A population-based epidemiological and health economic analysis of fracture-related infection.

Aims: The aim of this study was to perform the first population-based description of the epidemiological and health economic burden of fracture-related infection (FRI). Methods: This is a retrospective cohort study of operatively managed orthopaedic trauma patients from 1 January 2007 to 31 December 2016, performed in Queensland, Australia. Record linkage was used to develop a person-centric, population-based dataset incorporating routinely collected administrative, clinical, and health economic information. The FRI group consisted of patients with International Classification of Disease 10th Revision diagnosis codes for deep infection associated with an implanted device within two years following surgery, while all others were deemed not infected. Demographic and clinical variables, as well as healthcare utilization costs, were compared. Results: There were 111,402 patients operatively managed for orthopaedic trauma, with 2,775 of these (2.5%) complicated by FRI. The development of FRI had a statistically significant association with older age, male sex, residing in rural/remote areas, Aboriginal or Torres Strait Islander background, lower socioeconomic status, road traffic accident, work-related injuries, open fractures, anatomical region (lower limb, spine, pelvis), high injury severity, requiring soft-tissue coverage, and medical comorbidities (univariate analysis). Patients with FRI had an eight-times longer median inpatient length of stay (24 days vs 3 days), and a 2.8-times higher mean estimated inpatient hospitalization cost (AU$56,565 vs AU$19,773) compared with uninfected patients. The total estimated inpatient cost of the FRI cohort to the healthcare system was AU$156.9 million over the ten-year period. Conclusion: The results of this study advocate for improvements in trauma care and infection management, address social determinants of health, and highlight the upside potential to improve prevention and treatment strategies.

A bibliometric analysis of clinical research on fracture-related infection.

Background: Infection following orthopaedic trauma surgery is increasingly recognized as one of the major research priorities with as primary goal, improving patient care. This increased interest has been anecdotally recognized through published research, research grants, and, finally, with the development of the fracture-related infection (FRI) consensus group. In 2017, the accepted consensus definition of FRI was published, which has been followed by consensus recommendations from both a surgical and medical perspective. A bibliometric analysis was performed to objectively describe the trends in published clinical research related to FRI. Methods: The terms related to FRI were searched in the Web of Science database between 2000 and 2020. The characteristics of clinical research on FRI regarding the author, country, journal, institution, scientific output, top 100 most cited articles, and trend topics were analyzed using Bibliometrix and WPS Office. Results: A total of 2597 records were eligible for inclusion in this bibliometric approach, with studies originating from 89 countries, including eight languages. The United States of America (USA) published the highest number of articles and citations. International collaborations were present between 72 countries, with the most active country being the USA. The most contributive institution was the University of California. The highest number of papers and citations were from the Injury-International Journal of the Care of the Injured and the Journal of Orthopaedic Trauma. The top 100 most cited articles were published in 27 different journals, with the number of citations ranging between 97 and 1004. The latest trend topics were related to the diagnosis of FRI. Conclusion: The present bibliometric analysis shows the research characteristics and trends of FRI from multiple perspectives. The fact that there is an increasing number of studies being published on FRI shows the agreement among scientists and clinicians that standardization with respect to this topic is very important.

Cutibacterium acnes in shoulder surgery: a scoping review of strategies for prevention, diagnosis, and treatment.

BACKGROUND: Cutibacterium acnes is a commensal, gram-positive, facultatively anaerobic bacillus that resides in the dermis. Historically thought to be a contaminant when identified on cultured specimens, recent advances in diagnostic technology have now implicated it as the most common organism responsible for postoperative shoulder infections. Despite a recognition of the role of this organism and a significant research interest in recent years, there is clear lack of consensus guideline on strategies to prevent, diagnose, and treat postoperative shoulder infection. METHOD: The electronic databases PubMed, MEDLINE, CINAHL, Scopus, and Web of Science were searched in March 2020. All experimental and nonexperimental studies that investigate C acnes in shoulder surgery were included. Inclusion was limited to articles published after 2000 and written in English; reviews, gray literature, or abstracts were excluded. A total of 70 studies were included in this review. This scoping review was performed in accordance with the Extended Preferred Reporting Items of Systematic Reviews and Meta-Analyses Statement for Scoping Reviews (PRISMA-ScR). RESULTS: Standard surgical prophylactic regimens such as intravenous antibiotics and topical chlorhexidine are ineffective at removing C acnes from the deep layer of the dermis, and there is a shift toward using topical benzoyl peroxide with significantly improved efficacy. An improved understanding of the bacteria has demonstrated that a prolonged culture time of up to 14 days is needed, especially in cases of established infection. Advances in diagnostics such as sonication and molecular-based testing are promising. Although usually thought to be susceptible to a broad range of antibiotics, resistance is emerging to clindamycin. An improved understanding of its ability to form a biofilm highlights the difficulty in treating an established infection. CONCLUSION: The role of C acnes causing postoperative infection following shoulder surgery is being increasingly recognized. Strategies for prevention, diagnosis, and treatment have been outlined from both an antimicrobial and surgical perspective. A number of these strategies are emerging and require further research to demonstrate efficacy before implementation into clinical guidelines.

