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Bone & Joint Research
Vol. 13, Issue 8 | Pages 383 - 391
2 Aug 2024
Mannala GK Rupp M Walter N Youf R Bärtl S Riool M Alt V

Aims

Bacteriophages infect, replicate inside bacteria, and are released from the host through lysis. Here, we evaluate the effects of repetitive doses of the Staphylococcus aureus phage 191219 and gentamicin against haematogenous and early-stage biofilm implant-related infections in Galleria mellonella.

Methods

For the haematogenous infection, G. mellonella larvae were implanted with a Kirschner wire (K-wire), infected with S. aureus, and subsequently phages and/or gentamicin were administered. For the early-stage biofilm implant infection, the K-wires were pre-incubated with S. aureus suspension before implantation. After 24 hours, the larvae received phages and/or gentamicin. In both models, the larvae also received daily doses of phages and/or gentamicin for up to five days. The effect was determined by survival analysis for five days and quantitative culture of bacteria after two days of repetitive doses.


Bone & Joint Open
Vol. 5, Issue 8 | Pages 621 - 627
1 Aug 2024
Walter N Loew T Hinterberger T Alt V Rupp M

Aims. Fracture-related infections (FRIs) are a devastating complication of fracture management. However, the impact of FRIs on mental health remains understudied. The aim of this study was a longitudinal evaluation of patients’ psychological state, and expectations for recovery comparing patients with recurrent FRI to those with primary FRI. Methods. A prospective longitudinal study was conducted at a level 1 trauma centre from January 2020 to December 2022. In total, 56 patients treated for FRI were enrolled. The ICD-10 symptom rating (ISR) and an expectation questionnaire were assessed at five timepoints: preoperatively, one month postoperatively, and at three, six, and 12 months. Results. Recurrent FRI cases consistently exceeded the symptom burden threshold (0.60) in ISR scores at all assessment points. The difference between preoperative-assessed total ISR scores and the 12-month follow-up was not significant in either group, with 0.04 for primary FRI (p = 0.807) and 0.01 for recurrent FRI (p = 0.768). While primary FRI patients showed decreased depression scores post surgery, recurrent FRI cases experienced an increase, reaching a peak at 12 months (1.92 vs 0.94; p < 0.001). Anxiety scores rose for both groups after surgery, notably higher in recurrent FRI cases (1.39 vs 1.02; p < 0.001). Moreover, patients with primary FRI reported lower expectations of returning to normal health at three (1.99 vs 1.11; p < 0.001) and 12 months (2.01 vs 1.33; p = 0.006). Conclusion. The findings demonstrate the significant psychological burden experienced by individuals undergoing treatment for FRI, which is more severe in recurrent FRI. Understanding the psychological dimensions of recurrent FRIs is crucial for comprehensive patient care, and underscores the importance of integrating psychological support into the treatment paradigm for such cases. Cite this article: Bone Jt Open 2024;5(7):621–627


Bone & Joint Research
Vol. 13, Issue 3 | Pages 127 - 135
22 Mar 2024
Puetzler J Vallejo Diaz A Gosheger G Schulze M Arens D Zeiter S Siverino C Richards RG Moriarty TF

Aims. Fracture-related infection (FRI) is commonly classified based on the time of onset of symptoms. Early infections (< two weeks) are treated with debridement, antibiotics, and implant retention (DAIR). For late infections (> ten weeks), guidelines recommend implant removal due to tolerant biofilms. For delayed infections (two to ten weeks), recommendations are unclear. In this study we compared infection clearance and bone healing in early and delayed FRI treated with DAIR in a rabbit model. Methods. Staphylococcus aureus was inoculated into a humeral osteotomy in 17 rabbits after plate osteosynthesis. Infection developed for one week (early group, n = 6) or four weeks (delayed group, n = 6) before DAIR (systemic antibiotics: two weeks, nafcillin + rifampin; four weeks, levofloxacin + rifampin). A control group (n = 5) received revision surgery after four weeks without antibiotics. Bacteriology of humerus, soft-tissue, and implants was performed seven weeks after revision surgery. Bone healing was assessed using a modified radiological union scale in tibial fractures (mRUST). Results. Greater bacterial burden in the early group compared to the delayed and control groups at revision surgery indicates a retraction of the infection from one to four weeks. Infection was cleared in all animals in the early and delayed groups at euthanasia, but not in the control group. Osteotomies healed in the early group, but bone healing was significantly compromised in the delayed and control groups. Conclusion. The duration of the infection from one to four weeks does not impact the success of infection clearance in this model. Bone healing, however, is impaired as the duration of the infection increases. Cite this article: Bone Joint Res 2024;13(3):127–135


