Paediatric Enterobacteriaceae infections in hospitalised children in Durban, KwaZulu-Natal

Background: Community-acquired Gram-negative Enterobacteriaceae infections in malnourished and HIV-infected hospitalised children are not well documented and are of concern because of increasing antibiotic resistance and limited available treatment options. This study describes the clinical characteristics and outcomes of hospitalised children with positive Enterobacteriaceae cultures.Method: A retrospective chart review of children with Gram-negative Enterobacteriaceae infections was performed in King Edward VIII Hospital, a referral hospital in Durban, KwaZulu-Natal. Standard descriptive and analytical statistics, including regression analysis, were performed to determine the clinical characteristics associated with Enterobacteriaceae infections in children hospitalised in the study period.Results: Of all hospitalised children in the study period, 207 (3.5%) had positive cultures for Enterobacteriaceae isolates, with Escherichia coli 109 (44.5%) and Klebsiella spp. 59 (24.1%) making up most of the infections. Urine (126; 58%) followed by stool (34; 14.8%) and blood (35; 14.0%) were the commonest samples that yielded positive cultures. Diarrhoeal hospitalisations especially posed a higher risk for Enterobacteriaceae infections. Severe acutely malnourished and HIV-infected children were at higher risk. These comorbidities were independently associated with an increased risk of Enterobacteriaceae infection. Prolonged hospitalisation and increased risk of death were also associated with Enterobacteriaceae infection.Conclusion: Enterobacteriaceae infections were common in hospitalised children and posed an increased risk, especially in malnourished and HIV-infected children. Further studies investigating the relationships between diarrhoea, urinary tract infections and Enterobacteriaceae infections are needed.

Characteristics of fosA-carrying plasmids in E. coli and Klebsiella spp. isolates originating from food and environmental samples

Objectives Fosfomycin is an important antibiotic for the treatment of MDR Enterobacteriaceae infections. High susceptibility rates are, however, threatened by the spread of plasmids encoding fosfomycin-modifying enzymes. In this study, we sought to characterize the genetic context of fosA in plasmids from Escherichia coli and Klebsiella spp. isolates recovered from food, wastewater and surface water in Switzerland. Methods E. coli and Klebsiella spp. isolates collected between 2012 and 2019 in Switzerland were screened for fosfomycin resistance. Presence of fosA was verified by PCR and sodium phosphonoformate (PPF) disc potentiation testing, and transferability was tested using conjugation assays. Whole-genome sequences including complete fosA-containing plasmids were determined using long- and short-read sequencing. Results In 11 E. coli and two Klebsiella spp. isolates, high-level fosfomycin resistance was mediated by plasmids containing fosA3 (n = 12) or fosA8 (n = 1). Four isolates harboured a near-identical 45 kb IncN plasmid with fosA3, while replicon types varied in the remaining plasmids. The fosA genes were typically embedded in IS26-bounded transposition units and frequently located in the proximity of blaCTX-M transposition units. Conclusions Although fosfomycin resistance rates are currently low, the presence of fosA-encoding plasmids circulating in the Enterobacteriaceae population suggests that fosfomycin resistance may rapidly spread upon increased selection pressure. Transposition mobility of fosA and co-location on plasmids with other resistance genes may further promote its dissemination.

Genomic Characterization of VIM and MCR Co-Producers: The First Two Clinical Cases, in Italy

Background: the co-production of carbapenemases and mcr-genes represents a worrisome event in the treatment of Enterobacteriaceae infections. The aim of the study was to characterize the genomic features of two clinical Enterobacter cloacae complex (ECC) isolates, co-producing VIM and MCR enzymes, in Italy. Methods: species identification and antibiotic susceptibility profiling were performed using MALDI-TOF and broth microdilution methods, respectively. Transferability of the blaVIM- and mcr- type genes was verified through conjugation experiment. Extracted DNA was sequenced using long reads sequencing technology on the Sequel I platform (PacBio). Results: the first isolate showed clinical resistance against ertapenem yet was colistin susceptible (EUCAST 2020 breakpoints). The mcr-9.2 gene was harbored on a conjugative IncHI2 plasmid, while the blaVIM-1 determinant was harbored on a conjugative IncN plasmid. The second isolate, resistant to both carbapenems and colistin, harbored: mcr-9 gene and its two component regulatory genes for increased expression on the chromosome, mcr-4.3 on non-conjugative (yet co-transferable) ColE plasmid, and blaVIM-1 on a non-conjugative IncA plasmid. Conclusions: to our knowledge, this is the first report of co-production of VIM and MCR in ECC isolates in Italy.

In Vitro Activity of Imipenem/Relebactam Against Enterobacteriaceae Isolates Obtained from Intra-abdominal, Respiratory Tract, and Urinary Tract Infections in China: Study for Monitoring Antimicrobial Resistance Trends (SMART), 2015–2018

Background Considering the increasing incidence of carbapenem-resistant Enterobacteriaceae in China, this study aimed to establish the in vitro effectiveness of imipenem/relebactam (IMI/REL) on clinical Enterobacteriaceae isolates derived from intra-abdominal infections (IAIs), respiratory tract infections (RTIs), and urinary tract infections (UTIs) in China between 2015 and 2018. Methods In total, 8781 Enterobacteriaceae isolates from IAI, RTI, and UTI samples were collected from 22 hospitals across 7 geographic regions of China. Susceptibility to antimicrobial drugs was tested using the Clinical and Laboratory Standards Institute broth microdilution and breakpoints, and IMI/REL activity was assessed using United States Food and Drug Administration guidelines. Results In 2015–2018, the most frequently identified Enterobacteriaceae species was Escherichia coli (n = 4676 [53.3%]), followed by Klebsiella pneumoniae (n = 2949 [33.6%]) and Enterobacter cloacae (n = 542 [6.2%]). The Enterobacteriaceae isolates showed 95.2% overall susceptibility to IMI/REL, of which the susceptibility rates in isolates from IAI, RTI, and UTI were 95.8%, 91.4%, and 96.6%, respectively. Overall, the susceptibilities of both intensive care unit (ICU) and non-ICU Enterobacteriaceae isolates to colistin were 92.9%, followed by IMI/REL (90.7% [95.9%]) and amikacin (83.3% [92.3%]). In addition, IMI/REL restored 66.3% susceptibility in imipenem-nonsusceptible Enterobacteriaceae. Conclusions Given their high in vitro susceptibility, Enterobacteriaceae infections in China should be considered for IMI/REL treatment, especially with isolates that are not susceptible to carbapenems.