AUTHOR=Hao Haibin , Liu Yang , Cao Jin , Gao Kun , Lu Yingying , Wang Weiping , Wang Peng , Lu Sida , Hu Long , Tong Zhihui , Li Weiqin 

TITLE=Genomic New Insights Into Emergence and Clinical Therapy of Multidrug-Resistant Klebsiella pneumoniae in Infected Pancreatic Necrosis

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.669230

DOI=10.3389/fmicb.2021.669230

ISSN=1664-302X

ABSTRACT=<p>Infected pancreatic necrosis (IPN) is a key risk factor in the progression of severe acute pancreatitis, and use of antibiotics is one of the main clinical actions. However, early prophylactic or unreasonable use of antibiotics promotes drug resistance in bacteria and also delays optimum treatment. To explore genomic evidence of rational antibiotic use in intensive care units, we isolated <italic>Klebsiella pneumoniae</italic> from IPN samples that showed the highest positive-culture rate in 758 patients. Based on whole-genome sequencing from eight strains, 42 antibiotic-resistant genes were identified in the chromatin and 27 in the plasmid, which included classic resistance-mechanism factors such as β-lactamases [16.67% (7/42) in the chromatin and 25.93% (7/27) in the plasmid]. The <italic>K. pneumoniae</italic> isolates were identified to be resistant to multiple antibiotics used in clinics. <italic>In vivo</italic> and <italic>in vitro</italic>, ceftazidime-avibactam (CZA) plus aztreonam (ATM) (2.5:1) showed more significant antibacterial effectiveness than CZA alone. The isolated <italic>K. pneumoniae</italic> were of three different types according to the resistance phenotypes for CZA and ATM. Those co-harboring <italic>bla</italic><sub>NDM–5</sub>, <italic>bla</italic><sub>CTX–M–15</sub>, <italic>bla</italic><sub>OXA–1</sub>, and <italic>bla</italic><sub>SHV–187</sub> showed higher resistance to CAZ than <italic>bla</italic><sub>NDM–5</sub>. Those co-harboring <italic>bla</italic><sub>CTX–M–65</sub>, <italic>bla</italic><sub>SHV–182</sub>, and <italic>bla</italic><sub>TEM–181</sub> were significantly less resistant to β-lactam than to other extended-spectrum β-lactamases. However, β-lactamases were inhibited by avibactam (AVI), except for NDM-5. ATM plus AVI showed a significant inhibitory effect on <italic>K. pneumoniae</italic>, and the minimum dosage of ATM was &lt; 1 mg/L. In conclusion, we propose that ATM plus AVI could be a major therapy for complex infectious diseases caused by multidrug-resistant <italic>K. pneumoniae</italic>.</p>