Introduction. The treatment of chronic bone infection often involves excision of dead bone and implantation of biomaterials which elute antibiotics. Gentamicin is a preferred drug for local delivery, but its systemic use carries a well-established risk of nephrotoxicity. We aim to establish the risk of renal injury with local delivery in a ceramic carrier. Materials and Methods. 163 consecutive patients with Cierny-Mader Type 3 or 4 chronic osteomyelitis were treated with a single-stage operation which included filling of the osseous defect with a calcium sulphate-hydroxyapatite carrier containing gentamicin. The mean carrier volume used was 10.9mls, leading to a mean implanted gentamicin dose of 191.3mg (maximum 525mg). Serum creatinine levels were collected pre-operatively and during the first seven days post-operatively. Renal impairment was graded using the Chronic Kidney Disease (CKD) Staging system, and AKI was assessed using the RIFLE criteria. Results. 155 cases had adequate data to allow calculation of pre- and post-operative GFR. 7 patients had pre-existing renal disease. 70 patients (45.2%) had a temporary eGFR drop post-operatively, with the greatest decrease occurring a mean 3.06 days following surgery. Twenty cases had a >10% decline in eGFR, but 12 resolved within 7 days. 7 patients transiently fell into the “Risk” category according to RIFLE criteria, but no patient had a change consistent with “Injury”, “Failure” or “Loss” of renal function and none had clinical signs of new acute renal impairment post-operatively. Conclusions. The implantation of up to 525mg of gentamicin contained within Cerament G, as part of the surgical treatment of osteomyelitis, is safe and carries minimal risk of significant acute kidney injury. A small, transient increase in serum creatinine may be observed in the early post-operative period, and attention should be paid to limit patients exposure to other nephrotoxic agents. The majority of patients will return to their baseline renal function within 7 days following the operation. The presence of pre-existing renal disease is not a contraindication to local gentamicin therapy

Introduction. Rising incidence of fracture neck of femur (NOF) are associated with rising geriatric population. Majority of patients are suffering from comorbid factors. Impaired renal function is a common comorbid factor and most of the time it is attributed to an acute renal impairment following the fracture and surgery. Objective of this study was to identify the effect of renal comorbid factors and their probable relative risk for a fracture and compare the results with Asian and European data. Specific objective was to identify a possibility of presence of pretraumatic subclinical chronic renal failure among fractured Sri Lankans. Methodology. Data were collected from fractured patients (N=200) and non-fracture sample for a period of one year. Variables studied were, serum calcium, serum phosphate, blood hemoglobin level, blood urea and serum creatinine. Data were analyzed using binary logistic and multiple regressions, principal component statistical technique using STATA software. Results. The logistic regression of renal co morbid factors with fracture showed that relative risk of occurrence of higher blood urea (> 8.2 mmol/L) in a NOF patient is 3.35 times higher(p value 0.012), relative risks of occurrence of high serum creatinine (> 120 µmol/L) is 3.17 times higher(P value-0.027), risk of low hemoglobin (Hb < 12) is 2.58(p value 0.005) times higher than a non-fracture patient even after adjustments for blood loss following fracture. Results were compared with the Asian and European data. Conclusions. Pretraumatic high blood urea, serum creatinine and low hemoglobin are associated with NOF Sri Lankan patients. Comparative Asian data shows higher figures in Sri Lanka. Studies in Nordic countries and Europe shows higher incidence of renal impairment in fracture neck of femur patients. Further studies are required to assess the presence of pretraumatic sub clinical chronic renal insufficiency in Sri Lanka and in European countries

