One-stage revision for infected shoulder arthroplasty: prospective, observational study of 37 patients.

Background: Periprosthetic joint infection is a severe complication of joint replacement surgery. Thus two-stage exchange remains the gold standard, one-stage exchange is now widely recommended. We hypothesized that, for patients with chronic periprosthetic shoulder infection (PSI), treatment with a one-stage exchange would be an effective approach to eradicate infection, relieve pain, and restore function to the involved shoulder. Materials and methods: This monocenter cohort study in a Bone and Joint Infection Referral Center (11/2003-05/2020) included all patients with confirmed PSI treated by one-stage revision. Data were extracted from the prospective database, including demographics, infection characteristics, and functional evaluations (range of motion and Constant Score at admission and last follow-up). The primary outcome was the 2-year reinfection-free rate. Results: We included 37 patients. The refection-free rate was 5%. The most commonly isolated pathogen was Cutibacterium acnes (68%), isolated alone (15 patients, 41%) or as polymicrobial infections (10 patients, 27%). The Constant Score increased significantly from 24 to 53 (P = .001). Range of motion (forward elevation, abduction) was also significantly improved after surgery. Mean active forward elevation increased significantly by 45° from 60° to 105° postoperatively (P < .001), mean abduction increased by 42° from 55° to 97° (P < .001). Discussion: Results from our prospective cohort-extracted series suggest that one-stage revision is a reliable treatment with a low infection recurrence rate. Improved functional outcomes can be achieved with one-stage exchange. Our patients' overall functional results were similar to those previously reported for one-stage revision and better than those reported after two-stage exchange. Patients with multiple previous surgeries seem to have worse functional outcomes than the subgroup without surgery before the index arthroplasty. Conclusions: Our results and literature search findings suggest that one-stage revisions effectively eradicate PSIs, with good functional outcomes.

What clindamycin dose should be administered by continuous infusion during combination therapy with rifampicin? A prospective population pharmacokinetics study.

BACKGROUND: Despite its important drug-drug interaction, combined clindamycin/rifampicin therapy may achieve effective plasma clindamycin concentrations, provided clindamycin is administered by continuous infusion. However, the precise clindamycin dose remains unknown. OBJECTIVES: This study was undertaken to determine the daily clindamycin dose to be administered by continuous infusion in combination with rifampicin to achieve effective plasma clindamycin concentrations. PATIENTS AND METHODS: Two plasma clindamycin concentrations were determined prospectively for 124 patients with bone-and-joint infections treated with continuously infused clindamycin. Twenty patients received clindamycin monotherapy, 19 clindamycin combined with rifampicin and 85 received clindamycin successively without and with rifampicin. A population pharmacokinetic model was developed using NONMEM 7.5. Monte Carlo simulations were run to determine which regimens obtained clindamycin concentrations of at least 3 mg/L. RESULTS: A linear one-compartment model with first-order elimination accurately described the data. Clindamycin distribution volume was not estimated. Mean clindamycin clearances with rifampicin and without, respectively, were 33.6 and 10.9 L/h, with 12.8% interindividual variability. The lowest daily clindamycin dose achieving plasma concentrations of at least 3 mg/L in >90% of the patients, when combined with rifampicin, was 4200 mg/24 h. CONCLUSIONS: Our results support continuous infusion of 4200 mg of clindamycin/24 h, in combination with rifampicin. This high-dose regimen requires therapeutic drug monitoring-guided dose adaptation.

Doctor, what does my ceramic-on-ceramic hip arthroplasty weigh?

