BACKGROUND: Carbapenem-resistant Gram-negative bacteria (CRGNB) infections constitute a global threat for critically ill patients and the outcome of their hospitalization. Early identification of CRGNB through rectal surveillance cultures and routine infection control measures including contact precautions, use of appropriate disinfectants, staff education on cleaning, and hand hygiene may reduce the dissemination of CRGNB. AIM: To assess the impact of enhanced infection control measures on CRGNB infections in a nine-bed polyvalent intensive care unit in a tertiary level hospital in an endemic area. METHODS: A quasi-experimental study, which included patients with CRGNB infection retrospectively for six months and those participating in an active surveillance programme prospectively for the subsequent 22 months. Active surveillance programme (weekly rectal swabs) was implemented including two sub-periods with infection control measures and enhanced infection control measures. CRGNB incidence, prevalence, colonization pressure, infections and compliance with infection control measures and enhanced infection control measures were recorded. Analysis was performed through time-series and interrupted time-series. FINDINGS: During the active surveillance programme, enhanced infection control measures led to a steeper downwards trend in incidence, prevalence, and colonization pressure for CRGNB compared to the infection control measures sub-period. The linear trend was for carbapenem-resistant Klebsiella pneumoniae (CRKP) and Pseudomonas aeruginosa (CRPA) infections to decrease from 19.6 to 8.1 infections per 1000 bed-days (IBD) (P = 0.001) and from 5.1 to 1.79 IBD (P = 0.043), respectively. By contrast, carbapenem-resistant Acinetobacter baumannii infections increased from 5.2 to 15.3 IBD (P = 0.001). CONCLUSION: Enhanced infection control measures including enhanced hand hygiene, active surveillance combined with contact precautions, education, audits and feedback policies and interventions could reduce CRKP and CRPA in endemic areas.