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The Bone & Joint Journal
Vol. 102-B, Issue 6 Supple A | Pages 3 - 9
1 Jun 2020
Yang J Parvizi J Hansen EN Culvern CN Segreti JC Tan T Hartman CW Sporer SM Della Valle CJ

Aims. The aim of this study was to determine if a three-month course of microorganism-directed oral antibiotics reduces the rate of failure due to further infection following two-stage revision for chronic prosthetic joint infection (PJI) of the hip and knee. Methods. A total of 185 patients undergoing a two-stage revision in seven different centres were prospectively enrolled. Of these patients, 93 were randomized to receive microorganism-directed oral antibiotics for three months following reimplantation; 88 were randomized to receive no antibiotics, and four were withdrawn before randomization. Of the 181 randomized patients, 28 were lost to follow-up, six died before two years follow-up, and five with culture negative infections were excluded. The remaining 142 patients were followed for a mean of 3.3 years (2.0 to 7.6) with failure due to a further infection as the primary endpoint. Patients who were treated with antibiotics were also assessed for their adherence to the medication regime and for side effects to antibiotics. Results. Nine of 72 patients (12.5%) who received antibiotics failed due to further infection compared with 20 of 70 patients (28.6%) who did not receive antibiotics (p = 0.012). Five patients (6.9%) in the treatment group experienced adverse effects related to the administered antibiotics severe enough to warrant discontinuation. Conclusion. This multicentre randomized controlled trial showed that a three-month course of microorganism-directed, oral antibiotics significantly reduced the rate of failure due to further infection following a two-stage revision of total hip or knee arthroplasty for chronic PJI. Cite this article: Bone Joint J 2020;102-B(6 Supple A):3–9


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 55 - 55
1 Dec 2018
Honkanen M Jämsen E Karppelin M Huttunen R Syrjänen J
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Aim. Patients use antibiotics for various reasons before elective joint replacement surgery, but it is not known how common this is. The aim of this study was to investigate patients' use of oral antibiotics before elective joint replacement surgery and how this affects the risk for periprosthetic joint infection (PJI) in a one-year follow-up. Method. Patients with a primary hip or knee replacement performed in a tertiary care hospital between September 2002 and December 2013 were identified (23 171 joint replacements, 10 200 hips and 12 971 knees). Information on oral antibiotics purchased within 90 days before the operation was gathered from a national database. The occurrence of a PJI, identified by prospective infection surveillance, in a one-year follow-up was the primary outcome. The occurrence of any surgical site infection was analyzed as a secondary outcome. The association between antibiotic use and subsequent infection was examined using a multivariable logistic regression model that included information on the operated joint, age, gender, body mass index and patients' chronic diseases (according to medication data). Results. During the one-year follow-up, 158 (0.68%) PJIs were identified. 4 106 (18%) of the joint replacement operations were preceded by one or more courses of oral antibiotics. The most commonly prescribed group of antibiotics was 1st generation cephalosporins. The incidence of PJI for patients with preoperative oral antibiotic use was 0.29% (12/4 106), compared to 0.77% (146/19 065) in patients without preoperative antibiotics. A preoperative oral antibiotic course decreased the risk for subsequent PJI both in the univariate (OR 0.38, 95% CI 0.21 – 0.69) and multivariable model (OR 0.40, 95% CI 0.22–0.73). When superficial infection cases were included in the analysis, preoperative antibiotic use did not affect the overall risk for surgical site infection. Conclusions. The use of oral antibiotics before elective joint replacement surgery is common and is associated with a lower risk for subsequent PJI. Further studies are needed in order to confirm this finding and to evaluate factors affecting this result. Meanwhile, the indiscriminate use of antibiotics before elective joint replacement surgery cannot be recommended, even though the treatment of active infections remains important in the prevention of surgical site infections


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 46 - 46
24 Nov 2023
Fowler M Nocon A Chiu Y Tam K Carli A
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Aim. Prosthetic joint infection (PJI) is a devastating and costly complication of total joint arthroplasty (TJA). Use of extended oral antibiotic prophylaxis (EOAP) has become increasingly popular in the United States following a highly publicized study (Inabathula et al) from a single center demonstrating a significant protective effect (81% reduction) against PJI in ‘high-risk’ patients. However, these results have not been reproduced elsewhere and EOAP use directly conflicts with current antibiotic stewardship efforts. In order to study the role of EOAP in PJI prevention, consensus is needed for what defines ‘high-risk’ patients. The revision TJA (rTJA) population is an appropriate group to study due to having a higher incidence of PJI. The purpose of the current study was to rigorously determine which preoperative conditions described by Inabathula et al. (referred to as Inabathula criteria (IBC)) confer a higher rate of PJI in patients undergoing aseptic rTJA. Method. 2,256 patients that underwent aseptic rTJA at a single high-volume institution between 2016–2022 were retrospectively reviewed. Patient demographics and comorbidities were recorded to determine if they had 1 or more ‘IBC’, a long list of preoperative conditions including autoimmune diseases, active smoking, body mass index (BMI)>35, diabetes mellitus, and chronic kidney disease (CKD). Reoperation for PJI at 90-days and 1-year was recorded. Chi-squared or Fischer's exact tests were calculated to determine the association between preoperative presence/absence of IBC and PJI. Multivariable logistic regressions were conducted to determine if specific comorbidities within the IBC individually conferred an increased PJI risk. Results. 1223 patients (54.2%) had at least one IBC condition. IBC-positive patients were more likely to be female, have an increased ASA score, and higher BMI. IBC-positive patients had a significant increase in PJI risk at both 90-days (relative risk (RR)=2.32, p<0.0001) and 1-year (RR=2.14, p=0.002) versus IBC-negative patients. Within IBC-positive patients, every additional IBC condition conferred a 1.8× odds increase for 90-day PJI (p<0.0001), and 1.76× odds increase in 1-year PJI (p<0.0001). Multivariable logistic regression identified active smoking, BMI>35, CKD, and diabetes mellitus as being independently associated with PJI development (p<0.05). Conclusions. Over half of rTJA patients meet IBC and could be eligible to receive EOAP in the United States. However, the specific presence of active smoking, BMI>35, CKD, and diabetes mellitus appear to be responsible for the increased risk of PJI. Prospective studies investigating EOAP use for patients with these specific conditions are urgently needed to prevent unnecessary antibiotic use


