Aim. Debridement, Antibiotics, Irrigation, and implant Retention (DAIR) is a surgical treatment protocol suitable for some patients with fracture related infection (FRI). Clinically relevant pre-clinical models of DAIR are scarce and none have been developed in large animals. Therefore, this project aimed to develop a large animal model for FRI including a DAIR approach and compare outcomes after 2 or 5 weeks of infection. Method. Swiss Alpine sheep (n=8), (2–6 years, 50–80 kg) were included in this study. This study was approved by cantonal Ethical authorities in Chur, Switzerland. A 2 mm osteotomy was created in the tibia and fixed with a 10-hole 5.5 mm steel plate. Subsequently, 2.5 mL of saline solution containing 10. 6. CFU/mL of Staphylococcus aureus MSSA (ATCC 25923) was added over the plate. Sheep were observed for 2 (n=3) or 5 weeks (n=5) until revision surgery, during which visibly infected or necrotic tissues were removed, and the wound flushed with saline. All samples were collected for bacterial quantification. After revision surgery, the sheep were treated systemically for 2 weeks with flucloxacillin and for 4 weeks with rifampicin and cotrimoxazole. After 2 further weeks off antibiotics, the animals were euthanized. Bacteriological culture was performed at the end of the study. Bone cores were isolated from the osteotomy site and processed for Giemsa & Eosin and Brown and Brenn staining. A radiographical examination was performed every second week. Results. Bacteriological evaluation of the retrieved samples during revision surgery showed no significant difference between the 2 vs 5 weeks infection periods in term of total CFU counts. At the end of the study, radiographical examination showed callus formation over the osteotomy site in both groups, although the osteotomy was not completely healed in either group. At euthanasia, the 2 weeks infection group showed a higher soft tissue burden compared to the 5 weeks group, whereby the infection in the 5 weeks group was primarily located in the bone and bone marrow. Conclusions. The large animal model of FRI and DAIR was successfully established. Bacteriological outcomes highlight that the increasing duration of the infection does not change the outcome but the location of the infection from a predominantly soft tissue infection to a deeper bone and intramedullary (IM) channel infection. The debridement of the IM channel could potentially reduce the infection burden by eliminating those bacteria not easily reached by systemic antibiotics, though is not practical using conventional techniques

Abstract. Background. Infections are rare and poorly studied complications of unicompartmental knee athroplasty (UKA) surgery. They are significantly less common compared to infections after total knee arthroplasties (TKAs). Optimal management of periprosthetic joint infections (PJIs) after a UKA is not clearly defined in the literature. We present the results of a multicentre retrospective series of UKA PJIs treated with Debridement, Antibiotics and Implant Retention (DAIR). Methodology. Patients presenting between January 2016 and December 2019 with early UKA infection were identified at three specialist centres using the Musculoskeletal Infection Society (MSIS) criteria. All patients underwent a standardized treatment protocol consisting of the DAIR procedure and antibiotic therapy comprising two weeks of intravenous (IV) antibiotics followed by six weeks of oral therapy. The main outcome measure was overall survivorship free from reoperation for infection. Results. A total of 3225 UKAs (2793 (86.2%) medial and 432 (13.8%) lateral UKAs) were performed between January 2016 and December 2019. Nineteen patients had early infections necessitating DAIR. The mean follow-up period was 32.5 months. DAIR showed an overall survivorship free from septic reoperation of 84.2%, with an overall survivorship free from all-cause reoperation of 78.95%. The most common bacteria were Coagulase-negative Staphylococci, Staphylococcus aureus and Group B Streptococci. Three patients required a second DAIR procedure but remained free from re-infection at follow-up obviating the need for more demanding, staged revision surgery. Conclusions. In infected UKAs, the DAIR procedure produces a high rate of success, with a high survivorship of the implant

Introduction. Debridement, Antibiotics and Implant Retention (DAIR) remains the norm for the treatment of acute periprosthetic joint infection (PJI) despite less than optimal success rates. Intraosseous (IO) administration of vancomycin has been shown to have significantly increased local bone and tissue concentrations compared to systemic antibiotics, with lower systemic antibiotic levels compared to intravenous. The purpose of this study was to evaluate if the addition of IO regional antibiotics to our protocol at the time of DAIR would improve outcomes. Methods. A retrospective review of 35 PJI TKA patients who underwent DAIR combined with IO vancomycin (500mg) was performed with minimum 12-month follow-up. 26 patients were treated for acute perioperative or acute hematogenous infections following primary TKA. Nine were treated for chronic infections with components that were considered unresectable (ie) constructs with ingrown cones, sleeves, or long cemented stems in elderly comorbid patients. Primary outcome was defined by no reoperations for infection nor clinical signs or symptoms of PJI. Results. The average follow up for acute infection was 16.5 months (range 12.1–24.2) and 15.8 months (range 12–24.8) for chronic infections with unresectable components. Overall eradication rates for acute infection was 93.1% while only 44.4% for chronic infections with unresectable components. MSIS host grade was a significant indicator of failure (p<0.001). Conclusion. The use of IO vancomycin at the time of DAIR yielded improved results compared to standard irrigation and debridement in acute periprosthetic infections. Its use in chronic infections should remain cautious. While these results are encouraging, this technique requires longer follow-up before widespread adoption

Aims. Fracture-Related Infection (FRI) is a severe complication caused by microbial infection of bone. It is imperative to gain more insight into the potentials and limitations of Debridement, Antibiotics and Implant Retention (DAIR) to improve future FRI treatment. The aims of this study were to: 1) determine how time to surgery affects the success rate of DAIR procedures of the lower leg performed within 12 weeks after the initial fracture fixation operation and 2) evaluate whether appropriate systemic antimicrobial therapy affects the success rate of a DAIR procedure. Methods. This multinational retrospective cohort study included patients of at least 18-years of age who developed an FRI of the lower leg within 12 weeks after the initial fracture fixation operation, between January 1st 2015 to July 1st 2020. DAIR success was defined by the absence of recurrence of infection, preservation of the affected limb and retention of implants during the initial treatment. The antimicrobial regimen was considered appropriate if the pathogen(s) was susceptible to the given treatment at the correct dose as per guideline. Logistic regression modelling was used to assess factors that could contribute to the DAIR success rate. Results. A total of 120 patients were included, of whom 70 DAIR patients and 50 non-DAIR patients. Within a median follow-up of 35.5 months, 21.4% of DAIR patients developed a recurrent FRI compared to 12.0% of non-DAIR patients. The DAIR procedure was successful in 45 patients (64.3%). According to the Willenegger and Roth classification, DAIR success was achieved in 66.7% (n=16/24) of patients with an early infection (<2 weeks), 64.4% (n=29/45) of patients with a delayed infection (2–10 weeks) and 0.0% (0/1) of patients with a late infection (>10 weeks). Univariate analysis showed that the duration of infection was not associated with DAIR success in this cohort (p=0.136; OR: 0.977; 95%CI: [0.947–1.007]). However, an appropriate antimicrobial regimen was associated with success of DAIR (p=0.029; OR: 3.231; 95%CI: [1.138–9.506]). Conclusions. Although the results should be interpreted with caution, an increased duration of infection was not associated with a decreased success rate of a DAIR procedure in patients with FRI of the lower leg. The results of this study highlight the multifactorial contribution to the success of a DAIR procedure and emphasize the importance of adequate antimicrobial treatment. Therefore, time to surgery should not be the only key-factor when considering a DAIR procedure to treat FRI

INTRODUCTION. Surgical site infections (SSI) in orthopaedics are a major source of postoperative morbidity. Although perioperative antibiotic prophylaxis is a common practice, orthopaedic infections are still high in numbers, due to the increasing use of osteosynthesis material and implants. Implants are avascular and can be easily colonized with biofilm-producing germs. For both, effective prophylaxis and treatment of orthopaedic infections, the right choice of the antibiotics used, the mode of application (only systemic or systemic & local), the timing, dosage and the duration of antibiotics are of extremely high importance. Their inappropriate use does not only lead to failures in prevention or treatment of infections, but may also promote microbial resistance development and may cause serious side effects for the patients. SELECTION & USE OF ANTIBIOTICS. Prophylaxis. Broad-spectrum prophylactic antibiotics should help to eliminate the germs before they start to colonize the implant. For prophylactic purposes the recently published AAOS guidelines [1] recommend the use of cephalosporins, such as cefazolin or cefuroxim, administered within one hour prior to surgery. In cases of suspected beta-lactam allergy, clindamycin or vancomycin can be used. The latter one is also recommended in cases of MRSA colonisation. Due to extended infusion times, vancomycin should be started within two hours prior to incision. In cases of blood loss or long op duration, antibiotic administration must be repeated (e.g. cefazolin, every 2–5 hrs; vancomycin, every 6–12 hrs). There is no evidence of a benefit of continued antibiotic administration past 24 hrs of end of surgery [2]. Treatment. In cases of established infections, use of antibiotics is only considered as an adjuvant to surgical debridement. Typically, the choice of the appropriate antibiotic depends on the bacteria, its antibiotic sensitivity profile and the health state of the patient. A combination of rifampicin & a quinolone (or rifampicin & vancomycin in cases of MRSA) for at least 2 wks up to several months has shown good results [3]. In chronic infections with biofilm involvement, all foreign material must be removed and locally delivered antibiotics via e.g. PMMA as carrier (spacers, PMMA-chains) are of additional clinical benefit. ROLE OF LOCAL ANTIBIOTICS. There is general consensus that PMMA chains or PMMA spacers loaded with specific antibiotics support the eradication of bone and joint infections, because of the high local concentrations achieved. The exact treatment time is, however, variable, ranging from few weeks up to several months. Only small amounts of these local antibiotics are systemically detectable and do not represent a major risk for side effects. Still a matter of debate is the benefit of antibiotic impregnated PMMA for infection prophylaxis. Although common practice in Europe, its routine use in e.g. primary arthroplasty is still discussed in other world regions. Meanwhile, evidence accumulates that joint infection rates are, indeed, lower, if antibiotic loaded bone cement with high initial release rates is routinely used in arthroplasty. 4.

OBJECTIVE. Debridement, Antibiotics and Implant Retention (DAIR) procedure is well established for Prosthetic Joint Infection (PJI) in acute setting after total hip and knee replacements. We present our perspective of DAIR in a relatively a small cohort following hip and knee replacements in a District General Hospital (DGH) in United Kingdom, where we delivered comparable results to leading tertiary centers in short to mid-term followup. METHODS. We undertook a retrospective study involving 14 patients, who underwent DAIR in our DGH between August 2012 and December 2015. Patient cohort included primary, complex primary and revision hip and knee replacements. Multiple samples were taken intraoperatively for cultures and histology. mMicrobiological support was provided by a microbiologist with interest in musculoskeletal infections. RESULTS. 14 patients [9 males, 5 females; age 62–78 years (Mean 70.7); BMI 22–44.2 (Mean 33.8)] with multiple comorbidities underwent DAIR procedure within 3 weeks of onset of symptoms, (although the time from index surgery ranged from 15 days to 58 months). Patient selection was made by two Hip surgeons. 12 out of 14 grew positive cultures with two growing Vancomycin resistant Enterococcus. IV antibiotics were stated after samples intraoperatively and continued in six patients after discharge using (OPAT), while 8 were discharged with oral antibiotics. One patient died in immediate post operative period due to generalised sepsis. Another patient died of myocardial infarction 2 years after DAIR. 12 (85.7%) patients are doing well with regular followup (Mean 20 months) in clinics. CONCLUSIONS. With good patient selection, DAIR is a far simpler solution and a safe and reproducible surgical option in PJI in hip and knee replacements compared to one or two stage revisions with the implications. But published Data in contemporary literature is predominantly from specialized centers. Our small series provides a perspective of early to mid term results of DAIR from a DGH

Debridement Antibiotics Implant Retention (DAIR) is a recognised procedure in the management of acute prosthetic joint infection (PJI). We present an experience of DAIR following hip and knee replacements in a District General Hospital. A retrospective review of 14 patients who underwent DAIR procedures between August 2012 and December 1015 were collated. The cohort included primary, complex primary and revision hip and knee replacements. All patients received multidisciplinary care with surgery performed by one of two arthroplasty surgeons. 9 males and 5 females with age 62 − 78 years (Mean 70.7) and BMI 22–44.2 (Mean 33.8) with various co-morbidities underwent DAIR. Surgical criteria required DAIR to be performed within 3 weeks of the onset of symptoms of infection. The time from index surgery however ranged from 15 days to 58 months. 12 of 14 grew positive cultures including two growing Vancomycin Resistant Enterococcus. Intravenous antibiotics were commenced after intraoperative samples and tailored OPAT. Antibiotic schedule varied from six weeks to eight months. 12 (85.7%) patients remain under follow up. Mean follow is 20 months (RANGE 6months-3years10months) with no recurrence of infection or reoperation. With appropriate patient selection, DAIR is safe and reproducible surgical option in PJI in hip and knee replacements, avoiding the implications of a one or two stage revision. Published Data in contemporary literature is predominantly from specialised centres. Our small series provides a perspective of early to mid term results of DAIR to DGH. Interestingly each procedure is categorised as a failed implant on the National Joint Register

INTRODUCTION. Deep infection is a potentially catastrophic complication of joint replacement surgery. Early intervention in suspected prosthetic joint infection in the form of aggressive Debridement and targeted Antibiotics can lead to successful Implant Retention (DAIR). In our centre, we adopt an aggressive approach to suspected prosthetic joint infection, working in a multi-disciplinary team with microbiologists and an infection surveillance team to identify and treat suspected infected cases at the earliest opportunity. OBJECTIVES. To evaluate the efficacy of the treatment of prosthetic joint infection with DAIR. METHODS. All cases of primary prosthetic joint infection between March 2009 and September 2011 were identified. Data was retrospectively collected from root cause analysis data, patient records and hospital electronic results systems. RESULTS. 48 cases of confirmed deep infection were identified from a total of 5037 primary joint replacements. Mean age was 67.3. The mean time between index procedure and return to theatre for debridement was 18 days. 10 patients underwent a second debridement and 3 returned to theatre for a third debridement. Mean total duration of antibiotic treatment was 10.5 weeks with mean duration of intravenous antibiotics 2.7 weeks. There were two early and three late failures on antibiotics. These went on to have successful two stage revision. The mean interval to debridement in failed cases was 15 days. The primary implant was successfully retained in 90% of cases (n=43) at a mean follow up of 30 months. CONCLUSION. DAIR is an effective means of treating early prosthetic joint infection in a multi-disciplinary setting

Introduction: The effect of different temperatures to antibiotics is unknown. What is the dose-response curve of bone chips impregnated with different kinds of antibiotics?

