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agr functionality affects clinical outcomes in patients with persistent methicillin-resistant Staphylococcus aureus bacteraemia

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Abstract

Methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) often persists despite appropriate antibiotic therapy. It is unclear what microbiological factors contribute to poor clinical outcomes in persistent MRSAB (pMRSAB). We aimed to identify clinical and microbiological risk factors for in-hospital mortality in pMRSAB. We analysed MRSAB cases prospectively collected between 2009 and 2016 at 11 hospitals in Korea, defining cases of pMRSAB as MRSAB lasting ≥5 days despite administration of effective antibiotics. The first blood isolates from the pMRSAB cases were tested for staphylococcal cassette chromosome mec type, staphylococcal protein A type, accessary gene regulator (agr) type, genes for Panton-Valentine leukocidin and phenol-soluble modulin-mec, vancomycin minimum inhibitory concentration, vancomycin heteroresistance, and agr functionality. We also collected clinical information for each case. Of 960 MRSAB cases, 152 pMRSAB were finally eligible. Univariable analysis revealed that in-hospital mortality was significantly associated with Charlson’s comorbidity-weighted index (CCWI) score, Pitt bacteremia score, sequential organ failure assessment score, presentation with septic shock, pneumonia, agr dysfunction, and vancomycin heteroresistance. Bone and joint infections were negatively associated with in-hospital mortality. Multivariable analysis revealed the following independent risk factors for in-hospital mortality: CCWI score [adjusted odds ratio (aOR), per one point, 1.25; 95% confidence interval (CI), 1.08–1.44; P = 0.003), Pitt bacteremia score (aOR, per one point, 1.33; 95% CI, 1.09–1.62; P = 0.005), non-eradicated foci of infection (aOR, 3.12; 95% CI, 1.18–8.27; P = 0.022), and agr dysfunction (aOR, 2.48; 95% CI, 1.12–5.47; P = 0.025). agr dysfunction is an independent risk factor for in-hospital mortality in pMRSAB.

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Acknowledgements

This work was presented as an abstract (No. 1087) in the ID Week, New Orleans, LA, USA, 26–30 October 2016.

The study involved three SAB cohorts that were prospectively collected at 11 secondary- or tertiary-care hospitals in South Korea. The cohorts comprised SAB cases occurring from 2009 to 2011 (grants 02-2012-035 from the SNUBH Research Fund and 2009-E00609-00 from the Korea Centres for Disease Control and Prevention) [5, 6], from 2010 to 2012 (grant 03-2013-004 from the SNUBH Research Fund) [7], and from 2013 to 2015 (grant HI10C2020 from the National Strategic Coordinating Centre for Clinical Research). The analyses of cases from 2016 were also approved by the institutional review board of Seoul National University Bundang Hospital (IRB No. B-1702-384-302).

We thank the members of the Korea INfectious Diseases (KIND) study group and the associated staff for their cooperation in this study. In addition to the authors, the following were participants in the study group: Taek Soo Kim, Kyoung Un Park, Jeong Eun Cho, Yun Jung Choi, Jung In Park (Seoul National University Bundang Hospital); Hee Kyoung Choi, Myung Sook Han (Yonsei University Wonju Severance Christian Hospital); Su-Mi Choi (Chonnam National University Hospital); Nam Joong Kim, Su Jin Choi (Seoul National University Hospital); Seung-Ji Kang, Hyeon-jeong Hwang (Chonnam National University Hwasun Hospital); Jongyoun Yi, Sohee Park (Pusan National University Hospital); Shinhye Cheon, Jin Hee Hwang, Seon Jin Yun (Chungnam National University Hospital); Chong Rae Cho, Hyun Suk Song, Young Soon Lee (Inje University Ilsan Paik Hospital); Hye-In Kim, Seung Min Shin (Daegu Fatima Hospital); Jae Hyun Jeon, Dong-Kie Kim, Sae-Am Song, Min Ji Kang, and Jae Gyun Shin (Inje University Haeundae Paik Hospital).

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Author notes

  1. Chang Kyung Kang and Young Keun Kim contributed equally to this work.

Authors and Affiliations

  1. Seoul National University Bundang Hospital, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam, South Korea

    C. K. Kang, K.-H. Song, E. S. Kim & H. B. Kim

  2. Seoul National University College of Medicine, Seoul, South Korea

    C. K. Kang, W. B. Park, K.-H. Song, P. G. Choe, E. S. Kim & H. B. Kim

  3. Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, South Korea

    Y. K. Kim

  4. Chonnam National University Hospital, Gwangju, South Korea

    S.-I. Jung & K.-H. Park

  5. Seoul National University Hospital, Seoul, South Korea

    W. B. Park & P. G. Choe

  6. Chonnam National University Hwasun Hospital, Hwasun, South Korea

    H.-C. Jang

  7. Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, South Korea

    S. Lee

  8. Department of Internal Medicine, Chungnam National University School of Medicine, Daejon, South Korea

    Y.-S. Kim

  9. Inje University Ilsan Paik Hospital, Goyang, South Korea

    Y. G. Kwak

  10. Daegu Fatima Hospital, Daegu, South Korea

    K. T. Kwon

  11. Inje University Haeundae Paik Hospital, Busan, South Korea

    S. Kiem

  12. Ehwa Women’s University Hospital, Seoul, Republic of Korea

    C.-J. Kim

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  1. C. K. Kang
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  3. S.-I. Jung
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  4. W. B. Park
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  7. P. G. Choe
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  8. H.-C. Jang
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  9. S. Lee
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  13. S. Kiem
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  14. C.-J. Kim
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  15. E. S. Kim
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  16. H. B. Kim
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the Korea INfectious Diseases (KIND) study group

Corresponding author

Correspondence to E. S. Kim.

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Funding

This work was supported by grant No. 14–2016-002 from the SNUBH Research Fund.

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The authors declare that they have no conflicts of interest.

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Formal consent was not required in this study.

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Kang, C.K., Kim, Y.K., Jung, SI. et al. agr functionality affects clinical outcomes in patients with persistent methicillin-resistant Staphylococcus aureus bacteraemia. Eur J Clin Microbiol Infect Dis 36, 2187–2191 (2017). https://doi.org/10.1007/s10096-017-3044-2

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  • DOI: https://doi.org/10.1007/s10096-017-3044-2

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