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_3 | Pages 109 - 109
23 Feb 2023
Naufal E Shadbolt C Elsiwy Y Thuraisingam S Lorenzo Y Darby J Babazadeh S Choong P Dowsey M Stevens J
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This study aimed to evaluate the month-to-month prevalence of antibiotic dispensation in the 12 months before and after total knee arthroplasty (TKA) and total hip arthroplasty (THA) and to identify factors associated with antibiotic dispensation in the month immediately following the surgical procedure. In total, 4,115 THAs and TKAs performed between April 2013 and June 2019 from a state-wide arthroplasty referral centre were analysed. A cross-sectional study used data from an institutional arthroplasty registry, which was linked probabilistically to administrative dispensing data from the Australian Pharmaceutical Benefits Scheme. Multivariable logistic regression was carried out to identify patient and surgical risk factors for oral antibiotic dispensation. Oral antibiotics were dispensed in 18.3% of patients following primary TKA and 12.0% of patients following THA in the 30 days following discharge. During the year after discharge, 66.7% of TKA patients and 58.2% of THA patients were dispensed an antibiotic at some point. Patients with poor preoperative health status were more likely to have antibiotics dispensed in the month following THA or TKA. Older age, undergoing TKA rather than THA, obesity, inflammatory arthritis, and experiencing an in-hospital wound-related or other infectious complications were associated with increased antibiotic dispensation in the 30 days following discharge. A high rate of antibiotic dispensation in the 30 days following THA and TKA has been observed. Although resource constraints may limit routine wound review for all patients by a surgeon, a select cohort may benefit from timely specialist review postoperatively. Several risk factors identified in this study may aid in identifying appropriate candidates for such changes to follow-up care


Bone & Joint Open
Vol. 5, Issue 10 | Pages 832 - 836
4 Oct 2024
Kayani B Mancino F Baawa-Ameyaw J Roussot MA Haddad FS

Aims. The outcomes of patients with unexpected positive cultures (UPCs) during revision total hip arthroplasty (THA) and total knee arthroplasty (TKA) remain unknown. The objectives of this study were to establish the prevalence and infection-free implant survival in UPCs during presumed aseptic single-stage revision THA and TKA at mid-term follow-up. Methods. This study included 297 patients undergoing presumed aseptic single-stage revision THA or TKA at a single treatment centre. All patients with at least three UPCs obtained during revision surgery were treated with minimum three months of oral antibiotics following revision surgery. The prevalence of UPCs and causative microorganisms, the recurrence of periprosthetic joint infections (PJIs), and the infection-free implant survival were established at minimum five years’ follow-up (5.1 to 12.3). Results. Of the 297 patients undergoing aseptic revisions, 37 (12.5%) had at least three UPCs obtained during surgery. The UPC cohort included 23 males (62.2%) and 14 females (37.8%), with a mean age of 71.2 years (47 to 82). Comorbidities included smoking (56.8%), hypertension (48.6%), diabetes mellitus (27.0%), and chronic renal impairment (13.5%). The causative microorganisms included Staphylococcus epidermidis (49.6%), Bacillus species (18.9%), Micrococcus species (16.2%), and Cutibacterium acnes (16.2%). None of the study patients with UPCs developed further PJIs or required further surgical intervention during follow-up. Conclusion. The prevalence of UPCs during presumed aseptic revision THA and TKA was 12.5%. The most common causative microorganisms were of low virulence, and included S. epidermidis, Bacillus species, Micrococcus species, and C. acnes. Microorganism-specific antibiotic treatment for minimum three months’ duration of UPCs in presumed aseptic revision arthroplasty was associated with excellent infection-free implant survival at mid-term follow-up. Cite this article: Bone Jt Open 2024;5(10):832–836