Material and Methods: Five different antibiotic pills and solutions (cefazolin, clindamycin, linezolid, oxacillin, vancomycin) were stored at −80°C, −20°C, 4°C, 20°C and 37°C. Also, bone chips were impregnated with cefazolin and vancomycin solution and were stored at −80°C and −20°C. After 1 month, 6 months and 1 year, reaction of the antibiotics to Staphylococcus epidermidis was measured using an inoculated iso-agar. Activity of the antibiotics was measured as the diameter of the Staphylococcus epidermidis-free zone.

Also, five cefazolin and vancomycin solutions were used to impregnate bone chips and to make dose-response curves. Furthermore, 1 gram bone chips was impregnated with 5ml cefazolin or 5ml vancomycin solution.

Results: A decrease of the diameter free zone Staphylococcus epidermidis was seen when oxacillin and cefazolin solutions were stored at 37°C for 1 month and when vancomycin was stored for 6 months (37°C). Also, when cefazolin and oxacillin solutions were stored at 20°C, a decrease was noticed. The storage of other antibiotic solutions, pills and bone/antibiotics composite showed no differences in reaction. Dose-response curves show that with increasing antibiotic quantity, diameter free zone increases according to a logarithmic function.

Conclusion and discussion: With the dose-response curve the optimal concentration(s) for local application can be determined. It gives the opportunity to determine the amount of antibiotics present in the patient locally. Freezing of antibiotics does not affect the activity of the investigated antibiotics.

Introduction: Intraoperative tissue culture remains the “gold standard” in diagnosing periprosthetic infection (PPI). However, an organism is not always cultured and this has been attributed to the fact that preoperative antibiotics were administered. This study intends to examine if preoperative antibiotics prevent isolation of intraoperative organisms. Methods: 91 total joint arthroplasty patients diagnosed with PPI during (1999–2005) and who had positive aspiration culture were included in the study. All intravenous antibiotics that were given to the patient within seven days of surgery were documented. The total number of positive intraoperative fluid and tissue samples of patients who did and did not receive antibiotics was calculated. Susceptibility of the organism(s) to antibiotics was determined by antibiogram of the preoperative and intraoperative culture. Results: 60 out of 91 patients received preoperative antibiotics within seven days of surgery. Antibiotics prevented isolation of an intraoperative organism in 6 out of the 60 (10%) cases. All of the 31 patients who did not receive any preoperative antibiotics had positive intraoperative cultures. Chi-square analysis revealed no significant difference between giving preoperative antibiotics within 7 days and isolating an intraoperative organism (p=0.068). Giving antibiotics that specifically targets the culprit organism did not significantly affect the fluid (p=0.585) or tissue culture yield (p=0.152) either. Discussion: Although, giving preoperative antibiotics can prevent isolation of intraoperative organisms in 10% of cases, this is not statistically or clinically significant in patients with positive aspiration cultures because the organism is known beforehand. However, it is clinically and medicolegally relevant to withhold antibiotics in patients with negative aspiration cultures since the postoperative treatment antibiotic is tailored according to the organism cultured

Aim

The duration of systemic antibiotic therapy following first-stage surgery is contentious. Our Institution's philosophy is to perform an aggressive debridement, use high concentration targeted antibiotics through cement beads and systemic prophylactic antibiotics alone. In the presence of significant soft tissue infection or microbiological diagnostic uncertainty; systemic antibiotics may be prescribed for 5 days whilst awaiting tissue culture results. The aim of this study was to assess the success of our philosophy in the management of PJI of the hip using our two-stage protocol.

Aim. Debridement Antibiotics and Implant Retention(DAIR) is a procedure to treat a periprosthetic joint infection(PJI) after Total Hip Arthroplasty(THA) or Total Knee Arthroplasty(TKA). The timing between the primary procedure and the DAIR is likely a determinant for its successful outcome. There are few retrospective studies correlating timing of a DAIR with success (1,2). However, the optimal timing of a DAIR and the chance of success still remains unclear. We aimed to assess the risk of re-revision within one year after a DAIR procedure and to evaluate the timing of the DAIR in primary THA and TKA. An estimation of the chance of a successful DAIR will help clinicians and patients in their decision-making process in case of an acute postoperative PJI. Method. We used data from the Dutch Arthroplasty Register(LROI) and selected all primary THA and TKA in the period 2007–2016 who underwent a DAIR within 12 weeks after primary procedure. A DAIR was defined as a revision for infection in which only modular parts were exchanged. A DAIR was successful if not followed by a re-revision within 1 year after DAIR. The analyses were separated for THA and TKA procedures. Results. 207 DAIRs were performed <4 weeks after THA of which 41(20%) received a re-revision within 1 year; 87 DAIRs were performed between 4–8 weeks of which 15(17%) were re-revised and 11 DAIRs were performed >8 weeks and 2(18%) received a re-revision. 126 DAIRs were performed <4 weeks after TKA of which 27(21%) received a re-revision within 1 year; 68 DAIRs were performed between 4–8 weeks of which 14(21%) were re-revised and 15 DAIRs were performed >8 weeks and 3(20%) received a re-revision. Conclusions. There was no difference in 1-year re-revision rate after a DAIR procedure by timing of DAIR procedure for total hip and knee arthroplasty based on Dutch registry data

The aim of this study was to compare the clinical and radiographic results of a interlocking nail with a releasing antibiotic core of PMMA with a standard interlocking nail for the treatment of open fractures of the tibia. Prospective, controlled trial, randomized by surgeon preference, including 30 patients with open fractures of the tibia. Patients were divided into two groups according to the treatment method: Group I (STD), consisting of 14 patients treated by delayed interlocking standard nailing, after an antibiotic treatment and bed rest. Group II (SAFE) comprising 16 patients treated with a interlocking intramedullary nail with a core of PMMA cement with antibiotics, 5 of which had a temporary stabilization with an external fixator. Antibiotics chosen to impregnate the SAFE nail in cases without prior bacteriology were vancomycin (2gr) and flucloxacillin (2gr). There were no statistically significant differences between groups with respect to demographic data (age, gender), type of fracture and degree of exposure (p>0,05). The mean follow-up was 2.4 years (5 months to 4 years) for the STD group and 2.1 years (4 months to 3 years) for the SAFE group. 15 of the 30 patients had positive bacteriology, including 13 cases with aggressive agents predominating Enterobacter, Enterococcus, Pseudomonas and MSSA groups. The infection rate after nailing was 43% (6/14 patients) for the STD group and 6% (1/16 cases) to the SAFE group, a statistically significant difference (p=0.02). The mean time to union was 7.5 months (3 months to 1.5 years) for the STD group and 4.5 months (2 months to 8.5 months) for the SAFE group, a statistically significant difference (p=0.02). The complication rate was 64% (9/14) in the STD group and 25% (4/16) for the SAFE, including a infection rate of 43% in the STD group and 6% in the SAFE group, a statistically significant difference (p=0.03). We observed that the open fractures of the tibia treated with SAFE nails presented a statistically significant lower rate of infection, faster consolidation and fewer complications compared with treatment with deferred standard nails. Compared to similar devices available on the market, it has the advantage of allowing selection of the type and dose of antibiotics, it allows fixation with screws of intermediate bone segments, it shorten the period of hospitalization and treatment time, reducing the costs associated with the treatment of this pathology

The duration of systemic antibiotics following first-stage surgery is contentious. Our Institution's philosophy is to perform an aggressive debridement, high concentration of targeted antibiotics through cement beads and systemic prophylactic antibiotics alone. In the presence of significant soft tissue infection or microbiological diagnostic uncertainty; systemic antibiotics may be prescribed for 5 days whilst awaiting tissue culture results. The aim of this study was to assess the success of our philosophy for two-stage hip revision.

A retrospective review of our Institution's prospective database was performed to identify all intended two-stage hip revision procedures for PJI. All patients had a confirmed PJI as per MSIS 2013 criteria, minimum 5-years follow up and outcomes according to the MSIS working group outcome-reporting tool; then grouped into “successful” or “unsuccessful” (suppressive antibiotics, further revision for infection, death within 1 year).

383 intended two-stage hip revisions were identified; of which 299 met our inclusion criteria, in 289 patients (6 repeat ipsilateral two-stage, 4 bilateral two-stage). Median follow up was 10.7 years (IQR 6.3 – 15.0). 258 (86%) patients proceeded to 2^nd stage surgery. 91% success rate was observed for those patients who underwent reimplantation, although dropping to 86% when including the patients who did not proceed to second stage. The median duration of post-operative systemic antibiotics was 5 days (IQR 5–9). No significant difference was observed in patients who received either; < / = 48 hours (86%; n=70) compared to > 48 hours antibiotics (86%; n=229; p=0.96) or </= 5 days of antibiotics (88%; n=202) compared to > 5 days antibiotics (82%; p=0.38). A significant majority had gram-positive (88%) infection with 30% being polymicrobial. Greater success rates were observed with two-stage exchange or gram-positive PJI (86%); than for gram-negative PJI (81%) and polymicrobial infection (74%) (p=0.36). Fungal PJI was observed to have a significantly reduced rate of success (n=3; 33%; p=0.03).

Aggressive surgical debridement with high concentration, targeted local antibiotic delivery at time of first stage to manage PJI of the hip provides a high rate of success, responsible antibiotic stewardship and reduced hospital costs.

Introduction

The management of open long bone fractures is well described and has been standardised through a number of well-established guidelines. However, there is no consensus regarding the application of local antibiotics into the open fracture site as a means of reducing infection rates.

Background

Fracture-related infection (FRI) is treated by adequate debridement, lavage, fracture stabilization (if indicated), adequate soft tissue coverage and systemic antimicrobial therapy. Additional administration of local antibiotics (LA), placed directly in the surgical field, is thought to be beneficial for successful eradication of infection.

Aim: Antibiotics are currently used during fracture healing for prevention or treatment of infection. Quinolones are well known to delay fracture healing, but little is known about other antibiotics. Cefazolin is the most commonly used drug for antibiotic prophylaxis, but many centres use cefuroxime. When allergy to cephalosporins is present, current recommendations include clindamicin or vancomicin. The purpose of this study is to know if other commonly used antibiotics can delay fracture healing. Methods: 100 male 3-months-old Wistar rats were used. After anaesthesia with ketolar, a closed fracture in the middle third of the femur was carried out. Rats were divided in five groups (20 rats each): one receiving cefazolin (a first generation cephalosporin, CZ), other receiving cefuroxime (a second generation cephalosporine, CF), other vancomicin (group V), other clindamicin (group CL) and the other receiving placebo (P) for 4 weeks. Group CZ received a subcutaneous dose of 50mg/kg/daily, Group CF received a dose of 100 mg/Kg/daily, Group V received a dose of 20 mg/Kg/daily, Group CL received a dose of 25 mg/Kg/daily and group P received water. 4 weeks later rats were killed and femora extracted. A mechanical test (low speed torsion) was performed to evaluate healing. All four groups (CZ, CF, V, CL) were compared to placebo through ANOVA. Results: Six bones were discarded because of technical errors, no infections were found. The maximum torque achieved by the calluses before breaking were 240 mNm in group P (n=18), 238 in group CZ (n=20), 178 in group CF (n=19), 167 in group V (n=19), and 205 in group CL (n=18). When compared to placebo, cefazolin and clindamicin showed no statistical differences (N.S, p> 0,10), vancomicin had lower callus strength (p=0,015), and cefuroxime had also lower callus strength near the significance level (p=0,084). Conclusion: The mechanical strength of fracture callus is similar when rats are given cefazolin or clindamicin during fracture healing. The mechanical strength of fracture callus is lower when vancomicin (and probably cefuroxime) is given. If these results are similar to human, cefazolin and clindamicin are safe drugs to use during fracture healing. If possible, vancomicin (and perhaps cefiuroxime) use during fracture healing should be restricted

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.