Aim. The use of bone substitutes such as calcium sulfate (CaSO4) and hydroxyapatite with local antibiotics are crucial in the treatment of osteomyelitis. They allow the treatment of the dead space and locally provide large concentrations of antibiotics. However, it is unknown whether use of local vancomycin may elute and influence on vancomycin plasma levels. The aim of this study is to assess whether the addition of vancomycin to CaSO4 with hydroxyapatite may increase vancomycin plasma concentrations in in patients with osteomyelitis and therefore alter dosage adjustments. Method. The present study investigates the vancomycin plasma concentrations at 72–94 h post-surgery after the application of local vancomycin within CaSO4 (660mg vancomycin/10cc) and hydroxyapatite bone substitute in patients treated with empiric intravenous vancomycin and surgically treated for osteomyelitis. Vancomycin plasma concentrations were analyzed in twelve patients with osteomyelitis surgically treated with local release of vancomycin by CaSO4 and hydroxyapatite and undergoing therapeutic drug monitoring (TDM) of their vancomycin plasma concentrations as it is routinely done in our hospital. From 2019 to 2022, demographic data, microbiology, type of osteomyelitis, amount of local vancomycin applied, alteration of renal function, and vancomycin levels were retrospectively analyzed. Results. Twelve patients were included: 9(75%) were men. Median (range) demographic and clinical data: age: 51(26–67) years; body mass index: 27.7(18–46.4) kg/m2;baseline serum creatinine: 0.85 (0.7–1.24)mg/dl and 5(41.7%) with and glomerular filtration rate < 90ml/min(CPD-EPI, ml/min). Most frequently isolated microorganisms were Staphylococci (58%). Seven (54%) patients were classified as Cierny-Mader Osteomyelitis type III, 3(23%) as type IV and 2(23%) as type I. Treatment data: initial dose of vancomycin: 1g/8h in 9(75.0%) and 1g/12h in 3(25%) patients, total daily dose/body weight: 35.3(15.9–46.2) mg/kg. Pharmacokinetic data:days of iv vancomycin treatment until first TDM measurement: 3(3–4) days; minimum and maximum vancomycin plasma concentrations: 9.4(3–17.3) mg/L and 19.6(11.3–33.4) mg/L, respectively; patients with therapeutic concentrations: 6(50%); infratherapeutic: 4(33.3%) and supratherapeutic/potentially toxic: 2(16.7%). These 2 patients were young, had a baseline conserved renal function and were receiving the higher dose of 1g/8h. Conclusions. Vancomycin incorporated into the bone substitute appears not to increase blood concentrations of the glycopeptide in patients with osteomyelitis treated surgically and with intravenous vancomycin. However, 2 of the 12 patients presented supratherapeutic and potentially nephrotoxic vancomycin concentrations in the first TDM measurement, even though they were young and without renal impairment and needed and unexpected dose reduction. These results suggest the need to confirm the safety of local vancomycin in further larger clinical studies

BACKGROUND. High-dose antibiotic cement spacers are commonly used to treat prosthetic joint infections following knee arthroplasties. Several clinical studies have shown a high success rate with antibiotic cement spacers, however there is little data on the systemic complications of high-dose antibiotic spacers, particularly acute kidney injury (AKI). This study aims to determine the incidence of AKI and identify risk factors predisposing patients undergoing staged revision arthroplasty with antibiotic cement spacers. METHODS. A single-institution, retrospective review was used to collect and analyze clinical and demographic data for patients who underwent staged revision total knee arthroplasty with placement of an antibiotic-impregnated cement spacer from 2006 to 2016. A search was made through specific procedure (DRG) and diagnostic (CD) codes. Baseline descriptive data were collected for all patients including age, sex, medical comorbidities, type and quantity of antibiotics used in the cement spacer, pre- and postoperative hemoglobin (Hg), BMI, smoking status, peak creatinine levels, and random vancomycin levels. Acute kidney injury was defined as a more than 50% rise in serum creatinine from a preoperative baseline within 90 days postoperatively. RESULTS. A total of 54 staged revision TKA surgeries performed by 5 different surgeons between 2006 and 2016. The total incidence of AKI was 31% (n=17). There was a significant positive association between change in creatinine level and use of oral/intravenous antibiotics (p=0.03, Spearman's rho=0.33) and a significant positive association between AKI and the use of tobramycin cement (p=0.01, Spearman's rho=0.38). Factors that were not significantly associated with AKI include presence of preexisting hypertension (p = 0.26), hyperlipidemia (p = 0.83), coronary artery disease (p = 0.86), chronic kidney disease (p=0.56), and smoking status (p=.35). There was a trend towards increased risk of AKI in patients with diabetes mellitus (p= 0.12), however this was not significant. CONCLUSION. In single staged revision knee arthroplasty there is a significant association between acute kidney injury and type of oral/intravenous antibiotic used in the treatment. Both the use of intravenous vancomycin and tobramycin cement are independently associated with higher rates of AKI. Preexisting medical comorbidities are not independent risk factors for development of AKI. Serum creatinine and measurement of serum aminoglycoside and vancomycin levels should be performed after placement of an aminoglycoside-containing antibiotic cement spacer in a staged revision arthroplasty

