AUTHOR=Yu Hanbing , Ma Deyu , Liu Bo , Yang Suqing , Lin Qiuxia , Yu Renlin , Jia Xiaojiong , Niu Siqiang , Zhang Qun , Huang Shifeng 

TITLE=Differences in the Distribution of Species, Carbapenemases, Sequence Types, Antimicrobial Heteroresistance and Mortality Rates Between Pediatric and Adult Carbapenemase-Producing Enterobacterales in Bloodstream Infections

JOURNAL=Frontiers in Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.827474

DOI=10.3389/fmed.2022.827474

ISSN=2296-858X

ABSTRACT=<p>The dissemination of carbapenemase-producing <italic>Enterobacterales</italic> (CPE) is worrisome given their scarce treatment options. CPE bloodstream infections (BSIs) had a high mortality rate in adults, and there was little data on pediatric CPE-BSIs around the world. We comprehensively explored the differences in the clinical and microbiological characteristics between pediatric and adult CPE-BSIs. Forty-eight pediatric and 78 adult CPE-BSIs cases were collected. All-cause 30 day-mortality in children with CPE-BSIs (14.6%, 7/48) was significantly lower than that in adult patients (42.3%, 33/78, <italic>p</italic> = 0.001). The subgroup in adults empirically treated with tigecycline as an active drug displayed a significantly higher 30-days crude mortality (63.3%, 19/30) than the subgroup treated without tigecycline (29.2%, 14/48, <italic>p</italic> = 0.003). <italic>K. pneumoniae</italic> was the most prevalent species in both the pediatric (45.8%, 22/48) and adult populations (64.1%, 50/78), with discrepant carbapenemase genes in each population: 95.4% (21/22) of the pediatric <italic>K. pneumoniae</italic> isolates carried <italic>bla</italic><sub>NDM</sub>, while 82.0% (41/50) of the adult strains harbored <italic>bla</italic><sub>KPC</sub>. The ratio of <italic>E. coli</italic> in children (37.5%) was significantly higher than that in adults (12.8%, <italic>p</italic> = 0.002). In both populations, the majority of <italic>E. coli</italic> expressed <italic>bla</italic><sub>NDM</sub>, particularly <italic>bla</italic><sub>NDM−5</sub>. With statistical significance, <italic>bla</italic><sub>NDM</sub> was much more common in children (95.8%, 46/48) than in adults (34.6%, 27/78). The rate of multiple-heteroresistance phenotypes in children was as high as 87.5%, which was much lower in adults (57.1%). Agar dilution checkboard experiment against one pediatric carbapenemase-producing <italic>E. coli</italic> isolates showed that the combination of amikacin and fosfomycin yielded an additive effect. Overall, <italic>K. pneumoniae</italic> was the most common CPE-BSIs pathogen in both populations, with NDM-producing <italic>K. pneumoniae</italic> and KPC-producing ST11 <italic>K. pneumoniae</italic> being the most prevalent species in children and adults, respectively. <italic>E. coli</italic> was more prevalent in children than in adults, yet <italic>bla</italic><sub>NDM−5</sub> was the most common carbapenem-resistant mechanism in <italic>E. coli</italic> in both populations. The wide range of multiple-heteroresistance combination traits found in different pathogen species from different host populations should provide a good foundation for future combination therapy design. Further investigations from more CPE isolates of various species are needed to evaluate the possible <italic>in vitro</italic> partial synergy of the amikacin and fosfomycin combination.</p>