AUTHOR=Hao Mingju , Shi Xiaohong , Lv Jingnan , Niu Siqiang , Cheng Shiqing , Du Hong , Yu Fangyou , Tang Yi-Wei , Kreiswirth Barry N. , Zhang Haifang , Chen Liang 

TITLE=In vitro Activity of Apramycin Against Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae Isolates

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.00425

DOI=10.3389/fmicb.2020.00425

ISSN=1664-302X

ABSTRACT=<sec><title>Objective</title><p>The emergence of carbapenem-resistant and hypervirulent <italic>Klebsiella pneumoniae</italic> (CR-hvKp) strains poses a significant public threat, and effective antimicrobial therapy is urgently needed. Recent studies indicated that apramycin is a potent antibiotic with good activity against a range of multi-drug resistant pathogens. In this study, we evaluated the <italic>in vitro</italic> activity of apramycin against clinical CR-hvKp along with carbapenem-resistant non-hvKp (CR-non-hvKp) isolates.</p></sec><sec><title>Methods</title><p>Broth microdilution method was used to evaluate the <italic>in vitro</italic> activities of apramycin, gentamicin, amikacin, imipenem, meropenem, doripenem, ertapenem and other comparator “last-resort” antimicrobial agents, including ceftazidime-avibactam, colistin and tigecycline, against eighty-four CR-hvKp and forty CR-non-hvKp isolates collected from three Chinese hospitals. Multilocus Sequence typing (MLST), molecular capsule typing (<italic>wzi</italic> sequencing) and antimicrobial resistance genes were examined by PCR and Sanger sequencing. Pulsed-field gel electrophoresis and next generation sequencing were conducted on selected isolates.</p></sec><sec><title>Results</title><p>Among the 84 CR-hvKp isolates, 97.6, 100, 97.6, and 100% were resistant to imipenem, meropenem, doripenem and ertapenem, respectively. Apramycin demonstrated an MIC<sub>50</sub>/MIC<sub>90</sub> of 4/8 μg/mL against the CR-hvKp isolates. In contrast, the MIC<sub>50</sub>/MIC<sub>90</sub> for amikacin and gentamicin were &gt;64/&gt;64 μg/mL. All CR-hvKp isolates were susceptible to ceftazidime-avibactam, colistin and tigecycline with the MIC<sub>50</sub>/MIC<sub>90</sub> values of 0.5/1, 0.25/0.5, 1/1, respectively. For CR-non-hvKp, The MIC<sub>50/90</sub> values for apramycin, gentamicin and amikacin were 2/8, &gt;64/&gt;64, and &gt;64/&gt;64 μg/mL, respectively. There were no statistical significance in the resistance rates of antimicrobial agents between CR-hvKp and CR-non-hvKp groups (<italic>p</italic> &gt; 0.05). Genetic analysis revealed that all CR-hvKp isolates harbored <italic>bla</italic><sub>KPC–2</sub>, and 94% (<italic>n</italic> = 79) belong to the ST11 high-risk clone. 93.6% (44/47) of amikacin or gentamicin resistant strains carried 16S rRNA methyltransferases gene <italic>rmtB</italic>.</p></sec><sec><title>Conclusion</title><p>Apramycin demonstrated potent <italic>in vitro</italic> activity against CR-hvKp isolates, including those were resistant to amikacin or gentamicin. Further studies are needed to evaluate the applicability of apramycin to be used as a therapeutic antibiotic against CR-hvKp infections.</p></sec>