Bone & Joint Research
Vol. 13, Issue 3 | Pages 91 - 100
1 Mar 2024
Yamamoto Y Fukui T Sawauchi K Yoshikawa R Takase K Kumabe Y Maruo A Niikura T Kuroda R Oe K

Aims

Continuous local antibiotic perfusion (CLAP) has recently attracted attention as a new drug delivery system for orthopaedic infections. CLAP is a direct continuous infusion of high-concentration gentamicin (1,200 μg/ml) into the bone marrow. As it is a new system, its influence on the bone marrow is unknown. This study aimed to examine the effects of high-concentration antibiotics on human bone tissue-derived cells.

Methods

Cells were isolated from the bone tissue grafts collected from six patients using the Reamer-Irrigator-Aspirator system, and exposed to different gentamicin concentrations. Live cells rate, apoptosis rate, alkaline phosphatase (ALP) activity, expression of osteoblast-related genes, mineralization potential, and restoration of cell viability and ALP activity were examined by in vitro studies.


The Bone & Joint Journal
Vol. 106-B, Issue 1 | Pages 77 - 85
1 Jan 2024
Foster AL Warren J Vallmuur K Jaiprakash A Crawford R Tetsworth K Schuetz MA

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. Cite this article: Bone Joint J 2024;106-B(1):77–85


Bone & Joint Open
Vol. 4, Issue 10 | Pages 801 - 807
23 Oct 2023
Walter N Szymski D Kurtz SM Lowenberg DW Alt V Lau EC Rupp M

Aims. This work aimed at answering the following research questions: 1) What is the rate of mechanical complications, nonunion and infection for head/neck femoral fractures, intertrochanteric fractures, and subtrochanteric fractures in the elderly USA population? and 2) Which factors influence adverse outcomes?. Methods. Proximal femoral fractures occurred between 1 January 2009 and 31 December 2019 were identified from the Medicare Physician Service Records Data Base. The Kaplan-Meier method with Fine and Gray sub-distribution adaptation was used to determine rates for nonunion, infection, and mechanical complications. Semiparametric Cox regression model was applied incorporating 23 measures as covariates to identify risk factors. Results. Union failure occured in 0.89% (95% confidence interval (CI) 0.83 to 0.95) after head/neck fracturs, in 0.92% (95% CI 0.84 to 1.01) after intertrochanteric fracture and in 1.99% (95% CI 1.69 to 2.33) after subtrochanteric fractures within 24 months. A fracture-related infection was more likely to occur after subtrochanteric fractures than after head/neck fractures (1.64% vs 1.59%, hazard ratio (HR) 1.01 (95% CI 0.87 to 1.17); p < 0.001) as well as after intertrochanteric fractures (1.64% vs 1.13%, HR 1.31 (95% CI 1.12 to 1.52); p < 0.001). Anticoagulant use, cerebrovascular disease, a concomitant fracture, diabetes mellitus, hypertension, obesity, open fracture, and rheumatoid disease was identified as risk factors. Mechanical complications after 24 months were most common after head/neck fractures with 3.52% (95% CI 3.41 to 3.64; currently at risk: 48,282). Conclusion. The determination of complication rates for each fracture type can be useful for informed patient-clinician communication. Risk factors for complications could be identified for distinct proximal femur fractures in elderly patients, which are accessible for therapeutical treatment in the management. Cite this article: Bone Jt Open 2023;4(10):801–807


