DOI QR코드

DOI QR Code

Efficacy and Tolerability of Linezolid for Treatment of Infectious Spondylitis

그람양성균으로 인한 감염 척추염에서 Linezolid의 효과와 안전성

  • Jung, Jongtak (Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Lee, Eunyoung (Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Song, Kyoung-Ho (Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Choe, Pyoeng Gyun (Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Park, Wan Beom (Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Bang, Ji Hwan (Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Kim, Eu Suk (Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Kim, Hong Bin (Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Park, Sang Won (Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Kim, Nam Joong (Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Oh, Myoung-don (Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine)
  • 정종탁 (서울대학교 의과대학 서울대학교병원 내과) ;
  • 이은영 (서울대학교 의과대학 서울대학교병원 내과) ;
  • 송경호 (서울대학교 의과대학 서울대학교병원 내과) ;
  • 최평균 (서울대학교 의과대학 서울대학교병원 내과) ;
  • 박완범 (서울대학교 의과대학 서울대학교병원 내과) ;
  • 방지환 (서울대학교 의과대학 서울대학교병원 내과) ;
  • 김의석 (서울대학교 의과대학 서울대학교병원 내과) ;
  • 김홍빈 (서울대학교 의과대학 서울대학교병원 내과) ;
  • 박상원 (서울대학교 의과대학 서울대학교병원 내과) ;
  • 김남중 (서울대학교 의과대학 서울대학교병원 내과) ;
  • 오명돈 (서울대학교 의과대학 서울대학교병원 내과)
  • Received : 2018.03.10
  • Accepted : 2018.07.11
  • Published : 2018.10.01

Abstract

Background/Aims: Infectious spondylitis requires long-term antibiotic treatment; however, the use of intravenous antibiotics during this period has high social and monetary costs due to hospitalization. Linezolid has high oral bioavailability and is not affected by changes in renal or hepatic function. We investigated the clinical and microbiological effects of linezolid in infectious spondylitis caused by beta-lactam resistant gram-positive bacteria. Methods: Clinical data from patients who were treated with linezolid for at least four weeks were collected retrospectively from electronic medical records at the Seoul National University Hospital, Seoul National University Bundang Hospital, and Boramae Medical Center from 2006 to 2016. Results: Twenty Korean patients were treated with linezolid for at least four weeks during the study period. Of these, 14 patients were cured, four failed, and two cases of mortality occurred due to other causes than infectious spondylitis. Ten of 13 patients who had previously been assessed as vancomycin treatment failure were cured by linezolid. Bacteremia occurred in 14 patients, and 10 of these showed persistent bacteremia at the time of linezolid administration. Eight of these cases of persistent bacteremia were cured by linezolid. Median duration of linezolid treatment was 40.5 days (28-90 days). Severe cytopenia (grade II or more of National Cancer Institute criteria) was the most common adverse event, with incidences of 11.11% for neutropenia, 12.96% for anemia, and 20.37% for thrombocytopenia. Conclusions: Linezolid can be used as an effective antibiotic agent in patients with infectious spondylitis, especially when treatment failure of the first-line treatment is expected.

목적: 감염 척추염은 장기간의 항생제 치료를 필요로 하며, 이 기간 동안의 정주 항생제의 사용은 입원으로 인한 사회적 손실과 비용을 유발한다. Linezolid는 경구 생체 이용률이 100%이며 신기능과 간기능에 따라 linezolid의 약동학이 영향받지 않는 장점이 있다. Beta-lactam 항생제에 내성을 보이는 그람양성균에 의한 감염 척추염에서 linezolid의 임상적, 미생물학적 치료 효과를 분석하였다. 방법: 2006년부터 2016년까지 서울대병원, 분당서울대병원, 보라매병원에서 감염 척추염으로 진단된 환자 중 linezolid가 4주 이상 투약된 사례에서 임상정보를 후향적으로 수집하여 분석하였다. 결과: Linezolid가 4주 이상 투약된 환자는 총 20명이었다. 가장 흔한 원인균은 methicillin-resistant Staphylococcus aureus 였으며(n = 15), 다음으로 methicillin-resistant coagulase-negative Staphylococcus가 많았다(n = 3). 20명의 환자 중 14명을 성공적으로 치료하였고 4명에서는 치료에 실패하였다. 2명의 환자는 감염 척추염이 아닌 다른 원인으로 사망하였다. Vancomycin 치료 실패 환자 13명 중 10명에서 linezolid로 치료에 성공하였다. 지속적인 균혈증을 보인 10명의 환자 중 8명에서 linezolid 투약 이후 균음전이 확인되었다. Linezolid 사용 기간의 중앙값은 40.5일(28-90)이었다. 약물 이상 반응평가에서 항생제 중단을 고려할 만한 심한 혈구감소증은 호중구감소증 11.11%, 빈혈 12.96%, 혈소판감소증이 20.37%였다. 결론: Linezolid는 감염 척추염에서 치료제로 효과적으로 사용할 수 있으며 특히 1차 치료제의 치료 실패가 예상되는 경우 구제 치료로 사용할 경우 높은 치료 성공률을 기대할 수 있다.

