Periprosthetic Joint Infection After Total Knee Arthroplasty With or Without Antibiotic Bone Cement.

Importance: Despite increased use of antibiotic-loaded bone cement (ALBC) in joint arthroplasty over recent decades, current evidence for prophylactic use of ALBC to reduce risk of periprosthetic joint infection (PJI) is insufficient. Objective: To compare the rate of revision attributed to PJI following primary total knee arthroplasty (TKA) using ALBC vs plain bone cement. Design, Setting, and Participants: This international cohort study used data from 14 national or regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, New Zealand, Norway, Romania, Sweden, Switzerland, the Netherlands, the UK, and the US. The study included primary TKAs for osteoarthritis registered from January 1, 2010, to December 31, 2020, and followed-up until December 31, 2021. Data analysis was performed from April to September 2023. Exposure: Primary TKA with ALBC vs plain bone cement. Main Outcomes and Measures: The primary outcome was risk of 1-year revision for PJI. Using a distributed data network analysis method, data were harmonized, and a cumulative revision rate was calculated (1 - Kaplan-Meier), and Cox regression analyses were performed within the 10 registries using both cement types. A meta-analysis was then performed to combine all aggregated data and evaluate the risk of 1-year revision for PJI and all causes. Results: Among 2 168 924 TKAs included, 93% were performed with ALBC. Most TKAs were performed in female patients (59.5%) and patients aged 65 to 74 years (39.9%), fully cemented (92.2%), and in the 2015 to 2020 period (62.5%). All participating registries reported a cumulative 1-year revision rate for PJI of less than 1% following primary TKA with ALBC (range, 0.21%-0.80%) and with plain bone cement (range, 0.23%-0.70%). The meta-analyses based on adjusted Cox regression for 1 917 190 TKAs showed no statistically significant difference at 1 year in risk of revision for PJI (hazard rate ratio, 1.16; 95% CI, 0.89-1.52) or for all causes (hazard rate ratio, 1.12; 95% CI, 0.89-1.40) among TKAs performed with ALBC vs plain bone cement. Conclusions and Relevance: In this study, the risk of revision for PJI was similar between ALBC and plain bone cement following primary TKA. Any additional costs of ALBC and its relative value in reducing revision risk should be considered in the context of the overall health care delivery system.

How good are surgeons at disclosing periprosthetic joint infection at the time of revision, based on pre- and intra-operative assessment? A study on 16,922 primary total hip arthroplasties reported to the Norwegian Arthroplasty Register.

BACKGROUND AND PURPOSE: Revision due to infection, as reported to the Norwegian Arthroplasty Register (NAR), is a surrogate endpoint to periprosthetic joint infection (PJI). We aimed to find the accuracy of the reported causes of revision after primary total hip arthroplasty (THA) compared with PJI to see how good surgeons were at disclosing infection, based on pre- and intraoperative assessment. PATIENTS AND METHODS: We investigated the reasons for revision potentially caused by PJI following primary THA: infection, aseptic loosening, prolonged wound drainage, and pain only, reported to the NAR from surgeons in the region of Western Norway during the period 2010-2020. The electronic patient charts were investigated for information on clinical assessment, treatment, biochemistry, and microbiological findings. PJI was defined in accordance with the Musculoskeletal Infection Society (MSIS) definition. Sensitivity, specificity, and accuracy were calculated. RESULTS: 363 revisions in the NAR were eligible for analyses. Causes of revision were (reported/validated): infection (153/177), aseptic loosening (139/133), prolonged wound drainage (37/13), and pain only (34/40). The sensitivity for reported revision due to infection compared with PJI was 80%, specificity was 94%, and accuracy-the surgeons' ability to disclose PJI or non-septic revision at time of revision-was 87%. The accuracy for the specific revision causes was highest for revision due to aseptic loosening (95%) and pain only (95%), and lowest for revision due to prolonged wound drainage (86%). CONCLUSION: The accuracy of surgeon-reported revisions due to infection as representing PJI was 87% in the NAR. Our study shows the importance of systematic correction of the reported cause of revision in arthroplasty registers, after results from adequately taken bacterial samples.

