Keisuke Oka1, Akane Matsumoto2, Nobuyuki Tetsuka3, Hiroshi Morioka1, Mitsutaka Iguchi1, Nobuhisa Ishiguro4, Tsunehisa Nagamori5, Satoshi Takahashi6, Norihiro Saito7, Koichi Tokuda8, Hidetoshi Igari9, Yuji Fujikura10, Hideaki Kato11, Shinichiro Kanai12, Fumiko Kusama13, Hiromichi Iwasaki14, Kazuki Furuhashi15, Hisashi Baba16, Miki Nagao17, Masaki Nakanishi18, Kei Kasahara19, Hiroshi Kakeya20, Hiroki Chikumi21, Hiroki Ohge22, Momoyo Azuma23, Hisamichi Tauchi24, Nobuyuki Shimono25, Yohei Hamada26, Ichiro Takajo27, Hirotomo Nakata28, Hideki Kawamura29, Jiro Fujita30, Tetsuya Yagi31. 1. Department of Infectious Diseases, Nagoya University Hospital, Showa-ku, Nagoya, Aichi, Japan. 2. Department of Pediatrics, Kyoto Katsura Hospital, Saikyou-ku, Kyoto, Japan. 3. Department of Infection Control, Gifu University Graduate School of Medicine, Gifu, Japan. 4. Division of Infection Control, Hokkaido University Hospital, Sapporo, Hokkaido, Japan. 5. Department of Infection Control, Asahikawa Medical University Hospital, Asahikawa, Hokkaido, Japan. 6. Department of Infection Control and Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan. 7. Department of Clinical Laboratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan. 8. Department of Infection Control and Laboratory Diagnostics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. 9. Division of Infection Control, Chiba University Hospital, Chiba, Chiba, Japan. 10. Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan. 11. Infection Prevention and Control Department, Yokohama City University Hospital, Yokohama, Kanagawa, Japan. 12. Department of Infection Control, Shinshu University Hospital, Matsumoto, Nagano, Japan. 13. Department of Clinical Laboratory, Niigata University Medical and Dental Hospital, Niigata, Niigata, Japan. 14. Department of Infection Control and Prevention, University of Fukui, Fukui, Fukui, Japan. 15. Department of Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan. 16. Centre for Nutrition Support and Infection Control, Gifu University Hospital, Gifu, Gifu, Japan. 17. Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Kyoto, Japan. 18. Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan. 19. Centre for Infectious Diseases, Nara Medical University, Kashihara, Nara, Japan. 20. Department of Infection Control Science, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Osaka, Japan. 21. Centre for Infectious Diseases, Tottori University Hospital, Yonago, Tottori, Japan. 22. Department of Infectious Diseases, Hiroshima University Hospital, Hiroshima, Hiroshima, Japan. 23. Department of Infection Control, Tokushima University Hospital, Tokushima, Tokushima, Japan. 24. Division of Infectious Disease, Control and Prevention, Ehime University Hospital, Toon, Ehime, Japan. 25. Centre for the Study of Global Infection, Kyushu University Hospital, Fukuoka, Fukuoka, Japan. 26. Department of Infectious Disease and Hospital Epidemiology, Saga University Hospital, Saga, Saga, Japan. 27. Center for Infection Control, Miyazaki University Hospital, Miyazaki, Miyazaki, Japan. 28. Department of Infection Control, Kumamoto University Hospital, Kumamoto, Kumamoto, Japan. 29. Department of Infection Control, Kagoshima University Hospital, Kagoshima, Kagoshima, Japan. 30. Department of Infectious, Respiratory, and Digestive Medicine, Graduate School of Medicine, University of the Ryukyus, Nakagami-gun, Okinawa, Japan. 31. Department of Infectious Diseases, Nagoya University Hospital, Showa-ku, Nagoya, Aichi, Japan. Electronic address: tyagi@med.nagoya-u.ac.jp.
Abstract
OBJECTIVES: The dissemination of difficult-to-treat carbapenem-resistant Enterobacterales (CRE) is of great concern. We clarified the risk factors underlying CRE infection mortality in Japan. METHODS: We conducted a retrospective, multicentre, observational cohort study of patients with CRE infections at 28 university hospitals from September 2014 to December 2016, using the Japanese National Surveillance criteria. Clinical information, including patient background, type of infection, antibiotic treatment, and treatment outcome, was collected. The carbapenemase genotype was determined using PCR sequencing. Multivariate analysis was performed to identify the risk factors for 28-day mortality. RESULTS: Among the 179 patients enrolled, 65 patients (36.3%) had bloodstream infections, with 37 (20.7%) infections occurring due to carbapenemase-producing Enterobacterales (CPE); all carbapenemases were of IMP-type (IMP-1: 32, IMP-6: 5). Two-thirds of CPE were identified as Enterobacter cloacae complex. Combination therapy was administered only in 46 patients (25.7%), and the 28-day mortality rate was 14.3%. Univariate analysis showed that solid metastatic cancer, Charlson Comorbidity Index ≥3, bloodstream infection, pneumonia, or empyema, central venous catheters, mechanical ventilation, and prior use of quinolones were significant risk factors for mortality. Multivariate analysis revealed that mechanical ventilation (OR: 6.71 [1.42-31.6], P = 0.016), solid metastatic cancers (OR: 5.63 [1.38-23.0], P = 0.016), and bloodstream infections (OR: 3.49 [1.02-12.0], P = 0.046) were independent risk factors for 28-day mortality. CONCLUSION: The significant risk factors for 28-day mortality in patients with CRE infections in Japan are mechanical ventilation, solid metastatic cancers, and bloodstream infections.
OBJECTIVES: The dissemination of difficult-to-treat carbapenem-resistant Enterobacterales (CRE) is of great concern. We clarified the risk factors underlying CRE infection mortality in Japan. METHODS: We conducted a retrospective, multicentre, observational cohort study of patients with CRE infections at 28 university hospitals from September 2014 to December 2016, using the Japanese National Surveillance criteria. Clinical information, including patient background, type of infection, antibiotic treatment, and treatment outcome, was collected. The carbapenemase genotype was determined using PCR sequencing. Multivariate analysis was performed to identify the risk factors for 28-day mortality. RESULTS: Among the 179 patients enrolled, 65 patients (36.3%) had bloodstream infections, with 37 (20.7%) infections occurring due to carbapenemase-producing Enterobacterales (CPE); all carbapenemases were of IMP-type (IMP-1: 32, IMP-6: 5). Two-thirds of CPE were identified as Enterobacter cloacae complex. Combination therapy was administered only in 46 patients (25.7%), and the 28-day mortality rate was 14.3%. Univariate analysis showed that solid metastatic cancer, Charlson Comorbidity Index ≥3, bloodstream infection, pneumonia, or empyema, central venous catheters, mechanical ventilation, and prior use of quinolones were significant risk factors for mortality. Multivariate analysis revealed that mechanical ventilation (OR: 6.71 [1.42-31.6], P = 0.016), solid metastatic cancers (OR: 5.63 [1.38-23.0], P = 0.016), and bloodstream infections (OR: 3.49 [1.02-12.0], P = 0.046) were independent risk factors for 28-day mortality. CONCLUSION: The significant risk factors for 28-day mortality in patients with CRE infections in Japan are mechanical ventilation, solid metastatic cancers, and bloodstream infections.