Non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae (NC-CRKP) confers carbapenem resistance through a combination of chromosomal mutations and acquired non-carbapenemase resistance mechanisms. In this study, we aimed to evaluate the clinical and molecular profiles of NC-CRKP isolated from patients in a tertiary teaching hospital in Malaysia from January 2013 to October 2019. During the study period, 54 NC-CRKP-infected/colonised patients’ isolates were obtained. Clinical parameters were assessed in 52 patients. The all-cause in-hospital mortality rate among NC-CRKP patients was 46.2% (24/52). Twenty-three (44.2%) patients were infected, while others were colonised. Based on the Charlson Comorbidity Index (CCI) score, 92.3% (48/52) of the infected/colonised patients had a score of ≥ 1. Resistance genes found among the 54 NC-CRKP isolates were bla_TEM, bla_SHV, bla_CTX-M, bla_OXA, and bla_DHA. Porin loss was detected in 25/54 (46.3%) strains. None of the isolated strains conferred carbapenem resistance through the efflux pumps system. In conclusion, only 25/54 (46.3%) NC-CRKP conferred carbapenem resistance through a combination of porin loss and the acquisition of non-carbapenemase resistance mechanisms. The carbapenem resistance mechanisms for the remaining strains (53.7%) should be further investigated as rapid identification and distinction of the NC-CRKP mechanisms enable optimal treatment and infection control efforts.

Gastrointestinal carriage of multidrug resistant (MDR) Gram-negative bacilli, especially Klebsiella pneumoniae and Escherichia coli, was highly associated with severe nosocomial infections. The main objectives of this study were to determine the clonal relatedness of intestinal carriage and transmission risk factors of MDR E. coli and K. pneumoniae amongst preterm infants admitted to the neonatal intensive care unit (NICU). A prospective cohort study of preterm infants with gestational age < 37 weeks was conducted in the NICU of the University of Malaya Medical Centre (UMMC). Infants' stool specimens were collected on day 1 (meconium), week 1, week 2, week 8 and week 10 during their admission (from 1st June to 31st August 2017) until discharge. The presence and antibiotic resistance pattern of MDR E. coli and K. pneumoniae were determined. Strain clonality and relatedness were explored via pulsed-field gel electrophoresis (PFGE) fingerprints. The risk factors for MDR strains acquisition were evaluated using the Cox proportional-hazards model and Firth logistic regression. A total of 139 stool specimens were obtained from 50 subjects. Twenty-six (52%) infants were colonized with MDR K. pneumoniae and/or E. coli. High clonal dissemination between two clusters of ESBL-producing K. pneumoniae strains was seen from PFGE profile. We detected a persistent, dominant, aminoglycosides-resistant strains cluster (cluster B), which harbored blaTEM, blaSHV, blaOXA-1, blaCTX-M-1, ompK35 and ompK36 genes. Infants born to women who were anemic in pregnancy [OR = 0.01 (CI = 0.00-0.39), P-value = 0.042] and infants exposed to penicillin/β-lactams group antibiotics during the first week of life [OR = 0.02 (CI = 0.02-0.32), P-value = 0.013] were found to have a lower risk of MDR K. pneumoniae and E. coli colonization. The prevalence of dominant aminoglycosides-resistant strains cluster in the NICU is alarming. Awareness of and vigilance for the dominant cluster found will enable the reduction of cross-transmission amongst high-risk infants.

Background/Objectives: The emergence and dissemination of carbapenem-resistant organisms, particularly Acinetobacter baumannii and Klebsiella pneumoniae, pose a significant threat to healthcare systems worldwide. This retrospective study aims to characterise carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Klebsiella pneumoniae (CRKP) strains in a teaching hospital and to determine the risk factors associated with patients’ in-hospital mortality. Methods: A total of 90 CRAB and 63 CRKP were included in this study. Carbapenemase genes and MLST types of CRAB and CRKP were determined using specific primers. Risk factors associated with in-hospital mortality were analysed with collected data. Results: All the CRAB strains consisted of OXA carbapenemase genes, with 98% of the strains co-harbouring blaOXA-23-like and blaOXA-51-like carbapenemase genes. Conversely, blaNDM is the predominant carbapenemase gene in CRKP, followed by blaOXA-48-like carbapenemase genes. ST2 and ST20 are the dominant MLST types in CRAB and CRKP, respectively. In CRAB, multivariate analysis identified age, ethnicity, the presence of a mechanical ventilator, and patients who experienced previous exposure to clindamycin in the last 90 days as associated with an increased risk of in-hospital mortality. In contrast, older age, male, ICU admission, and the presence of an indwelling urinary catheter were significantly associated with an increased risk of mortality for patients with CRKP. Conclusions: Both CRAB and CRKP lead to high rates of mortality. The MLST profile showed that the genomic patterns of CRKP were highly diverse, whereas CRAB strains had low genetic diversity. To tackle these challenging pathogens, robust surveillance and an in-depth understanding of molecular epidemiology and genomics studies are needed to tailor infection control strategies and individualise treatment approaches.