Our study sought to establish the necessity of prolonged pre-operative antibiotic prophylaxis in patients presenting with zone II and zone V acute flexor tendon injuries (FTI). We hypothesized that a single dose of prophylactic antibiotic was adequate in prevention of post-operative wound infection in acute zone II and V FTI.

This was a prospective study of 116 patients who presented with zone II and zone V acute FTI. The study included patients who were 18 years and older. Those with macroscopic contamination, immunocompromised, open fractures, bite injuries, and crush injuries were excluded. Patients were randomised into a group receiving a single dose of prophylactic antibiotic and another group receiving a continuous 8 hourly antibiotic doses until the day of surgery. Each group was subdivided into occupational and non-occupational injuries. Their post-operative wound outcomes were documented 10 – 14 days after surgery. The wound outcome was reported as no infection, superficial infection (treated with wound dressings), and deep infection (requiring surgical debridement).

There was 0.9% rate of deep post-operative wound infections, which was a single zone V acute FTI case in a single dose prophylactic antibiotic group. There was a 7.8% superficial post-operative wound infection rate, which was mainly zone II acute FTI in both antibiotic groups. There was a strong association between zone II acute FTI and post-operative wound infection (p < 0.05). There was no association between (antibiotic dosage or place of injury) with post-operative wound infection (p > 0.05).

There is no benefit in prescribing prolonged pre-operative antibiotic in patients with acute, simple lacerations to zone II and zone V FTI if there is no macroscopic wound contamination.

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)

Aim

This study investigated the effect of the choice of antibiotic regime on outcome of patients treated for fracture-related infection (FRI) at 3 centres, in the UK and the Netherlands between 2015 and 2019.

Aim

The current antibiotic treatment of periprosthetic joint infection (PJI) is optimized by measuring concentrations in plasma. However, it remains unclear whether effective concentrations of the antibiotics are reached at the site of PJI. Nonetheless, adequate target site concentrations are important to achieve effective eradication of the micro-organism. In order to determine the efficacy of cefuroxime and flucloxacillin in synovial fluid, synovial tissue and bone tissue in relation to the minimal inhibitory concentration (MIC) of the pathogen causing the PJI, we perform a pharmacokinetic/pharmacodynamic (PK/PD) study. Therefore, we aimed to develop validated analytical methods for analysis of cefuroxime and flucloxacillin in synovial fluid, synovial tissue and bone tissue.

Aim

Analysis of microbiological spectrum and resistance patterns as well as the clinical outcome of patients who underwent a Debridement, antibiotics and implant retention (DAIR) procedure in the early phase following failed two-stage exchange arthroplasty of the knee and hip.

Introduction and Objective

Management of bone loss associated with bone contamination or infection represents a double biological and clinical challenge frequent in traumatology. The advent of new biomaterials can allow a different approach in the treatment of bone gap. The purpose of this study was to evaluate the prophylactic and therapeutic effectiveness of addition of a new absorbable bone substitute (BS) eluting different antibiotics in reconstruction of bone defects after infections and fractures with soft tissue damage.

Aim

Staphylococcus epidermidis (S. epidermidis) is one of the main pathogens responsible for bone and joint infections especially those involving prosthetic materials (PJI). Although less virulent than S. aureus, S. epidermidis is involved in chronic infections notably due to its ability to form biofilm. Moreover, it is frequently multiresistant to antibiotics. In this context, the development of additional or alternative antibacterial therapies targeting the biofilm is a priority.

This study aimed to identify the success rate of debridement, antibiotics and implant retention (DAIR) for prosthetic joint infection (PJI) in a large prospective cohort of patients undergoing total knee arthroplasty (TKA). The ability for different PJI classification systems to predict DAIR success was assessed.

A prospective, multicenter study of PJIs occurring between July 2014 and December 2017 in 27 hospitals across Australia and New Zealand was performed. First time PJIs following primary TKA that were managed with DAIR were analyzed. DAIR success was defined as the patient being alive with documented absence of clinical or microbiological evidence of infection and no ongoing antibiotics for the index joint at 2-year follow-up. Multivariate analysis was performed for multiple PJI classification systems to assess their ability to predict DAIR success using their respective definitions of “early” PJI (Coventry ≤1 month, International Consensus Meeting ≤90 days or Auckland <1 year), or as hematogenous versus chronic PJI (Tsukayama).

189 PJIs were managed with DAIR, with an overall success rate of 45% (85/189). Early PJIs had a higher rate of DAIR success when analyzed according to the Coventry system (adjusted odds ratio = 3.85, p = 0.008), the ICM system (adjusted odds ratio = 3.08, p = 0.005) and the Auckland system (adjusted odds ratio = 2.60, p = 0.01). DAIR success was lower in both hematogenous (adjusted odds ratio = 0.36, p = 0.034) and chronic PJIs (adjusted odds ratio = 0.14, p = 0.003) occurring more than one year since the primary TKA.

DAIR success is highest when performed in infections occurring within one year of the primary TKA. Late infections had a high DAIR failure rate irrespective of their classification as hematogenous or chronic. Time since primary is a useful predictor of DAIR success.

Aim

To analyse the prevalence of culture negative periprosthetic joint infections (PJI) when adequate culture techniques are applied, and to evaluate the outcome of patients who were treated with antibiotics for a culture negative PJI versus those in whom treatment was withheld.

Antibiotic-laden bone cement is an important strategy of treatment for an established bone infection. It was aimed to find the safe antibiotic dose intervals of the antibiotic cements soaked in Phosphate Buffered Saline solution and to determine whether there was a difference in terms of mechanical strength between the prepared samples.

This study was done in our institute Microbiology and Metallurgy laboratories. All samples were prepared using manual mixing technique using 40 g radiopaque Biomet® Bone cement (Zimmer Biomet, Indiana, USA) under sterile conditions at 19 ± 2 ºC.

In this study, vancomycin (4 groups − 0.5, 2, 4, 6 g), teicoplanin (4 groups − 0.8, 1.2, 2, 2.4 g), daptomycin (4 groups − 1, 2, 2.5, 3 g), piperacillin-tazobactam (4 groups − 0.125, 0.5, 1, 2 g) and meropenem (4 groups − 0.5, 2, 4, 6 g) were measured in a assay balance and added to the cement powder. Antibiotic levels ranged from the lowest 0.625% to the highest 15%.

80×10×4 mm rectangle prism-shaped sample for mechanical measurements in accordance to ISO 5833 standart and 12×6×1 mm disc-shaped samples for microbiological assesments were used. Four sample for each antibiotic dose and control group was made. Prepared samples were evaluated macroscopically and faulty samples were excluded from the study. Prepared samples were kept in Phosphate Buffered Saline solution renewed every 24 hours at 37 ºC. At the end of 6 weeks, all samples were tested with Instron ® 3369 (Norwood Massachusetts, USA) four point bending test.

Staphylococcus aureus (ATCC 29213) strain was used for samples of antibiotics containing vancomycin, teicoplanin and daptomycin after the samples prepared for antibiotic release were maintained under sterile conditions and kept in Phosphate Buffered Saline solution as appropriate. For samples containing meropenem and piperacillin - tazobactam antibiotics, Pseudomonas aeruginosa (ATCC 27853) strain was used.

The addition of more than 5% antibiotics to the cement powder was significantly reduced mechanical strength in all groups(p <0.05) however the power of significance was changed depending on the type of antibiotic. In general, adding antibiotics with 2.5% and less for cement amount was not cause significant changes in mechanical measurements. There was a negative correlation between the increase in the amount of antibiotics mixed with cement and the durability of the cement (p: <0.001, r: −0.883 to 0.914).

In this study, especially the antibacterial effects of piperacillin-tazobactam, containing 0.25 gr and 0.5 gr antibiotic doses, were found to be low. There was no bacterial growth in all other groups for 21 days. Considering the mechanical properties of groups containing meropenem, vancomycin, daptomycin and teicoplanin, it was observed that all antibiotic cements remained above the limit value of 50 MPa in the bending test at concentrations containing 2.5% and less antibiotics. This was not achieved for the piperacillin-tazobactam group. The findings of the study showed that each antibiotic has different MPa values at different doses. Therefore, it could be concluded that not only the antibiotic dose but also the type oould change the mechanical properties. In the light of these findings, mixing more than 2.5% antibiotics in cement for the antibiotic types included in the study was ineffective in terms of antibacterial effect and mechanically reduces the durability of cement below the standard value of 50 MPa.

Aim

Prompt and sufficient broad spectrum empirical antibiotic treatment is key to prevent 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 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.

Aim

Rifampicin plays an important role in the treatment of staphylococcal prosthetic joint infection, as rifampicin-containing combinations have shown a high efficacy against S. aureus biofilm infections. However, the emergence of rifampin-resistant strains is a feared complication and the use of rifampicin in those cases seems unwarranted. Therefore, we evaluated the activity of bacteriophage Sb1 in combination with different antibiotics against the biofilm of four rifampicin-resistant MRSA strains as alternative therapeutic approach.

Background

DAIR is an attractive treatment for PJI. The purpose of this study is to determine predictive factors of failure.

By modifying only the nanofeatures on material surfaces without changing surface chemistry, it is possible to increase tissue growth of any human tissue by controlling the endogenous adsorption of adhesive proteins onto the material surface. In addition, our group has shown that these same nanofeatures and nano-modifications can reduce bacterial growth without using antibiotics, which may further accelerate the growth of antibiotic resistant microbes. Inflammation can also be decreased through the use of nanomaterials. Finally, nanomedicine has been shown to stimulate the growth and differentiation of stem cells, which may someday be used to treat incurable disorders, such as neural damage. This strategy also accelerates FDA approval and commercialization efforts since new chemistries are not proposed, rather chemistries already approved by the FDA with altered nanoscale features. This invited talk will highlight some of the advancements and emphasize current ceramic nanomaterials approved by the FDA for human implantation. It will also emphasize the future of nanomaterials in medicine, such as their use in personalized medicine as internal sensors to detect and fight alterations in health.

Aims

Prophylactic antibiotic regimens for elective primary total hip and knee arthroplasty vary widely across hospitals and trusts in the UK. This study aimed to identify antibiotic prophylaxis regimens currently in use for elective primary arthroplasty across the UK, establish variations in antibiotic prophylaxis regimens and their impact on the risk of periprosthetic joint infection (PJI) in the first-year post-index procedure, and evaluate adherence to current international consensus guidance.

Aim

To describe the management of PJI due to S. aureus in CRIOAcs in 2019 and to particularly focus on the evaluation of the efficacy of DAIR regarding control of infection and risk factors for failure up to 12 months.

Aims

Here we used a mature seven-day biofilm model of Staphylococcus aureus, exposed to antibiotics up to an additional seven days, to establish the effectiveness of either mechanical cleaning or antibiotics or non-contact induction heating, and which combinations could eradicate S. aureus in mature biofilms.

Introduction

Perioperative antibiotic prophylaxis use in modern orthopaedic procedures is well established. Studies have shown significant reduction in risk of post-operative infections. However, as effectiveness of these antibiotics is dependent on achieving high serum and tissue concentrations that exceed the minimum inhibitory concentrations of infective organisms for operation duration, the timing of prophylaxis is crucial. Although, optimal timing for administering prophylaxis varies in the literature, 30 to 60 minutes prior to skin incision or inflation of tourniquet is considered best standards.

Aim

Prosthetic Joint Infection (PJI) remains one of the leading cause for revision arthroplasty.^1,2 Early recognition and appropriate initial treatment of early PJI with debridement, antibiotics and implant retention (DAIR) can eradicate infection on first attempt and prevent implant failure. We evaluated the outcome after one year of patients who were treated for an early PJI after primary total knee arthroplasty (TKA) or total hip arthroplasty (THA) with DAIR. Furthermore, we determined preoperative infection markers, microbiology, and treatment factors related to treatment failure after DAIR procedure.

Introduction

We aim to evaluate the outcome of debridement and implant retention (DAIR) procedures performed for primary total hip prosthetic joint infections (PJI) and to identify factors correlating with a successful outcome.

