A multicentre study to determine the in vitro efficacy of flomoxef against extended-spectrum beta-lactamase producing Escherichia coli in Malaysia.

Background: The high burden of extended-spectrum beta-lactamase-producing (ESBL)-producing Enterobacterales worldwide, especially in the densely populated South East Asia poses a significant threat to the global transmission of antibiotic resistance. Molecular surveillance of ESBL-producing pathogens in this region is vital for understanding the local epidemiology, informing treatment choices, and addressing the regional and global implications of antibiotic resistance. Methods: Therefore, an inventory surveillance of the ESBL-Escherichia coli (ESBL-EC) isolates responsible for infections in Malaysian hospitals was conducted. Additionally, the in vitro efficacy of flomoxef and other established antibiotics against ESBL-EC was evaluated. Results: A total of 127 non-repetitive ESBL-EC strains isolated from clinical samples were collected during a multicentre study performed in five representative Malaysian hospitals. Of all the isolates, 33.9% were isolated from surgical site infections and 85.8% were hospital-acquired infections. High rates of resistance to cefotaxime (100%), cefepime (100%), aztreonam (100%) and trimethoprim-sulfamethoxazole (100%) were observed based on the broth microdilution test. Carbapenems remained the most effective antibiotics against the ESBL-EC, followed by flomoxef. Antibiotic resistance genes were identified by PCR. The blaCTX-M-1 was the most prevalent ESBL gene, with 28 isolates (22%) harbouring blaCTX-M-1 only, 27 isolates (21.3%) co-harbouring blaCTX-M-1 and blaTEM, and ten isolates (7.9%) co-harbouring blaCTX-M-1, blaTEM and blaSHV. A generalised linear model showed significant antibacterial activity of imipenem against different types of infection. Besides carbapenems, this study also demonstrated a satisfactory antibacterial activity of flomoxef (81.9%) on ESBL-EC, regardless of the types of ESBL genes.

Characterisation of Non-Carbapenemase-Producing Carbapenem-Resistant Klebsiella pneumoniae Based on Their Clinical and Molecular Profile in Malaysia.

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 blaTEM, blaSHV, blaCTX-M, blaOXA, and blaDHA. 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.

Clonal relatedness in the acquisition of intestinal carriage and transmission of multidrug resistant (MDR) Klebsiella pneumoniae and Escherichia coli and its risk factors among preterm infants admitted to the neonatal intensive care unit (NICU).

BACKGROUND: 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). METHODS: 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. RESULTS: 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/ß-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. CONCLUSIONS: 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.

Methicillin-resistant Staphylococcus aureus bacteraemia, 2003-2015: Comparative evaluation of changing trends in molecular epidemiology and clinical outcomes of infections.

Methicillin-resistant Staphylococcus aureus (MRSA) is a prominent pathogen causing invasive infections such as bacteraemia. The continued excessive use of antibiotics to treat MRSA infections has resulted in the evolution of antimicrobial resistant of S. aureus. This study aims to perform a comparative evaluation of changing trends in molecular epidemiology of MRSA and clinical characteristics of patients. This study shows that ST22-MRSA-IV has gradually replaced ST239-MRSA-III as the predominant MRSA clone in the tertiary teaching hospital studied. Independent predictors of mortality among patients included devices in situ at the time of infection, pre-exposure to macrolides, catheter-related bloodstream infection and mono-microbial infection. Hence, our study affirmed community-associated MRSA, which was previously identified from individuals without any exposure to healthcare settings, has now emerged in healthcare settings, causing healthcare-associated MRSA infections.