The Korean Journal of Medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지
DOI QR코드

DOI QR Code

Non-carbapenem Drugs for Patients with Bacteremia caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: Piperacillin-Tazobactam

Extended-Spectrum β-Lactamase 생성 장내세균속균종 균혈증 환자들의 치료에서 비카바페넴 항생제의 단일 기관 치료 결과: Piperacillin-Tazobactam을 중점으로

  • Hyunjoo Oh (Department of Internal Medicine, Andong Medical Center, ) ;
  • Seunghee Lee (Department of Internal Medicine, Jeju National University Hospital) ;
  • Misun Kim (Department of Internal Medicine, Jeju National University Hospital) ;
  • Sang Taek Heo (Department of Internal Medicine, Jeju National University Hospital) ;
  • Jeong Rae Yoo (Department of Internal Medicine, Jeju National University Hospital)
  • Received : 2024.02.16
  • Accepted : 2024.04.09
  • Published : 2024.06.01
Download PDF
⟨ Previous Next ⟩

Abstract

Background/Aims: Carbapenems are recommended for treating bacteremia caused by extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae (ESBL-E). However, this has resulted in a significant rise in the utilization of carbapenems in cases of ESBL-E infection. We evaluated the clinical outcomes of patients with ESBL-E bacteremia treated with non-carbapenem antimicrobials. Methods: We conducted a retrospective case-control study of a cohort of patients with documented ESBL-E bacteremia from January 2021 to December 2021. The patients were divided into two groups according to whether they received non-carbapenem or carbapenem therapy. The rates of treatment failure, 30-day mortality and microbiologic failure, and the durations of hospitalization and of antimicrobial therapy were compared between the two groups. Antimicrobial susceptibility testing and phenotypic identification of ESBL-E were performed using the Vitek 2 system. Results: Of 118 patients with ESBL-E bacteremia, 54 received non-carbapenem drugs (non-carbapenem group [NCG]) and 64 received carbapenems (carbapenem group [CG]). Treatment failure at 30 days occurred in 16.7% of the patients in the NCG and in 18.8% in the CG (p = 0.65). The 30-day mortality rate was 14.8% in the NCG and 17.2% in the CG (p = 0.63). Extra-urinary tract infection and prior antimicrobial therapy within 30 days were risk factors for treatment failure in patients with ESBL-E bacteremia. The clinical outcomes did not differ significantly between the two groups, challenging the prevailing preference for carbapenems in the treatment of ESBL-E bacteremia. Conclusions: Non-carbapenem antimicrobials such as piperacillin/tazobactam are recommended for patients with mild ESBL-E bacteremia in South Korea.

목적: 장내세균에서 3세대 cephalosporin 계열 항생제에 내성을 나타내는 주된 내성 기전은 extended spectrum β-lactamase(ESBL)를 생성하는 것이다. ESBL 생성 장내세균은 ESBL 생성균이라고 하더라도 piperacillin/tazobactam 감수성 균인 경우 piperacillin/tazobactam을 사용해 볼 수 있으며 후향적 연구에서 carbapenem 계열 항생제를 투여한 경우에 비해 열등하지 않은 치료 효과가 보고된 바 있다. 하지만 미국감염학회 2023년 지침에서는 ESBL 생성 그람음성균 감염에서 carbapenem 계열 항생제를 권고하고 piperacillin/tazobactam 감수성인 그람음성균이더라도 carbapenem 계열 항생제를 투여하도록 하고 있다. 하지만 carbapenem 내성 장내세균의 증가 등으로 비 carbapenem 계열의 항생제들의 사용 필요성에 대한 평가는 아직도 필요한 상황이다. 이에 제주대학교병원의 ESBL 생성 장내세균속 균혈증 환자들의 carbapenem과 비 carbapenem 계열 항생제의 치료 효과를 보고한다. 방법: 2021년 1월부터 12월까지 527명의 성인 장내세균속 균혈증 환자들 중에서 ESBL 생성 장내세균속 환자 152명을 대상으로 후향적 자료를 수집하고 3개월 이내 장내세균 감염이 있었던 환자들과 30일 후 추적 관찰을 하지 못한 환자들을 제외하고 분석하였다. 결과: 총 118명의 ESBL 생성 장내세균속 균혈증 환자들중에서 54명의 환자가 확정적 항생제로 비 carbapenem 계열 항생제로 치료하였고 64명의 환자가 carbapenem 계열 항생제로 치료하였다. Kaplan-Meier 생존 분석 방법으로 30일 치료 실패율과 사망률을 분석한 결과 30일 치료 실패율은 비 carbapenem군이 16.7%, carbapenem군이 18.8%로 양 군 간의 유의한 차이는 없었다(p = 0.65). 30일 사망률은 비 carbapenem 계열군이 14.8%, carbapenem 계열군이 17.2%로 양 군 간의 유의한 차이는 없었다(p = 0.63). 전체 환자들 중에서 치료 실패한 환자들을 다변량 로지스틱 회귀 분석한 결과에서 요로 감염 외 감염과 이전 30일 이내 항생제 사용력이 있는 경우 치료 실패의 위험인자로 확인되었다. 결론: ESBL 생성 장내세균속 균혈증 환자들은 국내에서 확정적 항생제로 비 carbapenem 계열의 항생제를 사용해 볼수 있으나 중증 환자들을 포함한 다기관, 전향적 후속 연구들이 필요하다.