Thermostability is a key property in determining the suitability of local delivery of antibiotics in the treatment of orthopaedic infections. Herein, we aimed to assess the thermal stability and antibacterial activity of ciprofloxacin, ceftriaxone, gentamycine and vancomycine in high temperature conditions. Using a standardized E-test method, minimally inhibited concentration of each antibiotic substance against Staphylococcus aureus cultures were determined. The solutions of antimicrobial drugs ciprofloxacin 2 mg/ml, ceftriaxone 200 mg/ml, gentamycine 40 mg/ml and vancomycine 200 mg/ml were diluted twofold in deionised water. Acquired solutions were divided into three aliquots. The first aliquot was held at 40°C for 30 min in a waterbath, the second and the third aliquots were exposed to 80 and 100°C for 30 min in hot-air sterilizer, respectively. The treated solutions were tested for residual activity against S. aureus using a standardized disk diffusion method. Mediums with untreated antibiotic solutions and S. aureus were used as control. Plates were incubated at 37°C, at which time zones of inhibition (ZoI) were measured to the nearest whole millimeter for 14 days. The investigation indicated that the temperature elevation impacted considerably on antimicrobial activity and antibiotic stability overall. The in vitro temperature-response curves showed that ZoI diameter decreases logarithmically with elevated temperatures. Gentamicin was the only drug that was found to be affected to some extent. Results from the study provides a valuable dataset for orthopaedic surgeons considering local application of antibiotics and methods of antibiotic impregnation.

Introduction

Periprosthetic joinTt infection (PJI) remains an uncommon, yet devastating complication of total hip arthroplasty (THA) and total knee arthroplasty (TKA). Debridement with antibiotics and implant retention (DAIR) provides an alternative to staged revision. Chronic infection is considered to be a contraindication to DAIR, however, outcomes stratified by chronicity have not been documented.

Aim

To retrospectively evaluate infection eradication rate of DAIR procedures performed in our tertiary referral center. We analyzed whether the outcome was influenced by time of infection after arthroplasty, previous surgery or causative pathogen.

Aims

Intra-articular administration of antibiotics during primary total knee arthroplasty (TKA) may represent a safe, cost-effective strategy to reduce the risk of acute periprosthetic joint infection (PJI). Vancomycin with an aminoglycoside provides antimicrobial cover for most organisms isolated from acute PJI after TKA. However, the intra-articular doses required to achieve sustained therapeutic intra-articular levels while remaining below toxic serum levels is unknown. The purpose of this study is to determine the intra-articular and serum levels of vancomycin and tobramycin over the first 24 hours postoperatively after intra-articular administration in primary cementless TKA.

Introduction

Treatment of prosthetic joint infection (PJI) following total knee arthroplasty (TKA) may guided by PJI classification, taking into account infection duration and potential for biofilm formation. Debridement, antibiotics and implant retention (DAIR) is recommended for ‘post-operative’ and ‘acute’ haematogenous PJI. However, the time cut-off for ‘post-operative’ PJI varies across classification systems. Furthermore, poor DAIR success rates have been reported in acute haematogenous PJIs. This study aimed to determine the success of DAIR in a large cohort of PJIs, and assess the utility of current classification systems for predicting DAIR outcomes.

Aims

This study investigated vancomycin-microbubbles (Vm-MBs) and meropenem (Mp)-MBs with ultrasound-targeted microbubble destruction (UTMD) to disrupt biofilms and improve bactericidal efficiency, providing a new and promising strategy for the treatment of device-related infections (DRIs).

Aims

Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation.

The reported success rate after treatment with debridement, antibiotics and implant retention (DAIR) of hip prosthesis infections has been found variable. We evaluated all reoperations performed because of infection and reported to Swedish Hip Arthroplasty Register (SHAR) between 1999 and 2016. The analyses were separated into reoperations performed for the first time and those which had been preceded by at least one previous reoperation performed because of the same reason. The outcome was repeated reoperation performed because of infection.

1,882 were first-time procedures (Group I) and 2,275 had been preceded by at least one reoperation due to infection (Group II). Head and/or liner exchange had been performed in 47% of the cases in group I, and in 22% in Group II. The mean age varied between 70 and 71 years and there was a dominance of males in all groups (52–59%). Compared to all primary THR performed during this period (n=319,813) patients with inflammatory disease, idiopathic femoral head necrosis and sequel after childhood disease were overrepresented for this type of procedure.

Between 1999 and 2016 the number of DAIR procedures increased from 29 to 383 per year corresponding to 21 and 72 % of all reoperations performed due to infection. In first time reoperations the survival was 74.5±3.1% if the head/liner had been exchanged and 46.2±3.2% if only irrigation and synovectomy had been performed. In patients reoperated at least one time previously due to infection the survival rates dropped to 68.6±4.6% and 34.5±2.4%.

Compared to first time reoperation with exchange of femoral and/or liner, synovectomy and irrigation without exchange of any implant part(s) resulted in an almost tripled risk of a second reoperation due to same reason (Hazard Ratio: 2.8, 95% confidence interval: 2.4–3.3). In cases previously reoperated because of infection (Group II) exchange of head/liner and debridement had a 28% increased risk of failure compared to the corresponding first time reoperations (1.28 1.02–1.6). If none of the components were replaced in Group II, the risk ratio for a new failure increased almost 4 times (3.8 3.3–4.4). Presence of a cemented stem increased the risk for further reoperations due to infection (1.14 1.02–1.28), but not presence of a cemented cup (1.06 0.92–1.19). All hazard ratios were adjusted for age, gender, diagnosis and type of fixation.

The comparatively good results observed after exchange of head and liner might indicate that this is necessary to perform a sufficiently radical debridement. This observation could also be biased by a surgeon related factor suggesting that component exchange mainly is performed by surgeons with long experience of revision surgery.

Aim

The increase of antimicrobial resistance reduces treatment options for implant-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Bacteriophages present a promising alternative to treat biofilm-related infections due to their rapid bactericidal activity and activity on multi-drug resistant bacteria. In this study, we investigated the synergistic activity of lytic bacteriophage Sb-1 with different antibiotics against MRSA biofilm, using a real-time highly sensitive assay measuring growth-related heat production (microcalorimetry).

Aim

Previous studies of primary internal fixation of infected non-unions have reported high failure rates. Local antibiotic carriers and coatings have been advocated to reduce infection around implants and allow bone healing. We evaluated the effect of a calcium sulphate/hydroxyapatite antibiotic-loaded composite on bone healing and the eradication of infection in combination with internal fixation.

We describe a case series using calcium sulphate bio composite with antibiotics (Cerament/Stimulan) in treating infected metalwork in the lower limb.

Eight patients aged 22–74 (7 males, 1 female) presented with clinical evidence of infected limb metal work from previous orthopaedic surgery. Metal work removal with application of either cerement in 5 cases (10–20ml including 175mg–350mg gentamycin) or stimulan in 3 cases (10–20ml including either 1g vancomycin or clindamycin 1.2g or 100mg tigecycline) into the site was performed. Supplemental systemic antibiotic therapy (oral/intravenous) was instituted based on intraoperative tissue culture and sensitivity.

Four patients had infected ankle metalwork, 2 patients infected distal tibial metalwork and 2 had infected external fixators. Metal work was removed in all cases. The mean pre operative CRP was 15.8mg/l (range 1–56mg/l). The mean postoperative CRP at 1 month was 20.5mg/l (range 2–98mg/l). The mean pre op WCC was 7.9×10⁹(range 4.7–10.5 ×10⁹). Mean post op WCC at 1 month was 7.1×10⁹(range 5.0–9.2×10⁹). The organisms cultured included enterobacter, staphylococcus aureus, staphylococcus epidermidis, staphylococcus cohnii, stenotrophomonas, acinetobacter, group B streptococcus, enterococcus and escherichia coli. No additional procedures were required in any case. All surgical wounds went on to heal uneventfully. Infection control and union was achieved both clinically and radiologically in all cases.

Our results support the use of a calcium sulphate bio composite with antibiotic as an adjuvant for effective local infection control in cases with implant related bone sepsis. The technique is well tolerated with no systemic or local side effects. We believe that implant removal, debridement and local antibiotic delivery can minimise the need for prolonged systemic antibiotic therapy in such cases.

Introduction

Guidelines from the North American Spine Society (2009 and 2013) are the best evidence-based instructions on venous thromboembolism (VTE) and antibiotic prophylaxis in spinal surgery. NICE guidelines exist for VTE prophylaxis but do not specifically address spinal surgery. In addition, the ruling of the UK Supreme Court in 2015 resulted in new guidance on consent being published by the Royal College of Surgeons of England (RCSEng). This study assesses our compliance in antibiotic, VTE prophylaxis and consent in spinal surgery against both US and UK standards.

Preoperative antibiotic prophylaxis remains one of the most important strategies for preventing periprosthetic joint infection (PJI). Current guidelines recommend giving universal antibiotic prophylaxis to all total joint arthroplasty (TJA) patients regardless of their medical conditions or immune status. The aims of this study were to determine if comorbidities influence the organism profile of PJIs and to investigate if the efficacy of the two most frequently used perioperative antibiotics (cefazolin or vancomycin) are affected by patient comorbidities.

Using an institutional database, the influence of comorbidities on the organism profile of 1022 PJIs was evaluated. To investigate the influence of perioperative antibiotic monotherapy (cefazolin or vancomycin therapy) on PJI, 8575 primary TJAs were identified and analyzed based on their comorbidities. Patients with multiple perioperative antibiotics, prior septic arthritis, unavailable perioperative antibiotic information, or who underwent aseptic revision were excluded. PJI was determined from ICD-9 codes.

While no comorbidities were associated with an increased rate of gram-positive or gram-negative infections, metastatic disease (odds ratio [OR] 7.54, p=0.006), rheumatologic disease (OR 1.63, p=0.046), and chronic pulmonary disease (OR 1.46, p=0.030) demonstrated an increased risk of Staphylococcus aureus PJI. In addition, metastatic disease (OR 5.71, 95% confidence interval [CI] 1.12–26.93, p=0.018), congestive heart failure (OR 2.2, 95% CI 1.16–4.00, p=0.010), chronic pulmonary disease (OR 1.76; 95% CI 1.09–2.78, p=0.015), and diabetes (OR 1.66; 95% CI 1.08–2.52, p=0.019) were associated with PJI from antibiotic resistant organisms. However, there was no difference in the rate of PJI between cefazolin and vancomycin monotherapy when stratified for the aforementioned comorbidities.

The present study reveals that comorbidities do not significantly alter the organism profile of high-risk comorbidities and that comorbidities associated with immune deficits do not influence the rate of PJI between two different antibiotics. The results of this study thus support current guidelines, which provide a universal recommendation rather than a protocol that is tailored to a patient's preexisting comorbidities.

1. Continued follow-up of the 113 children with acute osteomyelitis previously reported and a study of a further thirty-eight proven cases has not changed our opinion that the correct management is rest and effective antibiotics. Operation should be undertaken only if pus is detectable clinically.

2. Bacteriological evidence shows that the flora causing this disease are less sensitive to benzylpenicillin than ten years ago and that a proportion are also likely to become resistant to methicillin and cloxacillin.

3. The most effective antibiotic combination used was fusidic acid and erythromycin. This lowered the failure rate to 10·5 per cent in thirty-eight proven cases. Two of the four failures were in haemophilus infections. No staphylococcal infection of a long bone became chronic, and all lesions were healed within three months of onset.

4. The duration of treatment (twenty-one days) and the method of splintage (removable plaster slabs) remained the same as in the previous series.

5. Careful watch must be kept on the incidence of haemophilus infections. If it rises, increasing the erythromycin or adding ampicillin may be necessary.

6. Use of the newer aqueous suspension of fusidic acid may lower the incidence of troublesome vomiting (12 per cent in this series).

7. Only 7 per cent of staphylococcus aureus infections in this hospital, and 17 per cent of such infections in our thirty-eight cases were sensitive to benzylpenicillin. It is thought that this drug has outlived its usefulness in osteomyelitis.

8. It is recommended that, on diagnosis, fusidic acid aqueous suspension 5 millilitres should be given three times a day to children aged one to five, and 10 millilitres twice a day for children aged six to twelve, with erythromycin stearate 30 milligrams per kilogram of body weight each day in divided doses.

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.

Introduction: Osteomyelitis often causes functional impairment due to tissue destruction and the incidence of this condition appears to be increasing. Antimicrobial peptides (AP) are effectors of the innate defence system and play a key role in host protection at cellular surfaces. Human beta-defensins (HBD) represent a major subclass of antimicrobial peptides and act as a first line defence through their broad spectrum of potent antimicrobial activity (1). The aim of the present in vitro and in vivo investigations was to study the expression and regulation of HBD-2 and -3 in the case of bacterial bone infection and to analyze the effects of immunosuppressive drugs on bone-derived AP-expression.

