INFECTIONS IN ORTHOPEDICS IMPACT PATIENT OUTCOMES, RECOVERY, AND PROSTHETIC IMPLANTATION: PREVENTION, DIAGNOSIS, AND TREATMENT

Ricciardi G. Infections in orthopedics impact patient outcomes, recovery, and prosthetic implantation: Prevention, diagnosis, and treatment. International Journal of Infection. 2025;9(1):9-10

G. Ricciardi^*

Department of orthopedics, San Severo Hospital “Masselli Mascia” UOC, San Severo, Italy.

*Correspondence to:
Dr. Giuseppe Ricciardi
Department of orthopedics,
San Severo Hospital “Masselli Mascia” UOC,
San Severo, Italy.
e-mail: peppe.ricciardi@virgilio.it

KEYWORDS: Infection, orthopedics, clinical, immune system, pathogen

INTRODUCTION

Infections are very common in orthopedics and a constant concern for the physician (1). Infections by microorganisms can impact patient outcomes, create prolonged recovery periods, and complicate the potential for implant failure (2). The molecular mechanisms of these infections are complex and involve the host immune system, microbial virulence, and inflammation. Infections can be of various types and can involve the bone tissue inside of a joint or a periprosthetic joint used for implants in orthopedics (3). In addition, soft tissue infections can also occur. The pathogens involved in these infections vary, however, the most common are Staphylococcus aureus, Staphylococcus epidermidis, Gram-negative bacteria, and anaerobic bacteria (4).

DISCUSSION

Different mechanisms are utilized by microbes during infection, including the formation of biofilms, which is a particular concern in periprosthetic joint infections. Biofilms form a protective shield around the bacteria which protects from immune cell attacks and antibiotics (5). Bacteria regulate biofilm formation through chemical signals, while exotoxins, such as those expressed by alpha-toxin in S. aureus, damage host tissues. Capsule, protein A, and other protective systems help the bacterium evade the immune system (for example, phagocytosis). Efflux pumps also contribute to antibiotic resistance by expelling drugs from bacterial cells.

The immune response against bacteria causes the release of innate immune cytokines, such as IL-1, TNF, IL-6, and IL-18 (6). The inflammatory response aims to fight the invading microorganism but also impairs patient outcomes, recovery, prosthetic implantation, and treatment. Pathogenic microorganisms can induce osteoclastogenesis via receptor activator of nuclear factor kappa-Β ligand (RANKL) signaling, leading to bone depletion and loss (7). Infection attracts neutrophil granulocytes that arrive at the inflamed site to phagocytose and destroy bacteria, but this biological effect causes neutrophils to degranulate, resulting in exacerbation of inflammation. Bacterial antigens bind to Toll-like receptors (TLRs) linked to pathogen-associated molecular patterns (PAMPs) and activate the immune response. In these reactions, nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) is activated, which leads to the generation of a major inflammatory cytokine, IL-1β. The immune and inflammatory response induces the activation of NF-kB and JAK/STAT signaling, which modulates immune cell activity and cytokine production (8).

Infections have diagnostic and therapeutic implications. In clinical pathology, elevated levels of biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin are useful for indicating infection. Pathogens can also be identified by next-generation gene sequencing. Antimicrobial therapy may include various strategies such as targeting biofilms with novel drugs or using nanoparticles for targeted drug delivery. Therapies may include inhibition of inflammatory cytokines with medication or even with novel anti-inflammatory cytokines such as IL-37 and IL-38. In addition, therapy may involve immune stimulation against pathogenic microorganisms.

CONCLUSIONS

Infections in orthopedics are a concern for the clinician and can impact patient outcomes, prolonged recovery periods, and potential implant failure. The molecular mechanisms of these infections are complex and involve the immune system and microbial virulence. In bacteria, biofilms form a protective shield from immune cell attacks and antibiotics, exotoxins damage host tissues, and the bacterial capsule helps evade the immune system. The anti-microbial immune response causes the release of pro-inflammatory cytokines and can induce osteoclastogenesis via RANKL signaling with bone depletion and loss. Treatment of infections in orthopedics certainly helps to improve the postoperative status and psychopathological recovery of the patient.

Conflict of interest

The author declares that they have no conflict of interest.

REFERENCES

1. Tsikopoulos K, Sidiropoulos K, Kitridis D, et al. Preventing Staphylococcus aureus stainless steel‐associated infections in orthopedics. A systematic review and meta‐analysis of animal literature. Journal of Orthopaedic Research. 2021;39(12):2615-2637. doi:https://doi.org/10.1002/jor.24999
2. Zimmerli W, Sendi P. Orthopaedic biofilm infections. APMIS. 2017;125(4):353-364. doi:https://doi.org/10.1111/apm.12687
3. Nelson SB, Pinkney JA, Chen AF, Tande AJ. Periprosthetic Joint Infection: Current Clinical Challenges. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 2023;77(7):e34-e45. doi:https://doi.org/10.1093/cid/ciad360
4. Montanaro L, Speziale P, Campoccia D, et al. Scenery of Staphylococcus implant infections in orthopedics. Future Microbiology. 2011;6(11):1329-1349. doi:https://doi.org/10.2217/fmb.11.117
5. Koo H, Allan RN, Howlin RP, Stoodley P, Hall-Stoodley L. Targeting microbial biofilms: current and prospective therapeutic strategies. Nature Reviews Microbiology. 2017;15(12):740-755. doi:https://doi.org/10.1038/nrmicro.2017.99
6. Zhu H, Lin J, Wei H, Bao B, Gao T, Zheng X. Does Training Innate Immunity Confer Broad-spectrum Protection Against Bone and Joint Infection in a Mouse Model? Clinical Orthopaedics & Related Research. 2020;478(11):2670-2681. doi:https://doi.org/10.1097/corr.0000000000001461
7. Dou C, Li N, Ding N, et al. HDAC2 regulates FoxO1 during RANKL-induced osteoclastogenesis. AJP Cell Physiology. 2016;310(10):C780-C787. doi:https://doi.org/10.1152/ajpcell.00351.2015
8. Chen Y, Wang Y, Tang R, et al. Dendritic cells-derived interferon-λ1 ameliorated inflammatory bone destruction through inhibiting osteoclastogenesis. Cell Death & Disease. 2020;11(6). doi:https://doi.org/10.1038/s41419-020-2612-z