Aim. Chronic bone infections and infected fractures are often treated with excision of the dead bone and implantation of biomaterials which elute antibiotics. Gentamicin has been a preferred drug for local delivery, but this could induce renal dysfunction due to systemic toxicity. This is a particular concern in patients with pre-existing chronic renal disease treated with new antibiotic carriers which achieve very high peak levels of gentamicin in the first few days after surgery. Method. 163 patients (109 males; average age 51.6 years) with Cierny-Mader Type 3 or 4 chronic osteomyelitis had a single-stage operation with excision of the dead bone, filling of the osseous defect with a calcium sulphate-hydroxyapatite carrier, containing gentamicin and immediate soft tissue closure. 2. No patient was given systemic gentamicin or other renal toxic antibiotics. Mean carrier volume was 10.9mls (range 1–30mls) and mean gentamicin dosing was 190.75mg (maximum 525mg). Seven patients had pre-existing renal disease (4 diabetic nephropathy, 1 nephrotic syndrome, 1 renal transplant and 1 previous acute kidney injury). Serum creatinine levels were collected pre-operatively and during the first seven days post-operatively. Glomerular filtration rate (GFR) was calculated using the CKD-epi creatinine equation. Renal function was defined using the Chronic Kidney Disease (CKD) Staging system. Results. 155 cases had adequate data to allow calculation of pre- and post-operative GFR. Pre-operative CKD staging demonstrated 118 Class I (normal renal function), 30 Class II, 3 Class IIIa, 3 Class IIIb, and 1 Class V disease. Mean pre-operative GFR (99.7ml/min/1.73m. 2. , SD 21.0) was no different to post-operative GFR (103.2ml/min/1.73m. 2. , SD 21.3), p= 0.0861. Four cases had a >10% decline in GFR below normal, with only one case dropping a CKD stage, from I (normal) to II (mildly decreased). Only 1/7 cases with pre-existing renal disease had a GFR drop of >10% (from 11ml/min/1.73m. 2. to 8ml/min/1.73m. 2. ). 70/155 (45.2%) had a temporary GFR drop post-operatively, with the biggest drop occurring a mean 3.06 days following surgery (SD 2.1). No patient had clinical signs of new acute renal impairment post-operatively. Conclusions. Renal function is not significantly affected by local implantation of gentamicin up to 525mg. The presence of pre-existing renal disease is not a contraindication to local gentamicin therapy