Single-stage revision of MRSA orthopedic device-related infection in sheep with an antibiotic-loaded hydrogel.

Local antimicrobial therapy is an integral aspect of treating orthopedic device-related infection (ODRI), which is conventionally administered via polymethyl-methacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability. In this study, we compare the efficacy of PMMA versus an antibiotic-loaded hydrogel in a single-stage revision for chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI in sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single-stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post-mortem. There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture-negative. Antibiotic delivery via hydrogel resulted in 10-100 times greater local concentrations for the first 2-3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits. This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use.

The influence of biomechanical stability on bone healing and fracture-related infection: the legacy of Stephan Perren.

Bone healing is a complicated process of tissue regeneration that is influenced by multiple biological and biomechanical processes. In a minority of cases, these physiological processes are complicated by issues such as nonunion and/or fracture-related infection (FRI). Based on a select few in vivo experimental animal studies, construct stability is considered an important factor influencing both prevention and treatment of FRI. Stephan Perren played a pivotal role in the evolution of our current understanding of the critical relationship between biomechanics, fracture healing and infection. Furthermore, his concept of strain theory and the process of fracture healing is familiar to several generations of surgeons and has influenced implant development and design for the past 50 years. In this review we describe the role of biomechanical stability on fracture healing, and provide a detailed analysis of the preclinical studies addressing this in the context of FRI. Furthermore, we demonstrate how Perren's concepts of stability are still applied to current surgical techniques to aid in the prevention and treatment of FRI. Finally, we highlight the key knowledge gaps in the underlying basic research literature that need to be addressed as we continue to optimize patient care.

Fracture-related infection: current methods for prevention and treatment.

Introduction: Fracture-related infection (FRI) is a serious complication related to orthopedic trauma, both from an infectious disease and a surgical point of view. The lack of scientific data with respect to diagnostic criteria and treatment principles of this entity has hampered efforts for an evidence-based approach and, as such, practices to prevent and treat FRI are often extrapolated from peri-prosthetic joint infection (PJI) literature. Recently, consensus guidelines were developed with respect to prevention, diagnosis and treatment of FRI.Areas covered: This review will define FRI and approaches to prevent and treat this complication will be discussed, with an emphasis on antimicrobial and surgical considerations. Guidelines focusing on FRI will be highlighted and aspects of pre-clinical research with imminent translational potential described.Expert opinion: New strategies are currently under investigation to improve the outcome of this sometimes-devastating complication. Local delivery of antimicrobials seems to be a promising approach; however, further high-quality clinical research is necessary to demonstrate efficacy. Delivery mechanisms for local antimicrobials include polymethyl methacrylate, implant coatings, collagen fleece, hydrogels and ceramics. The reintroduction of antimicrobials such as bacteriophage therapy has demonstrated promise in the management of drug-resistant organisms.

Anal Dysplasia in Human Immunodeficiency Virus-Infected Men Who Have Sex With Men With Sexually Acquired Early Hepatitis C Virus Infection.

BACKGROUND: Human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) are at increased risk of anorectal infection with high-risk human papillomavirus and subsequent high-grade squamous intraepithelial lesions (HSIL), the putative precursor to anal cancer. Recently, an epidemic of sexually transmitted hepatitis C virus (HCV) has emerged that shares this anorectal route of transmission. We hypothesized that the prevalence of anal HSIL would be high in HIV-infected MSM with sexually acquired early HCV infection. METHODS: High-resolution anoscopy (HRA) findings from a cohort of HIV-infected MSM with sexually acquired early HCV infection were compared with HRA findings from a contemporary cohort of HIV-infected MSM without HCV infection who underwent HRA due to abnormal anal cytology found during routine screening. RESULTS: Sixty HIV-infected MSM with sexually acquired early HCV infection and the comparator group of 1150 HIV-infected MSM with abnormal anal cytology but without HCV underwent HRA. The HIV-infected MSM with sexually acquired early HCV had higher CD4 counts compared with the comparator group (656 and 541 cells/µL, respectively; P = .02). Despite this, the prevalence of anal dysplasia was as high among MSM with early HCV as in the comparator group of MSM with abnormal cytology (47 [78%] and 941 [82%], respectively; P = .50), as was the proportion with HSIL (25 [42%] and 379 [33%], respectively; P = .17). CONCLUSIONS: The prevalence of anal dysplasia in HIV-infected MSM with sexually acquired early HCV infection was as high as that of HIV-infected MSM with abnormal anal cytology. These findings suggest that primary screening with HRA may be warranted for HIV-infected MSM with early HCV.

