Transmission of Carbapenem Resistance Between Human and Animal NDM-Positive Escherichia coli Strains

Although carbapenem use is prohibited in animals in China,carbapenem-resistant Escherichia coli(CREC),especially New Delhi metallo-β-lactamase(NDM)-producing strains,are widely prevalent in foodproducing animals.At present,the impact of livestock-associated CREC strains on human populations at the national level is unknown.Here,we conduct a retrospective cross-sectional study to investigate the prevalence of CREC from clinical settings across 22 Chinese provinces or municipalities and analyze anthropogenic factors associated with their presence.We also ascertain the blaNDMand blaKPCabundance among pig and chicken farms and present a detailed genomic framework for CREC of animal and human origin.Overall,631/29799(2.1%)clinical Escherichia coli(E.coli)isolates were identified as CREC.Multivariable analysis revealed that being male,an age below 1,an age between 13 and 18,provinces with greater chicken production,and provinces with higher pig production were associated with higher odds of CREC infection.In general,73.8%(n=45/61)of pig farms and 62.2%(n=28/45)of chicken farms had a blaNDMabundance of 1×10^(-5)to 1×10^(-3)and 1×10^(-3)to 1×10^(-2),respectively.Among all the Chinese NDM-positive E.coli(n=463)available at the National Center for Biotechnology Information(NCBI),the genomic analysis revealed that blaNDM-5and Inc X3 were the predominant carbapenemase gene-plasmid combination,while a highly homogeneous relationship between NDM-positive isolates from humans and animals was demonstrated at the plasmid and core genome levels.All the findings suggest frequent CREC transmission between humans and animals,indicating that further discussions on the use of antibiotics in animals and humans are needed,both in China and across the globe.

Risk Factors Associated with MDR and CR Acinetobacter baumannii Carriage among ICU Patients Hospitalized at MOI Teaching and Referral Hospital, Kenya

Background: Multi-drug resistant and Carbapenem-Resistant Acinetobacter baumannii (CRAB) infections present a significant challenge in hospital ICU settings worldwide and the threat posed is worse in developing countries including Kenya. Despite the limited treatment options, there is inadequate comprehensive data on factors associated with MDR and CR Acinetobacter baumannii carriage among ICU patients hospitalized at hospitals. This study therefore aimed to address this gap and determined risk factors associated with MDR and CR Acinetobacter baumannii carriage among ICU patients hospitalized at MOI Teaching and Referral Hospital, Kenya. Methods: Through cross-sectional study design, a total of 132 ICU admitted patients were purposively enrolled in this study between July 2019 and July 2020. Demographic and risk factors associated with MDR and CR Acinobacter baumannii were collected using structured questionnaire. Descriptive statistics and bivalent analysis were used for data analysis obtained. Level of statistical significance was 95% confidence interval (CI) for all analysis. Results: Bivariable analysis showed that employed participants were 3.4 times more likely to have A. baumannii compared to the unemployed (cOR = 3.38, 95%, CI: 1.09 - 10.43, p = 0.035). Patients who were having high BMI were likely to be infected by A. baumannii compared to those who had normal/low BMI (aOR = 11.2, 95%, CI: 3.57 - 21.11, p = 0.004). Those who were aged ≥ 50 years were 21 times more likely to be carbapenem-resistant Acinetobacter baumannii, COR = 21.0, 95% CI: 1.83 - 240.52, p = 0.011. Those who stayed in ICU for more than 30 days were 16 times more likely to be carbapenem-resistant Acinetobacter baumannii compared to those who had been admitted (COR = 16.0, 95% CI: 1.45 - 176.45, p = 0.019). Conclusion: Increased length of hospital stay, obesity and marital status were the factors found to be significantly associated with A. baumannii infections among ICU admitted patients. On the other hand, gender, age, level of education, occupation, referral status and presence of infection were found to have no significant association with A. baumannii infections among ICU admitted patients. All patients admitted to the intensive care units should be screened for colonization with A. baumannii, owing to the poor treatment outcomes associated with carriage of this multidrug resistant pathogen. Proper infection control in the ICU settings should be upheld to mitigate the spread of A. baumannii in the intensive care units.