Bone & Joint Open
Vol. 4, Issue 8 | Pages 643 - 651
24 Aug 2023
Langit MB Tay KS Al-Omar HK Barlow G Bates J Chuo CB Muir R Sharma H

Aims

The standard of wide tumour-like resection for chronic osteomyelitis (COM) has been challenged recently by adequate debridement. This paper reviews the evolution of surgical debridement for long bone COM, and presents the outcome of adequate debridement in a tertiary bone infection unit.

Methods

We analyzed the retrospective record review from 2014 to 2020 of patients with long bone COM. All were managed by multidisciplinary infection team (MDT) protocol. Adequate debridement was employed for all cases, and no case of wide resection was included.


Bone & Joint Research
Vol. 12, Issue 8 | Pages 467 - 475
2 Aug 2023
Wu H Sun D Wang S Jia C Shen J Wang X Hou C Xie Z Luo F

Aims

This study was designed to characterize the recurrence incidence and risk factors of antibiotic-loaded cement spacer (ALCS) for definitive bone defect treatment in limb osteomyelitis.

Methods

We included adult patients with limb osteomyelitis who received debridement and ALCS insertion into the bone defect as definitive management between 2013 and 2020 in our clinical centre. The follow-up time was at least two years. Data on patients’ demographics, clinical characteristics, and infection recurrence were retrospectively collected and analyzed.


Bone & Joint Open
Vol. 4, Issue 3 | Pages 146 - 157
7 Mar 2023
Camilleri-Brennan J James S McDaid C Adamson J Jones K O'Carroll G Akhter Z Eltayeb M Sharma H

Aims

Chronic osteomyelitis (COM) of the lower limb in adults can be surgically managed by either limb reconstruction or amputation. This scoping review aims to map the outcomes used in studies surgically managing COM in order to aid future development of a core outcome set.

Methods

A total of 11 databases were searched. A subset of studies published between 1 October 2020 and 1 January 2011 from a larger review mapping research on limb reconstruction and limb amputation for the management of lower limb COM were eligible. All outcomes were extracted and recorded verbatim. Outcomes were grouped and categorized as per the revised Williamson and Clarke taxonomy.


Bone & Joint Research
Vol. 11, Issue 11 | Pages 835 - 842
17 Nov 2022
Wiesli MG Livio F Achermann Y Gautier E Wahl P

Aims

There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO4) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO4 applied locally to treat ODAI.

Methods

A total of 30 operations with ceftriaxone-loaded CaSO4 had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS).


Bone & Joint Research
Vol. 11, Issue 10 | Pages 700 - 714
4 Oct 2022
Li J Cheung W Chow SK Ip M Leung SYS Wong RMY

Aims. Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models. Methods. Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted. Results. A total of 43 studies were included. Animal models used included fracture-related infections (ten studies), periprosthetic joint infections (five studies), spinal infections (three studies), other implant-associated infections, and osteomyelitis. The most common bacteria were Staphylococcus species. Biofilm was most often observed with scanning electron microscopy. The natural history of biofilm revealed that the process of bacteria attachment, proliferation, maturation, and dispersal would take 14 days. For systemic mono-antibiotic therapy, only two of six studies using vancomycin reported significant biofilm reduction, and none reported eradication. Ten studies showed that combined systemic and topical antibiotics are needed to achieve higher biofilm reduction or eradication, and the effect is decreased with delayed treatment. Overall, 13 studies showed promising therapeutic potential with surface coating and antibiotic loading techniques. Conclusion. Combined topical and systemic application of antimicrobial agents effectively reduces biofilm at early stages. Future studies with sustained release of antimicrobial and biofilm-dispersing agents tailored to specific pathogens are warranted to achieve biofilm eradication. Cite this article: Bone Joint Res 2022;11(10):700–714


The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1095 - 1100
1 Sep 2022
McNally MA Ferguson JY Scarborough M Ramsden A Stubbs DA Atkins BL

Aims

Excision of chronic osteomyelitic bone creates a dead space which must be managed to avoid early recurrence of infection. Systemic antibiotics cannot penetrate this space in high concentrations, so local treatment has become an attractive adjunct to surgery. The aim of this study was to present the mid- to long-term results of local treatment with gentamicin in a bioabsorbable ceramic carrier.

