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Infection by ‘low virulence’ organisms often a misnomer
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Infection is a challenging and dreaded complication of any surgical procedure, particularly so in orthopedic surgery. Infection may be caused by a variety of organisms, and convention dictates isolation of a pathogen from a culture should not be considered representative of infection unless the organism is a “true” pathogen.
In recent years and with improvements in detection of infection, we have come to realize some organisms, such as Propionibacterium acnes or coagulase-negative Staphylococcus, conventionally considered as “contaminants” may be true pathogens. These organisms that are not readily isolated using conventional modalities have been termed “low-virulence” organisms.
True pathogens
Based on emerging evidence, it appears not only are these organisms true pathogens, they may be fastidious organisms that are difficult to diagnose and treat. Take the case of P. acnes, as the literature is fraught with examples describing this as a low-virulence organism. However, both recent evidence and our institutional experience dictate P. acnes can cause a challenging orthopedic infection that may be difficult to treat.
Coagulase-negative Staphyloccous aureus is another example. The intriguing factor is these organisms are capable of flying under the radar and escaping our ability to detect them as pathogens. They rarely, if ever, cause a physiological response in elevating C-reactive protein, erythrocyte sedimentation rate or other serological markers of inflammation. As a result, an infection caused by these organisms may easily be missed. In fact, the original workgroup of the Musculoskeletal Infection Society stated a disclaimer in introducing the criteria for periprosthetic joint infection in that infection with organisms such as P. acnes may escape detection because of its inability, as well as other organisms, to cause physiologically significant inflammation.
We believe the term “low virulence” should be replaced with “slow growing,” as these organisms are capable of causing disastrous infections. These clinical infections may escape detection due to the slow growing nature of the pathogens in conventional cultures which may escape isolation. P. acnes, for instance, is so slow growing it may not be isolated in conventional cultures unless the cultures are kept for an extended period of time, sometimes up to or exceeding 14 days.
Definition of virulence
How does one define virulence? To do so, one must first define the terms pathogen and pathogenicity. A pathogen has traditionally been defined as an organism causing disease in a host.
This ability represents the genetic component of the pathogen, which encodes various virulence factors. The existing definitions do not account for both the contribution of the pathogen and the susceptibility of the host. In that respect, a 1999 article by Casadevall and Pirofski proposed a definition based on an integrated view of the host and microbe. They suggested medical intervention as a third factor that can alter the course and apparent virulence of an organism. For instance, administering antibiotics can cause superinfection or, more commonly, resistance, which we are already seeing in some P. acnes isolates.
This brings us to the term virulence. Virulence refers to the degree of pathogenicity caused by an infecting organism. By applying the definitions above, we can define virulence as the extent to which the genetic component of a pathogen interacts with the host’s innate susceptibility in the midst of external medical intervention to cause clinically evident disease.
Whole picture
In conclusion, we cannot stereotype a species of organisms without looking at the whole picture. When cultures come back negative or when an organism is detected after 14 days of growth instead of the usual 3 days to 5 days, it is not always due to less virulence. On the contrary, it is likely due to an intricate interaction of various factors that allow for its slow growth, including culture medium, time for detection and medical intervention.
Such an organism may well be highly virulent to a specific host with an optimal milieu. If we can replace the term low virulence with the term slow growing, then it may better enable us to deal with clinical situations of infection when the infecting organism is not easily identified.
- References:
- Achermann Y, et al. Clin. Microbiol Rev. 2014;doi:10.1128/CMR.00092-13.
- Casadevall A, et al. Infect Immun. 1999; 67(8): 3703-3713.
- Culture negative periprosthetic joint infection: Strategies to improve yield. Accessed March 5, 2016.
- Pathogenicity - MeSH – NCBI. www.ncbi.nlm.nih.gov/mesh/81000472. Accessed March 5, 2016.
- Portillo ME, et al. Biomed Res Int. 2013;doi:10.1155/2013/804391.
- Virulence - MeSH – NCBI. www.ncbi.nlm.nih.gov/mesh/68014774. Accessed March 5, 2016.
- Zmistowski B, et al. J Arthroplasty. 2014;doi:10.1016/j.arth.2013.09.040.
- For more information:
- Michael M. Kheir, MD, and Javad Parvizi, MD, FRCS, can be reached at The Rothman Institute at Thomas Jefferson University Hospital, Sheridan Building, Suite 1000, 125 S. 9th St., Philadelphia, PA 19107; emails: mikemkheir@gmail.com and parvj@aol.com.
Disclosures: Kheir reports no relevant financial disclosures. Parvizi reports he is a consultant to Zimmer Biomet, Ceramtec, Convatec and TissueGene; and has ownership in CD Diagnostics, Hip Innovation Technology, ForMD, Alphaeon and Joint Purification Systems.