Methods: Samples of healthy human bone, osteomyelitic bone and cultured osteoblasts (primary-, hFOB- and SAOS-2 cells) were assessed for the expression of HBD-2/-3 by RT-PCR, immunohistochemistry or ELISA. Regulation of HBD-2/-3 was studied after exposure to Staphylococcus aureus (SAS) or Pseudomonas aeruginosa (PAS), proinflammatory cytokines (IL-1, 10ng/ml) and immunosuppressive drugs (glucocorticoids, methotrexate) and was assayed by ELISA. An osteomyelitis mouse model was performed to demonstrate the regulation of the murine homologues of HBD-2/-3 by real time RT-PCR and immunohistochemistry.

Results: ELISA experiments demonstrated, that samples of infected bone produce higher levels of endogenous antibiotics such as HBD-2 when compared with samples of healthy bone. After exposure of osteoblasts to bacteria or proinflammatory cytokines a clear HBD-2/-3 induction was observed. Additional treatment with glucocorticoids or methotrexate prevented bacteria mediated HBD-2 induction in cultured osteoblasts. The osteomyelitis mouse model demonstrated transcriptional up-regulation of the murine HBD-homologues in bone after intra-osseous contamination of the tibia.

Discussion: Our study firstly demonstrate that osteoblasts are able to produce anti-inflammatory peptides such as HBD-2 in vitro and in an animal model of staphylococcal osteomyelitis. We provide evidence for a new role of osteoblasts during infection of bone tissues, namely, the ability to produce antimicrobial peptides and modulating immune responses in inflammatory bone diseases.

Immunosuppressive drugs such as glucocorticoids or methotrexate may increase the susceptibility to bone infection by decreasing AP-expression levels in case of microbial challenge. Novel approaches to management are required particularly in the era of multi-resistant bacterial strains. Current investigation will focus on the regulation of human β-Defensins in bone and may allow artificial amplification for prevention of bacterial bone infection in the future.

The treatment of chronic osteomyelitis requires both appropriate surgical and antibiotic management. Prolonged intravenous antibiotic therapy followed by oral therapy is widely adopted. Despite this, the long-term recurrence rate is around 20% to 30%.

The aim of this cohort study was to examine the effectiveness of surgical marginal resection in combination with local application of antibiotics (Collatamp G - gentamicin in a collagen fleece). Post-operatively this was followed by a short course of intravenous antibiotics, then oral antibiotics, to 6 weeks in total.

A cohort of 50 patients from a 10-year period, 2000 to 2010, with chronic osteomyelitis was identified. Most were male (n= 35, 70%) and the average age is 40.9 years (SD 15.9). The mean follow-up duration was 3.2 years (SD 1.8). The average length of admission was 9.8 days (SD 11.4). 6 patients (12%) suffered recurrence of infection requiring further treatment. We used the Cierny and Mader classification to further stratify the patients. ‘A’ hosts had a shorter duration of admission (7.1 days) than ‘B’ hosts (12.3 days). There was no significant difference between recurrence rates of ‘A’ and ‘B’ hosts. Where available, we found pre-operative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels had no correlation with disease recurrence. Disease-free probability for this cohort compared favourably with a cohort treated with prolonged systemic and oral antibiotics (Simpson and colleagues, JBJS Br 2001).

We believe local administration of gentamicin in a collagen fleece is a useful component in the management of chronic osteomyelitis.

Aim

Infection is one of the worst complications following total joint arthroplasty, which is often associated with significant morbidity and increased medical costs. Although Gram–positive bacteria remains the most prevalent causative agents, an increase in prosthetic joint infections (PJI) due to gram-negative bacteria (GNB) has been reported. Additionally, the emergence of multidrug resistant resistance (MDR) in GNB impacts the therapeutic options and may increase the rate of treatment failure and drug toxicity adverse effects due the prescription of harmful and toxics antimicrobial schemes. The purpose of the present study was to describe the predisposing factors associated to PJI caused by MDR-GNB in a specialized orthopedic reference hospital in Brazil from 2014 through 2018.

Aims

Poly(methyl methacrylate) (PMMA)-based bone cements are the industry standard in orthopaedics. PMMA cement has inherent disadvantages, which has led to the development and evaluation of a novel silorane-based biomaterial (SBB) for use as an orthopaedic cement. In this study we test both elution and mechanical properties of both PMMA and SBB, with and without antibiotic loading.

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.

Bone is a dynamic tissue with a quarter of the trabecular and a fifth of the cortical bone being replaced continuously each year in a complex process that continues throughout an individual’s lifetime. Bone has an important role in homeostasis of minerals with non-stoichiometric hydroxyapatite bone mineral forming the inorganic phase of bone. Due to its crystal structure and chemistry, hydroxyapatite (HA) and related apatites have a remarkable ability to bind molecules. This review article describes the accretion of trace elements in bone mineral giving a historical perspective. Implanted HA particles of synthetic origin have proved to be an efficient recruiting moiety for systemically circulating drugs which can locally biomodulate the material and lead to a therapeutic effect. Bone mineral and apatite however also act as a waste dump for trace elements and drugs, which significantly affects the environment and human health.

Cite this article: Bone Joint Res 2020;9(10):709–718.

Aim

Debridement, antibiotics and implant retention (DAIR) is a widely used treatment modality for early acute prosthetic joint infection (PJI). A preoperative risk score was previously designed for predicting DAIR failure, consisting of chronic renal failure (K), liver cirrhosis (L), index surgery (I), cemented prosthesis (C) and C-reactive protein >115mg/L (KLIC). The aim of this study was to validate the KLIC score in an external cohort.

The effectiveness of different antibiotics mixed with Simplex P has been tested in vitro. A laboratory model was designed to simulate the constant immersion of bone cement in tissue fluid. Clindamycin, and to a lesser extent Cephalothin, were shown to be effective when used in this manner against Staphylococcus aureus and epidermidis. Effective inhibition of Gram-negative organisms could not be demonstrated with any of the antibiotics tested. The addition of up to 3 grams of antibiotic powder per unit of 40 grams of Simplex P did not appear to alter the expansive properties of the cement. Such release of antibiotic as did occur was thought to be related to the slow absorption of water by the slightly porous methyl methacrylate.

Aims

Infections of bone usually require multiple surgery and prolonged periods of treatment. One reason for problems is found in the presence of stationary phase bacteria embedded in biofilms that show increased resistance against conventional antibiotic therapy (up to 1000x MIC). Biofilms adhere to surfaces of avital material making radical debridement a prerequisite for cure. Osseous defects are common in such conditions and need to be addressed. To avoid re-infection high local antbiotic concentrations are necessary. Allograft bone may be impregnated with high loads of antibiotics using a special incubation technique. The resulting antibiotic bone compound (ABC) provides high and long lasting concentrations at the site of infection and is likely to restore bone stock simultaneously. Based on this technology we have developed a new surgical technique.

Acute periprosthetic infection, acute and chronic course of the infection with unknown spectrum of organism, hardly to treat and loss of mobility due to long lasting immobilization after implant removal are the indications for this special design of a spacer. The management of a bacterial periprosthetic infection by two-stage reimplantation using an implanted applicationspacer for antibiotics maintains mobility and soft tissue balance and ensures simultaneous local delivery of antibiotics.

After a complete synovectomy the implant components and all foreign material are removed. The implant bed is then prepared for implantation of the application-spacer for antibiotics. Silicone catheters are advanced through two separate drill holes into the intramedullary canal and then inserted into the perforated implant stems. After the applicationspacer for antibioticss has been implanted, the wound is closed.

Daily parenteral doses of antibiotics are delivered through the percutaneous silicone catheters directly into the intramedullary canal at the site of the infection. The applicationspacer for antibiotics allows daily physiotherapy and even mobilization on a CPM device. Partial weight bearing may even be allowed if there is sufficient stability. Once the CRP values have decreased to normal levels, the definitive implant is placed using antibiotic-impregnated cement according to current resistance studies. The implant beds are debrided to remove the synovial tissue that has developed in the interim. Then the revision implants can be placed in the prepared bone because the same templates are used for both the applicationspacer for antibioticss and the revision implants.

36 patients have been treated with this method since 1993. Two-stage reimplantation of a total knee was performed in 27 cases.. The longest postoperative follow-up period is now 12 years. Till now, no revision surgery has been required on a joint treated in this manner, and no periprosthetic infections have been observed. In the knee, a range of motion of 0/0/106 degrees was achieved after an average follow-up period of 7,1 years. In the hip, values of 10/0/110 degrees were achieved after an average of 7,3 years. Revision surgery for infection included cases of fungal and tubercular infection. A postoperative Hospital for Special Surgery rating of 79,5 was achieved in the knee and a rating of 81,3 in the Harris hip score.

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.

It is widely accepted by orthopaedic surgeons that antibiotics should be withheld until aspiration has been performed to increase the odds of identifying an organism in septic arthritis. Patients often present to other specialties that may not be as familiar with these principles.

Twenty-five of forty-nine patients with septic arthritis of the native or prosthetic knee had received antibiotics prior to review by the orthopaedic service. Patients were significantly less likely to demonstrate an organism on initial microscopy (entire cohort p=0.001, native knees p=0.006, prosthetic knees p=0.033) or on subsequent culture (entire cohort p=0.001, native knees p=0.017, prosthetic knees p=0.012) of their aspirate if they had received antibiotics. The sensitivity of microscopy dropped from 0.58 to 0.12 when patients had received antibiotics (native knees 0.46 to 0, prosthetic knees 0.72 to 0.27). The sensitivity of the culture dropped from 0.79 to 0.28 when the patient had received antibiotics (native knees 0.69 to 0.21, prosthetic knees 0.91 to 0.36).

Patients treated with empirical antibiotics are less likely to demonstrate an organism on microscopy and culture of their initial aspirate. There is a significantly high false negative rate associated with knee aspiration, particularly with prior administration of antibiotics.

Bacterial resistance in joint replacement surgery is an emerging problem. A review of the bacteriology from infected revisions performed at Wrightington over the past 5 years has shown that the most common organism is coagulase negative staphylococcus (59%), followed by staphylococcus aureus (17%).

The sensitivity profiles are shown below.

Gentamicin is the most commonly pre formulated antibiotic added to acrylic bone cement. The above data clearly demonstrates that for 32% of infected cases gentamicin alone is inadequate prophylaxis. As a consequence of this the use of additional antibiotics for resistant cases is becoming commonplace.

The aim of this study was to investigate the mechanical properties of additional antibiotics in acrylic bone cement.

The 7 antibiotics listed above were selected on the basis of sensitivity to organisms isolated at revision for deep infection. Each was added at a loading of 1g active to CMW1 RO (plain) and CMW1 G (gentamicin). The antibiotics were mixed with the polymer by hand. The cement was then mixed as per manufacturer’s instructions.

Dough and setting times were noted. Standard samples were produced using ISO approved moulds. Each antibiotic/cement combination was tested for compression strength, impact strength and flexural strength.

All antibiotic/cement combinations performed as well as the control mix when tested for compression and impact strength. The flexural strength results for fusidic acid and erythromycin when added to acrylic cement were comparable to the control mix. Flucloxacillin, clindamycin and teicoplanin did lower the flexural strength to just below acceptable limits. However Vancomycin when added at 1g active reduced the flexural strength of acrylic bone cement significantly.

Although vancomycin may remain one of the last bastions of antibiotic therapy our study suggests that’s its addition to acrylic bone cement significantly weakens its mechanical properties. We would advise caution in its use as this may reduce the chances of long term success when undertaking revision for deep infection.

Introduction: The use of prolonged courses of parenteral or oral antibiotic therapy in combination with a two-stage exchange procedure in the management of the infected total hip arthroplasty is reported by many major series.

Methods: We present a series of 114 patients, all with microbiologically proven chronic deep infection, treated with a two-stage exchange with antibiotic loaded cement and where a prolonged course of antibiotic therapy has not been used. The mean follow-up for all patients is 74months (range 2–175months) with all surviving patients having a minimum 2 year follow-up.

Results: Infection was successfully eradicated in 100 patients (88%). The infection cure rate in our series is similar to that reported elsewhere where prolonged adjuvant antibiotic therapy was used.

Discussion: Using the technique described a prolonged course of systemic antibiotics does not appear to be necessary; the high costs of antibiotic administration, both to the patient and care facility are not incurred.

Introduction

The value of Debridement-Antibiotics-and-Implant-Retention (DAIR) in prosthetic-joint-infection (PJI) is still a matter of debate as most studies to-date are underpowered with variable end-points. In our, tertiary referral, bone infection unit we consider DAIR to be a suitable option in all PJIs with soundly fixed prostheses, despite chronicity. The aims of this study were to define the long-term outcome following DAIR in hip PJI and identify factors that influence it.

The visco-elastic behaviour of acrylic bone cement is a key feature of cement-implant performance. The ability of the cement to creep in conjunction with a force-closed design of stem (collarless polished taper) affords protection of the vital bone-cement interface. Most surgeons in the UK use antibiotic-laden PMMA in primary total joint arthroplasty. In revision surgery the use of bespoke antibiotic-cement combinations is common.

