Background. Exebacase, an antistaphylococcal lysin in Phase 3 of development as a treatment for S. aureus bacteremia/right-sided endocarditis has demonstrated antibiofilm activity in vitro and has previously been used as salvage therapy in four patients with relapsing multidrug-resistant (MDR) S. epidermidis knee prosthetic joint infection (PJI) using a procedure called LysinDAIR (administration of the lysin during the performance of an arthroscopic DAIR). Materials/methods. We performed a single center, exploratory, open-label prospective study using the LysinDAIR procedure in patients with chronic (inoculation >3 months prior to treatment) coagulase-negative staphylococci (CNS) PJI of the knee with two different clinical presentations and treatment paradigms. Cohort A: first episode of CNS knee PJI, for whom the LysinDAIR was followed by clindamycin + levofloxacin planned to be prescribed for three months and then stopped; and Cohort B: relapsing episodes of MDR CNS knee PJI for whom the LysinDAIR was followed by primary antimicrobial therapy for three months, followed by suppressive antimicrobial therapy (SAT). Exebacae susceptibility testing was performed before treatment for each patient. In agreement with the French Health authority, exebacase (2 to 3.5 total mg in 30–50 ml (∼0.067 – 0.075 mg/m) was administered directly into the joint during arthroscopy. Results. Eight patients were treated. Exebacase administration was well tolerated by all patients and no serious adverse drug reactions to exebacase were reported. In cohort A (n=4), patients had susceptible S. epidermidis PJI, a painful joint effusion without fistula and without loosening, and received three months of levofloxacin + clindamycin (one patient received an alternative regimen following antibiotic adverse events) and then antibiotics were stopped. During a follow-up of 14, 19, 26 and 36 months, no relapse, no recurrence of the joint effusion and no loosening occurred. In cohort B (n=4), patients had MDR CNS, clinical signs of septic arthritis with a joint effusion without fistula and without loosening and received daptomycin + linezolid or doxycycline. One patient died from COVID-19 at week 4. SAT (tedizolide, n=2; doxycycline, n=1) was then prescribed to other patients. One experienced an infection relapse involving S. caprae under tedizolid therapy at six months. The two other patients continue to do well under SAT 8 and 12 months after the LysinDAIR procedure. Conclusions. The LysinDAIR procedure is a minimally invasive procedure, which has been shown to be easy-to-perform, safe, and has the potential for use as initial treatment or salvage therapy in patients with CNS chronic knee PJI

Aims. This study aimed to assess the performance of an automated multiplex polymerase chain reaction (mPCR) technique for rapid diagnosis of native joint septic arthritis. Patients and Methods. Consecutive patients with suspected septic arthritis undergoing aseptic diagnostic joint aspiration were included. The aspirate was used for analysis by mPCR and conventional microbiological analysis. A joint was classed as septic according to modified Newman criteria. Based on receiver operating characteristic (ROC) analysis, the area under the ROC curve (AUC) values of the mPCR and the synovial fluid culture were compared using the z-test. A total of 72 out of 76 consecutive patients (33 women, 39 men; mean age 64 years (22 to 92)) with suspected septic arthritis were included in this study. Results. Of 72 patients, 42 (58%) were deemed to have septic joints. The sensitivity of mPCR and synovial fluid culture was 38% and 29%, respectively. No significant differences were found between the AUCs of both techniques (p = 0.138). A strong concordance of 89% (Cohen’s kappa: 0.65) was shown. The mPCR failed to detect Staphylococcus aureus (n = 1) and Streptococcus pneumoniae (n = 1; no primer included in the mPCR), whereas the synovial fluid culture missed six microorganisms (positive mPCR: S. aureus (n = 2), Cutibacterium acnes (n = 3), coagulase-negative staphylococci (n = 2)). Conclusion. The automated mPCR showed at least a similar performance to the synovial fluid culture (the current benchmark) in diagnosing septic arthritis, having the great advantage of a shorter turnaround time (within five hours). Cite this article: Bone Joint J 2019;101-B:288–296