BACKGROUND: While total hip arthroplasty (THA) is generally very successful, certain patients remain dissatisfied. A common concern, especially in younger and more active patients, is the weight the implant will add to the hip. However, there is very little data available to help guide surgeons in addressing this concern. The goal of this study was therefore to compare the weight of the total hip arthroplasty implants to that of tissue removed. HYPOTHESIS: That the weight of the total hip arthroplasty implants would exceed that removed tissue. PATIENTS AND METHODS: A prospective study was conducted in 104 patients, without interfering with surgical plans. To account for different implant designs, especially relating to stem fixation, we included both cementless (n=51) and cemented (n=53) femoral stems. During the procedure, the removed bone and soft tissues, as well as the post-implantation cement were collected and weighed. The weight of the implants was provided by the manufacturer. RESULTS: Both cemented and cementless THA implants proved significantly heavier than the removed bone and soft tissues. The median weight gained was 145g [IQR: 123-168] with the cementless implant and 241g [221-364] with the cemented implant (p<0.001). Multivariable regression analysis of patient- or implant factors influencing weight gain after THA revealed that weight gain decreased with patient BMI (ß=-1.0, 95% CI: -2.0--0.1 (p=0.034)). In contrast, weight gain increased slightly with total implant weight (ß=0.7, 95% CI: 0.6-0.8 (p≤0.001)). Further, weight gain was greater for women (ß=19.0, 95% CI: 9.1-29.0 (p≤0.001) (men 150g [135-219], women 211g [157-250] (p=0.010)) and patients who received the cemented stem (ß=40.0, 95% CI, 19.4-46.5, p≤0.001). DISCUSSION: Current models cause a two- to three-fold gain of weight at the hip joint after THA. While it is not clear whether this weight increase has any clinical repercussions, this finding can be helpful when a patient raises questions on this topic during the preoperative counseling. More research is necessary to determine whether lighter implants may be beneficial for patients. LEVEL OF EVIDENCE: III, case control study.

Cutibacterium acnes Prosthetic Joint Infections: Is Rifampicin-Combination Therapy Beneficial?

No consensus has been reached on the optimal antibiotic regimen to treat Cutibacterium acnes PJIs (Ca-PJIs). In vitro studies showed excellent rifampicin efficacy against biofilm-associated C. acnes infections, but clinical studies did not confirm the superiority of rifampicin-combined therapy over monotherapy. This prospective cohort study was undertaken to analyze the outcomes of 70 patients who underwent exchange arthroplasty for chronic monomicrobial Ca-PJI and were treated with rifampicin or without between 2004 and 2019. The 37 patients treated from January 2004 to August 2014 were prescribed rifampicin-combination therapy and the 33 treated from September 2014 to December 2019 received monotherapy without rifampicin. The primary endpoint was the 2-year Kaplan-Meier-estimated reinfection-free probability, including relapses and new-pathogen PJIs. The 2-year reinfection-free rate was high and not different for patients who had received rifampicin or not (89.2% vs. 93.8%, respectively; p = 0.524). None of the patients relapsed and six developed new-pathogen PJIs. Our results do not support a benefit of rifampicin-combination therapy for patients who underwent exchange arthroplasty for chronic Ca-PJIs.

Pseudomonas aeruginosa prosthetic joint-infection outcomes: Prospective, observational study on 43 patients.

Objectives: Analysis the outcomes of Pseudomonas aeruginosa prosthetic joint infection (PJI), and of their clinical and microbiological characteristics, surgical strategies and antibiotic treatments. Methods: Monocenter cohort study in a Bone-and-Joint-Infection Referral Center (08/2004 to 10/2018) including all consecutive P. aeruginosa PJIs. Data were extracted from the prospective database, including the following events: relapses, new PJIs, related deaths. Results: Median [IQR]: among the 43 patients included (28 females; 72 [63-80] years old; 27 hip, 15 knee, and 1 shoulder PJIs), 29 (67%) had underlying comorbidities, 12 (28%) had previously been treated for another PJI and 9 (21%) had undergone previous surgeries for their P. aeruginosa PJI. Eleven (26%) PJIs were polymicrobial, 16 (37%) strains were wild type, 8 (19%) ciprofloxacin-resistant. PJIs were classified as late chronic (n = 33), early postoperative (n = 9) or acute hematogenous infection (n = 1). Forty patients underwent surgery: 27 one-stage and 5 two-stage exchanges, 3 debridement and implant retention, and 5 other surgical strategies. Antibiotic treatments were: 29 received 41 [37-43] days of combination therapy (IV anti-pseudomonal ß-lactam and 3-5 days of amikacin, then ß-lactam and oral ciprofloxacin), followed by oral ciprofloxacin for a total of 12 weeks; 10 received only IV antibiotics for 83 [77-86] days, including 37 [32-46] days of combination therapy; 49 days of ceftazidime alone for 1. During follow-up lasting 33 [24-64.5] months, 2 relapses, 3 new PJIs, and 2 related deaths occurred. Thirty-three (82%) patients and 93% of those managed with one-stage exchange experienced no event. Conclusion: Outcomes of our cohort's P. aeruginosa PJIs-predominantly monomicrobial, chronic, ciprofloxacin-susceptible, treated with one-stage exchange and prolonged IV antibiotics-were 82% favorable.