The use of antibiotic-loaded bone cement and systemic antibiotic prophylactic use in 2,971,357 primary total knee arthroplasties from 2010 to 2020: an international register-based observational study among countries in Africa, Europe, North America, and Oceania.

BACKGROUND AND PURPOSE: Antibiotic-loaded bone cement (ALBC) and systemic antibiotic prophylaxis (SAP) have been used to reduce periprosthetic joint infection (PJI) rates. We investigated the use of ALBC and SAP in primary total knee arthroplasty (TKA). PATIENTS AND METHODS: This observational study is based on 2,971,357 primary TKAs reported in 2010-2020 to national/regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, the Netherlands, New Zealand, Norway, Romania, South Africa, Sweden, Switzerland, the UK, and the USA. Aggregate-level data on trends and types of bone cement, antibiotic agents, and doses and duration of SAP used was extracted from participating registries. RESULTS: ALBC was used in 77% of the TKAs with variation ranging from 100% in Norway to 31% in the USA. Palacos R+G was the most common (62%) ALBC type used. The primary antibiotic used in ALBC was gentamicin (94%). Use of ALBC in combination with SAP was common practice (77%). Cefazolin was the most common (32%) SAP agent. The doses and duration of SAP used varied from one single preoperative dosage as standard practice in Bolzano, Italy (98%) to 1-day 4 doses in Norway (83% of the 40,709 TKAs reported to the Norwegian arthroplasty register). CONCLUSION: The proportion of ALBC usage in primary TKA varies internationally, with gentamicin being the most common antibiotic. ALBC in combination with SAP was common practice, with cefazolin the most common SAP agent. The type of ALBC and type, dose, and duration of SAP varied among participating countries.

Amoxicillin Did Not Reduce Modic Change Edema in Patients With Chronic Low Back Pain: Subgroup Analyses of a Randomised Trial (the AIM Study).

STUDY DESIGN: Exploratory subgroup analyses of a randomised trial [Antibiotics in Modic changes (AIM) study]. OBJECTIVE: The aim was to assess the effect of amoxicillin versus placebo in reducing Modic change (MC) edema in patients with chronic low back pain. SUMMARY OF BACKGROUND DATA: The AIM study showed a small, clinically insignificant effect of amoxicillin on pain-related disability in patients with chronic low back pain and MC type 1 (edema type) on magnetic resonance imaging (MRI). MATERIALS AND METHODS: A total of 180 patients were randomised to receive 100 days of amoxicillin or placebo. MC edema was assessed on MRI at baseline and one-year follow-up. Per-protocol analyses were conducted in subgroups with MC edema on short tau inversion recovery (STIR) or T1/T2-weighted MRI at baseline. MC edema reductions (yes/no) in STIR and T1/T2 series were analyzed separately. The effect of amoxicillin in reducing MC edema was analyzed using logistic regression adjusted for prior disk surgery. To assess the effect of amoxicillin versus placebo within the group with the most abundant MC edema on STIR at baseline ("STIR3" group), we added age, STIR3 (yes/no), and STIR3×treatment group (interaction term) as independent variables and compared the marginal means (probabilities of edema reduction). RESULTS: Compared to placebo, amoxicillin did not reduce MC edema on STIR (volume/intensity) in the total sample with edema on STIR at baseline (odds ratio 1.0, 95% CI: 0.5, 2.0; n=141) or within the STIR3 group (probability of edema reduction 0.69, 95% CI: 0.47, 0.92 with amoxicillin and 0.61, 95% CI: 0.43, 0.80 with placebo; n=41). Compared with placebo, amoxicillin did not reduce MC edema in T1/T2 series (volume of the type 1 part of MCs) (odds ratio: 1.0, 95% CI: 0.5, 2.3, n=104). Edema declined in >50% of patients in both treatment groups. CONCLUSIONS: From baseline to one-year follow-up, amoxicillin did not reduce MC edema compared with placebo. LEVEL OF EVIDENCE: 2.

Increasing but levelling out risk of revision due to infection after total hip arthroplasty: a study on 108,854 primary THAs in the Norwegian Arthroplasty Register from 2005 to 2019.