Methods

A prospective series of 100 patients with Cierny-Mader Types III and IV chronic ostemyelitis, affecting 105 bones, were treated with a single-stage procedure including debridement, deep tissue sampling, local and systemic antibiotics, stabilization, and immediate skin closure. Chronic osteomyelitis was confirmed using strict diagnostic criteria. The mean follow-up was 6.05 years (4.2 to 8.4).


Bone & Joint Research
Vol. 11, Issue 8 | Pages 541 - 547
17 Aug 2022
Walter N Hierl K Brochhausen C Alt V Rupp M

Aims

This observational cross-sectional study aimed to answer the following questions: 1) how has nonunion incidence developed from 2009 to 2019 in a nationwide cohort; 2) what is the age and sex distribution of nonunions for distinct anatomical nonunion localizations; and 3) how high were the costs for surgical nonunion treatment in a level 1 trauma centre in Germany?

Methods

Data consisting of annual International Classification of Diseases (ICD)-10 diagnosis codes from German medical institutions from 2009 to 2019, provided by the Federal Statistical Office of Germany (Destatis), were analyzed. Nonunion incidence was calculated for anatomical localization, sex, and age groups. Incidence rate ratios (IRRs) were determined and compared with a two-sample z-test. Diagnosis-related group (DRG)-reimbursement and length of hospital stay were retrospectively retrieved for each anatomical localization, considering 210 patients.


Bone & Joint Research
Vol. 11, Issue 6 | Pages 409 - 412
22 Jun 2022
Tsang SJ Ferreira N Simpson AHRW


Bone & Joint Research
Vol. 11, Issue 2 | Pages 112 - 120
16 Feb 2022
Vittrup SØ Hanberg P Knudsen MB Tøstesen SK Kipp JO Hansen J Jørgensen NP Stilling M Bue M

Aims

Prompt and sufficient broad-spectrum empirical antibiotic treatment is key to preventing infection following open tibial fractures. Succeeding co-administration, we dynamically assessed the time for which vancomycin and meropenem concentrations were above relevant epidemiological cut-off (ECOFF) minimal inhibitory concentrations (T > MIC) in tibial compartments for the bacteria most frequently encountered in open fractures. Low and high MIC targets were applied: 1 and 4 µg/ml for vancomycin, and 0.125 and 2 µg/ml for meropenem.

Methods

Eight pigs received a single dose of 1,000 mg vancomycin and 1,000 mg meropenem simultaneously over 100 minutes and 10 minutes, respectively. Microdialysis catheters were placed for sampling over eight hours in tibial cancellous bone, cortical bone, and adjacent subcutaneous adipose tissue. Venous blood samples were collected as references.


Bone & Joint Research
Vol. 11, Issue 2 | Pages 49 - 60
1 Feb 2022
Li J Wong RMY Chung YL Leung SSY Chow SK Ip M Cheung W