Population Pharmacokinetics of Orally Administered Clindamycin to Treat Prosthetic Joint Infections: A Prospective Study.

A population PK model of clindamycin orally administered to patients with prosthetic joint infections (PJIs) was developed using NONMEM 7.5. Monte-Carlo simulations were run to determine the probability of obtaining bone clindamycin concentrations equal to at least the MIC or four times the MIC for several MIC values and dosing regimens. One hundred and forty plasma concentrations prospectively obtained from 20 patients with PJIs were used. A one-compartment model with first-order absorption and elimination appropriately described the data. Mean PK-parameter estimates (F being the bioavailability) were: apparent clearance, CL/F = 23 L/h, apparent distribution volume, V/F = 103 l and absorption rate constant, Ka = 3.53/h, with respective interindividual variabilities (coefficients of variation) of 14.4%, 8.2% and 59.6%. Neither goodness-of-fit curves nor visual predictive checks indicated bias. The currently recommended 600 mg q8h regimen provided a high probability of obtaining concentrations equal to at least the MIC, except for MIC ≥ the clinical breakpoint for Staphylococcus spp. (0.25 mg/L). For such MIC values, higher daily doses and q6h regimens could be considered.

Streptococcal and Staphylococcus aureus prosthetic joint infections: are they really different?

BACKGROUND: Staphylococci and streptococci are the most frequent pathogens isolated from prosthetic joint infections (PJIs). The aim of this study was to analyze the outcome of streptococcal and methicillin-susceptible Staphylococcus aureus (MSSA) PJIs. METHODS: All monomicrobial streptococcal and MSSA PJIs managed in a French Referral Center (2010-2017) were sampled from the prospective PJIs cohort study. The primary outcome of interest was the cumulative reinfection-free survival at a 2-year follow-up. RESULTS: Two hundred and nine patients with 91 streptococcal and 132 staphylococcal infections were analyzed. Patients with streptococcal PJI were older, and infection was more frequently hematogenous. Reinfection-free survival rates at 2-years after all treatment strategies were higher for patients with streptococcal PJI (91% vs 81%; P = .012), but differed according to the strategy. After exchange arthroplasty, no outcome differences were observed (89% vs 93%; P = .878); after debridement, antibiotics and implant retention (DAIR), the reinfection-free survival rate was higher for patients with streptococcal PJI (87% vs 60%; P = .062). For patients managed with prolonged suppressive antibiotic therapy (SAT) alone, those with streptococcal PJIs had a 100% infection-free survival (100% vs 31%; P < .0001). CONCLUSIONS: Reinfection-free survival after DAIR and SAT was better for patients with streptococcal than those with MSSA PJIs. No difference was observed after prosthesis exchange.

Arthroplasty after septic arthritis of the native hip and knee: retrospective analysis of 49 joints.

Background: Arthroplasty after septic arthritis (SA) treatment raises diagnostic and therapeutic questions. The main objective was to evaluate infection-free survival of patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA) post-SA. Other objectives were to describe the population's characteristics, surgical strategies, results of preoperative examinations and cultures of intraoperative samples taken at implantation, and postoperative antibiotic therapy. Methods: This is a retrospective, observational, monocenter study, from January 2005 to May 2019, including all patients undergoing TKA or THA with prior or ongoing SA in the same joint. Infection-free survival was analyzed and reported. Results: Forty-seven patients, 29 men, 49 joints operated on (30 knees, 19 hips), were included. Median SA-to-arthroplasty interval was 32 [1-216] weeks. It was < 2  years for 43 joints and < 6  months for 19 joints. Six patients underwent arthroplasty while still on SA treatment. One-stage arthroplasty was done for 43 joints and two-stage arthroplasty for 6 joints. Eight (16 %) cultures of intraoperative specimens were positive. Median durations of postoperative antibiotic therapy were 10 d for sterile cultures and 82 d for those that were positive. At 2 years, infection-free survival rate was 95.9 % ( ± 0.02 ). After a median follow-up of 47 [18-142] months, no SA relapse was observed, but five patients developed new periprosthetic joint infections (PJIs) with a different microorganism. Conclusion: Arthroplasty may be a post-SA option, even within a short period of time. One-stage arthroplasty can be done if synovectomy is thorough, intraoperative samples are taken and antibiotics are administered until those culture results become available. We observed no SA relapse, but new PJIs occurred.