INTRO. Two-stage revision arthroplasty for PJI may make use of an antibiotic-loaded cement spacer (ACS), as successful long- term prevention of reinfection have been reported using this technique.[i] However, there is little data on systemic complications of high-dose antibiotic spacers. Acute kidney injury (AKI) is of clinical significance, as the drugs most commonly utilized, vancomycin and aminoglycosides, can be nephrotoxic. We intended to determine the incidence of AKI in patients that underwent staged revision arthroplasty with an ACS, as well as to identify potential predisposing risk factors for the disease. METHODS. Local databases of six different orthopaedic surgeons were retrospectively reviewed for insertion of either a static or articulating antibiotic cement spacer by from 2007–2017. Dose of antibiotic powder implanted, as well as IV antibiotic used, was collected from operative records. Demographics, comorbidities, and preoperative and postoperative creatinine and hemoglobin values were recorded from the EHR. AKI was defined by a more than 50% rise in serum creatinine from preoperative baseline to at least 1.4 mg/dL, as described by Menge et al.[ii] Variables were analyzed for the primary outcome of AKI within the same hospital stay as insertion of the ACS. Categorical variables were analyzed with Chi-Square test, and continuous variables with univariate logistic regression. RESULTS. 75 patients (39 M, 36 F) receiving an ACS were identified, with a mean age of 70.0 (SD=10.6) and a mean BMI of 31.3 (SD=7.3). Incidence of in-hospital AKI was 13.3%. Patients reached AKI at a mean 6.7 days (SD=4.5), during a median length of stay of 13.5 days (IQR=21.8). No significant correlation was found between AKI and the variables of age (p=.430), BMI (p=.569) or gender (p=.181). AKI was also not associated with increased dose of vancomycin (p=.416), tobramycin (p=.440), or gentamycin (p=.846) within the cement spacer, or the comorbidities of hypertension (p=.094), diabetes (p=.146), coronary artery disease (p=1.00) and renal disease (p=.521). However, decreased baseline hemoglobin showed significantly increased risk for AKI (OR=1.67, p =.049), and increased creatinine showed a trend (OR=2.9, p=.059). Percentage of hemoglobin decrease (preoperative to postoperative) did not increase odds for AKI (p=.700). CONCLUSION. The incidence of acute kidney injury in patients that receive antibiotic cement spacers is relatively high when compared to the data reported in primary TKA. ii,[iii]. Our results suggest that patient related risk factors, such as low preoperative hemoglobin, may be involved in the etiology of AKI in this population. Therefore, it may be clinically appropriate to monitor anemic patients for AKI when implanting an ACS

To progress to a same day surgery program for arthroplasty, it is important that we examine and resolve the issues of why patients stay in the hospital. The number one reason is fear and anxiety of the unknown and of surgical pain. The need for hospital stay is also related to risk arising from comorbidities and medical complications. Patients also need an extended stay to manage the side effects of our treatment, including after effects of narcotics and anaesthesia, blood loss, and surgical trauma. The process begins pre-operatively with an appropriate orthopaedic assessment of the patient and determination of the need for surgery. The orthopaedic team must motivate the patient, and ensure that the expectations of the patient, family and surgeon are aligned. In conjunction with our affiliated hospitalist group that performs almost all pre-admission testing, we have established guidelines for patient selection for outpatient arthroplasty. The outpatient surgical candidate must have failed conservative measures, must have appropriate insurance coverage, and must be functionally independent. Previous or ongoing comorbidities that cannot be optimised for safe outpatient care may include: congestive heart failure, or valve disease; chronic obstructive pulmonary disease, or home use of supplemental oxygen; untreated obstructive sleep apnea with a BMI >40 kg/m2; hemodialysis or severely elevated serum creatinine; anemia with hemoglobin <13.0 g/dl; cerebrovascular accident or history of delirium or dementia; and solid organ transplant. Pre-arthroplasty rehabilitation prepares the patient for peri-operative protocols. Patients meet with a physical therapist and are provided with extensive educational materials before surgery to learn the exercises they will need for functional recovery. Enhancement of our peri-operative pain management protocols has resulted in accelerated rehabilitation. The operative intervention must be smooth and efficient, but not hurried. Less invasive approaches and techniques have been shown to decrease pain, reduce length of stay, and improve outcomes, especially in the short term. Between June 2013 and December 2015, 1957 primary knee arthroplasty procedures (1010 total, 947 partial) were performed by the author and his 3 associates at an outpatient surgery center. Seven percent of patients required an overnight stay, with a majority for reasons of convenience related to travel distance or later operative time. Importantly, no one has required overnight stay for pain management. Outpatient arthroplasty is safe, it's better for us and our patients, and it is here now. In an outpatient environment the surgeon actually spends more time with the patients and family in a friendly environment. Patients feel safe and well cared for, and are highly satisfied with their arthroplasty experience