Aim. Periprosthetic joint infections (PJI) are increasing due to our elderly population with the need of a joint prosthesis. These infections are difficult to treat, because bacteria form biofilms within one day on the orthopedic implant surface. Notably, most of the current available antibiotics do not penetrate the biofilm or are not active against the sessile forms of bacteria. Therefore, prevention is key. In the current paradigm, bacteria from the skin surface or dermis - such as Staphylococcus aureus, coagulase-negative staphylococci, or Cutibacterium sp. – contaminate the periimplant tissue during surgery. Cutibacterium avidum, which has increasingly been reported in hip PJIs, colonizes the skin in the groin area in 32.3%. We were wondering if standard skin antisepsis before hip arthroplasty is effective to eliminate C. avidum colonization in the surgical field. Method. In a single-center, prospective study, we preoperatively screened all patients undergoing a hip arthroplasty through a direct anterior approach for different skin bacteria in the groin area. Only in patients colonized with C. avidum, we intraoperatively searched for persistent bacterial growth during and after triple skin antisepsis with povidone-iodine/alcohol. For that, we collected skin scrapings after first and third antisepsis and biopsies from the dermis at the surgical incision and evaluated bacterial growth and species. In addition, thin sections of the dermis biopsies were submitted to Fluorescence in situ Hybridization (FISH) using pan-bacteria probe EUB338. Results. From October 2018 until March 2019, 53 patients (47.2% female) were screened. Patients were mainly colonized with coagulase-negative staphylococci (41, 77.4%; 41), C. avidum (12, 22.6%), and Cutibacterium acnes (8, 15.1%). Intraoperative skin antisepsis of patients colonized with C. avidum was ineffective to eliminate any bacteria in 75% (5 out of 7) after the first and 28.6% (2 out of 7) after the third antisepsis. Focusing on C. avidum, antisepsis was ineffective in 43% (3 out of 7) and 14% (1 out of 7), respectively. Dermis biopsies were all culture negative, but FISH showed positive ribosome-rich bacteria in 50%. Conclusions. We show in our ongoing study that the commensal C. avidum resists the standard skin antisepsis and bacteria visually persist in the dermis as demonstrated by FISH technique. Standard skin antisepsis is of limited effectiveness, resulting in a risk for intraoperatively acquired PJIs. Thus, new and more effective techniques to improve skin antisepsis are urgently needed

Aim. We reviewed a cohort of individuals with recurrent orthopaedic infection to describe the relative rates of microbial persistence vs re-infection at recurrence surgery. Method. A cohort of 125 individuals with recurrent infection (prosthetic joint infection, fracture-related infection and osteomyelitis) from two centres in the UK between 2007 and 2021. Electronic patient records were reviewed to identify culture results from surgical samples at index surgery and the next operation for recurrent infection. Antibiotic sensitivity results were recorded as sensitive, intermediate or resistant according to contemporary sensitivity testing guidelines. Results. Among patients with recurrent infection, 78/125 (62.4%) were male, with a median age 64 years (IQR 51–73y). 76 had prosthetic joint infection, and 49 had fracture related infection or osteomyelitis. Culture results at index procedure showed the most frequently isolated species were Staphylococci (Table 1). A single species was isolated in 75/125 (60%) and mixed species in 36/125 (28.8%). No organisms were cultured in 14/125 (11.2%). At re-operation 48/125 (38.4%) individuals had an organism from the same species or group as at the index operation. In 49/125 (39.2%), none of the organisms isolated at re-operation were grown at first operation. In 28/125 (22.4%), re-operative cultures yielded no growth. For each species isolated at the index procedure, the proportion with the same, different or no organisms isolated at the next procedure were reviewed (Table 1). Staphylococci (including S. aureus and coagulase-negative staphylococci) and Pseudomonas species showed the highest rate of persistence at the species level. Among coagulase-negative staphylococci, changes in antimicrobial sensitivity that make it unclear if these infections were truly persistent, or represented re-infection. Conclusions. Infection with different organisms was seen at similar rates (39.2% vs 38.4%) to persistent infection with the same species in this cohort. Staphylococcus aureus is the organism most likely to be persistently identified in recurrent infections

