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Characteristics of cefazolin inoculum effect-positive methicillin-susceptible staphylococcus aureus infection in a multicentre bacteraemia cohort

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Abstract

Cefazolin treatment failure has been observed in high-inoculum infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) with a cefazolin inoculum effect (CIE). However, data on the characteristics and risk factors for the acquisition of CIE-positive MSSA infection are scarce. CIE positivity was measured as an MIC ≥ 16 μg/ml with a high inoculum (∼5 × 107 CFU/ml). The blaZ gene type was assessed through sequence analysis. The clinical characteristics and risk factors for the acquisition of CIE-positive MSSA infection were assessed. The association between the antimicrobial susceptibility profile and CIE positivity was evaluated. A total of 303 MSSA bacteraemia cases and their corresponding isolates were collected from ten hospitals: 61 (20.1 %) isolates showed a positive CIE; 254 (83.8 %) were positive for the blaZ gene. No significant association was found between CIE positivity and the site of infection. Metastatic cancer (aOR 2.86, 95 % CI, 1.10–7.48) and recent (≤1 month) close contact with a chronically ill patient (aOR 4.69, 95 % CI, 1.76–12.50) were identified as significant risk factors for CIE-positive MSSA infection through multivariate analyses. Resistances to clindamycin (OR 3.55, 95 % CI, 1.62–7.80) and erythromycin (OR 5.00, 95 % CI, 2.50–9.99) were associated with CIE positivity, presenting high specificity (92.9 %) and a negative predictive value (82.3 %). CIE-positive MSSA constituted approximately one-fifth of MSSA bacteraemia cases. Although CIE positivity was not clinically discernible, CIE positivity was associated with clindamycin or erythromycin susceptibility. Therefore, our findings suggest that cefazolin can be used in the treatment of high-inoculum MSSA infection if the isolates are susceptible to clindamycin or erythromycin.

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Acknowledgments

This work was summarized in an abstract (Abstract No. C-1067) for the 55th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, USA, 2015.

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 individuals participated in the study: Su-Mi Choi (Chonnam National University Hospital); Kyoung Un Park, Eu Suk Kim, Jeong Eun Cho, Yun Jung Choi, Jung In Park (Seoul National University Bundang Hospital); Taek Soo Kim, Pyoeng Gyun Choe, Wan Beom Park, Nak-Hyun Kim, Myung Jin Lee, Su Jin Choi (Seoul National University Hospital); Jae Hyun Jeon, Dong-Kie Kim, Sae-Am Song, Min Ji Kang, Jae Gyun Shin (Inje University Haeundae Paik Hospital); Jongyoun Yi (Pusan National University Hospital); Hee Kyoung Choi, Myung Sook Han (Yonsei University Wonju Severance Christian Hospital); Chong Rae Cho, Hyun Suk Song, Young Soon Lee (Inje University Ilsan Paik Hospital); Seung-Ji Kang, Hyeon-jeong Hwang, (Chonnam National University Hwasun Hospital); Shinhye Cheon, Jin Hee Hwang, Seon Jin Yun (Chungnam National University Hospital); Ki Tae Kwon, Seung Min Shin (Daegu Fatima Hospital).

We give special thanks to B. E. Murray and her colleagues at the University of Texas Medical School for providing strain TX 0117, a high-level producer of type A β-lactamase.

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Author notes

  1. C. J. Kim

    Present address: Ewha Woman’s University Medical Center, Seoul, Republic of Korea

Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

    K.-H. Song, C. J. Kim & H. B. Kim

  2. Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Republic of Korea

    S.-I. Jung & K.-H. Park

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

    S. Lee, S. Park & S. H. Lee

  4. Department of Internal Medicine, Inje University College of Medicine, Busan, Republic of Korea

    S. M. Kiem

  5. Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Republic of Korea

    Y. G. Kwak

  6. Department of Internal Medicine, Yonsei University Medical School, Wonju, Republic of Korea

    Y. K. Kim

  7. Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun, Jeollanam-do, Republic of Korea

    H.-C. Jang

  8. Division of Infectious Diseases, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Republic of Korea

    Y.-S. Kim

  9. Department of Internal Medicine, Daegu Fatima Hospital, Daegu, Republic of Korea

    H.-I. Kim

  10. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea

    N. J. Kim & M.-D. Oh

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The Korea INfectious Diseases (KIND) study group

Corresponding author

Correspondence to S. Lee.

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Funding

This work was supported by a Biomedical Research Institute Grant (2015–05) of Pusan National Hospital.

Clinical MSSA isolates were collected from the prospective cohort study ‘Establishment of Network for Clinical Research of Staphylococcus aureus Infection’, which was supported by Grant No. HI10C2020 from the National Strategic Coordinating Center for Clinical Research.

Conflict of interest

No conflict of interest.

Ethical approval

The study entitled ‘Establishment of Network for Clinical Research of Staphylococcus aureus Infection’ had been approved by the IRB at each participating hospital, and the protocol used in this study involving the utilization of previously collected clinical information and corresponding isolates was approved by the IRB at Pusan National University Hospital (IRB No. E-2016032).

Informed consent

Written informed consent was obtained or waived according to the recommendations from each Institutional Review Board when the patients were enrolled in the ‘Establishment of Network for Clinical Research of Staphylococcus aureus Infection’ study.

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K-H Song and S-I Jung contributed equally to this work.

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Song, KH., Jung, SI., Lee, S. et al. Characteristics of cefazolin inoculum effect-positive methicillin-susceptible staphylococcus aureus infection in a multicentre bacteraemia cohort. Eur J Clin Microbiol Infect Dis 36, 285–294 (2017). https://doi.org/10.1007/s10096-016-2799-1

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