Background and purpose - Focus on prevention, surveillance, and treatment of infection after total hip arthroplasty (THA) in the last decade has resulted in new knowledge and guidelines. Previous publications have suggested an increased incidence of surgical revisions due to infection after THA. We assessed whether there have been changes in the risk of revision due to deep infection after primary THAs reported to the Norwegian Arthroplasty Register (NAR) over the period 2005-2019.Patients and methods - Primary THAs reported to the NAR from January 1, 2005 to December 31, 2019 were included. Adjusted Cox regression analyses with the first revision due to deep infection after primary THA were performed. We investigated changes in the risk of revision as a function of time of primary THA. Time was stratified into 5-year periods. We studied the whole population of THAs, and the subgroups: all-cemented, all-uncemented, reverse hybrid (cemented cup), and hybrid THAs (cemented stem). In addition, we investigated factors that were associated with the risk of revision, and changes in the time span from primary THA to revision.Results - Of the 108,854 primary THAs that met the inclusion criteria, 1,365 (1.3%) were revised due to deep infection. The risk of revision due to infection, at any time after primary surgery, increased through the period studied. Compared with THAs implanted in 2005-2009, the relative risk of revision due to infection was 1.4 (95% CI 1.2-1.7) for 2010-2014, and 1.6 (1.1-1.9) for 2015-2019. We found an increased risk for all types of implant fixation. Compared to 2005-2009, for all THAs, the risk of revision due to infection 0-30 days postoperatively was 2.2 (1.8-2.8) for 2010-2014 and 2.3 (1.8-2.9) for 2015-2019, 31-90 days postoperatively 1.0 (0.7-1.6) for 2010-2014 and 1.6 (1.0-2.5) for 2015-2019, and finally 91 days-1 year postoperatively 1.1 (0.7-1.8) for 2010-2014 and 1.6 (1.0-2.6) for 2015-2019. From 1 to 5 years postoperatively, the risk of revision due to infection was similar to 2005-2009 for both the subsequent time periodsInterpretation - The risk of revision due to deep infection after THA increased throughout the period 2005-2019, but appears to have levelled out after 2010. The increase was mainly due to an increased risk of early revisions, and may partly have been caused by a change of practice rather than a change in the incidence of infection.

Clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes - secondary analyses of a randomised, placebo-controlled trial (the AIM study).

BACKGROUND: Randomised trials on antibiotic treatment for patients with chronic low back pain and vertebral endplate changes visible on MRI (Modic changes) have shown mixed results. A possible explanation might be a real treatment effect in subgroups of the study populations. The purpose of the present study was to explore potential clinical effect modifiers of 3-months oral amoxicillin treatment in patients with chronic low back pain and type I or II Modic changes at the level of a previous lumbar disc herniation. METHODS: We performed analyses of effect modifiers on data from AIM, a double-blind parallel-group multicentre trial. One hundred eighty patients with chronic low back pain, previous disc herniation, Modic change type I (n = 118) or type II (n = 62) were randomised to 3-months oral treatment with 750 mg amoxicillin (n = 89) or placebo (n = 91) three times daily. The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (possible values 0-24) at 1-year follow-up in the intention-to-treat population. The predefined minimal clinically important between-group mean difference was 4 RMDQ points (not reached in the primary analysis of AIM). Predefined baseline characteristics were analysed as potential effect modifiers, four primary (type I Modic changes, previous disc surgery, positive pain provocation test, high CRP) and five exploratory (disturbed sleep, constant low back pain, short duration of low back pain, younger age, and male) using ANCOVA with interaction terms. RESULTS: None of the four primary potential effect modifiers had strong evidence of modifying the treatment effect. In patients younger than 40 years the difference in mean RMDQ score between the treatment groups was - 4.0 (95%CI, - 6.9 to - 1.2), compared to - 0.5 (95%CI, - 2.3 to 1.3) in patients 40 years or older, both in favour of amoxicillin treatment (exploratory analysis). CONCLUSIONS: We did not find evidence for convincing clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes. Our results for younger age in these explorative analyses should not affect clinical treatment decisions without confirmation in future studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT02323412 , First registered 23 December 2014.

Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial.

