Activity of Apramycin Against Carbapenem-Resistant and Hypervirulent Isolates.

OBJECTIVE

The emergence of carbapenem-resistant and hypervirulent (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 activity of apramycin against clinical CR-hvKp along with carbapenem-resistant non-hvKp (CR-non-hvKp) isolates.

METHODS

Broth microdilution method was used to evaluate the 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 ( 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.

RESULTS

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/MIC of 4/8 μg/mL against the CR-hvKp isolates. In contrast, the MIC/MIC for amikacin and gentamicin were >64/>64 μg/mL. All CR-hvKp isolates were susceptible to ceftazidime-avibactam, colistin and tigecycline with the MIC/MIC values of 0.5/1, 0.25/0.5, 1/1, respectively. For CR-non-hvKp, The MIC values for apramycin, gentamicin and amikacin were 2/8, >64/>64, and >64/>64 μg/mL, respectively. There were no statistical significance in the resistance rates of antimicrobial agents between CR-hvKp and CR-non-hvKp groups ( > 0.05). Genetic analysis revealed that all CR-hvKp isolates harbored , and 94% ( = 79) belong to the ST11 high-risk clone. 93.6% (44/47) of amikacin or gentamicin resistant strains carried 16S rRNA methyltransferases gene .

CONCLUSION

Apramycin demonstrated potent 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.