Skip to main content

Advertisement

SpringerLink
Log in

Risk factors for and clinical outcomes of ceftazidime-avibactam-resistant carbapenem-resistant Klebsiella pneumoniae nosocomial infections: a single-center retrospective study

  • Original Paper
  • Published:
Infection Aims and scope Submit manuscript

Abstract

Purpose

The emergence of ceftazidime-avibactam (CZA) resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP) has been increasingly reported in recent years. We aimed to identify the risk factors of CZA-resistant CRKP infection and assess clinical outcomes of the patients.

Methods

The study retrospectively analyzed the clinical and microbiological data of patients with CRKP infection to identify risk factors, clinical features, and outcomes using multivariate logistic regression analysis.

Results

A total of 103 patients with CRKP infection were enrolled in this study. Multivariate analysis showed previous renal replacement therapy (OR 3.966, 95% CI 1.301–12.090, P = 0.015) was an independent risk factor for CZA-resistant CRKP infection. The 28-day mortality was higher in patients infected with CZA-resistant CRKP (27.9%) than those with CZA-susceptible CRKP (7.1%) (P = 0.009). CZA-resistant CRKP infection (OR 20.308, 95% CI 1.461–282.293, P = 0.025), and mechanical ventilation (OR 14.950, 95% CI 1.034–216.212, P = 0.047) were independent predictors for 28-day mortality in patients with CRKP infection. Lower level of platelet count (OR 0.987, 95% CI 0.975–0.999, P = 0.032) on the day of CRKP infection onset was related to 28-day mortality. Kaplan–Meier curves showed that the CZA-resistant CRKP group had a shorter survival time than the CZA-susceptible CRKP group.

Conclusion

The prevalence and mortality of CZA-resistant CRKP are still increasing. Strengthening the hospital infection control of renal replacement therapy and mechanical ventilation may help to prevent CZA-resistant CRKP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Availability of data and material

All data generated or analyzed during this study are included in the published article.

References

  1. Peleg AY, Hooper DC. Hospital-acquired infections due to gram-negative bacteria. N Engl J Med. 2010;362:1804–13.

    Article  CAS  Google Scholar 

  2. Agyeman AA, Bergen PJ, Rao GG, Nation RL, Landersdorfer CB. A systematic review and meta-analysis of treatment outcomes following antibiotic therapy among patients with carbapenem-resistant Klebsiella pneumoniae infections. Int J Antimicrob Agents. 2020;55:105833.

    Article  CAS  Google Scholar 

  3. Who publishes list of bacteria for which new antibiotics are urgently needed [Internet]. https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed. Accessed 25 Jan 2022.

  4. Shields RK, Nguyen MH, Chen L, Press EG, Potoski BA, Marini RV, et al. Ceftazidime-avibactam is superior to other treatment regimens against carbapenem-resistant Klebsiella pneumoniae bacteremia. Antimicrob Agents Chemother. 2017;61:e00883-e917.

    Article  CAS  Google Scholar 

  5. Fiore M, Alfieri A, Di Franco S, Pace MC, Simeon V, Ingoglia G, et al. Ceftazidime–avibactam combination therapy compared to ceftazidime–avibactam monotherapy for the treatment of severe infections due to carbapenem-resistant pathogens: a systematic review and network meta-analysis. Antibiotics. 2020;9:388.

    Article  CAS  Google Scholar 

  6. Giddins MJ, Macesic N, Annavajhala MK, Stump S, Khan S, McConville TH, et al. Successive emergence of ceftazidime–avibactam resistance through distinct genomic adaptations in blaKPC-2-harboring Klebsiella pneumoniae sequence type 307 isolates. Antimicrob Agents Chemother. 2018;62:e02101-e2117.

    Article  Google Scholar 

  7. Wilson WR, Kline EG, Jones CE, Morder KT, Mettus RT, Doi Y, et al. Effects of KPC variant and porin genotype on the in vitro activity of meropenem-vaborbactam against carbapenem-resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2019;63:e02048.

    Article  CAS  Google Scholar 

  8. Kritsotakis EI, Tsioutis C, Roumbelaki M, Christidou A, Gikas A. Antibiotic use and the risk of carbapenem-resistant extended-spectrum-β-lactamase-producing Klebsiella pneumoniae infection in hospitalized patients: results of a double case-control study. J Antimicrob Chemother. 2011;66:1383–91.

    Article  CAS  Google Scholar 

  9. Xiao T, Zhu Y, Zhang S, Wang Y, Shen P, Zhou Y, et al. A retrospective analysis of risk factors and outcomes of carbapenem-resistant Klebsiella pneumoniae bacteremia in nontransplant patients. J Infect Dis. 2020;221:S174–83.

    Article  Google Scholar 

  10. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections, 1988. AJIC Am J Infect Control. 1988;16:128–40.

    Article  CAS  Google Scholar 

  11. CDC. CDC/NHSN surveillance definitions for specific types of infections. Surveill Defin. 2016;36:309–32.

  12. Hu Y, Ping Y, Li L, Xu H, Yan X, Dai H. A retrospective study of risk factors for carbapenem-resistant Klebsiella pneumoniae acquisition among ICU patients. J Infect Dev Ctries. 2016;10:208–13.

    Article  CAS  Google Scholar 

  13. Wayne PA. Performance standards for antimicrobial susceptibility testing. CLSI supplement M100. Clin. Lab. Stand. Inst. 2020.

  14. Karlowsky JA, Biedenbach DJ, Kazmierczak KM, Stone GG, Sahm DF. Activity of ceftazidime-avibactam against extended-spectrum- and AmpC β-lactamase-producing enterobacteriaceae collected in the INFORM global surveillance study from 2012 to 2014. Antimicrob Agents Chemother. 2016;60:2849–57.