Successive new-pathogen prosthetic joint reinfections: Observational cohort study on 61 patients.

OBJECTIVES: Prosthetic joint infection (PJI) treatment failure may be due to relapsing infection (same microorganism) or new-pathogen reinfection (npPJI). The aim was to describe npPJI epidemiological, clinical and microbiological characteristics, their treatments and outcomes, and identify their risk factors. METHODS: This observational, single-center, cohort study was conducted in a French Referral Center for Bone-and-Joint Infections between September 2004 and December 2015. Patients treated for at least two successive hip or knee PJIs in the same joint with a different pathogen were identified in the prospective database. We compared each patient's first PJI and subsequent npPJI(s) to analyze the type and microbiological characteristics of npPJIs. To search for npPJI risk factors, we compared those cases to a random selection of 122 "unique-episode" PJIs treated during the study period. RESULTS: Among 990 PJIs, 79 (8%) npPJIs occurring in 61 patients were included. New-pathogen prosthetic joint infections (npPJIs) developed more frequently in knee (14%) than hip prostheses (5%). Median interval from the first PJI to the npPJI was 26 months. New-pathogen prosthetic joint reinfections (npPJIs) more frequently spread hematogenously (60% vs 33%) and were predominantly caused by Staphylococcus (36%) or Streptococcus (33%) species. Multivariate analysis identified two risk factors: chronic dermatitis (odds ratio: 6.23; P<0.05) and cardiovascular diseases (odds ratio: 2.71; P<0.01). A curative strategy was applied to 70%: DAIR (29%), one-stage (28%), two-stage exchange arthroplasty (7%) or other strategies (7%). The others received prolonged suppressive antibiotic therapy (30%). CONCLUSIONS: New-pathogen prosthetic joint infections (npPJIs) are complex infections requiring management by multidisciplinary teams that should be adapted to each clinical situation.

One-Stage Exchange Arthroplasty for Fistulizing Periprosthetic Joint Infection of the Hip: An Effective Strategy.

Background: Prosthetic hip infection (PHI) is a disastrous scenario after an arthroplasty. International guidelines contraindicate one-stage exchange arthroplasty for fistulizing chronic prosthetic hip infection (FCPHI), nevertheless few surgical teams, mostly from Europe, support one stage procedure for this indication. Questions/Purposes: Analysis of infection recurrence and implant failure of a series of FCPHIs treated with one stage arthroplasty. Patients and Methods: Sixty-six FCPHIs treated with one-stage exchange arthroplasty were prospectively followed up at least 2 years. Clinical, radiological and bacteriological signs suggestive of reinfection were sought, as well as implant failures and PHI related deaths. Results: Thirty-four females and thirty-two males with median age of 69.5 years [61-77] and BMI of 26 kg/m2 [22-31] were included. Fistulae were productive in 50 patients (76%). Staphylococcus was responsible for 45% of PHI and 21% were polymicrobial. Twenty-nine patients (44%) received preoperative antibiotic therapy. After a median 60-month follow-up [35-82], 3 patients (4.5%) presented reinfection (two new infections, one relapse) and 3 patients experienced implant failure (1 femoral fracture, 1 stem breakage, 1 recurrent dislocation). One death was related to PHI. After a minimum of 2 years, the infection control rate was of 95.3% (±0.02). Conclusion: One-stage exchange arthroplasty for FCPHIs showed a good infection control rate similar to that of non-fistulizing PHI. Systematic preoperative microbiological documentation with joint aspiration and, in some specific cases, the use of preoperative antibiotic therapy are among the optimizations accounting for the success of the one-stage arthroplasty. In light of these results, and those of other studies, international recommendations could evolve. Level of Evidence: Descriptive therapeutic prospective cohort study. Level of evidence: IV.

Minocycline Combined with Vancomycin for the Treatment of Methicillin-Resistant Coagulase-Negative Staphylococcal Prosthetic Joint Infection Managed with Exchange Arthroplasty.