Purpose. Fracture-related infection (FRI) is an important complication related to orthopaedic trauma. Although the scientific interest with respect to the diagnosis and treatment of FRI is increasing, data on the microbiological epidemiology remains limited. Therefore, the primary aim of this study was to evaluate the microbiological epidemiology related to FRI, including the association with clinical symptoms and antimicrobial susceptibility data. The secondary aim was to analyze whether there was a relationship between the time to onset of infection and the microbiological etiology of FRI. Methods. Over a five-year period, FRI patients treated at the University Hospitals of Leuven, Belgium, were retrospectively included. The microbiological etiology and antimicrobial susceptibility data were analyzed. Patients were classified as having an early (<2 weeks after implantation), delayed (2–10 weeks) or late-onset (> 10 weeks) FRI. Results. One hundred ninety-one patients with 194 FRIs, mainly involving the tibia (23.7%) and femur (18.6%), were included. Staphylococcus aureus was the most frequently isolated pathogen, regardless of time to onset (n=61; 31.4%), followed by S. epidermidis (n=50; 25.8%) and non-epidermidis coagulase-negative staphylococci (n=35; 18.0%). Polymicrobial infections (n=49; 25.3%), mainly involving Gram-negative bacilli (n=32; 65.3%), were less common than monomicrobial infections (n=138; 71.1%). Virulent pathogens in monomicrobial FRIs were more likely to cause pus or purulent discharge (n=45;54.9%; p=0.002) and fistulas (n=21;25.6%; p=0.030). Susceptibility to piperacillin/tazobactam for GNB was 75.9%. Vancomycin covered 100% of Gram-positive cocci. Conclusion. The high frequency of polymicrobial infections, including Enterobacterales and enterococci, should be considered when choosing an empirical regimen, especially for early FRI. However, since antibiotic stewardship is the cornerstone of good antibiotic practice, overuse and misuse of broad-spectrum empiric therapy should be avoided at all costs. Large multicenter prospective studies are necessary to gain more insight into the added value of (broad) empirical antibiotic therapy

Background. Data regarding the diagnostic value of ultrasound (US)-determined fluid film and joint aspiration prior to revision total hip arthroplasty (THA) for suspected periprosthetic joint infections (PJIs) is limited. This study aimed to analyse (1) the value of US-determined fluid film, (2) characterisation of the pre- and intraoperative microbiological spectrum and resistance patterns and (3) the concordance between preoperative synovial fluid and intraoperative culture results. Methods. We analysed 366 US-examinations from 340 patients prior to revision THA. Selected cases were categorized into clearly infected, non-infected and inconclusive, according to the International Consensus Meeting (ICM) 2018 Criteria. If US-determined fluid film was <1mm, no aspiration was performed based on our institutional standard protocol. Patients were grouped into no-aspiration (144/366;[39.3%]), dry-tap (21/366;[5.7%]) and a successful-tap (201/366;[54.9%]). The microbiological spectrum and antibiotic resistance patterns were determined and differences were compared between pre- and intraoperative results. Results. The absence of US-determined fluid film showed no correlation with the presence of hip PJI. Overall, 29.9% cases of the no-aspiration-group had a confirmed PJI. Discrepancies were found in 43.2% between successful taps and intraoperative cultures. The most prevalent microorganisms in preoperative synovial fluid were Staphylococcus epidermidis (20.9%), Staphylococcus aureus (20.9%) and Enterococcus faecalis (9.3%). The most prevalent microorganisms in intraoperative cultures were Staphylococcus epidermidis, Cutibacterium acnes and other coagulase-negative Staphylococci (14.2%). Additional microorganisms were identified in 43.8% intraoperatively. Staphylococcus aureus was more often detected preoperatively (20.9% vs. 5.8%;P=0.003), and Cutibacterium acnes intraoperatively (2.3% vs. 14.4%;P=0.01). There were no differences between the antibiotic resistance patterns of pre- and intraoperative concordant microorganisms. Conclusion. Absence of US-determined fluid film cannot rule out the presence of hip PJI. US-guided joint aspirations is a well-established technique. However, the preoperative analysis of synovial fluid shows high discrepancies especially in Cutibacterium acnes and other rare gram-positive microorganisms compared to intraoperative cultures