Keywords

References

  1. Kim YI, Kim SE, Jang HC, Jung SI, Song SK, Park KH. Analysis of the clinical characteristics and prognostic factors of infectious spondylitis. Infect Chemother 2011;43:48-54. https://doi.org/10.3947/ic.2011.43.1.48
  2. Kim CJ, Song KH, Park WB, et al. Microbiologically and clinically diagnosed vertebral osteomyelitis: impact of prior antibiotic exposure. Antimicrob Agents Chemother 2012;56:2122-2124. https://doi.org/10.1128/AAC.05953-11
  3. World Health Organization. Antimicrobial resistance: global report on surveillance. World Health Organization, 2014. Geneva: World Health Organization, 2014.
  4. Kim HB. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Korean J Med 2007;72: 120-130.
  5. Li Y, Xu W. Efficacy and safety of linezolid compared with other treatments for skin and soft tissue infections: a meta-analysis. Biosci Rep 2018;38:BSR20171125.
  6. Jang HC, Kim SH, Kim KH, et al. Salvage treatment for persistent methicillin-resistant Staphylococcus aureus bacteremia: efficacy of linezolid with or without carbapenem. Clin Infect Dis 2009;49:395-401. https://doi.org/10.1086/600295
  7. Rana B, Butcher I, Grigoris P, Murnaghan C, Seaton RA, Tobin C. Linezolid penetration into osteo-articular tissues. J Antimicrob Chemother 2002;50:747-750. https://doi.org/10.1093/jac/dkf207
  8. Traunmuller F, Schintler MV, Spendel S, et al. Linezolid concentrations in infected soft tissue and bone following repetitive doses in diabetic patients with bacterial foot infections. Int J Antimicrob Agents 2010;36:84-86. https://doi.org/10.1016/j.ijantimicag.2010.03.007
  9. Aneziokoro CO, Cannon JP, Pachucki CT, Lentino JR. The effectiveness and safety of oral linezolid for the primary and secondary treatment of osteomyelitis. J Chemother 2005;17:643-650. https://doi.org/10.1179/joc.2005.17.6.643
  10. Dunphy L, Iyer S, Brown C. Rare cause of back pain: staphylococcus aureus vertebral osteomyelitis complicated by recurrent epidural abscess and severe sepsis. BMJ Case Rep 2016;2016:bcr2016217111.
  11. Fukuda Y, Yanagihara K, Nakamura S, et al. Successful treatment with linezolid in two cases of methicillin-resistant Staphylococcus aureus infections in the orthopedic field. Kansenshogaku zasshi 2003;77:622-626. https://doi.org/10.11150/kansenshogakuzasshi1970.77.622
  12. Howden BP, Ward PB, Charles PG, et al. Treatment outcomes for serious infections caused by methicillin-resistant staphylococcus aureus with reduced vancomycin susceptibility. Clin Infect Dis 2004;38:521-528. https://doi.org/10.1086/381202
  13. Hoyo I, Martinez-Pastor J, Garcia-Ramiro S, et al. Decreased serum linezolid concentrations in two patients receiving linezolid and rifampicin due to bone infections. Scand J Infect Dis 2012;44:548-550. https://doi.org/10.3109/00365548.2012.663931
  14. Melzer M, Goldsmith D, Gransden W. Successful treatment of vertebral osteomyelitis with linezolid in a patient receiving hemodialysis and with persistent methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus bacteremias. Clin Infect Dis 2000;31:208-209. https://doi.org/10.1086/313897
  15. Yunde A, Inage K, Orita S, et al. Effective treatment of post-spinal fusion methicillin-resistant Staphylococcus aureus vertebral osteomyelitis with linezolid in a renal-transplant patient. BMC Res Notes 2015;8:708. https://doi.org/10.1186/s13104-015-1694-7
  16. Rao N, Hamilton CW. Efficacy and safety of linezolid for Gram-positive orthopedic infections: a prospective case series. Diagn Microbiol Infect Dis 2007;59:173-179. https://doi.org/10.1016/j.diagmicrobio.2007.04.006
  17. Rayner CR, Baddour LM, Birmingham MC, Norden C, Meagher AK, Schentag JJ. Linezolid in the treatment of osteomyelitis: results of compassionate use experience. Infection 2004;32:8-14. https://doi.org/10.1007/s15010-004-3029-9
  18. Vazquez JA, Arnold AC, Swanson RN, Biswas P, Bassetti M. Safety of long-term use of linezolid: results of an open-label study. Ther Clin Risk Manag 2016;12:1347-1354. https://doi.org/10.2147/TCRM.S109444
  19. Sotgiu G, Centis R, D'Ambrosio L, et al. Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: systematic review and meta-analysis. Eur Respir J 2012;40:1430-1442. https://doi.org/10.1183/09031936.00022912
  20. Lawyer MC, Lawyer EZ. Linezolid and reversible myelosuppression. JAMA 2001;286:1973-1974.
  21. Bernstein WB, Trotta RF, Rector JT, Tjaden JA, Barile AJ. Mechanisms for linezolid-induced anemia and thrombocytopenia. Ann Pharmacother 2003;37:517-520. https://doi.org/10.1345/aph.1C361

Cited by

  1. Detection of Linezolid-Resistant Enterococcus faecalis and Enterococcus faecium Isolates from the Layer Operation System in Korea vol.27, pp.10, 2018, https://doi.org/10.1089/mdr.2020.0028