Introduction: Treatment of methicillin-resistant (MR) staphylococcal prosthetic joint infections (PJIs) remains a matter of discussion, with vancomycin-rifampin combination therapy being the preferred treatment for DAIR and one-stage exchange arthroplasty strategies. This study analyzes the outcomes of patients with chronic methicillin-resistant coagulase-negative staphylococcal PJIs treated with vancomycin-minocycline combination therapy. Methods: This prospective, single center cohort study included all chronic MR coagulase-negative staphylococcal PJIs (01/2004-12/2014) treated with exchange arthroplasty and at least 4 weeks of minocycline-vancomycin. The following endpoints were considered: reinfection including relapse (same microorganism) and a new infection (different microorganism) and PJI-related deaths. Their outcomes were compared with PJIs treated with rifampin-vancomycin during the same period. Results: Thirty-four patients (median age, 69 years) with 22 hip and 12 knee arthroplasty infections were included. Sixteen (47%) had previously been managed in another center. Median vancomycin MIC of strains was 3 mg/L. Nineteen underwent one-stage, 15 two-stage exchange arthroplasty. After a median [IQR] follow-up of 43 [26-68] months, 2 patients relapsed and 6 developed a new PJI. Compared to 36 rifampin-vancomycin treated PJIs, relapse- or reinfection-free survival rates didn't differ, but more new infections developed in the minocycline group (6 vs 3; P 0.3). Conclusions: Minocycline-vancomycin combination therapy for chronic MR coagulase-negative staphylococcal PJIs seems to be an interesting therapeutic alternative.

One- or two-stage exchange for periprosthetic shoulder infection: Systematic review and meta-analysis.

INTRODUCTION: One-stage exchange is the gold-standard for management of periprosthetic shoulder infection. The present review compares efficacy between 1- and 2-stage exchange in this indication. MATERIAL AND METHODS: We performed a systematic literature review and meta-analysis following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) criteria. The literature search used the Medline, Embase and Central data-bases. The studies included assessed 1- and 2-stage exchange in periprosthetic shoulder infection. The main outcome was reinfection rate, and the secondary outcome postoperative complications rate. RESULTS: Twenty-one studies, for 501 patients, were included: 5 assessing 1-stage exchange, 11 2-stage, and 5 both. Mean follow-up was 4.3 years (range, 2-6.1 years). Mean reinfection rates ranged between 0 and 50% in 1-stage exchange and between 0 and 36.8% in 2-stage exchange. The combined rate was 7% (95% CI, 3.8-12.5%) in 1-stage and 21.3% (95% CI, 16-27.9%) in 2-stage exchange. Mean complications rates ranged between 0 and 50% in 1-stage exchange and between 5.7% and 73%% in 2-stage exchange. The combined rate was 17% (95% CI, 11.9-23.9%) in 1-stage and 32.8% (95% CI, 25.8-40.6%) in 2-stage exchange. DISCUSSION: To our knowledge, the present meta-analysis is the first to assess results in 1- and 2-stage exchange for chronic periprosthetic shoulder infection. CONCLUSION: One-stage exchange seemed to provide better results, with less reinfection and fewer complications than 2-stage exchange. LEVEL OF EVIDENCE: I, meta-analysis.

Haematogenous prosthetic knee infections: Prospective cohort study of 58 patients.