Aim. S. aureus and coagulase-negative staphylococci are the most frequent bacteria responsible for PJI. In patients with acute PJI (i.e. <1 month following the implantation), DAIR with exchange of removal components followed by a combination of antibiotics that includes rifampin (particularly rifampin+fluoroquinolone) are recommended. Unfortunately, some patients could not receive rifampin due to drug-drug interaction or stopped it due to an adverse event. Finally, it was unclear if the dose and the duration of rifampin influenced the prognosis. Method. We performed a retrospective cohort study in 4 hospitals and included patients with staphylococcal acute post-operative (< 1 month) PJI treated with DAIR in 2011–2016 period. Univariate and multivariate Cox analysis and Kaplan Meier curves were used to determine the risk factors for treatment failure (persistence of clinical signs, new surgery w/o persistence or superinfection, infection-related death). Results. 79 patients were included (median age: 71 years IQR 53–89]; 55 men [69.6 %]; median ASA score: 2 [IQR 2–3]). Bacterial cultures revealed 65 S. aureus (82.3 %) and 15 coagulase-negative staphylococci (19.0 %) infections, including 14 methicillin-resistant isolates (17.7 %). Among all isolates, only 2 (2.5 %) were resistant to rifampin and 16 (20.3 %) were resistant to fluoroquinolone. The median duration of antimicrobial therapy was 92 days (IQR 31–152). Only 59 patients received rifampin (74.7 %), and 35 (44.3 %) the combination rifampin + fluoroquinolone. Median duration of rifampin was 56.5 days (IQR 15.8–86.0) and median dose 14.6mg/kg/d (IQR 13.0–16.7). Forty patients (50.6 %) received rifampin in the first 2 weeks and 43 patients (54.4 %) received at least 2 weeks of rifampin. Six patients (7.6 %) developed an adverse event leading to rifampin interruption. During a median follow-up of 443 days (IQR 219.5–790.5), 21 patients (26.6 %) experienced a treatment failure including 12 persistence of the initial pathogen (57.1 %) and 9 superinfections (42.9 %). An ASA score >2 (HR 2.8; 95%CI 1.26–6.15), the use of rifampin (HR 0.4; 95% CI 0.17–0.95) and the duration of rifampin treatment (HR 0.83; 95%CI 0.75–0.92 per additional week of treatment) were significant determinants of the outcome (but not methicillin-resistance). Receiving >2 weeks of rifampin prevented the failure, but an introduction during the first 2 weeks did not influence the outcome. Conclusions. In patients with staphylococcal acute PJI, the use of rifampin and its duration strongly influenced the prognosis. As 25% of patients could not receive rifampin, new drugs with anti-biofilm activity are required

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

The aim of this study was to re-assess whether the use of a ‘one-knife technique’ can be considered as safe as the alternative practice of using separate skin and inside knives for elective orthopaedic surgery. A total of 609 knife blades from 203 elective orthopaedic operations, with equal numbers of skin, inside and control blades, were cultured using direct and enrichment media. We found 31 skin blades (15.3%), 22 inside blades (10.8%), and 13 control blades (6.4%) gave bacterial growth. Of the 31 contaminated skin blades only three (9.7%) had growth of the same organism as found on the corresponding inside blade. It is not known whether contamination of deeper layers in the remaining 90% was prevented by changing the knife after the skin incision. The organisms cultured were predominantly coagulase-negative staphylococci and proprionibacterium species; both are known to be the major culprits in peri-prosthetic infection. Our study suggests that the use of separate skin and inside knives should be maintained as good medical practice, since the cost of a single deep infection in human and financial terms can be considerable

