic medical center between February 12 and July 31, 2001. Observation of clinical practices led us to culture in-use intravenous (i.v.) fluids and medications. We monitored rates of i.v. fluid contamination, clinical sepsis and mortality after interventions to establish new procedures for handling and disposal of i.v. fluids, infection control training and improved clinical laboratory capacity.Among infants in the retrospective cohort group, 88 (77%) of 115 had clinical sepsis, and 59 (51%) died. In the case series group, we documented the time of initial positive blood culture; 21 (64%) of 33 were septic24 hours after birth. Klebsiella pneumoniae accounted for 24 (73%) of 33 isolates; 14 (58%) of 24 were extended spectrum beta-lactamase-producing and aminoglycoside-resistant. On admission, all neonates received glucose-containing i.v. fluids; i.v. bottles (500 mL) were divided among multiple infants. The i.v. fluids were prepared at the bedside; poor hand hygiene and poor adherence to aseptic techniques were observed. K. pneumoniae was isolated from 13 (65%) of 20 in-use glucose-containing i.v. fluids. Fluid contamination, sepsis and mortality rates declined significantly after intervention.Extrinsically contaminated i.v. fluids resulted in sepsis and deaths. Standard infection control precautions significantly improve mortality and sepsis rates and are prerequisites for safe NICU care.