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 51 - 51
1 Oct 2022
Azamgarhi T Scobie A Karunaharan N Mepham SO Mack D Vekaria K Crick K Chin SH Warren S
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Aim. There is a lack of data supporting the use of doxycycline as a single agent after removing infected orthopaedic metalwork. We evaluated the efficacy and safety of doxycycline compared with other single antibiotic regimens used at our specialist orthopaedic hospital. Methods. A retrospective observational study including all adult patients diagnosed with an orthopaedic metalwork infection due to staphylococci. All patients were managed with the removal of metalwork, and multiple intraoperative samples were sent for culture, followed by the administration of at least four weeks of oral antibiotics. Antibiotic selection was on the recommendation of an infection consultant. Infection outcome was assessed as the proportion of patients meeting the OVIVA Trial definition of definite failure at follow-up. The probability of definite failure for doxycycline and the alternatives group was estimated using the Kaplan-Meier survival method. All adverse drug reactions (ADR) during treatment were analysed. Results. Seventy-nine orthopaedic metalwork infections were identified between July 2017 and July 2021. Forty-four were prosthetic joints, and 35 were fracture-related metalwork. In 54 cases, the infecting organism was Staphylococcus aureus, and 25 were due to coagulase-negative staphylococci. Forty-four were treated with doxycycline 100mg 12 hourly, and 35 were treated with alternatives (flucloxacillin 1g 6-hourly n=21 and clindamycin 450mg 6-hourly n=14). Overall, 70 patients (88.6%) were infection-free after a median follow-up of 23 months (IQR, 19 – 44). 38 (82.3%) were infection-free in the doxycycline group compared with 32 (91.4%) patients treated with alternatives. Of the failures in the alternatives group, all 3 received flucloxacillin. Survival analysis showed no significant difference in time to treatment failure between doxycycline and alternative antibiotics. Eighteen patients experienced an ADR: 2 nausea, one rash and one vaginal candidiasis due to doxycycline. Four diarrhoea, one reflux, two rashes and one headache due to clindamycin; 1 nausea and five diarrhoea due to flucloxacillin. Four patients required discontinuation therapy, two due to clindamycin and two due to flucloxacillin. Conclusions. In our cohort of patients, doxycycline monotherapy was an effective and well-tolerated oral option for treating staphylococcal infection following debridement and removal of orthopaedic metalwork


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_22 | Pages 27 - 27
1 Dec 2016
Higuera C
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Background. The clinical benefit of chronic suppression with oral antibiotics as a salvage treatment for periprosthetic joint infection is unclear. The purpose of this study was to compare infection-free prosthetic survival rates between patients who received chronic oral antibiotics and those who did not following irrigation and debridement with polyethylene exchange or two-stage revision for periprosthetic joint infection. Methods. We reviewed the records on all irrigation and debridement procedures with polyethylene exchange and two-stage revisions performed at our institution from 1996 to 2010 for hip or knee periprosthetic joint infection. Of 625 patients treated with a total of 655 eligible revisions, ninety-two received chronic oral antibiotics for a minimum of six months and were eligible for inclusion in our study. These patients were compared with a matched cohort (ratio of 1:3) who did not receive chronic oral antibiotics. Results. The five-year infection-free prosthetic survival rate was 68.5% (95% confidence interval = 59.2% to 79.3%) for the antibiotic-suppression group and 41.1% (95% CI = 34.9% to 48.5%) for the non-suppression group (hazard ratio = 0.63, p = 0.008). Stratification by the type of surgery and the infecting organism showed a higher five-year survival rate for the patients in the suppression group who underwent irrigation and debridement with polyethylene exchange (64.7%) compared with those in the non-suppression group who underwent irrigation and debridement with polyethylene exchange (30.4%, p < 0.0001) and a higher five-year survival rate for the patients in the suppression group who had a Staphylococcus aureus infection (57.4%) compared with those in the non-suppression group who had a Staphylococcus aureus infection (40.1%, p = 0.047). Conclusions. Chronic suppression with oral antibiotics increased the infection-free prosthetic survival rate following surgical treatment for periprosthetic joint infection. Patients who underwent irrigation and debridement with polyethylene exchange and those who had a Staphylococcus aureus infection had the greatest benefit


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_16 | Pages 5 - 5
19 Aug 2024
Gevers M Vandeputte F Welters H Corten K
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High doses of intra-articular (IA) antibiotics has been shown to effectively achieve a minimal biofilm eradication concentration which could mitigate the need for removal of infected but well-ingrown cementless components of a total hip arthroplasty (THA). However, there are concerns that percutaneous catheters could lead to multi-resistance or multi-organism peri-prosthetic joint infections (PJI) following single stage THA revisions for PJI. Eighteen single-stage revision procedures were performed for acute (N=9) or chronic (N=9) PJI following a primary (N=12) or revision (N=6) cementless THA. Modular and loosened components were replaced. All well ingrown components were retained. Two Hickmann catheters were placed in the joint space. Along with intravenous antibiotics, IA antibiotics were injected twice a day for two weeks, followed by 3 months of oral antibiotics. Per-operative cultures demonstrated 4 multi-bacterial PJIs. None of the patients developed post-operatively an AB related renal or systemic dysfunction. At a mean follow-up of 38 months [range, 8–72] all patients had normal erythrocyte sedimentation rate and white blood cell count. Four had a slightly elevated C-reactive protein but were completely symptom free and did not show any sign of loosening at a mean of 27 months [range, 16–59]. Addition of high doses of IA antibiotics following single-stage revision for PJI in cementless THA, is an effective and safe treatment option that allows for retention of well-ingrown components. We found no evidence for residual implant infection or catheter induced multi-resistance. Total hip arthroplasty, revision surgery, Periprosthetic Joint Infection, Intra-articular antibiotics. Level 4 (Case series)