Aim. metagenomic next-generation sequencing (mNGS) has shown to be a useful method for pathogen detection in prosthetic joint infections (PJI). The technique promises to minimize the PJIs without the known causative agent. Our study aimed to compare diagnostic accuracies of cultures and mNGS. Method. In this study, a meta-analysis following PRISMA recommendations was performed. PubMed and OVID Medline databases were used for article search. The studies using mNGS whole-genome sequencing method and the ones where PJI diagnosis was based on one of the currently recognized criteria were included. Studies were excluded if they comprised less than twenty cases, the ones with insufficient data for the analyses (true positive, true negative, false positive and false negative values for both mNGS and culture results) and publications with strong duplication bias. Univariate metanalysis using a random-effect model has been performed in R studio with a “meta” package. Pooled sensitivity and pooled specificity were calculated. Results. Seven studies with a total of 822 cases were included in the meta-analysis, 476 cases defined as PJI and 346 controls. Two studies used IDSA (Infectious Diseases Society of America) diagnostic criteria and the Illumina HiSeq 2500 platform for sequencing and five studies used MSIS (MusculoSkeletal Infection society). Four of those used the BGISEQ-500 sequencing platform. For one study there was no data available. Studies were performed on prosthetic hip and knee joints. Through meta-analysis, it was observed that mNGS technique is more sensitive than cultures with 90% (CI 79%– 95%) and 74% (CI 68%-79%) respectively (p=0.006). The specificity between methods was similar, for mNGS reaching 94% (CI 89%-96%) and for cultures 97% (CI 90%-99%) (p=0.285). In the PJI group, 117 new possible pathogens that were not isolated by microbiological culture were detected by the mNGS, most frequently anaerobes and coagulase-negative staphylococci both in 20/117 (17.1%) cases. Fourteen new organisms were detected in the control group and were mostly regarded as contaminants. Conclusions. Metagenomic sequencing has shown to be more sensitive than microbiological cultures in pathogen detection and thus has a great potential to improve the diagnosis and treatment of PJI. More studies on different prosthetic joints and comparing different diagnostic criteria for PJI would be needed to better understand the true diagnostic power of this method

Aim. Dalbavancin is a lipoglycopeptide with a half-life of 14 days (range 6.1 to 18.4), significantly longer than other antimicrobials, which avoids the need for daily antibiotic dosing. This multi-centre observational study aims to describe the use of dalbavancin to facilitate discharge in treating bone and joint infections. Method. All adult patients treated with dalbavancin from January 2017 to September 2022 in four UK bone infection units were included. Data collected through a standardised data collection form included:. Clinical and microbiological characteristics. Hospital length of stay. Complications. Patient suitability for hypothetical treatment options, such as Outpatient Parenteral. Antibiotic Team (OPAT). Clinical outcome. Treatment-related costs were calculated for dalbavancin and the preferred hypothetical treatment option that would have been administered for the same duration. The costs were subtracted to calculate the cost difference. Clinical success was defined as the absence of definite failure in accordance with the OVIVA Trial protocol. Results. Thirty-six patients were included: 20 males and 16 females, with a median age of 53 (IQR 43–73): Thirteen were septic arthritis, twelve were prosthetic joints, seven were spondylodiscitis and five were other orthopaedic-related implant infections. In twenty cases the infecting organism was Staphylococcus aureus, fourteen were due to coagulase-negative staphylococci and two no cultured organism. Reasons for dalbavancin. The reasons for choosing dalbavancin over alternatives were due to either:. Necessity due to poor adherence (21), or lack of viable OPAT options due to antibiotic resistance or intolerance (7). OR. Convenience to avoid the need for OPAT (8). Dalbavancin was initiated at 1500mg after a median of 12 days (IQR 6–17) of in-hospital antimicrobial therapy. Subsequent dalbavancin doses were based on clinical decisions and ranged from 1000mg to 1500mg. Healthcare benefits. Switching to dalbavancin reduced treatment costs by a median of £3526 (IQR 1118 - 6251) compared with the preferred theoretical alternatives. A median of 31 hospital days (IQR 23–47) was avoided among patients who would have required a prolonged inpatient stay. Outcome. Overall, 20 patients (55.6%) were successfully treated after a median follow-up of 8 months (IQR, 5.8 – 18.4). No patients developed an adverse drug reaction. Conclusions. Dalbavancin can safely facilitate outpatient treatment in patients with limited oral options and in whom OPAT is unsuitable. Dalbavancin is cost-effective compared with the alternative of an inpatient stay