The aim of this study was to elicit the effect of antibiotics upon the physical properties of bone cement.

Methods: The static properties of the cements were assessed following protocols described in ISO 5833: 2002, while the viscoelastic properties of the cement were measured with in-house developed apparatus in quasi-static conditions. Creep tests were performed in four point bending configuration over a 72 hour period in physiological conditions. Porosity was measured on the mid cross section of the creep samples using a digital image technique.

The cements used were Palacos R40 and Palacos R with gentamicin. The antibiotics added included fucidin, erythromycin, teicoplanin and vancomycin in 500mg powder aliquots up to a maximum of 1g per 40 g mix.

All data were analysed using ANOVA with Bonfer-roni post-hoc test. Pearson’s correlation coefficient was used to investigate the association between physical factors (SPSS).

Results: The static and working properties did not vary significantly with antibiotic additions. The mean creep of the cement increased in line with the amount of antibiotic added. The specific antibiotic was not relevant. The differences were statistically significant. Mean porosity also increased with antibiotic mass. There was a linear relationship between cement porosity and creep!

Conclusions: Despite modern mixing techniques the porosity of bone cement increases with antibiotic additions. This increased porosity is related to the greater creep seen in the cement. Surgeons should apply these findings when planning revision hip surgery.

Aim

Advocates of Debridement-Antibiotics-and-Implant-Retention (DAIR) in hip peri-prosthetic joint infection (PJI) argue that a procedure not disturbing a sound prosthesis-bone interface is likely to lead to better survival and functional outcome compared to revision. However, no evidence supports this. This case-control study's aims were to compare outcome of DAIRs for infected 1° total hip arthroplasty (THA) with outcomes following 1° THA and 2-stage revisions of infected 1° THAs.

Introduction: The role of prophylactic antibiotics in reducing the incidence of infection following hip and knee arthroplasty is well established. The British Orthopaedic Association (BOA) published best practice guidance on the use of prophylactic antibiotics in hip and knee arthroplasty. The guidance stated that all patients should receive prophylactic antibiotics at induction of anaesthesia and that each unit should have a locally agreed policy with advice from microbiologist. The aim of this audit was to compare the practice in our unit with the BOA guidance and implement necessary changes.

Patients and Methods: A prospective audit was conducted over a one month period in 2007 and included all patients undergoing elective primary hip and knee replacements. A similar re-audit was conducted over one month period in 2008 after the initial audit recommendations were implemented.

Results: Forty patients (40) were included in the initial audit. All patients received prophylactic antibiotics at induction but the choice, dose and duration of administration of antibiotics varied widely among surgeons in the unit. After discussion with the local microbiologist, we recommended a departmental policy for prophylactic antibiotics. The policy recommended a single dose of Cefuroxime and Gentamycin for standard cases and a single dose of Teicoplanin and Gentamycin for high-MRSA risk cases. A re-audit was conducted after the new policy was agreed. The re-audit included 33 patients. All patients received prophylactic antibiotics at induction. The choice of antibiotics was concordant with the policy in 79% of cases and duration of administration was appropriate in 85% of cases. Overall, the policy was adhered to in 22 cases (67 %).

Discussion & Conclusions: The closed audit cycle resulted in improvement of our practice but the compliance rate with the new policy was lower than expected. Although it is the primary responsibility of the operating surgeon to ensure the appropriate prophylactic antibiotics are administered, more awareness of other team members is necessary to improve the compliance rate with the new policy.

Debridement, antibiotics and implant retention (DAIR) is a surgical option in the treatment of prosthetic joint infection (PJI). It is thought to be most appropriate in the treatment of early (≤6 weeks post-op) PJI. Most studies to-date reporting on DAIRs in hip PJI have been underpowered by reporting on small cohorts (n= <45), or report on registry data with associated biases and limitations. In our, tertiary referral, bone infection unit we consider DAIR to be a suitable option in all cases of PJI with a soundly fixed prosthesis, with early or late presentation, especially in patients who are too elderly or infirm to undergo major surgery.

Aim: To define the 10-year outcome following DAIR in hip PJI and identify factors that influence it.

We retrospectively reviewed all DAIRs performed in our unit between 1997 and 2013 for hip PJI. Only infected cases confirmed by histological and microbiological criteria were included. Data recorded included patient demographics and medical history, type of surgery performed (DAIR or DAIR + exchange of modular components), organism identified and type/duration of antibiotic treatment. Outcome measures included complications, mortality rate, implant survivorship and functional outcome.

121 DAIRs were identified with mean age of 71 years (range: 33–97). 67% followed an index procedure of 1° arthroplasty. 53% included exchange of modular components. 60% of DAIRs were for early onset PJI. Isolated staphylococcus was present in 50% of cases and 25% had polymicrobial infection. At follow-up (mean:7 years, range: 0.3 – 18), 83 patients were alive; 5- and 10- year mortality rates were 15% and 35% respectively. 45% had a complication (persistence of infection: 27%, dislocation: 10%) and 40% required further surgery. Twenty hips have been revised to-date (17%). Performing a DAIR and not exchanging the modular components was associated with an almost 3× risk (risk ratio: 2.9) of subsequent implant failure (p=0.04). 10-yr implant survivorship was 80% (95%CI: 70 – 90%). Improved 10-year implant survivorship was associated with DAIR performed for early PJI (85% Vs 68%, p=0.04). Functional outcome will be discussed.

DAIR is a particularly valuable option in the treatment of hip PJI, especially in the early post-operative period. Whenever possible, exchange of modular implants should be undertaken, however DAIRs are associated with increased morbidity even in early PJI. Factors that predict success of DAIR in late PJI need to be identified.

The management of a bacterial periprosthetic infection by two-stage re-implantation should be presented using an implanted application spacer for antibiotics to maintain mobility and soft tissue balance and ensure simultaneous local delivery of antibiotics. Indication is an acute periprosthetic infection, acute and chronic course of the infection with unknown spectrum of organism, hardly to treat and with a probable loss of mobility due to protracted immobilization after implant removal. Acute infections with a known spectrum of organisms that can be controlled by synovectomy and antibiotic treatment or by one-stage re-implantation are contraindications for this treatment. Spacers are available for hip and knee replacements including surface replacements of the knee. First a complete synovectomy is performed; the implant bed is then prepared for implantation of the application spacer for antibiotics. Silicone catheters are advanced through two separate drill holes into the intramedullary canal and then inserted into the perforated implant stems. Daily parenteral doses of antibiotics in parenteral doses are delivered through the percutaneous silicone catheters directly into the intramedullary canal. The application spacer for antibiotics allows daily physiotherapy and even mobilization on a CPM device. Partial weight bearing may even be allowed, if there is sufficient stability. Once the CRP values have decreased to normal levels, the definitive implant is placed using antibiotic-impregnated cement according to current resistance studies. 36 patients have been treated with this method since 1993. Two-stage re-implantation of a total knee was performed in 20 cases, and re-implantation of a total hip in 16 cases. The longest postoperative follow-up period is now 10 years. Till now, no revision surgery has been required on a joint treated in this manner, and no periprosthetic re-infections have been observed. In the knee, a range of motion of 0/0 /106 degrees was achieved after an average follow-up period of 6.1 years. In the hip, values of 10/0/110 degrees were achieved after an average of 6.3 years. Revision surgery for infection included cases of fungal and tubercular infection. A postoperative Hospital for Special Surgery rating of 79.5 was achieved in the knee and a rating of 81.3 in the Harris hip score.

Purpose: To analyse prolonged combinations of oral intracellular-effective antibiotics plus two-stage exchange surgery for treatment of chronic THA and TKA infections.

Materials and Methods: Definition of infected case: more than 3 months from surgery; multiple positive intraoperative cultures and/or active fistulae.

33 patients were treated from 1996 to 2002: 8 THA, 5 hip hemiarthroplasties, 20 TKA.

Bacteriology: 24 Staphylococci of which 16 were methycillin-resistant, 7 multi-resistant Gram-negative, 2 Cory-nebacteriae; 7 polymicrobian.

Antibiotic therapy: two simultaneous oral antibiotics, selected according to bacterial sensitivity and intracel-lular effectiveness (rifampin, ofloxacin, ciprofloxacin, levofloxacin, trimethoprim-sulfamethoxazole, fosfomicin, linezolid, doxiciclin), were used on an outpatient basis (between 1st and 2nd surgery, and after 2nd surgery until serological normalization). Patients received intravenous antibiotics and were in-hospital only for one week after surgery.

Surgery: two-stage exchange with 2nd stage delayed until clinical and serological normalization.

Healing of infection: absence of clinical, serological and radiological evidence of infection along all follow-up.

Prospective follow-up: 24-96 months.

Results: Healing of infection: 32/33 patients (97%).

Treatment failure: 1 patient (TKA) (3%).

THA: 8/8 infections healed: 1 Girdlestone patient (1st stage of exchange) rejected reimplantation; 7 two-stage exchange (good/excellent objective and subjective result).

Hip hemiarthroplasty: 5/5 infections healed: 3 Girdlestone (1st stage of exchange surgery, 2nd stage rejected because of hemiplegia or Alzheimer); 2 two-stage exchange (good/excellent objective and subjective result).

TKA: 19/20 infections healed: 3 resection-arthroplasty (1st stage of exchange surgery, 2nd stage rejected because of Buerger, cirrhosis or Alzheimer); 17 two-stage exchange (15 good/excellent objective and subjective results, 1 patient needed a debridement 2 months after 2nd surgery because of prolonged aseptic drainage and healed uneventfully, 1 failure described).

Conclusions: Prolonged combinations of oral intracellular-effective antibiotics associated with two-stages exchange surgery is a promising alternative for treating deep chronic THA and TKA infections. Longer follow-up and larger series are necessary.

Objective: To compare the in-vitro antimicrobial action of surgical irrigation fluids: 0.9% saline, 2g/L cephradine, 80mg/L gentamicin, 10% povidone-iodine (PVP-I) and 40ppm aqueous iodine (laq) for activity against Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli in the presence of blood, plasma and saline.

Materials and Methods: 5mL of antimicrobial agent was added to 5ml of blood, plasma or saline containing 10^5–10⁶ CFU/mL of the test bacterium. At 15 seconds, 1 minute, 5 minutes, 1 hour and 2 hours, a 1mL sample was inactivated in 9mL of 0.5% sodium thiosulphate. The bacterial numbers were determined using a biochemical assay (Chemiluminescence) with a calibration curve and by spread plate counts. The data were transformed by a logarithmic function and analysed by linear regression to give 95% confidence intervals for their gradient of change over 2 hours. Significant differences were defined at the 5% level.

Results: In saline. All bacteria were killed within 15 seconds with PVP-I and Iaq, but showed no significant reduction with saline, cephradine or gentamicin. In plasma. E. coli was killed within 15 seconds with all irrigation fluids. S. aureus and S. epidermidis showed no significant reduction with saline, Iaq or cephradine, but did show a significant reduction in the presence of gentamicin. With PVP-I, all S. epidermidis were killed within 15 seconds and all S. aureus within 5 minutes. In blood. E.coli with PVP-I, Iaq and cephradine showed no significant reduction. E. coli with gentamicin did show a significant reduction. Both staphylococci showed a significant reduction over 2 hours with PVP-I and gentamicin, but no significant reduction with saline, cephradine and Iaq.

Conclusions: As blood has a strong chemical inactivating effect on iodine – based formulations, Iaq and PVP-I cannot be recommended for surgical irrigation. Gentamicin should be used in preference to cephradine in surgical irrigation fluids if an antimicrobial agent is required. The residual immunological components (particularly complement) in blood and plasma may enhance the susceptibility of bacteria to antimicrobial agents.

Objective: The purpose of this study was to evaluate the type and the dosage regimer the antibiotics administered prophylactically or curatively in six orthopaedic departments of «KAT» hospital.

Material-Method: Our study group consisted of 1231 patients who were hospitalized between September and November 2003. 1002 patients were treated surgically whilst 229 patients were managed conservatively. Among the patients who were operated 270 underwent THR or TKR, 306 patients were operated for NOF fracture, 195 patients were admitted because of long-bone fractures, 30 patients were operated for fracture or chronic deformity of the hand or the foot, 26 patients for open fractures, 52 patients underwent spine surgery and finally 53 patients were admitted for metal work removal.

Results: All patients were given antibiotics as prophylaxis for a period of 1–7 days 8 patients received antibiotics based on the cultures whilst 113 patients received empiric chemotherapy for some kind of infection. The microbiology lab recorded the microflora in every department and the percentage of resistance of the most important pathogens. Those were: 47% Gram(+) (45% staphylococcus) and 53% Gram(−). Of the identified staphylococci 44% were MR. MRSA-CNS was detected to be completely resistant to b-lactams and at a percentage up to 80% to amynoglycosides. The percentage of resistance of Pseudomonas was 55% to quinolones, 48% to aminoglycosides and 90% to b-lactams. We did notice that the use of the antibiotics was not based on a specific antibiotic policy and in a high percentage; the empirical use of chemotherapy was not documented on the laboratory data.