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 41 - 41
2 Jan 2024
Singh S Dhar S Kale S
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The management of comminuted metaphyseal fractures is a technical challenge and satisfactory outcomes of such fixations often remain elusive. The small articular fragments and bone loss often make it difficult for standard fixation implants for proper fixation. We developed a novel technique to achieve anatomical reduction in multiple cases of comminuted metaphyseal fractures at different sites by employing the cantilever mechanism with the help of multiple thin Kirschner wires augmented by standard fixation implants. We performed a retrospective study of 10 patients with different metaphyseal fractures complicated by comminution and loss of bone stock. All patients were treated with the help of cantilever mechanism using multiple Kirschner wires augmented by compression plates. All the patients were operated by the same surgeon between November 2020 to March 2021 and followed up till March 2023. Surgical outcomes were evaluated according to the clinical and radiological criteria. A total of 10 patients were included in the study. Since we only included patients with highly unstable and comminuted fractures which were difficult to fix with traditional methods, the number of patients in the study were less. All 10 patients showed satisfactory clinical and radiological union at the end of the study with good range of motion. One of the patient in the study had post-operative wound complication which was managed conservatively with regular dressings and oral antibiotics. Comminuted metaphyseal fractures might differ in pattern and presentation with every patient and there can be no standard treatment for all. The cantilever technique of fracture fixation is based on the principle of cantilever mechanism used in bridges and helps achieve good anatomical reduction and fixation. It provides a decent alternative when standard modes of fixation don't give desired result owing to comminuted nature of fractures and deficiency of bone stock


The Bone & Joint Journal
Vol. 103-B, Issue 6 Supple A | Pages 185 - 190
1 Jun 2021
Kildow BJ Patel SP Otero JE Fehring KA Curtin BM Springer BD Fehring TK

Aims. Debridement, antibiotics, and implant retention (DAIR) remains one option for the treatment of acute periprosthetic joint infection (PJI) despite imperfect success rates. Intraosseous (IO) administration of vancomycin results in significantly increased local bone and tissue concentrations compared to systemic antibiotics alone. The purpose of this study was to evaluate if the addition of a single dose of IO regional antibiotics to our protocol at the time of DAIR would improve outcomes. Methods. A retrospective case series of 35 PJI TKA patients, with a median age of 67 years (interquartile range (IQR) 61 to 75), who underwent DAIR combined with IO vancomycin (500 mg), was performed with minimum 12 months' follow-up. A total of 26 patients with primary implants were treated for acute perioperative or acute haematogenous infections. Additionally, nine patients were treated for chronic infections with components that were considered unresectable. Primary outcome was defined by no reoperations for infection, nor clinical signs or symptoms of PJI. Results. Mean follow-up for acute infection was 16.5 months (12.1 to 24.2) and 15.8 months (12 to 24.8) for chronic infections with unresectable components. Overall non-recurrence rates for acute infection was 92.3% (24/26) but only 44.4% (4/9) for chronic infections with unresectable components. The majority of patients remained on suppressive oral antibiotics. Musculoskeletal Infection Society (MSIS) host grade was a significant indicator of failure (p < 0.001). Conclusion. The addition of IO vancomycin at the time of DAIR was shown to be safe with improved results compared to current literature using standard DAIR without IO antibiotic administration. Use of this technique in chronic infections should be applied with caution. While these results are encouraging, this technique requires longer follow-up before widespread adoption. Cite this article: Bone Joint J 2021;103-B(6 Supple A):185–190


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_2 | Pages 23 - 23
10 Feb 2023
Silva A Walsh T Gray J Platt S
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Swelling following an ankle fracture is commonly believed to preclude surgical fixation, delaying operative treatment to allow the swelling to subside. This is in an attempt to achieve better soft tissue outcomes. We aim to identify whether pre-operative ankle swelling influences postoperative wound complications following ankle fracture surgery. This is a prospective cohort study of 80 patients presenting to a tertiary referral centre with operatively managed malleolar ankle fractures. Ankle swelling was measured visually and then quantitatively using the validated ‘Figure-of-eight’ technique. Follow-up was standardised at 2, 6, and 12 weeks post-operatively. Wound complications, patient co-morbidities, operative time, surgeon experience, and hospital stay duration were recorded. The complication rate was 8.75% (n=7), with 1 deep infection requiring operative intervention and all others resolving with oral antibiotics and wound cares. There was no significant difference in wound complication rates associated with quantitative ankle swelling (p=0.755), visual assessment of ankle swelling (p=0.647), or time to operative intervention (p=0.270). Increasing age (p=0.006) and female gender (p=0.049) had a significantly greater probability of wound complications. However, BMI, smoking status, level of the operating surgeon, and tourniquet time were not significantly different. Visual assessment of ankle swelling had a poor to moderate correlation to ‘Figure-of-eight’ ankle swelling measurements ICC=0.507 (0.325- 0.653). Neither ankle swelling nor time to surgery correlates with an increased risk of postoperative wound complication in surgically treated malleolar ankle fractures. Increasing patient age and female gender had a significantly greater probability of wound infection, irrespective of swelling. Visual assessment of ankle swelling is unreliable for quantifying true ankle swelling. Operative intervention at any time after an ankle fracture, irrespective of swelling, is safe and showed no better or worse soft tissue outcomes than those delayed for swelling