Aim. The gold standard treatment for late acute hematogenous (LAH) periprosthetic joint infection (PJI) is surgical debridement, antibiotics and implant retention (DAIR). However, this strategy is still controversial in the case of total knee arthroplasty (TKA) as some studies report a higher failure rate. The aim of the present study is to report the functional outcomes and cure rate of LAH PJI following TKA treated by means of DAIR at a long-term follow-up. Method. A consecutive prospective cohort consisting of 2,498 TKA procedures was followed for a minimum of 10 years (implanted between 2005 and 2009). The diagnosis of PJI and classification into LAH was done in accordance with the Zimmerli criteria (NEJM 2004). The primary outcome was the failure rate, defined as death before the end of antibiotic treatment, a further surgical intervention for treatment of infection was needed and life-long antibiotic treatment or chronic infection. The Knee Society Score (KSS) was used to evaluate clinical outcomes. Surgical management, antibiotic treatment, the source of infection (primary focus) and the microorganisms isolated were also assessed. Results. Among the 2,498 TKA procedures, 10 patients were diagnosed with acute hematogenous PJI during the study period (0.4%). All those 10 patients were operated by means of DAIR, which of course included the polyethylene exchange. They were performed by a knee surgeon and/or PJI surgeon. The failure rate was 0% at the 8.5 years (SD, 2.4) follow-up mark. The elapsed time between primary total knee replacement surgery and the DAIR intervention was 4.7 years (SD, 3.6). DAIR was performed at 2.75 days (SD 1.8) of the onset of symptoms. The most common infecting organism was S. aureus (30%) and E. coli (30%). There were 2 infections caused by coagulase-negative staphylococci and 2 culture-negative PJI. All culture-positive PJI microorganisms were susceptible to anti-biofilm antibiotics. The source of infection was identified in only 3 cases. The mean duration of antibiotic treatment was 11.4 weeks (SD 1.9). The postoperative clinical outcomes were excellent, with a mean KSS of 84.1 points (SD, 14.6). Conclusions. Although the literature suggests that TKA DAIR for acute hematogenous periprosthetic joint infection is associated with high rates of failure, the results presented here suggest a high cure rate with good functional outcomes. Some explanations for this disparity in results may be the correct diagnosis of LHA, not misdiagnosing acute chronic PJI, and a thorough debridement by surgeons specialized in PJI

Clear differentiation between aseptic failure and prosthetic joint infection remains one of the goals of modern orthopaedic surgery. The development of new diagnostic methods enabled more precise evaluation of the etiology of prosthetic joint failure. With the introduction of sonication an increasing number of culture-negative prosthetic joint infection were detected. The aim of our study was to evaluate culture-negative prosthetic joint infections in patients who were preoperatively evaluated as aseptic failure. For the purpose of the study we included patients planed for revision surgery for aseptic failure. Intraoperatively acquired samples of periprosthetic tissue and explanted prosthesis were microbiologicaly evaluated using standard microbiologic methods and sonication. If prosthetic joint infection was discovered, additional therapy was introduced. Between October 2010 and April 2013 54 patients were operated (12 revision knee arthroplasty, 42 revision hip arthroplasty). 10 (18,6%) patients had positive sonication and negative periprosthetic tissue sample, 5 (9,2%) patients had positive tissue samples, but negative sonication, in 9 (16,7%) patients both tests were positive and in 30 (55,5%) patients all microbiologic tests were negative. The microbiologic isolates of sonicate fluid were in 12 cases coagulase-negative staphylococci, in 3 cases P.acnes in 3 cases mixed flora, in 1 case enterococcus and in 1 case SA. From periprosthetic tissue cultures 5 samples have yielded coagulase-negative staphylococci in 5 cases P.acnes in 2 cases mixed flora, in 1 case enterococcus and in 1 case SA were isolated. With the increasing number of patients requiring revision arthroplasty, a clear differentiation between aseptic failure and prosthetic joint infection is crucial for the optimal treatment. Sonication of explanted material is more successful in the isolation of pathogens compared to periprosthetic tissue cultures. Sonication of explanted prosthetic material is helpful in the detection of culture-negative prosthetic joint infections