In two-stage revision surgery of infected joint prosthesis, temporary bone cement spacers have been used for several years. By adding antibiotics to the cement, high local antibiotic concentrations that exceed the minimum inhibiting and bactericidal concentration of the respective pathogen during the first days after surgery, are achieved. Currently, aminoglycosides (e.g. gentamicin and tobramycin), as well as glycopetides (e.g vancomycin) are used as antibiotic agents and mixed into the acrylic cement. In order to increase the quantity of active antibiotic substances, we established a novel surgical technique of additional superficial vancomycin coating (SVC) of temporary bone cement spacer. The aim of this study was to analyze the safety of this method by measuring postoperative joint and serum vancomycin concentrations, as well as the creatinine levels. We reviewed prospectively collected data on all patients, which were treated by explanting the prosthetic components, following temporary spacer implantation and SVC between 05/2013 and 04/2015 at the Department of Orthopedic Surgery, Medical University of Graz. In total 13 patients were treated by addition SVC during the study period. Before hardening, vancomycin powder (2 grams) was pressed manually onto the surface of the bone cement. Vancomycin levels were obtained from drains and blood samples on postoperative days 1 to 5. Forty-six blood serum samples and 52 drain fluid samples were available for further. On postoperative day one to five, a median serum vancomycin level of < 2.0 μg/mL was present (range <2.0 – 3.9). The highest median vancomycin level from the drain was documented on postoperative day 1 with a value of 388.0 μg/mL (range 44.4–1650.0), continually decreasing until postoperative day 4. After SVC, neither an anaphylactic reaction nor side effects such as a red man syndrome, fever and chills were observed. Furthermore, no patient complained about subjective hearing loss. No serum creatinine increase of 0.5 mg/dL from creatinine baseline value or a ≥50% increase from baseline was detected. After a median of 64 days (range 18–82), the temporary cement spacer was explanted followed by prosthesis implantation. During this time no reinfection occurred. One patient suffered from a dislocation of the spacer with a distal femur fracture and was therefore re-operated after 18 days. Powdered vancomycin as an additional superficial coating of bone cement spacer results in much higher local antibiotic concentrations than in conventional spacers. The newly introduced method is feasible, safe and promising to enhance local inhibiting concentrations of vancomycin

To progress to a same day surgery program for arthroplasty, it is important that we examine and resolve the issues of why patients stay in the hospital. The number one reason is fear and anxiety for the unknown and for surgical pain. The need for hospital stay is also related to risk arising from comorbidities and medical complications. Patients also need an extended stay to manage the side effects of our treatment, including after-effects of narcotics and anesthesia, blood loss, and surgical trauma. The process begins pre-operatively with an appropriate orthopaedic assessment of the patient and determination of the need for surgery. The orthopaedic team must motivate the patient, and ensure that the expectations of the patient, family and surgeon are aligned. In conjunction with our affiliated hospitalist group that performs almost all pre-admission testing, we have established guidelines for patient selection for outpatient arthroplasty. The outpatient surgical candidate must have failed conservative measures, must have appropriate insurance coverage, and must be functionally independent. Previous or ongoing comorbidities that contraindicate the outpatient setting include: cardiac – prior revascularization, congestive heart failure, or valve disease; pulmonary – chronic obstructive pulmonary disease, or home use of supplemental oxygen; untreated obstructive sleep apnea – BMI >40 kg/m2; renal disease – hemodialysis or severely elevated serum creatinine; gastrointestinal – history or post-operative ileus or chronic hepatic disease; genitourinary – history of urinary retention or severe benign prostatic hyperplasia; hematologic – chronic Coumadin use, coagulopathy, anemia with hemoglobin <13.0 g/dl, or thrombophilia; neurological – history of cerebrovascular accident or history of delirium or dementia; solid organ transplant. Pre-arthroplasty rehabilitation prepares the patient for peri-operative protocols. Patients meet with a physical therapist and are provided with extensive educational materials before surgery to learn the exercises they will need for functional recovery. Enhancement of our peri-operative pain management protocols has resulted in accelerated rehabilitation. The operative intervention must be smooth and efficient, but not hurried. Less invasive approaches and techniques have been shown to decrease pain, reduce length of stay, and improve outcomes, especially in the short term. In 2014, 385 primary partial knee arthroplasty procedures (7 patellofemoral replacement, 13 lateral, and 365 medial) were performed by the author and his 3 associates at an outpatient surgery center. Of those, 348 (95%) went home the same day while 17 (5%) required an overnight stay, with 11 for convenience related to travel distance or later operative time and 6 for medical issues. Outpatient arthroplasty is safe, it's better for us and our patients, and it is here now. In an outpatient environment the surgeon actually spends more time with the patients and family in a friendly environment. Patients feel safe and well cared for, and are highly satisfied with their arthroplasty experience