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 143 - 143
11 Apr 2023
Lineham B Pandit H Foster P
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Management of ankle arthritis in young patients is challenging. Although ankle arthrodesis gives consistent pain relief, it leads to loss of function and adjacent joint arthritis. Ankle joint distraction (AJD) has been shown to give good outcomes in adults with osteoarthritis or post-traumatic arthritis. The efficacy in children or young adults and those with juvenile idiopathic arthritis is less well evidenced. Clinical notes and radiographs of all patients (n=6) managed with AJD in one tertiary referral centre were retrospectively reviewed. Radiographs were taken pre-surgery, intra-operatively, 1 month following frame removal and at the last follow up, tibiotalar joint space was assessed using ImageJ software. Measurements were taken at the medial, middle and lateral talar dome using frame components as reference. Radiographic data for patients with a good clinical outcome was compared with those who did not. At time of surgery mean age was 16.1 years (12 – 25 years). Mean follow up was 3.4 years (1.5 – 5.9 years). Indications were juvenile idiopathic arthritis (4) post-traumatic (1) and post-infective arthritis (1). Three patients at last follow up had a good clinical outcome. Two patients required revision to arthrodesis (1.3 and 2.4 years following distraction). One patient had spontaneous fusion. One patient required oral antibiotics for pin site infection. Inter-observer reliability was 95%. Mean joint space was 1.17mm (SD = 0.87mm) pre-operatively which increased to 6.72mm (SD = 2.23mm) at the time of distraction and 2.09mm (SD = 1.14mm) at the time of removal. At one-year follow up, mean joint space was 1.96mm (SD = 1.97mm). Outcomes following AJD in this population are variable although significant benefits were demonstrated for 50% of the patients in this series. Radiographic joint space preoperatively did not appear to be associated with need for arthrodesis. Further research in larger groups of young patients is required


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 26 - 26
24 Nov 2023
Morovic P Benavente LP Karbysheva S Perka C Trampuz A
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Aim. Antibiotics have limited activity in the treatment of multidrug-resistant or chronic biofilm-associated infections, in particular when implants cannot be removed. Lytic bacteriophages can rapidly and selectively kill bacteria, and can be combined with antibiotics. However, clinical experience in patients with surgical infections is limited. We investigated the outcome and safety of local application of bacteriophages in addition to antimicrobial therapy. Method. 8 patients (2 female and 6 male) with complex orthopedic and cardiovascular infections were included, in whom standard treatment was not feasible or impossible. The treatment was performed in agreement with the Article 37 of the Declaration of Helsinki. Commercial or individually prepared bacteriophages were provided by ELIAVA Institute in Tbilisi, Georgia. Bacteriophages were applied during surgery and continued through drains placed during surgery three times per day for the following 5–14 days. Follow-up ranged from 1 to 28 months. Results. Median age was 57 years, range 33–75 years. Two patients were diagnosed with a persistent knee arthrodesis infection, one chronic periprosthetic joint infection (PJI), one cardiovascular implantable electronic device (CIED) infection and four patients with left ventricular assist device (LVAD) infection. The isolated pathogens were multi-drug-resistant Pseudomonas aeruginosa (n=3), methicillin-sensitive Staphylococcus aureus (n=4), methicillin-resistant Staphylococcus aureus (MRSA) (n=1) and methicillin-resistant Staphylococcus epidermidis (MRSE) (n=1). 4 infections were polymicrobial. 5 patients underwent surgical debridement with retention of the implant, 1 patient with PJI underwent the exchange of the prosthesis and one patient with LVAD infection was treated conservatively. All patients received intravenous and oral antibiotic therapy and local application of bacteriophages. At follow-up of 12 month, 5 patients were without signs or symptoms of infection, whereas in one patient with LVAD infection, a relapse was observed with emergence of phage-resistant Pseudomonas aeruginosa. In this patient, no surgical revision was performed. Conclusions. Bacteriophage therapy may represent a valid additional approach, when standard antimicrobial and surgical treatment is not possible or feasible, including in difficult-to-treat infections. In our case series, 5 of 6 patients were infection free after 1 year. Further studies need to address the optimal bacteriophage administration route, concentration, duration of treatment and combination with antimicrobials


