Article

In vitro activity of minocycline combined with aminoglycosides against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae

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Abstract

This study assessed the in vitro antibacterial activity of minocycline-aminoglycoside combination against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. Seventy non-duplicate clinical isolates of KPC-producing K. pneumoniae were collected from patients with bloodstream infections. The synergistic activity of minocycline-aminoglycoside combination was studied by the checkerboard method and time-kill assays in strains with different susceptibilities, and the mutant prevention concentration (MPC) and mutant selection window (MSW) of drugs alone and in combination were determined. The checkerboard method found this combination displayed synergistic and partial synergistic activity against aminoglycoside-susceptible isolates, but indifferent activity against aminoglycoside-resistant isolates. Time-kill assays further demonstrated strong synergistic and bactericidal effect of this combination existed against isolates which were susceptible to both drugs. But for resistant isolates, the time-kill assays showed no synergy. The MPCs of minocycline or aminoglycosides were 8- to 32-fold higher than the MICs, suggesting the MSWs of these drugs were quite wide. For the antibiotic combinations, the addition of 1×MIC concentration of amikacin or gentamicin could reduce the MPCs of minocycline by 4- to 16-fold. Generally, no mutants recovered in the plates containing 1×MIC concentration of minocycline and 2×MIC concentration of amikacin or gentamicin. In summary, these results suggest that minocycline-aminoglycoside combination can be an alternative for infections caused by KPC-producing K. pneumoniae because this combination displays strong synergistic and bactericidal activity in susceptible isolates, and can effectively prevent the emergence of resistant mutants. Further in vitro pharmacokinetic/pharmacodynamic studies and clinical trials should be performed to fully evaluate the efficacy of this drug combination.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China under Grant No. 81371855, and the Shenzhen’s Sanming Project.

Author information

Author notes

  1. Ni Wentao and Li Guobao contributed equally to this work

Affiliations

  1. Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, China

    • Ni Wentao
    •  & Gao Zhancheng
  2. Department of Respiratory Diseases, Chinese PLA General Hospital, Beijing, 100853, China

    • Ni Wentao
    • , Zhao Jin
    • , Cui Junchang
    •  & Liu Youning
  3. Pulmonary Department, The Third People’s Hospital of Shenzhen, Shenzhen, 518112, China

    • Li Guobao
  4. Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing, 100853, China

    • Wang Rui

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Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding authors

Correspondence to Gao Zhancheng or Liu Youning.