Sofosbuvir in the treatment of early HCV infection in HIV-infected men.

BACKGROUND: There is an international epidemic of hepatitis C virus (HCV) infection among HIV-infected men who have sex with men. We previously showed that adding telaprevir to pegylated interferon (IFN) and ribavirin (RBV) both shortened treatment and increased the cure rate of early HCV in these men. Whether shortening treatment of early HCV using IFN-free regimens would be similarly successful has not yet been demonstrated. METHODS: We performed a pilot study of treatment with sofosbuvir (SOF) + RBV for 12 weeks in early genotype 1 HCV infection in HIV-infected men. The primary endpoint was SVR 12. RESULTS: Twelve men were treated with 12 weeks SOF + RBV and 11 (92%) achieved SVR 12. Most (63%) were actively using recreational drugs, mostly methamphetamine. The one man who failed had laboratory results more characteristic of chronic than of early HCV infection. The overall safety profile was similar to that known for SOF + RBV. CONCLUSIONS: The success of this short-duration IFN-free treatment in early HCV infection is proof in principle that enhanced treatment responsiveness is an inherent characteristic of early HCV infection and not a function of IFN treatment itself. Future studies should now be done with more potent regimens to try to further shorten therapy. In the mean time, in clinical practice early HCV infection should be treated immediately after detection to take advantage of short-duration treatments, as well as to decrease further HCV transmission among HIV-infected MSM.

Shedding of Hepatitis C Virus Into the Rectum of HIV-infected Men Who Have Sex With Men.

BACKGROUND: For over a decade we have known of an epidemic of sexually transmitted hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM), but there still remains significant controversy over which bodily fluid(s) are responsible for HCV transmission in these men. METHODS: We enrolled HIV-infected MSM with recent and chronic HCV infection and quantified HCV from rectal fluid obtained by blind swab. We compared the rectal HCV viral load (VL) with paired blood HCV VL. RESULTS: We found rectal HCV shedding in 20 (47%) of 43 men, only one (2%) of whom had visible bleeding. Detection of rectal HCV shedding was associated with blood VL > 5 log10 IU/mL (p = .01), and 85% with blood VL > 5 log10 IU/mL had rectal shedding. The HCV VL of the rectal fluid ranged from 2.6 to 5.5 log10 IU/mL. Based on the median rectal fluid VL, the surface of an average human penis would be exposed to at least 2,300 IU of HCV for the duration of anal intercourse. CONCLUSION: This study provides the first direct evidence to our knowledge that a sufficient quantity of HCV is shed into the rectum in HIV-infected men with HCV infection to directly infect an inserted penis or be passed indirectly through fomite-like transmission to the rectum of sex partner. We must develop an appropriate public health campaign to educate MSM about these routes of HCV infection to reverse the HCV epidemic among HIV-infected MSM.

Shedding of Hepatitis C Virus in Semen of Human Immunodeficiency Virus-Infected Men.

Background. The epidemic of sexually transmitted hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) has been documented for over a decade. Despite this, there is no consensus as to the risk factors for sexual acquisition of HCV in these men. Methods. We obtained paired semen and blood samples at 2-week intervals from HIV-infected MSM with recent and chronic HCV infection and quantified HCV in semen. Results. Hepatitis C virus was quantified in 59 semen specimens from 33 men. Hepatitis C virus was shed in 16 (27%) of semen specimens from 11 (33%) of the men. Median HCV viral load (VL) in semen was 1.49 log10 IU/mL. Hepatitis C virus VL in blood was significantly higher at the time of HCV shedding in semen than when HCV shedding in semen was not detected (P = .002). Furthermore, there was a significant correlation between the HCV VL in blood and semen overall (rs = 0.41; P = .001), and in the subgroup with recent HCV infection (rs = 0.37; P = .02), but not in the subgroup with chronic HCV infection (rs = 0.34; P = .1). Conclusions. One third of HIV-infected MSM coinfected with HCV shed HCV into their semen. Based on the HCV VL in semen in this study, an average ejaculate would deliver up to 6630 IU of virus into the rectum of the receptive partner. Therefore, our data strongly support that condoms should be used during anal intercourse among MSM to prevent transmission of HCV.