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 48 - 48
24 Nov 2023
Dos Santos MV Meller S Perka C Trampuz A Renz N
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Aim. Antimicrobial suppression has shown to significantly improve treatment success of streptococcal periprosthetic joint infection (PJI) compared to 12-week standard antimicrobial therapy, however, only short-term follow-up was investigated. In this study we assessed the impact of suppression on the long-term outcome of streptococcal PJI. Method. Consecutive patients with streptococcal PJI (defined by EBJIS criteria) treated 2009–2021 were prospectively included and allocated into standard and suppression (> 6 months) treatment group. Infection-free survival was assessed with Kaplan-Meier-method and compared between the groups with log rank test. Rates of infection-free, streptococcal infection-free and relapse-free status as well as tolerability of suppression were assessed. Results. Sixty-three PJI episodes (36 knee, 26 hip and one shoulder prosthesis) of patients with a median age of 70 (35–87) years were included. Twenty-seven (43%) were females. Predominant pathogens were S. agalactiae (n=20), S. dysgalactiae (n=18) and S. mitis/oralis (n=13). The main surgical procedures used were two-stage exchange (n=35) and prosthesis retention (n=21). Standard 12-week treatment was administered in 33 patients and suppression in 30 patients, of whom 10 had ongoing suppression and 20 had discontinued antibiotics at time of follow-up. Used oral antibiotics for suppression were amoxicillin (n=29), doxycycline (n=5) and clindamycin (n=2); 6 patients changed antibiotic substance due to side effects. The median follow-up time was 3.9 (0.3–13.3) years. Infection-free survival after 7.5 years was 38% with standard treatment and 62% with suppression (p=0.038). Of all failures, 52% (14/27) were due to streptococci. Suppression was effective in preventing streptococcal infection for the duration of antimicrobial treatment, however, after discontinuation relapses or new infections due to streptococci occurred in 5/20 (25%) patients and infection with any Streptococcus spp. was observed in 9/19 (47%) failures with standard treatment, 5/6 (83%) failures after discontinuing suppression and none during suppression. All failures in patients with ongoing suppression were caused by gram-negative rods. Conclusion. At long-term follow-up, the success rate was superior with suppression compared to standard treatment. Most failures after stopping suppression were caused by streptococci, whereas failures under suppression were caused by aerobic gram-negative rods


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 43 - 43
1 Dec 2017
Alvand A Li HK Rombach I Zambellas R Kendrick B Taylor A Atkins B Bejon P McNally M Scarborough M
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Aim. To assess the influence of route of antibiotic administration on patient-reported outcome measures (PROMS) of individuals treated for hip and knee infections in the OVIVA multi-centre randomised controlled trial. Method. This study was designed to determine whether oral antibiotic therapy is non-inferior to intravenous (IV) therapy when given for the first six weeks of treatment for bone and joint infections. Of the 1054 participants recruited from 26 centres, 462 were treated for periprosthetic or native joint infections of the hip or knee. There were 243 participants in the IV antibiotic cohort and 219 in the oral cohort. Functional outcome was determined at baseline through to one year using the Oxford Hip/Knee Score (OHS/OKS) as joint-specific measures (0 the worse and 48 the best). An adjusted quantile regression model was used to compare functional outcome scores. Results. Of the 214 participants in the hip sub-group, 110 were randomized to IV antibiotics and 104 to oral. Of the 248 participants in the knee cohort, 133 were treated with IV antibiotics and 115 with oral. The OHS/OKS questionnaire response rate was 68%. Baseline median OHS of the hip sub-group was 14 (Interquartile range [IQR]:8–22) for the IV cohort and 12 (IQR:7–22) for the oral cohort. The one-year median OHS was 35 (IQR: 23–44) for the IV cohort and 27 (IQR:16–40) for the oral cohort with no significant difference between cohorts (p=0.181). The baseline median OKS of the knee sub-group, was 14 (IQR:8–23) for the IV cohort and 12 (IQR:8–21) for the oral cohort. The one-year median OKS was 24 (IQR: 15–35) for the IV cohort and 27 (IQR:17–38) for the oral cohort with a statistically significant difference in favour of oral therapy (p=0.036). Conclusions. At one year, there was improvement in functional outcome of patients treated with either IV or oral antibiotics in this RCT. It suggests that joint function generally improved progressively following the start of treatment irrespective of the route of antibiotic therapy. Functional outcome of patients with hip infections was similar irrespective of the route of antibiotic therapy, whereas there was statistically greater improvement in functional outcome of patients with knee infections treated with oral antibiotics. The PROMS findings of this trial support the clinical findings (i.e. infection eradication rates) and suggest that there is no advantage of using prolonged intravenous therapy as compared to oral therapy in the early treatment of infections around the hip and knee joint