Study of OmpK35 and OmpK36 Expression in Carbapenem Resistant ESBL Producing Clinical Isolates of Klebsiella pneumoniae

Background: Carbapenem resistant extended spectrum β-lactamase (ESBL) producing Klebsiella pneumoniae (K. pneumoniae) is increasing worldwide. Carbapenem resistance (CR) has been attributed not only to production of carbapenemases but also to permeability barriers due to outer membrane proteins (OmpK35 and OmpK36) disruption. Objective: Phenotypic detection of CR among ESBL producing K. pneumoniae isolates, followed by the evaluation of the role of ompK35 and ompK36 gene expression among carbapenem resistant K. pneumoniae (CR-KP) isolates. Methods: 100 ESBL producing K. pneumoniae isolates were included in this study. Minimum inhibitory concentration (MIC) of imipenem was performed for all isolates by broth microdilution method. For CR-KP isolates, phenotypic detection of K. pneumoniae carbapenemase (KPC), metallo-β-lactamase (MBL) and AmpC enzymes was performed followed by Realtime qRT-PCR to detect and quantify ompK35 and ompK36 gene expression. Results: 42% of our isolates were carbapenem resistant, and all of them were KPC producers either singly or in combination with MBL and/or AmpC production. Reduced expression of both ompK35 and ompK36 was detected in (52.38%) of CR-KP isolates, while reduced expression of ompK36 or ompK35 alone was found in (2.38%) and (33.33%) respectively. Twenty of 42 CR-KP isolates (47.62%), showing reduced ompK35 and ompK36 expression, exhibited high level resistance (HLR) (>32 μg/ml) to imipenem. There was a significant correlation between reduced expression of ompK36 and increase MIC values (p < 0.05). The combined production of MBL or AmpC together with reduced expression of ompK35 and/or ompK36 resulted in significant increase in imipenem MIC (p < 0.05). Conclusion: The combined OmpK35/OmpK36 loss resulted in HLR. However OmpK36 seems to play a major role in those strains. Imipenem MIC was markedly increased among K. pneumoniae showing carbapenemase and/or AmpC production together with loss of OmpK35 and/or OmpK36.

New Delhi Metallo-β-Lactamase-Mediated Carbapenem Resistance： Origin, Diagnosis, Treatment and Public Health Concern

Objective： To review the origin, diagnosis, treatment and public health concern of New Delhi metallo-β-lactamase （NDM）-producing bacteria. Data Sources： We searched database for studies published in English. The database of PubMed from 2007 to 2015 was used to conduct a search using the keyword term ＂NDM and Acinetobacter or Enterobacteriaceae or Pseudomonas aeruginosa.＂ Study Selection： We collected data including the relevant articles on international transmission, testing methods and treatment strategies of NDM-positive bacteria. Worldwide NDM cases were reviewed based on 22 case reports. Results： The first documented case of infection caused by bacteria producing NDM- 1 occurred in India, in 2008. Since then, 13 blaNDM variants have been reported. The rise of NDM is not only due to its high rate of genetic transfer among unrelated bacterial species, but also to human factors such as travel, sanitation and food production and preparation. With limited treatment options, scientists try to improve available therapies and create new ones. Conclusions： In order to slow down the spread of these NDM-positive bacteria, a series of measures must be implemented. The creation and transmission of blaNDM are potentially global health issues, which are not issues for one country or one medical community, but for global priorities in general and for individual wound care practitioners specifically.

Control of an Intermittent Outbreak Caused by an Emerging Pandrug-Resistant Acinetobacter baumannii Clone ST457 in a Tertiary Hospital

Acinetobacter baumannii is a frequent cause of nosocomial infections.Here we report an intermittent outbreak caused by the emerging carbapenem-resistant A.baumannii(CRAB)clone ST457 and assess the effectiveness of patient screening for outbreak control.CRAB isolates were collected from 74 patients admitted to the respiratory intensive care unit of a tertiary hospital between May 2018 and March 2019.Fourteen CRAB isolates were assigned to ST457,and 13 belonged to an outbreak clone,as determined by phylogenomic analysis.Strict patient screening was started at the respiratory intensive care unit on May 2019,through which a ST457-positive patient transferred from the intensive care unit was detected.No positive patients were detected within 3months onwards.The results of this study highlight the importance of rigorous infection prevention and control measures,combined with patient screening,in controlling the CRAB outbreak.