Conclusion: Taking into consideration the modern scientific data regarding the antibiotic treatment; the rational use of antibiotics in clinical practice requires the implementation of policies, the continuous education of the doctors as well as the intervention for proper prescriptions.

INTRODUCTION

We have conducted interface bioactive bone cement method (IBBC) in total hip arthoplasty (THA) to prevent generation of connective tissue and osteolysis for the longevity of cemented THA since 1985, in which non-resorbable crystalline osteoconductive hydroxyapatite (HA) granules were interposed on the interface between bone and bone cement. To prevent the patients from infection, we use HA granules impregnated with antibiotics. However, there have been no reports on the loading and release of antibiotics from fine granules of HA. Here, we have investigated the loading of antibiotics on HA and their release in vitro.

Prophylactic antibiotics administered prior to joint arthroplasty have become standard practice. Due to concern over the risk that 2nd generation cephalosporins posed to the elderly, as regards clostridium difficile associated infections the antimicrobial management team in our unit changed the protocol for prophylactic antibiotics. As of 1st September 2009, flucloxacillin and gentamicin were preferred over cefuroxime as the first choice of prophylactic antibiotic. However, it was noted that postoperatively patients were experiencing a decrease in renal function.

One hundred patients who underwent a total hip replacement following the policy change were randomly selected from the departmental joint arthroplasty database. This group was age and sex matched to 100 patients undergoing their surgery prior to the change. Data was collected on renal function, length of stay, antibiotic and age. Any change in renal function was categorised using the RIFLE criteria.

Exclusion secondary to variations from protocol or treatment for femoral neck fractures resulted in a total number of 156 patients with 78 in each arm. The average age for both groups was 64 years. Non-parametric analysis of preoperative and postoperative serum creatinine concentrations and Glomerular Filtration Rate (GFR) demonstrated a significant difference between the two groups, showing that GFR decreased (p=0.041) and serum creatinine concentration increased (p=0.037) in the cohort receiving gentamicin. Classing the impaired renal function as: risk, injury or failure (RIFLE criteria) demonstrated a statistically significant difference for any criterion positive (p=0.016) but no significant difference for the specific RIFLE groups (p=0.068).

Acknowledging the small numbers and potential confounders for renal impairment, this study was able to show a difference in renal function for patients receiving gentamicin over cefuroxime as prophylaxis for joint arthroplasty.

Aim

Treatment success of debridement, antibiotics and implant retention (DAIR) is in early periprosthetic joint infection (PJI) is largely dependent on the presence or absence of a mature biofilm. In what time interval a mature biofilm develops is still unclear, and therefore, the time point at which DAIR should be disrecommended remains to be established. This large multicenter trial evaluated the failure rates of DAIR for different time intervals from index arthroplasty to DAIR in early PJI.

Introduction:

Infection as an indication for revision has increased to 12% of the total revisions (UK NJR 9^th report). However, it is next to impossible to find out the cause for a delayed prosthetic infection. With increasing number of arthroplasty procedures, is there a need for prophylactic antibiotics in patients with prostheses?

Background

Periprosthetic joint infections (PJI), caused by pathogens, for which no biofilm-active antibiotics are available, are often referred to as difficult-to-treat (DTT). It is unclear whether DTT PJI has worse outcome due to unavailability of biofilm-active antibiotics. We evaluated the outcome of DTT and non-DTT PJI managed according to a standardized treatment regimen.

Open debridement, irrigation with implant retention and antibiotic treatment (DAIR) is an accepted approach for early prosthetic joint infections (PJI). Our aim was to design a score to predict patients with a higher risk of failure.

From 1999 to 2014 early (<90 days) PJIs without signs of loosening of the prosthesis were treated with DAIR and were prospectively collected and retrospectively reviewed. The primary end-point was early failure defined as: 1) the need of an unscheduled surgery, 2) death-related infection within the first 60 days after debridement or 3) the need for suppressive antibiotic treatment. A score was built-up according to the logistic regression coefficients of variables available before debridement.

A total of 222 patients met the inclusion criteria. The most frequently isolated microorganisms were coagulase-negative staphylococci (95 cases, 42.8%) and Staphylococcus aureus (81 cases, 36.5%). Fifty-two (23.4%) cases failed. Independent predictors of failure were: chronic renal failure (OR:5.92, 95%CI:1.47–23.85), liver cirrhosis (OR:4.46, 95%CI:1.15–17.24), revision surgery (OR:4.34, 95%CI:1.34–14.04) or femoral neck fracture (OR:4.39, 95%CI:1.16–16.62) compared to primary arthroplasty, CRP >11.5 mg/dL (OR:12.308, 95%CI:4.56–33.19), cemented prosthesis (OR:8.71, 95%CI:1.95–38.97) and when all intraoperative cultures were positive (OR:6.30, 95%CI:1.84–21.53). Furthermore, CRP showed a direct relationship with the percentage of positive cultures (Linear equation, R2=0,046, P=0.002) and an inverse association with the time between the debridement and failure (Logarithmic equation, R2=0.179, P=0.003). A score for predicting the risk of failure was done using pre-operative factors (KLIC-score, figure 1) and it ranged between 0–9.5 points. Patients with a score ≤2, >2–3.5, 4–5, >5–6.5 and ≥7 had a failure rate of 4.5%, 19.4%, 55%, 71.4% and 100%, respectively.

The KLIC-score was highly predictive of early failure after debridement. In the future, it would be necessary to validate our score using cohorts from other institutions.

Summary

There is little knowledge in surgeons about the guidelines for prophylactic antibiotics in patients with prosthetic joints when undergoing a dental procedure. This study confirms this and there is need for robust and universal guidelines given the disastrous nature of prosthetic infection.

Aim

Treatment of complicated wound healing after total joint arthroplasty is controversial. What exactly constitutes prolonged wound drainage is matter of debate and recommendations to manage it vary considerably. Nonoperative measures are often recommended. If drainage persists, surgery may be indicated. To further intricate decision-making, differentiating superficial from deep surgical site infection is also controversial and inherently complex. Specific cutoffs for synovial fluid leukocyte count and blood C-reactive protein (CRP) in the acute stage have been suggested as a way to superficial infection requiring superficial wound washout from deep infection requiring a formal debridement, antibiotics and implant retention (DAIR) procedure. The goal of this study is to analyze clinical and laboratory findings of an institutional protocol of “aggressively” proceeding with formal DAIR in all patients with complicated wound healing

Despite modern surgical techniques, reported rates of deep infection following Total Knee Replacement (TKR) persist between 1–2.5%. Coagulase-negative staphylococcus (CNS) has become the most common causative organism, and while growth of CNS is more indolent thanstaphylococcus aureus, it has a relatively higher minimum inhibitory concentration (MIC) against cephalosporins. Tissue concentrations of prophylactic antibiotics may fall below this level during TKR with conventional ‘systemic’ dosing.

Regional administration of prophylactic antibiotics via a foot vein following tourniquet inflation has been shown to provide tissue concentrations approximately 10 times higher than systemic dosing, however cannulation of a foot vein is difficult, time consuming, and may compromise sterility.

Intraosseous cannulation offers an alternative method of accessing the vascular system, and the aim of this study was to assess its effectiveness in administration of prophylactic antibiotics. 22 patients undergoing primary total knee arthroplasty were randomised into two groups. Group 1 received 1g of cephazolin systemically 10 minutes prior to tourniquet inflation. In Group 2 the EZ-IO tibial cannulation system was used, and 1g of cephazolin was administered intraosseously in 200ml of normal saline following tourniquet inflation and prior to skin incision. Subcutaneous fat and femoral bone samples were taken at set intervals during the procedure, and antibiotic concentrations measured using High Performance Liquid Chromatography (HPLC).

There were no significant differences in patient demographics, comorbidities, or physical parameters between groups. The overall mean tissue concentration of cephazolin in subcutaneous fat was 185.9μg/g in the intraosseous group and 10.6μg/g in the systemic group (p<0.01). The mean tissue concentration in bone was 129.9 μg/g in the intraosseous group and 11.4μg/g in the systemic group (p<0.01). These differences were consistent across all sample time points throughout the procedure. No complications occurred in either group.

Intraosseous regional administration can achieve tissue levels of antibiotic over an order of magnitude higher than systemic administration. Further work is required to determine if there is clinical benefit in preventing infection, particularly against CNS. This novel mode of drug administration may also have other applications, allowing ‘surgical site delivery’ of medication while minimising systemic side effects.

Open fractures are common, and infection a frequent complication. There is still uncertainty regarding the urgency of initial treatment. The majority of animal studies indicate that early irrigation and debridement reduces infection; unfortunately, these studies often do not involve antibiotics. Clinical studies indicate that the timing of initial debridement does not affect the infection rate. These studies are observational and fraught with confounding variables. The purpose of this study was to control for these variables using an animal model incorporating both systemic antibiotics and surgical treatment.

This study used a segmental defect rat femur model contaminated with Staphylococcus aureus and treated with a 3 day course of systemic cefazolin (5 mg/Kg 12 hourly) and surgical treatments, both of which were initiated independently at 2, 6 and 24 hour time points. After 14 days bone and hardware was harvested for separate microbiological analysis.

These results show that the earlier systemic antibiotic treatment or surgery is initiated. When antibiotics are started at 2 hours, delaying surgical treatment from 2 to 6 hours significantly increases infection (p=0.047). However, delaying surgery to 24 hours increases infection, but not significantly (p=0.054). The timing of antibiotics had a more significant effect on the proportion of positive samples than earlier surgery. At the 2 and 6 hour treatments, the p value was 0.004 and for the 6 and 24 timings it was 0.003.

Surgery and antibiotics at 2 hours completely eradicates the bacteria, but surgical delay for 6 hours appears to allow the bacteria to form non-susceptible colonies. Delaying antibiotics to 6 or 24 hours had a profound detrimental effect on the infection rate regardless of timing of surgery. These findings are consistent with the concept that bacteria progress from a vulnerable planktonic form to a treatment-resistant biofilm.

Background

Despite aggressive debridement, thorough irrigation, administration of systemic antibiotics and staged treatment, many open fractures still become infected. A graft that can promote bone regeneration and prevent infection could decrease complications. Polyurethane (PUR) scaffolds have been previously shown in separate studies to be non-toxic, osteoconductive, can promote bone growth through BMP delivery and prevent infection by having sustained release of an antibiotic. This scaffold can deliver both BMP and vancomycin simultaneously; the purpose of this study is to determine if the co-delivery of the antibiotic inhibits bone formation.

Aim

Periprosthetic joint infection (PJI) is a major complication of prosthetic implantation and needs a combined surgical and antimicrobial treatment. One-stage revision results usually in similar cure rate than two-stage (around 85–92%), but antibiotic therapy duration is not well established. The aim of study was to evaluate the efficacy of a short six-weeks antibiotic course in hip and knee PJIs after one-stage replacement arthroplasty (RA).

Antibiotic-loaded PMMA spacers are used with increased frequency in two-stage revision arthroplasty. The release of aminoglycosides and vancomycin, the most commonly used antibiotics, is prompt, and concentrations are inhibitory. The release kinetic from PMMA bone cement shows a biphasic profile, consisting in an initially high and rapid drug release followed by a slower but sustained phase.

However, this general profile of drug release kinetics from PMMA spacers in vitro may have great variability in terms of drug amount, modality, and duration of elution. Initial drug concentration, cement surface area and porosity are essential and well-known factors in determining the drug release. Moreover, viscosity, vacuum-preparation and the different technical characteristics of commercially available spacers are additional factors of variability. Industrial preformed spacers are considered superior to custom-made devices because of uniform mixing and standardized procedures.

Spacers produced by different manufacturers vary in their mechanical properties and antibiotic elution characteristics. Small changes in the formulation of a bone cement can also affect these properties.

Similar bone cements produced by various brands release different amount of drugs. Gentamicin diffuses from Palacos in a larger amount and for a longer period than from Simplex and CMV. Spacers produced in France (Synicem™) and in Argentina (Subiton™) elute less total amount of gentamicin than those produced in Italy (Spacer G™) and show a delayed peak drug release. The low initial release of antibiotic can contribute to unsatisfactory antimicrobial effect and to the risk of selection of resistant bacteria. Some spacers release gentamicin for longtime (months), while others release antibiotic for only two weeks.

In the last years an evolution of PMMA spacers production occurred and modifications in the polimerization process of cement can increase cement porosity and antibiotic elution from spacers.

The current commercial preformed spacers for 10 days elution (Spacer G™, prepared with Cemex HP) release more gentamicin (34.1 mg) than previous models, which were prepared with Cemex SP (16.4 mg). Furthermore, they maintain a high elution rate (1.4–1.6 mg/day after one month).