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 43 - 43
24 Nov 2023
Rasmussen HC Stilling M Lilleøre JG Petersen E Jørgensen AR Hvistendahl MA Hanberg P Bue M
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Aim. The β-lactam penicillin is often used in the treatment of soft tissue infections and osteomyelitis caused by penicillin susceptible Staphylococcus aureus. Oral antibiotic treatment has been shown to be non-inferior to intravenous (IV) therapy when used during the first 6 weeks in complex orthopedic infections (OVIVA trial). However, the use of oral β-lactams in osteomyelitis treatment remains a topic of debate due to low and variable bioavailability. The aim was to assess the time for which the unbound penicillin concentration exceeded targeted minimum inhibitory concentrations (fT>MIC) in cancellous bone and subcutaneous tissue after IV (penicillin G) and oral (penicillin V) treatment in a porcine microdialysis model. Method. 12 female pigs (75kg) were assigned to standard clinical regimens of either three doses of IV penicillin G (1.2g) or oral penicillin V (0.8g) every 6h over 18h. Microdialysis catheters were placed for sampling in tibial cancellous bone and adjacent subcutaneous tissue. Data was collected in the first dosing interval (0–6h; prophylactic situation) and the third dosing interval (12–18h; assumed steady state). Plasma samples were collected for reference. MIC targets of 0.125μg/mL (Staph. aureus breakpoint), 0.25μg/mL (Strep. Group A, B, C and G breakpoint) and 0.5μg/mL (4xMIC) were applied. Results. For all investigated MIC targets, IV penicillin G resulted in a longer mean fT>MIC in cancellous bone during the first dosing interval, and in both cancellous bone and subcutaneous tissue during the third dosing interval compared to oral penicillin V. Across compartments, mean fT>MIC for IV penicillin G (MIC: 0.125, 0.25 and 0.5μg/mL) were ≥97%, ≥84% and ≥75% during the first dosing interval, and 100%, ≥95% and ≥88%, during the third dosing interval. The mean fT>MIC for oral penicillin V were ≥40%, ≥24% and ≥7% during the first dosing interval, and ≥42%, ≥36% and ≥18% during the third dosing interval. Conclusions. The findings suggest that standard clinical dosing of IV penicillin G provides superior fT>MIC in cancellous bone and subcutaneous tissue compared to oral penicillin V, particularly in the third dosing interval. This emphasizes the importance of appropriate route of administration when applying penicillin treatment. Acknowledgements. Funding was received from The Kirsten and Freddy Johansen Foundation, The Novo Nordisk Foundation, The Beckett Foundation, The Hede Nielsen Family Foundation, King Christian the 10. th. Foundation, The A.P. Møller Foundation, The Dagmar Marshalls Foundation, and The Carl and Ellen Hertz Foundation


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 42 - 42
1 Dec 2017
Scarborough M Li HK Rombach I Zambellas R Walker S Kumin M Lipsky BA Hughes H Bose D Warren S Geue C McMeekin N Woodhouse A Atkins B McNally M Berendt T Angus B Byren I Thwaites G Bejon P
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Aim. Current standard of care in the management of bone and joint infection commonly includes a 4–6 week course of intravenous (IV) antibiotics but there is little evidence to suggest that oral antibiotic therapy results in worse outcomes. The primary objective was to determine whether oral antibiotics are non-inferior to IV antibiotics in this setting. Method. This was a parallel group, randomised (1:1), open label, non-inferiority trial across twenty-six NHS hospitals in the United Kingdom. Eligible patients were adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least six weeks of antibiotics and who had received ≤7 days of IV therapy from the date of definitive surgery (or the start of planned curative treatment in patients managed non-operatively). Participants were randomised to receive either oral or IV antibiotics for the first 6 weeks of therapy. Follow-on oral therapy was permitted in either arm. The primary outcome was the proportion of participants experiencing definitive treatment failure within one year of randomisation. The non-inferiority margin was set at 7.5%. Results. Of 1054 participants randomised (527 to each arm) endpoint data were available for 1015 (96.30%). Definitive treatment failure was identified in 141/1015 (13.89%) participants, 74/506 (14.62%) of those randomised to IV therapy and 67/509 (13.16%) of those randomised to oral therapy. In the intention to treat analysis, the imputed risk difference (PO-IV) for definitive treatment failure was −1.38% (90% CI: −4.94, 2.19), thus meeting the non-inferiority criterion (i.e. the upper limit of 95%CI being <7.5%). A complete cases analysis, a per-protocol analysis and sensitivity analyses for missing data confirmed this result. With the exception of intravenous catheter complications, there was no significant difference between the two arms in the incidence of serious adverse events (SAEs). Health economic analysis suggests that the non-surgical treatment costs over one year for patients randomised to oral therapy were approximately £2,700 less than those of IV therapy. Conclusions. Oral antibiotic therapy is non-inferior to IV therapy when used during the first six weeks in the treatment for bone and joint infection, as assessed by definitive treatment failure within one year of randomisation. These findings challenge the current standard of care and provide an opportunity to realise significant benefits for patients, antimicrobial stewardship and the health economy. Funding. The OVIVA study was funded by the National Institute for Health Research Health Technology Assessment programme (Project number 11/36/29)


