Emergence of multidrug-resistant strain of Klebsiella pneumoniae has led to limited number of antimicrobial options for treatment. Even though outbreaks of colistin-carbapenem-resistant K. pneumoniae (CCRKp) are evolving, reported literature is scarce. This is a retrospective case series of three infants who acquired CCRKp sepsis during an outbreak in a Level III neonatal intensive care unit (NICU) of a tertiary care centre in Northern India. Data were retrieved from medical records of patients. Three babies developed new onset clinical worsening during an outbreak of sepsis. All had respiratory comorbidities and previous antibiotic exposure prior to isolation of CCRKp sepsis from blood. The organism was sensitive to combination of ceftazidime plus avibactam and tetracyclines in two infants
in one other newborn, no sensitive antibiotic was found. Two neonates deceased due to multiorgan dysfunction. An outbreak investigation revealed one common source of sterile water used in a humidifier. The outbreak was resolved by temporarily closing the NICU, segregating the infected infants and using corrective measures such as procuring a fresh batch of sterile water bottles, disinfecting the NICU, and reinforcing the use of antiseptic techniques. The emergence of CCRKp is alarming, particularly in low- and middle-income countries and tropical regions where such outbreaks are difficult to control due to limited healthcare infrastructure. These findings highlight the urgent need for stringent antimicrobial stewardship practices, enhanced infection control, and tailored interventions in resource-limited settings. It is also to be emphasized that the main mechanism of carbapenem resistance in Kp organisms in Asia seems to be different from the West and is mainly mediated by metallo-beta-lactamases and Class D carbapenemases.