The combination of Gentamicin and Vancomycin mantains an elution pharmacokinetic profile that is superimposable to that of Gentamicin and Vancomycin alone, with synergistic effects against multiresistant bacteria in prosthetic infection site.

In conclusion, the antibiotic release from PMMA spacers of various brands is not equivalent. The old elution data are no longer valid for new preparations. Consequently, this additional factor of variability should be considered in clinical practice and literature data utilisation.

Background: Despite aggressive debridement, thorough irrigation, systemic antibiotics, and staged treatment, many open fractures still become infected. A graft that can promote bone regeneration and prevent infection could decrease complications. Polyurethane (PUR) scaffolds have previously been shown in separate studies to be nontoxic, osteoconductive, can promote bone growth by delivering BMP, and prevent infection by the sustained release of an antibiotic. This scaffold can deliver both BMP and vancomycin simultaneously; the purpose of this study is to determine if the co-delivery of the antibiotic inhibits bone formation.

Methods: Using an established critical size defect rat femur model, the amount of bone formation created by PUR scaffolds containing low and high doses of rhBMP-2 (2.4 μg and 22.4 μg respectively) and 0.8 mg vancomycin (8% of graft by weight) were compared to scaffolds that contained rhBMP-2 without antibiotics. After 4 weeks, the femurs were harvested and bone growth was assessed using microCT.

Results: There was no significant difference in bone growth between the groups that had the high dose of rhBMP-2. Surprisingly, the scaffolds that had the low dose of rhBMP-2 and vancomycin promoted more bone formation than scaffolds that had rhBMP-2 and no antibiotics.

Conclusions: The addition and co-delivery of vancomycin to the scaffolds did not inhibit bone growth. The addition of vancomycin to the PUR scaffolds may have altered the release kinetics of the rhBMP-2; this may explain the increase of bone formation in this group. This study demonstrates that incorporation of a therapeutic and a clinically-relevant level of vancomycin does not inhibit bone formation. These results suggest that a dual delivery bone graft has potential to reducing complications associated with open fractures.

Summary Statement

Combination of antibiotics with N-acetylcisteine and sub-MIC concentration of erythromycin was evaluated in two collection and 16 clinical strains of staphylococci isolated from PJI. The results were strain-dependent, so it evidences the necessity of perform individual studies of biofilm susceptibility.

INTRODICTION

Since 1985, not resorbable crystalline osteoconductive hydroxyapatite (HA) granules were interposed on the interface between bone and bone cement at the cementation (Interface Bioactive Bone Cement: IBBC) of total hip arthoplasty (THA) to prevent generation of connective tissue and osteolysis for the longevity of cemented THA. To prevent the patients from infection, we are planning to use b-tricalcium phosphate (Beta-TCP) impregnated with antibiotics along with HA granules. However, there have been no reports on the loading and release of antibiotics from fine granules of Beta-TCP. Here, we have investigated the loading of antibiotics on Beta-TCP and their release in vivo.

The aims of the study were primarily to establish the overall success of debridement, antibiotics and implant retention (DAIR) in the management of infected total hip replacements (THRs) and secondarily to identify risk factors for failure.

Using a standardised and recognised study protocol (“Meta-analysis of observational studies in epidemiology (MOOSE) guidelines) a systematic review and meta-analysis of the literature was performed. The primary outcome measure of interest was treatment success. The search strategy and inclusion criteria plus quality assessment yielded 39 articles eligible for analysis.

The proportion of success from the literature following DAIR in the management of infected THRs is improving over time – the pooled mean proportion of success is 84.5% in studies from 2011–15. There was improved success with early debridement (75.7%) compared with delayed debridement (48.1%) (p=0.006).

The reported outcomes following DAIR appear to be improving with time. One of the most influential determinants of outcome is timing of debridement from onset of symptoms.

Surgeons should have a low threshold for investigating deep infection when presented with an acutely symptomatic THR and be aware of the updated reported outcomes associated with DAIR when considering management options.

The objective of this study was to compare the elution characteristics, antimicrobial activity and mechanical properties of antibiotic-loaded bone cement (ALBC) loaded with powdered antibiotic, powdered antibiotic with inert filler (xylitol), or liquid antibiotic, particularly focusing on vancomycin and amphotericin B.

Cement specimens loaded with 2 g of vancomycin or amphotericin B powder (powder group), 2 g of antibiotic powder and 2 g of xylitol (xylitol group) or 12 ml of antibiotic solution containing 2 g of antibiotic (liquid group) were tested.

Vancomycin elution was enhanced by 234% in the liquid group and by 12% in the xylitol group compared with the powder group. Amphotericin B elution was enhanced by 265% in the liquid group and by 65% in the xylitol group compared with the powder group. Based on the disk-diffusion assay, the eluate samples of vancomycin-loaded ALBC of the liquid group exhibited a significantly larger inhibitory zone than samples of the powder or the xylitol group. Regarding the ALBCs loaded with amphotericin B, only the eluate samples of the liquid group exhibited a clear inhibitory zone, which was not observed in either the xylitol or the powder groups. The ultimate compressive strength was significantly reduced in specimens containing liquid antibiotics.

Adding vancomycin or amphotericin B antibiotic powder in distilled water before mixing with bone cement can significantly improve the efficiency of antibiotic release than can loading ALBC with the same dose of antibiotic powder. This simple and effective method for preparation of ALBCs can significantly improve the efficiency of antibiotic release in ALBCs.

We thank H.Y. Hsu for performing the bioassay.

Recent work has demonstrated that intra-operative contamination of spinal surgical wounds is relatively common. The most frequently isolated wound contaminants are Propionibacterium spp. and coagulase negative Staphylococcus spp. The aim of this study is to examine the efficacy of prophylactic antibiotics used for spinal surgery against bacterial contaminants isolated from intra-operative samples retrieved during spinal surgical procedures.

Intra-operative wound samples were taken from 94 patients undergoing spinal surgery. Samples including skin, subcutaneous tissue and wound washings were processed, inoculated onto agar and incubated under both aerobic and anaerobic conditions for a period of 2 weeks. Bacterial growth was identified using commercially available biochemical test galleries. Thirty-six bacterial isolates were identified. The predominant bacteria isolated included Propionibacterium spp. (n=21) and coagulase negative Staphylococcus spp. (n=15). Each bacterial isolate was tested for its susceptibility to antibiotics used as antimicrobial prophylaxis during spinal surgery. Antibiotic sensitivities were determined in accordance with National Committee for Clinical Laboratory Standards (NCCLS) guidelines.

The antibiotic that performed best against Staphylococcus spp. isolated was ciprofloxacin with 93% of isolates being susceptible to this antibiotic. Cefamandole and cefuroxime also performed well against Staphylococcus spp. isolates.

The antibiotic that performed best against Propioni-bacterium spp. isolates was cefamandole with 100% of isolates being susceptible. Cefuroxime and ciprofloxacin also performed well. The antibiotic that performed least well against bacterial isolates was erythromycin with only 76% of Propionibacterium spp. and 47% of Staphylococcus spp. exhibiting susceptibility.

The results of this study demonstrate that ciprofloxacin, cefuroxime and cefamandole are effective against the majority of Propionibacterium spp. and Staphylococcus spp. isolated from within the spinal wound during surgery. The use of erythromycin in the penicillin allergic patient is questioned and ciprofloxacin proposed as a possible alternative.

Use of allograft bone has become standard for bridging defects unlikely to heal by simple fixation and routinely used in revision arthroplasties for implant stabilization. Unfortunately, this decellularized allograft provides an ideal surface for bacterial colonization, necessitating repeated surgeries, extensive debridement and lengthy antibiotic treatments. With up to 18% infection rate following allograft surgeries, a need for more effective means to prevent this process is evident. We describe a novel modification of native bone allografts that renders their surface bactericidal while increasing the effectiveness of systemic antibiotic treatments.

Allograft modification: Morselized human bone was washed extensively and sequentially coupled: 2X with Fmoc-aminoethoxyethoxyacetate (Fmoc-AEEA); deprotected with 20% piperidine in Dimethylformamide (DMF); and then coupled with vancomycin (VAN) for 12–16 hours. The VAN-bone was washed extensively with DMF and PBS for at least 1 day. VAN immuno-fluorescence: Control or VAN-bone was washed 5X with PBS, blocked with 10% FBS (1hr), incubated with rabbit anti-VAN IgG (4oC, 12h) followed by an Alexa-Fluor 488-coupled goat anti-rabbit IgG (1hr), and visualized by confocal laser microscopy. Antibiotic Activity. Equal dry weights of control and VANbone were sterilized with 70% ethanol, rinsed with PBS, and incubated with either Staphylococcus aureus (S. aureus) or Escherichia Coli (Ci=104 cfu) in TSB, 37oC, for 2, 5, 8 and 12 hrs. Antibiotic treatment: Clinical grade vancomycin was added to the solution with bacteria or following infection at a final concentration of 10μg/ml. Bacterial counts: Non-adherent bacteria were removed by washing and adherent bacteria suspended by sonication in 0.3% Tween-80 for 10mins followed by plating on 3M^® Petrifilms. Bacterial visualization: Non-adherent bacteria were removed by washing extensively with PBS and adherent bacteria stained with the Live/Dead BacLight Kit (20mins, RT) to cause viable bacteria to fluoresce green. Samples were visualized by confocal microscopy.

In comparison to controls, VAN-bone consistently reduced the graft bacterial load by ~90% at all time points. After staining and visualization of adherent bacteria, biofilm formation was apparent on controls by 12 hrs and absent from VAN-bone. E.coli, a gramnegative organism that is not sensitive to VAN, readily colonized both control and VANbone, confirming retention of VAN specificity. We then evaluated VAN-bone activity in a system that modeled systemic antibiotic therapy and antibiotic prophylaxis. In the absence of solution antibiotics, VAN-bone exhibited a significant decrease in bacterial colonization as compared to controls. When 10 μg/ml VAN was added to the medium for the last 4 h (modeling systemic antibiotic therapy), colonization of control surfaces was reduced, while colonization of VAN-allograft was almost eliminated. When 10 μg/ml VAN was added concomitantly with S. aureus, VAN-bone colonization was undetectable, while colonization of control surfaces still occurred.

We have previously described an antibiotic-tethered allograft that resists bacterial colonization. In this abstract, we test this technology with an vitro model of bone implantation in the presence of solution antibiotics. In these models, solution antibiotics failed to prevent infection of control bone while completely clearing the bacteria on VAN-bone. Furthermore, VAN bone exhibited high activity against S. aureus, a gram positive organism, whereas it was ineffective against E. coli, a gram negative organism. The specificity of the tethered antibiotic supported the view that the antibacterial properties of the allograft were related to the tethered antibiotic and not to undefined aspects of the attachment chemistry. In terms of antibacterial activity, when challenged with 104 CFU S. aureus (with concentrations reaching > 107 CFU by 24 h), the antibiotic -modified allograft consistently decreased bacterial colonization by > 90%; S. aureus inocula < 102 CFU resulted in no detectable colonization of the VAN-allograft. Thus, development of these allografts may not only combat allograft colonization but increase the effectiveness of prophylactic antibiotics to ultimately result in a new therapy for allograft-associated infection.

Purpose: Prophylactic antibiotics are frequently withheld until cultures are obtained in revision TKA. A prospective study was undertaken to determine whether prophylactic pre-operative IV antibiotics would affect the results of cultures obtained intra-operatively.

Method: A consecutive series of 25 TKA’s with a known infecting organism were enrolled over 36 months. Inclusion criteria: clinically infected TKA, a known preoperative infecting organism, and no recent antibiotic therapy. Re-aspiration of the infected TKA was performed following anesthesia and sterile prep. IV antibiotic prophylaxis was then administered and the tourniquet was then inflated. Intra-operative culture swabs and tissue were obtained at arthrotomy. The timing of events was recorded. Pre/post antibiotic culture data were analyzed to determine the effect of IV preoperative prophylactic antibiotics on cultures obtained intra-operatively.

Results: Mean time from end of antibiotic infusion to tourniquet inflation was 15 minutes; to arthrotomy culture was 25 minutes. In all 25 knees the organism(s) cultured at arthrotomy were the same as obtained at pre-operative aspiration. In 24 knees the organism cultured was sensitive to the preoperative prophylactic antibiotics given (Ancef and Vancomycin); one patient grew Candida albicans.

Conclusion: Pre-operative prophylactic antibiotics did not affect the results of intra-operative cultures, and should not be withheld prior to infected TKA surgery when an organism has been identified on aspiration. Based on these results, holding pre-operative antibiotics prior to revision TKA is rarely justified.

Aim

Thermal stability is a key property determining the suitability of an antibiotic agent for local application. Long-term data describing thermal stability without interference from carrier materials are scarce.