OBJECTIVE: To assess the efficacy of three months of antibiotic treatment compared with placebo in patients with chronic low back pain, previous disc herniation, and vertebral endplate changes (Modic changes). DESIGN: Double blind, parallel group, placebo controlled, multicentre trial. SETTING: Hospital outpatient clinics at six hospitals in Norway. PARTICIPANTS: 180 patients with chronic low back pain, previous disc herniation, and type 1 (n=118) or type 2 (n=62) Modic changes enrolled from June 2015 to September 2017. INTERVENTIONS: Patients were randomised to three months of oral treatment with either 750 mg amoxicillin or placebo three times daily. The allocation sequence was concealed by using a computer generated number on the prescription. MAIN OUTCOME MEASURES: The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (range 0-24) at one year follow-up in the intention to treat population. The minimal clinically important between group difference in mean RMDQ score was predefined as 4. RESULTS: In the primary analysis of the total cohort at one year, the difference in the mean RMDQ score between the amoxicillin group and the placebo group was -1.6 (95% confidence interval -3.1 to 0.0, P=0.04). In the secondary analysis, the difference in the mean RMDQ score between the groups was -2.3 (-4.2 to-0.4, P=0.02) for patients with type 1 Modic changes and -0.1 (-2.7 to 2.6, P=0.95) for patients with type 2 Modic changes. Fifty patients (56%) in the amoxicillin group experienced at least one drug related adverse event compared with 31 (34%) in the placebo group. CONCLUSIONS: In this study on patients with chronic low back pain and Modic changes at the level of a previous disc herniation, three months of treatment with amoxicillin did not provide a clinically important benefit compared with placebo. Secondary analyses and sensitivity analyses supported this finding. Therefore, our results do not support the use of antibiotic treatment for chronic low back pain and Modic changes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02323412.

Antibiotic treatment In patients with chronic low back pain and Modic changes (the AIM study): study protocol for a randomised controlled trial.

BACKGROUND: A previous randomised controlled trial (RCT) of patients with chronic low back pain (LBP) and vertebral bone marrow (Modic) changes (MCs) on magnetic resonance imaging (MRI), reported that a 3-month, high-dose course of antibiotics had a better effect than placebo at 12 months' follow-up. The present study examines the effects of antibiotic treatment in chronic LBP patients with MCs at the level of a lumbar disc herniation, similar to the previous study. It also aims to assess the cost-effectiveness of the treatment, refine the MRI assessment of MCs, and further evaluate the impact of the treatment and the pathogenesis of MCs by studying genetic variability and the gene and protein expression of inflammatory biomarkers. METHODS/DESIGN: A double-blinded RCT is conducted at six hospitals in Norway, comparing orally administered amoxicillin 750 mg, or placebo three times a day, over a period of 100 days in patients with chronic LBP and type I or II MCs at the level of a MRI-confirmed lumbar disc herniation within the preceding 2 years. The inclusion will be stopped when at least 80 patients are included in each of the two MC type groups. In each MC type group, the study is designed to detect (ß = 0.1, α = 0.05) a mean difference of 4 (standard deviation 5) in the Roland Morris Disability Questionnaire score between the two treatment groups (amoxicillin or placebo) at 1-year follow-up. The study includes cost-effectiveness measures. Blood samples are assessed for security measures and for possible inflammatory mediators and biomarkers at different time points. MCs are evaluated on MRI at baseline and after 12 months. A blinded intention-to-treat analysis of treatment effects will be performed in the total sample and in each MC type group. DISCUSSION: To ensure the appropriate use of antibiotic treatment, its effect in chronic LBP patients with MCs should be re-assessed. This study will investigate the effects and cost-effectiveness of amoxicillin in patients with chronic LBP and MCs at the level of a disc herniation. The study may also help to refine imaging and characterise the biomarkers of MCs. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02323412 . Registered on 21 November 2014.

Bacterial and Hematological Findings in Infected Total Hip Arthroplasties in Norway Assessment of 278 Revisions Due to Infection in the Norwegian Arthroplasty Register.

