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Antagonistic effect between tigecycline and meropenem: successful management of KPC-producing Klebsiella pneumoniae infection

  • Sheng Bi
  • Xin Yao
  • Cheng Huang
  • Xia Zheng
  • Tianming Xuan
  • Jifang Sheng
  • Kaijin Xu
  • Beiwen ZhengEmail author
  • Qing YangEmail author
Case Report



A woman infected by carbapenem-resistant Klebsiella pneumoniae is reported in this study.

Case report

Tigecycline and meropenem combination was used, and indeed, in vitro checkerboard synergy test confirmed the antagonism between the two antibiotics. Thus, meropenem was ceased and single high-dose tigecycline was successful against the infection. Subsequent experiments showed that the isolates of the KPC-2-producing K. pneumoniae ST11 clone caused the infection.


Therefore, tigecycline and meropenem combination should be used with caution.


Carbapenem-resistance KPC-2-producing Klebsiella pneumoniae Tigecycline Meropenem Antagonistic effect 



This study was supported by the following fundings: National Key Research and Development Program of China (No. 2016YFC1201603); National Natural Science Foundation of China (No. 81741098); Zhejiang Provincial Natural Science Foundation of China (No. LY17H190003).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This is a research involving a human participant.

Informed consent

The patient provided written informed consent to publish the clinical record.

Supplementary material

15010_2019_1274_MOESM1_ESM.pdf (40 kb)
Supplementary material 1 (PDF 40 KB)


  1. 1.
    Munoz-Price LS, Poirel L, Bonomo RA, Schwaber MJ, Daikos GL, Cormican M, et al. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis. 2013;13:785–96.CrossRefGoogle Scholar
  2. 2.
    Pitout JD, Nordmann P, Poirel L. Carbapenemase-producing Klebsiella pneumoniae, a key pathogen set for global nosocomial dominance. Antimicrob Agents Chemother. 2015;59:5873–84.CrossRefGoogle Scholar
  3. 3.
    Murri R, Fiori B, Spanu T, Mastrorosa I, Giovannenze F, Taccari F, et al. Trimethoprim-sulfamethoxazole therapy for patients with carbapenemase-producing Klebsiella pneumoniae infections: retrospective single-center case series. Infection. 2017;45:209–13.CrossRefGoogle Scholar
  4. 4.
    Iacovelli A, Spaziante M, Al Moghazi S, Giordano A, Ceccarelli G, Venditti M. A challenging case of carbapenemase-producing Klebsiella pneumoniae septic thrombophlebitis and right mural endocarditis successfully treated with ceftazidime/avibactam. Infection. 2018;46:721–4.CrossRefGoogle Scholar
  5. 5.
    Zheng B, Xu H, Yu X, Lv T, Jiang X, Cheng H, et al. Identification and genomic characterization of a KPC-2-, NDM-1- and NDM-5-producing Klebsiella michiganensis isolate. J Antimicrob Chemother. 2018;73:536–8.CrossRefGoogle Scholar
  6. 6.
    Chinese XDRCWG, Guan X, He L, Hu B, Hu J, Huang X, et al. Laboratory diagnosis, clinical management and infection control of the infections caused by extensively drug-resistant Gram-negative bacilli: a Chinese consensus statement. Clin Microbiol Infect. 2016;22(Suppl 1):15–25.Google Scholar
  7. 7.
    Elemam A, Rahimian J, Doymaz M. In vitro evaluation of antibiotic synergy for polymyxin B-resistant carbapenemase-producing Klebsiella pneumoniae. J Clin Microbiol. 2010;48:3558–62.CrossRefGoogle Scholar
  8. 8.
    Hu L, Liu Y, Deng L, Zhong Q, Hang Y, Wang Z, et al. Outbreak by ventilator-associated ST11 K. pneumoniae with co-production of CTX-M-24 and KPC-2 in a SICU of a tertiary teaching hospital in central China. Front Microbiol. 2016;7:1190.Google Scholar
  9. 9.
    Lubbert C, Baars C, Dayakar A, Lippmann N, Rodloff AC, Kinzig M, et al. Environmental pollution with antimicrobial agents from bulk drug manufacturing industries in Hyderabad, South India, is associated with dissemination of extended-spectrum beta-lactamase and carbapenemase-producing pathogens. Infection. 2017;45:479–91.CrossRefGoogle Scholar
  10. 10.
    Michail G, Labrou M, Pitiriga V, Manousaka S, Sakellaridis N, Tsakris A, et al. Activity of tigecycline in combination with colistin, meropenem, rifampin, or gentamicin against KPC-producing Enterobacteriaceae in a murine thigh infection model. Antimicrob Agents Chemother. 2013;57:6028–33.CrossRefGoogle Scholar
  11. 11.
    Toledo PV, Aranha Junior AA, Arend LN, Ribeiro V, Zavascki AP, Tuon FF. Activity of antimicrobial combinations against KPC-2-producing Klebsiella pneumoniae in a rat model and time-kill assay. Antimicrob Agents Chemother. 2015;59:4301–4.CrossRefGoogle Scholar
  12. 12.
    Toledo PV, Tuon FF, Arend L, Aranha Junior AA. Efficacy of tigecycline, polymyxin, gentamicin, meropenem and associations in experimental Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae non-lethal sepsis. Braz J Infect Dis. 2014;18:574–5.CrossRefGoogle Scholar
  13. 13.
    Pournaras S, Vrioni G, Neou E, Dendrinos J, Dimitroulia E, Poulou A, et al. Activity of tigecycline alone and in combination with colistin and meropenem against Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae strains by time-kill assay. Int J Antimicrob Agents. 2011;37:244–7.CrossRefGoogle Scholar
  14. 14.
    Ocampo PS, Lazar V, Papp B, Arnoldini M, Abel zur Wiesch P, Busa-Fekete R, et al. Antagonism between bacteriostatic and bactericidal antibiotics is prevalent. Antimicrob Agents Chemother. 2014;58:4573–82.CrossRefGoogle Scholar
  15. 15.
    Brochado AR, Telzerow A, Bobonis J, Banzhaf M, Mateus A, Selkrig J, et al. Species-specific activity of antibacterial drug combinations. Nature. 2018;559:259–63.CrossRefGoogle Scholar
  16. 16.
    Bodmann KF, Heizmann WR, von Eiff C, Petrik C, Loschmann PA, Eckmann C. Therapy of 1,025 severely ill patients with complicated infections in a German multicenter study: safety profile and efficacy of tigecycline in different treatment modalities. Chemotherapy. 2012;58:282–94.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Sheng Bi
    • 1
  • Xin Yao
    • 2
  • Cheng Huang
    • 1
    • 3
  • Xia Zheng
    • 4
  • Tianming Xuan
    • 5
  • Jifang Sheng
    • 1
  • Kaijin Xu
    • 1
  • Beiwen Zheng
    • 1
    • 7
    Email author
  • Qing Yang
    • 6
    Email author
  1. 1.State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
  2. 2.Department of Gastroenterology, The First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
  3. 3.Department of Respiratory Medicine, Lihuili HospitalNingbo Medical CenterNingboChina
  4. 4.Intensive Care Unit, The First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
  5. 5.Department of Cardiovascular, The First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
  6. 6.Center of Clinical Laboratory, The First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
  7. 7.Institute of Animal QuarantineChinese Academy of Inspection and QuarantineBeijingChina

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