BACKGROUND: Prosthetic joint infection (PJI) is a rare (incidence, 0.15% to 0.9%) but serious complication of knee arthroplasty. Haematogenous PJI of the knee (KhPJI) which accounts for 10% of cases, has been less studied than PJI due to other mechanisms. The primary objective of this study in patients with KhPJI of the knee was to determine the 2-year infection eradication failure rate after either exchange arthroplasty or arthrotomy/synovectomy/irrigation (ASI), combined with prolonged peri-operative antibiotic therapy, at a referral centre for complex osteo-articular infections. HYPOTHESIS: ASI within 2 weeks after symptom onset and one-stage exchange arthroplasty produce similar 2-year success rates in patients with KhPJI of the knee. MATERIAL AND METHODS: A prospective observational cohort study was performed in patients managed for PJI of the knee between 2003 and 2015. The primary outcome measure was the occurrence of a septic event or of KhPJI -related death during a minimum follow-up of 2 years. RESULTS: Of 265 patients with PJI after total knee arthroplasty, 58 (22.1%) had KhPJI with onset more than 3 months after the last arthroplasty procedure and were included in the study. Among them, one-third had immune deficiencies. The most common causative organisms were streptococci (n=25, 43%) and Staphylococcusaureus (n=20, 34%). The primary focus of infection was identified in only 64% of patients and was most often cutaneous (n=19, 33%) or dental (n=11, 19%). A septic event or KhPJI-related death occurred in 5/34 (15%) patients after one-stage exchange arthroplasty and 6/19 (32%) patients after ASI within 15 days after symptom onset (p=0.03). Patient characteristics, type of prosthesis, and causative organism were not significantly associated with failure to eradicate the infection. CONCLUSION: ASI carried a high failure rate despite being performed within 15 days after symptom onset. One-stage exchange arthroplasty seems to be the best surgical option, particularly as the exact time of symptom onset may be difficult to determine. Identifying and eradicating the primary focus of infection is crucial. LEVEL OF EVIDENCE: II, low-powered prospective cohort study.

Curative treatment of prosthetic joint infection in patients younger than 80 vs. 80 or older.

OBJECTIVE: Prosthetic joint infection (PJI) is a serious complication of joint replacement surgery. The major pharmacological and surgical treatments required by PJI increase the risk of peri-operative complications in elderly patients. The increase in life expectancy combined with procedural advances make these treatments possible even in the oldest patients. Here, our objective was to compare the characteristics and outcomes of curative PJI treatment in patients < 80 years vs. ≥ 80 years. METHODS: A prospective single-center design was used to compare the characteristics and outcomes of curative treatment for hip or knee PJI in patients < 80 years and ≥ 80 years admitted in 2004-2014. RESULTS: Of 765 patients admitted for PJI, 590 were < 80 years and 124 were ≥ 80 years. Medical history and comorbidities were similar in the two groups. The older group had a significantly higher proportion of patients with American Society of Anesthesiologists Scores ≥ 3 and with streptococcal infection (20% vs. 13%, P < 0.05). After complete surgical excision and prolonged antibiotic therapy, the only event whose frequency differed significantly between the two groups was PJI-related death, which was more common in the older patients (6.5% vs. 0.8%, P < 0.05). The 2-year survival rate after one-stage exchange arthroplasty was > 90% in the ≥80 year group. CONCLUSION: Patients aged 80 years or older are eligible for the same curative pharmacological and surgical PJI treatments used in their younger counterparts. Before surgery, the risk/benefit ratio of the major surgical procedure required to treat PJI must be assessed on a case-by-case basis.

Analysis of postoperative and hematogenous prosthetic joint-infection microbiological patterns in a large cohort.

OBJECTIVES: This study was undertaken to analyze prosthetic joint infection (PJI)-causing microorganisms and compare their distribution patterns according to PJI classification. METHODS: Cohort study from a single referral center for bone-and-joint infections from January 2004 to December 2015. RESULTS: Nine hundred and twenty-six patients, who developed 997 PJIs, involving the hip (62%), knee (35%) and/or shoulder (1%), were included. PJIs were classified as early postoperative (19%), late chronic (30%), hematogenous (35%) and undetermined (16%). Pathogens most frequently isolated from early-postoperative PJIs were staphylococci (57%), with 25% each Staphylococcus aureus or Staphylococcus epidermidis; 21% were polymicrobial and 10% Gram-negative rods. For late-chronic PJIs, the most frequent microbes were staphylococci (61%), predominantly S. epidermidis (35%); anaerobic bacteria were isolated from 15%; 11% were polymicrobial. Hematogenous PJIs were 99% monomicrobial. Although S. aureus was the most frequently isolated species (28%), streptococci were isolated slightly more often than staphylococci (39% vs. 36%). Among streptococci, group B streptococci were the most frequent (15%). The portal of entry was identified for 52% of hematogenous PJIs: 15% cutaneous, 11% dental, 9% gastrointestinal, 6% urinary, and 11% miscellaneous. CONCLUSION: Although a wide variety of microorganisms was isolated from PJIs, specific microbiological patterns were observed according to infection classification.