Aims. With the ageing population, fragility fractures have become one of the most common conditions. The objective of this study was to investigate whether microbiological outcomes and fracture-healing in osteoporotic bone is worse than normal bone with fracture-related infection (FRI). Methods. A total of 120 six-month-old Sprague-Dawley (SD) rats were randomized to six groups: Sham, sham + infection (Sham-Inf), sham with infection + antibiotics (Sham-Inf-A), ovariectomized (OVX), OVX + infection (OVX-Inf), and OVX + infection + antibiotics (OVX-Inf-A). Open femoral diaphysis fractures with Kirschner wire fixation were performed. Staphylococcus aureus at 4 × 10. 4. colony-forming units (CFU)/ml was inoculated. Rats were euthanized at four and eight weeks post-surgery. Radiography, micro-CT, haematoxylin-eosin, mechanical testing, immunohistochemistry (IHC), gram staining, agar plating, crystal violet staining, and scanning electron microscopy were performed. Results. Agar plating analysis revealed a higher bacterial load in bone (p = 0.002), and gram staining showed higher cortical bone colonization (p = 0.039) in OVX-Inf compared to Sham-Inf. OVX-Inf showed significantly increased callus area (p = 0.013), but decreased high-density bone volume (p = 0.023) compared to Sham-Inf. IHC staining showed a significantly increased expression of TNF-α in OVX-Inf compared to OVX (p = 0.049). Significantly reduced bacterial load on bone (p = 0.001), enhanced ultimate load (p = 0.001), and energy to failure were observed in Sham-Inf-A compared to Sham-Inf (p = 0.028), but not in OVX-Inf-A compared to OVX-Inf. Conclusion. In osteoporotic bone with FRI, infection was more severe with more bone lysis and higher bacterial load, and fracture-healing was further delayed. Systemic antibiotics significantly reduced bacterial load and enhanced callus quality and strength in normal bone with FRI, but not in osteoporotic bone. Cite this article: Bone Joint Res 2022;11(2):49–60


Bone & Joint Research
Vol. 11, Issue 1 | Pages 6 - 7
3 Jan 2022
Walter N Rupp M Baertl S Alt V


Bone & Joint Research
Vol. 10, Issue 11 | Pages 742 - 743
1 Nov 2021
Rupp M Walter N Baertl S Lang S Lowenberg DW Alt V


Bone & Joint Research
Vol. 10, Issue 6 | Pages 351 - 353
1 Jun 2021
Baertl S Metsemakers W Morgenstern M Alt V Richards RG Moriarty TF Young K


Bone & Joint Research
Vol. 10, Issue 5 | Pages 321 - 327
3 May 2021
Walter N Rupp M Hierl K Pfeifer C Kerschbaum M Hinterberger T Alt V

Aims. We aimed to evaluate the long-term impact of fracture-related infection (FRI) on patients’ physical health and psychological wellbeing. For this purpose, quality of life after successful surgical treatment of FRIs of long bones was assessed. Methods. A total of 37 patients treated between November 2009 and March 2019, with achieved eradication of infection and stable bone consolidation after long bone FRI, were included. Quality of life was evaluated with the EuroQol five-dimension questionnaire (EQ-5D) and German Short-Form 36 (SF-36) outcome instruments as well as with an International Classification of Diseases of the World Health Organization (ICD)-10 based symptom rating (ISR) and compared to normative data. Results. With a mean follow-up of 4.19 years (SD 2.7) after the last surgery, the mean SF-36 score was 40.1 (SD 14.6) regarding the physical health component and 48.7 (SD 5.1) regarding the mental health component, compared to German normative values of 48.4 (SD 9.2) (p < 0.001) and 50.9 (SD 8.8) (p = 0.143). The mean EQ-5D index reached 0.76 (SD 0.27) with a mean EQ-5D visual analogue scale (VAS) rating of 65.7 (SD 22.7) compared to reference scores of 0.88 (p < 0.001) and 72.9 (p < 0.001). Mean scores of the ISR did not reveal significant psychological symptom burden, while an individual analysis showed moderate to severe impairments in 21.6% (n = 8) of the patients. Conclusion. Even a mean 4.2 years (SD 2.7) after surgically successful treatment of FRI of long bones, patients report significantly lower quality of life in comparison to normative data. Future clinical studies on FRIs should focus on patient-related outcome measures enabling best possible shared treatment decision-making. Prevention methods and interdisciplinary approaches should be implemented to improve the overall quality of life of FRI patients. Cite this article: Bone Joint Res 2021;10(5):321–327