Keywords

Acknowledgement

We appreciate the data collection efforts of the Infection Control Unit team at Jeju National University Hospital.

References

  1. Castanheira M, Simner PJ, Bradford PA. Extended-spectrum β-lactamases: an update on their characteristics, epidemiology and detection. JAC Antimicrob Resist 2021;3:dlab092.
  2. Jernigan JA, Hatfield KM, Wolford H, et al. Multidrug-resistant bacterial infections in U.S. hospitalized patients, 2012-2017. N Engl J Med 2020;382:1309-1319. https://doi.org/10.1056/NEJMoa1914433
  3. Karlowsky JA, Lob SH, DeRyke CA, et al. Prevalence of ESBL non-CRE Escherichia coli and Klebsiella pneumoniae among clinical isolates collected by the SMART global surveillance programme from 2015 to 2019. Int J Antimicrob Agents 2022;59:106535.
  4. Baek YJ, Kim YA, Kim D, et al. Risk factors for extended-spectrum-β-lactamase-producing Escherichia coli in community-onset bloodstream infection: impact on long-term care hospitals in Korea. Ann Lab Med 2021;41:455-462. https://doi.org/10.3343/alm.2021.41.5.455
  5. Johnson JR, Urban C, Weissman SJ, et al. Molecular epidemiological analysis of Escherichia coli sequence type ST131 (O25:H4) and blaCTX-M-15 among extended-spectrum-β-lactamase-producing E. coli from the United States, 2000 to 2009. Antimicrob Agents Chemother 2012;56:2364-2370. https://doi.org/10.1128/AAC.05824-11
  6. Lee CM, Lee S, Kim ES, et al. Disease burden of bacteraemia with extended-spectrum beta-lactamase-producing and carbapenem-resistant Enterobacterales in Korea. J Hosp Infect 2024;144:85-93. https://doi.org/10.1016/j.jhin.2023.11.013
  7. Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America guidance on the treatment of extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Clin Infect Dis 2021;72:e169-e183. https://doi.org/10.1093/cid/ciaa1478
  8. Seo YB, Lee J, Kim YK, et al. Randomized controlled trial of piperacillin-tazobactam, cefepime and ertapenem for the treatment of urinary tract infection caused by extended-spectrum beta-lactamase-producing Escherichia coli. BMC Infect Dis 2017;17:404.
  9. Kim YJ, Lee JM, Cho J, Lee J. Change in the annual antibiotic susceptibility of Escherichia coli in community-onset urinary tract infection between 2008 and 2017 in a tertiary care hospital in Korea. J Korean Med Sci 2019;34:e228.
  10. Ma J, Song X, Li M, et al. Global spread of carbapenem-resistant Enterobacteriaceae: epidemiological features, resistance mechanisms, detection and therapy. Microbiol Res 2023;266:127249.
  11. Paterson DL, Ko WC, Von Gottberg A, et al. International prospective study of Klebsiella pneumoniae bacteremia: implications of extended-spectrum beta-lactamase production in nosocomial Infections. Ann Intern Med 2004;140:26-32. https://doi.org/10.7326/0003-4819-140-1-200401060-00008
  12. Harris PNA, Tambyah PA, Lye DC, et al. Effect of piperacillin-tazobactam vs meropenem on 30-day mortality for patients with E coli or Klebsiella pneumoniae bloodstream infection and ceftriaxone resistance: a randomized clinical trial. JAMA 2018;320:984-994. https://doi.org/10.1001/jama.2018.12163
  13. Henderson A, Paterson DL, Chatfield MD, et al. Association between minimum inhibitory concentration, beta-lactamase genes and mortality for patients treated with piperacillin/tazobactam or meropenem from the MERINO study. Clin Infect Dis 2021;73:e3842-e3850. https://doi.org/10.1093/cid/ciaa1479
  14. Kang CI, Cha MK, Kim SH, et al. Clinical and molecular epidemiology of community-onset bacteremia caused by extended-spectrum β-lactamase-producing Escherichia coli over a 6-year period. J Korean Med Sci 2013;28:998-1004. https://doi.org/10.3346/jkms.2013.28.7.998
  15. Kim YC, Choi H, Kim YA, et al. Risk factors and microbiological features of recurrent Escherichia coli bloodstream infections. PLoS One 2023;18:e0280196.
  16. Choi HJ, Jeong SH, Shin KS, et al. Characteristics of Escherichia coli urine isolates and risk factors for secondary bloodstream infections in patients with urinary tract infections. Microbiol Spectr 2022;10:e0166022.
  17. Sharara SL, Amoah J, Pana ZD, Simner PJ, Cosgrove SE, Tamma PD. Is piperacillin-tazobactam effective for the treatment of pyelonephritis caused by extended-spectrum β-lactamase-producing organisms? Clin Infect Dis 2020;71:e331-e337. https://doi.org/10.1093/cid/ciz1205
  18. Chow JW, Yu VL. Combination antibiotic therapy versus monotherapy for gram-negative bacteraemia: a commentary. Int J Antimicrob Agents 1999;11:7-12. https://doi.org/10.1016/S0924-8579(98)00060-0