Our aim was to assess the bacterial findings in infected total hip arthroplasties (THAs) in Norway. We also wanted to investigate the relationship between causal bacteria and hematological findings. Revisions reported to the Norwegian Arthroplasty Register (NAR) due to infection after total hip arthroplasty during the period 1993 through September 2007 were identified. One single observer visited ten representative hospitals where clinical history, preoperative blood samples and the bacterial findings of intraoperative samples were collected. Bacterial growth in two or more samples was found in 278 revisions, and thus included. The following bacteria were identified: Coagulase-negative staphylococci (CoNS) (41%), Staphylococcus aureus (S. aureus) (19%), streptococci (11%), polymicrobial infections (10%), enterococci (9%), Gram-negative bacteria (6%) and others (4%). CoNS were the most common bacteria throughout the period but in the acute postoperative infections (< 3 weeks) S. aureus was the most frequent bacterial finding. We found no change in the distribution of the bacterial groups over time. S. aureus appears correlated with a higher C-reactive protein value (CRP) (mean 140 (95% Confidence interval (CI): 101-180)) than CoNS (mean 42 (CI: 31-53)). S. aureus also correlated with a higher erythrocyte sedimentation rate value (ESR) (mean 67 (CI: 55-79)) than CoNS (mean 47 (CI: 39-54)).

Increasing Resistance of Coagulase-Negative Staphylococci in Total Hip Arthroplasty Infections: 278 THA-Revisions due to Infection Reported to the Norwegian Arthroplasty Register from 1993 to 2007.

We investigated bacterial findings from intraoperative tissue samples taken during revision due to infection after total hip arthroplasty (THA). The aim was to investigate whether the susceptibility patterns changed during the period from 1993 through 2007. Reported revisions due to infection in the Norwegian Arthroplasty Register (NAR) were identified, and 10 representative hospitals in Norway were visited. All relevant information on patients reported to the NAR for a revision due to infection, including bacteriological findings, was collected from the medical records. A total of 278 revision surgeries with bacterial growth in more than 2 samples were identified and included. Differences between three 5-year time periods were tested by the chi-square test for linear trend. The most frequent isolates were coagulase-negative staphylococci (CoNS) (41%, 113/278) and Staphylococcus aureus (19%, 53/278). The proportion of CoNS resistant to the methicillin-group increased from 57% (16/28) in the first period, 1993-1997, to 84% (52/62) in the last period, 2003-2007 (P = 0.003). There was also significant increase in resistance for CoNS to cotrimoxazole, quinolones, clindamycin, and macrolides. All S. aureus isolates were sensitive to both the methicillin-group and the aminoglycosides. For the other bacteria identified no changes in susceptibility patterns were found.

[Paracetamol poisonings after the lifting of the place of sale restriction]. / Paracetamolforgiftninger etter innføring av ny salgsordning.

BACKGROUND: Before 2003, the sale of paracetamol in Norway was restricted to pharmacies only. In November 2003 this place of sale restriction was lifted, allowing sale of paracetamol in non-pharmacy locations. The purpose of this study was to investigate the incidence, severity and mortality of paracetamol poisoning before and after the lifting of the place of sale restriction. MATERIAL AND METHODS: Incidence was assessed using discharge data from three selected hospitals and the enquiry database of the National Poisons Information Centre (PIC). Evaluation of poisoning severity was based on degree of hepatotoxicity in admitted patients, number of requests regarding evaluation for liver transplantation at the National Transplantation Unit and PIC severity grading of cases. Data regarding mortality of paracetamol poisoning was obtained from the National Cause of Death Register. Data for the two-year period before (2001-2002) the place of sale restriction was lifted was compared with two years after (2005-2006). RESULTS: There was no significant change in the number of hospital admissions due to paracetamol poisoning in any of the three hospitals following the lifting of the place of sale restriction. The number of inquiries to PIC regarding paracetamol intake showed a statistical significant increase. The extent of severe paracetamol poisoning might be rising, but the mortality of paracetamol poisoning does not appear to have increased since the place of sale restriction was lifted. INTERPRETATION: There is no evidence that the number of paracetamol poisonings or deaths has increased since the place of sale restriction was lifted. The proportion of patients with liver toxicity/liver damage, and the number of patients evaluated for liver transplantation may be increasing. However, the development in paracetamol poisoning should be monitored in the coming years.