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_5 | Pages 43 - 43
1 Apr 2022
Clesham K Storme J Donnelly T Wade A Meleady E Green C
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Introduction. Hip arthrodiastasis for paediatric hip conditions such as Perthes disease is growing in popularity. Intended merits include halting the collapse of the femoral head and maintaining sphericity by minimising the joint reaction force. This can also be applied to protecting hip reconstruction following treatment of hip dysplasia. Our aim was to assess functional outcomes and complications in a cohort of paediatric patients. Materials and Methods. A retrospective single-surgeon cohort study was performed in a University teaching hospital from 2018–2021. Follow-up was performed via telephone interview and review of patient records. Complications, time in frame and functional scores using the WOMAC hip score were recorded. Results. Following review, 26 procedures were identified in 24 patients. Indications included 16 cases of Perthes disease, 4 following slipper upper femoral epiphysis, 3 avascular necrosis, and single cases following infection, dysplasia and a bone cyst. Pre-treatment WOMAC scores averaged 53.9, improving to 88.5 post-removal. Pin site infections were encountered in 11 patients, all treated with oral antibiotics. Two patients required early removal of frame due to pin loosening. Average time in frame was 3.9 months. Conclusions. This series displays how hip arthrodiastasis can be used to manage paediatric hip conditions. Complex reconstructions may be required in patients with severe deformity following perthes disease, DDH or SUFE. The use of arthrodiastasis in these patients aims to protect the reconstruction and potentially improve outcomes. A dedicated team of specialist nurses, physiotherapists and psychologists are crucial to the treatment program


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_1 | Pages 19 - 19
1 Jan 2018
Cordero-Ampuero J
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To analyze the evolution of “Tsukayama type IV” infections (unexpected positive intraoperative cultures in hip arthroplasty -THA- exchange because of supposedly mechanical failure) treated with an extended protocol of combined oral antibiotics. Prospective cohort: 14 patients, 66.9+/−10.9 years (40–85), 11 males (78.6%). Eleven suffered isolated cup exchange: 6/14 first cup-exchange, 4/14 second (one with a 1st Slooff impaction-grafting reconstruction and 2 with a 2nd Slooff reconstruction), 1/14 third cup-exchange. Two were operated of isolated stem exchange. One patient received a complete exchange. Cultures identified 10 epidermidis (5 methicillin-resistant -MR-), 4 aureus (3 MR), 1 Propionibacterium, 1 Enterococcus, 1 Escherichia, 1 Streptococcus, 1 Corynebacterium, and 1 Ruminococcus. Patients received 2 oral combined intracellular and biofilm-effective antibiotics for 6 months: ciprofloxacin (8 patients), rifampin (6), amoxicillin-clavulanic (3), levofloxacin (2), clindamycin (3), trimethoprim-sulfamethoxazole (2), fosfomicin (2). Follow-up: 4.5+/−4.3 years (1–14). Healing: absence of clinical, serological and radiographic signs of infection along all followup. Infection reappeared in 1/14 patients (7.1%) with pain, distance limitation and elevated ESR&CRP; patient rejected surgery and was treated with a 2nd cycle of oral antibiotics, disappearing symptoms and serological abnormality along the following 7 years. The other 13 cases maintained normal ESR&CRP along follow-up. At the end of follow-up, 4/14 hips remain asymptomatic and with no limitation of function, 11/14 present no pain, 10/14 walk over 1Km without support, 1/11 uses a cane, 1/14 two crutches, and 2/14 a walker. In conclusión, oral combined antibiotics may be a useful alternative therapy for Tsukayama type IV hip arthroplasty infections


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_4 | Pages 22 - 22
1 Apr 2022
Lewis C Baker M Brooke B Metcalf B McWilliams G Sidhom S
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Constrained acetabular inserts provide a solution for both complex primary and revision hip arthroplasty, but there have been ongoing concerns for high risk of failure and their longevity. The Stryker® Trident acetabular insert is pre-assembled with its constrained ring. We believe this to be the largest series of constrained acetabular inserts with a minimum of 5 year follow-up. We retrospectively reviewed all Stryker® Trident ‘All-Poly’ constrained acetabular inserts cemented into bone in our unit between 2008 and 2016. We collated demographic details and reviewed all patients’ radiographs and clinical notes. Indications for surgery, latest Oxford Hip Scores (OHS) and clinical and radiographic complications were identified. 117 consecutive Stryker® Trident ‘All-Poly’ constrained inserts were cemented into bone in 115 patients during the study period with a mean age of 80 (47–97). Most common indications for surgery were recurrent dislocation (47), complex primary arthroplasty (23), revision arthroplasty (19) and failed hemiarthroplasty (12). 41 patients required revision of the acetabular component only. Follow-up was a minimum of 5 years (mean 8.6, range 5–13). There were three 30-day mortalities and six 1-year mortalities. The mean latest OHS was 37 (24–45). Four cups failed in three patients, one at the cement-bone interface, two at the cement-prosthesis interface and one at the bipolar interface. These were treated conservatively in three patient and with excision arthroplasty in one patient. There were four peri-prosthetic fractures, one Vancouver C distal femur fracture treated conservatively and three Vancouver B1 fractures, two treated conservatively and one treated with open reduction internal fixation. There was breakage of one constrained ring with no adverse effects and one superficial wound infection requiring oral antibiotics only. This series demonstrated that despite the elderly and complex nature of these patients’ clinical situations, constrained acetabular inserts offer a useful and pragmatic solution, with relatively low complications, including in our series a cup failure rate of 3% and peri-prosthetic fracture rate of 3%