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We evaluated the effects of enhanced infection control measures (ICMs) on carriage and infections of carbapenem-resistant Gram-negative bacteria (CRGNB) in a pediatric intensive care unit. We conducted a quasi-experimental study, including patients with infections of CRGNB retrospectively for 13 months and those participating in an active surveillance program prospectively for 22 months. Active surveillance (weekly rectal swabs) was implemented during a 63-week subperiod with standard ICMs and a subsequent 27-week subperiod with enhanced ICMs (intensified ICMs supplemented with audits and feedback). Prevalence, colonization pressure, incidence, and infections of CRGNB and compliance with ICMs and enhanced ICMs were recorded. Evaluation of results was performed using time series (TS) and interrupted TS. Compliance with hand hygiene improved during the second subperiod of active surveillance compared with the first; prevalence, colonization pressure, and incidence of CRGNB decreased significantly. The linear trend of centered moving average for carbapenem-resistant Klebsiella pneumoniae (CRKP) decreased from 1.2 to 0.1 infections/1,000 bed-days (IBD) (p = 0.046), while it remained unchanged for carbapenem-resistant Acinetobacter baumannii (CRAB) and increased for carbapenem-resistant Pseudomonas aeruginosa (CRPA) from 0.0 to 2.1 IBD (p < 0.001). Enhanced ICMs can reduce CRKP infections in endemic units, in contrast to CRPA and CRAB infections, which are more difficult to eradicate. [ABSTRACT FROM AUTHOR]