Treatment outcome of non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae infections: a multicenter study in Taiwan

  • Chin-Fang Su
  • Chien Chuang
  • Yi-Tsung Lin
  • Yu-Jiun Chan
  • Jung-Chung Lin
  • Po-Liang Lu
  • Ching-Tai Huang
  • Jann-Tay Wang
  • Yin-Ching Chuang
  • L. Kristopher Siu
  • Chang-Phone Fung
Original Article


Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are associated with high mortality, and experiences with its treatment are usually based on carbapenemase-producing strains. Non-carbapenemase-producing CRKP is of clinical significance, but relevant studies are lacking. This nationwide study aimed to evaluate the outcome of antimicrobial therapy in patients with non-carbapenemase-producing CRKP infections. Patients with non-carbapenemase-producing CRKP infections were enrolled from 16 hospitals during January 2013 to December 2014 in Taiwan. Carbapenem resistance was defined as reduced susceptibility with a minimum inhibitory concentration of ≥2 mg/L for imipenem or meropenem. The resistance mechanisms of CRKP isolates were analyzed, and the clinical data of these patients were collected retrospectively. Independent risk factors of 14-day morality were determined by Cox regression analysis. A total of 99 patients with non-carbapenemase-producing CRKP infections were enrolled, and 14-day mortality was 27.3%. Among 67 patients treated with appropriate antimicrobial therapy, most (n = 61) patients received monotherapy. The 14-day mortality was lower in patients treated with appropriate monotherapy (21.3%) than in those with inappropriate therapy (37.5%). The multivariate regression model identified monotherapy (hazard ratio [HR], 0.30; 95% confidence interval [CI], 0.13–0.71; P = 0.005) as protective factor, and APACHE II scores (HR, 1.09; 95% CI, 1.01–1.18; P = 0.022) as risk factor associated with 14-day mortality. Tigecycline, colistin, and carbapenem were the most commonly used drugs in monotherapy. This study provides evidence supporting the efficacy of monotherapy in the treatment of non-carbapenemase-producing CRKP infections, and provides a future target for antibiotics stewardship for CRKP infection.



The authors thank the Taiwan Carbapenem Resistance Study Group for the collection of isolates from Keelung Chang Gung Memorial Hospital, Tri-Service General Hospital, Taipei Veterans General Hospital, Linkou Chang Gung Memorial Hospital, China Medical University Hospital, Chiayi Chang Gung Memorial Hospital, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung Medical University Hospital, National Taiwan University Hospital, Taoyuan Armed Forces General Hospital, Buddhist Tzu Chi General Hospital, Hualien Armed Forces General Hospital, National Yang-Ming University Hospital, Taichung Armed Forces General Hospital, Chi Mei Medical Center, Kaohsiung Armed Forces General Hospital, and Kaohsiung Municipal Hsiao-Kang Hospital.

The authors thank Ms. Chiu-Mei Yeh for her endorsement and assistance in the statistical analyses. We also thank the Medical Science & Technology Building of Taipei Veterans General Hospital for providing experimental space and facilities.

Some of the results from this study were presented in oral section at ECCMID 2017 in Vienna, Austria.


This work was supported by grants from the Ministry of Science and Technology in Taiwan, Taipei Veterans General Hospital (V104B-001, V105B-001, and V106B-001), and Centers for Disease Control, R.O.C. (Taiwan) (DOH101-DC-1204, DOH102-DC-1508, MOHW103-CDC-C-114-134,504, and MOHW104-CDC-C-114-144,406).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this retrospective study, formal consent is not required.

Supplementary material

10096_2017_3156_MOESM1_ESM.pdf (275 kb)
ESM 1 (PDF 274 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Chin-Fang Su
    • 1
  • Chien Chuang
    • 1
  • Yi-Tsung Lin
    • 2
    • 3
  • Yu-Jiun Chan
    • 2
    • 4
    • 5
  • Jung-Chung Lin
    • 6
  • Po-Liang Lu
    • 7
  • Ching-Tai Huang
    • 8
  • Jann-Tay Wang
    • 9
  • Yin-Ching Chuang
    • 10
  • L. Kristopher Siu
    • 11
  • Chang-Phone Fung
    • 12
  1. 1.Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
  2. 2.Division of Infectious Diseases, Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
  3. 3.Institute of Emergency and Critical Care MedicineNational Yang-Ming UniversityTaipeiTaiwan
  4. 4.Division of Microbiology, Department of Pathology and Laboratory MedicineTaipei Veterans General HospitalTaipeiTaiwan
  5. 5.School of MedicineNational Yang-Ming UniversityTaipeiTaiwan
  6. 6.Division of Infectious Diseases and Tropical Medicine, Department of Internal MedicineTri-Service General Hospital, National Defense Medical CenterTaipeiTaiwan
  7. 7.Department of Internal MedicineKaohsiung Medical University HospitalKaohsiungTaiwan
  8. 8.Division of Infectious Diseases, Department of Internal MedicineLinkou Chang Gung Memorial HospitalTaoyuan CityTaiwan
  9. 9.Division of Infectious Diseases, Department of MedicineNational Taiwan University HospitalTaipeiTaiwan
  10. 10.Department of Internal Medicine and Medical ResearchChi Mei Medical CenterTainanTaiwan
  11. 11.Institute of Infectious Diseases and VaccinologyNational Health Research InstitutesMiaoliTaiwan
  12. 12.Division of Infectious DiseasesSijhih Cathy General HospitalNew Taipei CityTaiwan

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