Background. We switched our antibiotic prophylaxis for elective hip and knee surgery from cefuroxime to flucloxacillin with single dose gentamicin in order to reduce the incidence of C. Diff diarrhoea. More patients subsequently appeared to develop acute kidney injury (AKI). Methods. During a twelve month period we examined the incidence of AKI sequentially in 198 patients undergoing elective hip or knee surgery: cefuroxime (n = 48); high dose flucloxacillin (median 8g) (n = 52); low dose flucloxacillin (median 4g) (n = 46); and cefuroxime again (n = 52). Results. There were no statistically significant differences between the four groups by chi-square tests for age, gender, nature of operation (hip or knee surgery), American Society of Anaesthesia (ASA) grade, mode of anaesthesia (spinal ± general anaesthetic v GA), baseline serum creatinine, pre-operative co-morbidity (hypertension, diabetes), pre-operative medication (NSAIDs, ACEI/ARBs or betablockers) and post-operative hypotension. Patients receiving high dose flucloxacillin required more vasopressors during surgery (p = 0.02 by Kruskal-Wallis test). The proportion of patients in each antibiotic group with any form of AKI by RIFLE criteria was: first cefuroxime group (8%), high dose flucloxacillin (52%), low dose flucloxacillin (22%), second cefuroxime (14%) (p < 0.0001). Odds ratios (OR) for AKI derived from a multivariate logistic regression model and arbitrarily assigning an OR of 1 to first cefuroxime group, were: high dose flucloxacillin 14.5 (95% CI, 4.2–49.7); low dose flucloxacillin 3.0(0.8–10.8); cefuroxime again 2.0(0.5–7.7). Three patients required temporary haemodialysis. Biopsies in two of these showed acute tubulo-interstitial nephritis. All three patients belonged to the high dose flucloxacillin group. None of the patients developed C Diff diarrhoea. Summary. We have shown a strong association between high dose flucloxacillin with single dose gentamicin prophylaxis and subsequent development of AKI which was not confounded by any of the co-variates we measured

Aims

Calcium sulphate (CaSO₄) is a resorbable material that can be used simultaneously as filler of a dead space and as a carrier for the local application of antibiotics. Our aim was to describe the systemic exposure and the wound fluid concentrations of vancomycin in patients treated with vancomycin-loaded CaSO₄ as an adjunct to the routine therapy of bone and joint infections.

Little information is available about several important aspects of the treatment of melioidosis osteomyelitis and septic arthritis.

We undertook a retrospective review of 50 patients with these conditions in an attempt to determine the effect of location of the disease, type of surgical intervention and duration of antibiotic treatment on outcome, particularly complications and relapse.

We found that there was a 27.5% risk of osteomyelitis of the adjacent bone in patients with septic arthritis in the lower limb. Patients with septic arthritis and osteomyelitis of an adjacent bone were in hospital significantly longer (p = 0.001), needed more operations (p = 0.031) and had a significantly higher rate of complications and re-presentation (p = 0.048).

More than half the patients (61%), most particularly those with multifocal bone and joint involvement, and those with septic arthritis and osteomyelitis of an adjacent bone who were treated operatively, needed more visits to theatre.

Cite this article: Bone Joint J 2015;97-B:277–82.