ObjectiveCentral line associated bloodstream infection (CLABSI) is an important cause of morbidity and mortality in the neonatal intensive care unit (NICU). We designed a CLABSI Prevention Package (CPP) to decrease NICU CLABSI rates, using evidence-proven interventions.DesignThis was a quality improvement (QI) project. Data collection was divided into three phases (pre-implementation, implementation and post implementation). SQUIRE2.0 guidelines were used to design, implement and report this QI initiative.SettingA tertiary care level 3 NICU at the Aga Khan University Hospital (AKUH), Karachi, Pakistan.PatientsAll patients admitted to the AKUH NICU from 1 January 2016 to 31 March 2018 who had a central line in place during their NICU admission.InterventionsCPP used evidence-based interventions focusing on hand hygiene, aseptic central line insertion techniques and central line care, prevention of fungal infections and nurse empowerment.Main outcome measuresCLABSI rates pre and post intervention were recorded. Secondary outcomes were risk factors for CLABSI, device (central line) utilisation ratio, CLABSI related mortality and micro-organism profile.ResultsCLABSI rates decreased from 17.1/1000 device days to 5.0/1000 device days (relative risk (RR)=0.36, CI=0.17–0.74). Device (central line) utilisation ratio declined from 0.30 to 0.25. Out of 613 patients enrolled in our study, 139 (22.7%) died. Mortality was higher in CLABSI group (n=20, 44%) as compared with non CLABSI group (n=119, 21.1%) (p<0.001). Gestational age of <27 weeks was an independent risk factor for CLABSI (RR=4.45, CI=1.10–18.25, p=0.03). A total of 158 pathogens were isolated among which 68 were associated with CLABSI. Gram-negative bacteria 31 (47.7%) were the most common cause of CLABSI. Ninety-seven (61%) micro-organisms were multi-drug resistant.ConclusionsCPP was effective in decreasing NICU CLABSI rates and can be used as a model to decrease NICU CLABSI rates in low or middle-income countries.