We aim to describe the microbiological spectrum and relevant antibiotic susceptibility profile of PJI in our institution over a five-year period(2009–2013) and determine its evolution considering the preceding six years(2003–2008) thus evaluating the adequacy of our empirical antibiotic regimen. We retrospectively reviewed the records of 96 consecutive PJI (51 hips:45 knees) treated from May 2009-December 2013. Demographics, microbial species and antibiotic susceptibility were recorded. These results were then compared to those previously obtained by studying the 2003–2008 time period. Infections were polymicrobial in 27 cases(28.1%) and only two cases(2.1%) were culture-negative accounting for a total of 132 different culture results. S.aureus grew in 37 samples(28.0%) being the most frequently isolated microorganism. Coagulase-negative staphylococci grew in 32 samples(24.2%) and gram negative bacteria in 35 samples(26.5%). Other Gram positive species (most commonly enterococci and streptococci) were isolated in 26 samples(19.7%). Comparing 2009–2013 to 2003–2008, there was a significant increase of polymicrobial infections – 28% vs. 8%(OR=4.6, 95%CI [1.9–11.3]) and a significant decrease of culture-negative cases – 2% vs. 18%(OR=0.1, 95%CI [0.02–0.4]). It is also noteworthy that the prevalence of gram negative isolates was significantly increased – 26.5% vs. 13.3%(OR=1.3, 95%CI [1.1–1.6]). Antibiotic susceptibilities study showed a 41.4% methicillin resistance among S.aureus and even higher among coagulase-negative staphylococci isolates(57.7%). This is a not quite significant decrease compared to the earlier period(p=0.10). We also found a high rate antibiotic resistance among gram negative: ampiciline(81.8%), amoxicilin/clavulanate(59.1%), ciprofloxacin(19.2%), aminoglycosides(17%), third generation cephalosporins(14.6%) and even carbapenems(13.6%). These results show that our sampling protocol has improved considerably as the proportion of culture-negative cases has dramatically decreased. On the other hand this may also help explain the increase in polymicrobial infections. We have no clear explanation for the increase in gram negative bacteria. Despite the downward trend we still face a very significant proportion of methicillin-resistant staphylococci infections. The antibiotic resistance profile among gram negative bacteria is also worrying. As such we believe a regimen consisting of vancomycin and gram-negative coverage such as aminoglycosides or a third generation cephalosporin is still warranted in our institution

Prosthetic joint infections (PJI) occur in 0.8–1.9 % of arthroplasties, but the absolute number is increasing because of the frequency of procedures. Two stage exchange is the most effective strategy, but failures are often described. Culture of perioperative tissues during removal of arthroplasty is a standard procedure but culture during second step is equally important to define a success or a failure. We retrospectively reviewed PJI treated with two stage-exchange from January 2011 and December 2012 at “Ospedale S. Maria Misericordia”, Albenga-Italy. The procedure calls for bacterial culture not only during first step but also during reimplantation. Antibiotic treatment is prolonged after reimplantation until the cultures availability. A failure was defined by persistence of infection for positive culture or reocurrence of infection during a follow up of at least 2 years in patients with negative cultures. Three positive cultures yielding phenotypically identical organisms, or a single specimen of a virulent microorganism (e.g. Staphylococcus aureus) were required to rule out false positive for contaminants. Patients with persistence of infection were treated for 3 months with antibiotics. 86 patients underwent the two stage treatment: 45 hip and 41 knee prosthesis. The average ESR before arthroplasty removal was 59 mm/ 1st h (range 5–120), the average CRP was 3.9 mg/dl (range 0.3 – 34). Coagulase-negative staphylococci were isolated in 31 cases, Staphylococcus aureus in 19, Streptococcus spp in 8 and enterococci in 4. Gram-negatives were isolated in 4 patients and polymicrobial infection in 6 patients. In 14 patients (16%) no pathogen was identified. A positive culture during reimplantation was documented in 11 (13%) cases: 8 coagulase-negative staphylococci, 2 Staphylococcus aureus, 1 Candida sp. All patients received 3 months of therapy after surgery and 6 of them were free of infection at 2 years of follow up after the end of treatment. Among the 75 patients with negative cultures, a relapse was documented in 2 (3%), after 5 and 24 months, respectively. These cases were treated with arthrodesis and 6 weeks antibiotic treatment, with resolution of infection but poor functional results. Overall the success rate of our strategy was 92% (79/86). In patients treated with two-stage exchange, the combination of cultures at reimplantation and antibiotic suppressive treatment for 3 months in presence of positive cultures, are associated with a high rate of success. Only a prolonged follow up can rule out a relapse and agree with a true resolution of infection

