Management of Resistant, Atypical and Culture-negative Periprosthetic Joint Infections after Hip and Knee Arthroplasty

Alexander S. McLawhorn*, Danyal H. Nawabi, Amar S. Ranawat
Department of Orthopedic Surgery, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA

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© McLawhorn et al.; Licensee Bentham Open

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA; Tel: 212-606-1065; Fax: 212-774-7317; E-mail:



Periprosthetic joint infection (PJI) is a devastating complication following lower extremity total joint arthroplasty (TJA). It is a leading cause of morbidity and revision following TJA. As such, PJI is a significant driver of healthcare costs. The prevalence of PJI related to resistant and atypical organisms is increasing, and approximately 10-30% of PJIs are culture-negative. The purpose of this review is to summarize the current epidemiology, diagnostics, and management of PJI associated with resistant and atypical pathogens and of culture-negative PJIs.


The published literature related to the epidemiology, diagnosis, and management of atypical, drug-resistant, and culture-negative PJI is reviewed.


The clinical diagnosis of PJI is often challenging, particularly when pathogens are fastidious or when antibiotics have been administered empirically. Molecular diagnostic studies, such as synovial α-defensin, may provide rapid, accurate identification of PJI, even in the setting of concurrent antibiotics administration or systemic inflammatory disease. Once PJI is diagnosed, two-stage exchange arthroplasty remains the gold standard for treating PJI with resistant microorganisms, since there is a high rate of treatment failure with irrigation and debridement and with one-stage exchange arthroplasty.


Additional research is needed to define the optimal treatment of PJIs associated with rare pathogens, such as fungi and mycobacteria. There is a need for inexpensive, reliable tests that rapidly detect specific microbial species and antimicrobial susceptibilities. Additional research is also required to define the specific organisms, clinical scenarios, surgical techniques, and antimicrobial regimens that allow for reproducible treatment success with prosthetic retention strategies.

Keywords: Arthroplasty, Drug Resistance, Joint, Microbial, Prosthesis-Related Infections, Revision, Total Hip Arthroplasty, Total Knee Arthroplasty.