    Article  CAS  Google Scholar 

  15. Shirley M. Ceftazidime-avibactam: a review in the treatment of serious gram-negative bacterial infections. Drugs. 2018;78:675–92.

    Article  CAS  Google Scholar 

  16. Senchyna F, Gaur RL, Sandlund J, Truong C, Tremintin G, Kültz D, et al. Diversity of resistance mechanisms in carbapenem-resistant enterobacteriaceae at a health care system in Northern California, from 2013 to 2016. Diagn Microbiol Infect Dis. 2019;93:250–7.

    Article  CAS  Google Scholar 

  17. Yin D, Wu S, Yang Y, Shi Q, Dong D, Zhu D, et al. Results from the China Antimicrobial Surveillance Network (CHINET) in 2017 of the in vitro activities of ceftazidime-avibactam and ceftolozane-tazobactam against clinical isolates of enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2019;63:e02431-e2518.

    Article  CAS  Google Scholar 

  18. Zuo Y, Zhao D, Song G, Li J, Xu Y, Wang Z. Risk factors, molecular epidemiology, and outcomes of carbapenem-resistant Klebsiella pneumoniae infection for hospital-acquired pneumonia: a matched case–control study in Eastern China during 2015–2017. Microb Drug Resist. 2021;27:204–11.

    Article  CAS  Google Scholar 

  19. Rueda VG, Zuleta TJJ. Risk factors for infection with carbapenem-resistant Klebsiella pneumoniae: a case–control study. Colomb Med. 2014;45:54–60.

    Article  Google Scholar 

  20. Shields RK, Nguyen MH, Chen L, Press EG, Kreiswirth BN, Clancy CJ. Pneumonia and renal replacement therapy are risk factors for ceftazidime-avibactam treatment failures and resistance among patients with carbapenem-resistant enterobacteriaceae infections. Antimicrob Agents Chemother. 2018;62:e02497-e2517.

    Article  CAS  Google Scholar 

  21. Hernández-García M, Castillo-Polo JA, Cordero DG, Pérez-Viso B, García-Castillo M, Fuente JS de la, et al. Impact of ceftazidime-avibactam treatment in the emergence of novel KPC variants in ST307-Klebsiella pneumoniae high-risk clone and consequences for their routine detection. J Clin Microbiol. Online 2 Feb 2022.

  22. Zhang H, Guo Z, Chai Y, Fang YP, Mu X, Xiao N, et al. Risk factors for and clinical outcomes of carbapenem-resistant Klebsiella pneumoniae nosocomial infections: a retrospective study in a tertiary hospital in Beijing. China Infect Drug Resist. 2021;14:1393–401.

    Article  CAS  Google Scholar 

  23. Xu L, Sun X, Ma X. Systematic review and meta-analysis of mortality of patients infected with carbapenem-resistant Klebsiella pneumoniae. Ann Clin Microbiol Antimicrob. 2017;16:18.

    Article  Google Scholar 

  24. Kohler PP, Volling C, Green K, Uleryk EM, Shah PS, McGeer A. Carbapenem resistance, initial antibiotic therapy, and mortality in Klebsiella pneumoniae bacteremia: a systematic review and meta-analysis. Infect Control Hosp Epidemiol. 2017;38:1319–28.

    Article  Google Scholar 

  25. Zhang G, Zhang M, Sun F, Zhou J, Wang Y, Zhu D, et al. Epidemiology, mortality and risk factors for patients with K. pneumoniae bloodstream infections: clinical impact of carbapenem resistance in a tertiary university teaching hospital of Beijing. J Infect Public Health. 2020;13:1710–4.

    Article  CAS  Google Scholar 

  26. Li Y, Li J, Hu T, Hu J, Song N, Zhang Y, et al. Five-year change of prevalence and risk factors for infection and mortality of carbapenem-resistant Klebsiella pneumoniae bloodstream infection in a tertiary hospital in North China. Antimicrob Resist Infect Control. 2020;9:79.

    Article  Google Scholar 

  27. Venkata C, Kashyap R, Christopher Farmer J, Afessa B. Thrombocytopenia in adult patients with sepsis: incidence, risk factors, and its association with clinical outcome. J Intensive Care. 2013;1:9.

    Article  Google Scholar 

  28. Bor M, Ilhan O. Carbapenem-resistant Klebsiella pneumoniae outbreak in a neonatal intensive care unit: risk factors for mortality. J Trop Pediatr. 2021;67:fmaa057.

    Article  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (no. 61905280) and the Natural Science Foundation of Jiangsu Province (no. BK20180292).

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacy, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, 210002, Jiangsu, China

    Liu Xuejiao, Chu Yanan, Yue Huijie, Huang Xiaohui & Zhou Guohua

Authors
  1. Liu Xuejiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chu Yanan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yue Huijie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Huang Xiaohui
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhou Guohua
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

LX and CY carried out the medical records database search, statistical analysis, and drafted the manuscript. YH, HX, and ZG participated in the design and coordination of the study and helped to draft the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Huang Xiaohui.

Ethics declarations

Conflict of interest

None declared.

Ethics approval

This retrospective study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the Declaration of Helsink. The ethics committee of the Jinling Hospital, Medical School of Nanjing University approved this study and waived informed consent as a retrospective study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, X., Chu, Y., Yue, H. et al. Risk factors for and clinical outcomes of ceftazidime-avibactam-resistant carbapenem-resistant Klebsiella pneumoniae nosocomial infections: a single-center retrospective study. Infection 50, 1147–1154 (2022). https://doi.org/10.1007/s15010-022-01781-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s15010-022-01781-3

Keywords

Search

Navigation