Aim. Bacteriophages, viruses specific of bacteria, are receiving substantial attention as alternative antibacterial agents to treat bacteria frequently multi-resistant to antibiotics and/or able to form biofilms, such as staphylococci. The latter are responsible for very difficult to treat bone and joint infections (BJIs). In this context, our consortium aims to develop a production of therapeutic phages in accordance with the will of ANSM (French National Agency for the Safety of Medicines and Health Products) to encourage the development of a national academic platform for phage therapy. We report the isolation and characterization of new anti-Staphylococcus phages as well as the evaluation of their activity on a collection of clinical strains of S. aureus (SA) and coagulase-negative staphylococci (CNS) in order to assess their therapeutic potential. Method. Seventeen phages were isolated from wastewater samples. Their identification was obtained by Illumina whole genome sequencing. To evaluate their spectrum of activity, 30 genetically characterized SA strains representative of the main genetic backgrounds as well as 32 strains belonging to 7 CNS species responsible for BJIs were included. The spot test technique, based on the determination of the Efficiency Of Plating ratio, was used (EOP, ratio between the phage titer obtained on a tested strain/titer on a reference strain, close to 1 if high sensitivity to the phage). Results. All isolated phages belonged to the Myoviridae family: 14/17 and 3/17 to the Kayvirus and Silviavirus genera respectively. Silviavirus phages were more active on SA strains (EOP>0.001 for 73–90% of strains) than Kayvirus phages (EOP>0.001 for 13–70% of strains, except for V1SA21: 80%). In total, 83% of strains were susceptible to the phage with the broadest spectrum in each genus, their combination representing a promising opportunity to prevent the emergence of resistance. Kayvirus phages had polyvalent activity on several CNS species (maximum 47% of tested strains), mainly S. lugdunensis, S. capitis and S. caprae, whereas Silviavirus phages were only active on 6–12% of the tested strains. Conclusions. We report the characterization of a large collection of novel phages with complementary spectra against a collection of SA and CNS strains. Further work is currently focused on i) the isolation of anti-S. epidermidis phages, bacterial species against which the present collection of phages was insufficiently active, while it is a major pathogen in this context, ii) the development of production and purification protocols in order to meet the requirements of ANSM for human use

Aim. Empiric antibiotic therapy for suspected pyogenic spondylodiscitis (SD) should be initiated immediately with severely ill patients and may also be necessary for culture-negative SD. The aim of this study was to infer an appropriate empiric antibiotic regimen by analyzing the antimicrobial susceptibility of isolated pathogens from microbiologically proven pyogenic spondylodiscitis. Method. We performed a retrospective review of adult patients with clinically proven SD treated at our level 1 trauma center between 2013 and 2020. Demographic data, radiologic findings, and treatment modalities were evaluated. The appropriateness of empiric antibiotic regimens was assessed based on the antibiograms of the isolated pathogens. Anamneses were used to distinguish between community-acquired (CA) and healthcare-associated (HA) pathogens, which included cases that had a hospital stay or invasive intervention in the past 6 months. Results. A total of 155 patients (male: N=88; female: N=67; mean age 66.1 ± 12.4 years) with SD were identified. In n= 74 (47.7%) cases, the infections were associated with the healthcare system (HA). N=34 (21.9%) patients suffered from sepsis. The lumbar spine was involved in 47.1% of the cases, the thoracic spine in 37.3%, and the cervical spine in 7.8%. In 7.8% of the cases, SD occurred in multiple spinal segments. N=96 (62.0%) patients were treated surgically. The mean hospital stay was 36.4 ± 36.3 days. Antibiograms of n=45 patients (HA: N=22; CA: N=23) could be retrospectively evaluated: The most frequently identified pathogens were Staphylococcus aureus (46.7%), Coagulase-negative Staphylococci (17.8%), Enterobacteriaceae (15.6%) and Streptococcus species (15.6%). Overall, 82.2% (HA: 68.2%; CA: 95.5%) of the isolated pathogens were sensitive to piperacillin/tazobactam, 77.8% (HA: 81.8%; CA: 72.2%) to vancomycin, 64.4% (HA: 68.2%; CA: 59.1%) to clindamycin, and 55.6% (HA: 36.4%; CA: 72.7%) to ceftriaxone. To a combination of vancomycin plus meropenem 97.8% of pathogens were sensitive (HA: 95.5%; CA: 100.0%), to vancomycin plus ciprofloxacin 91.1% (HA: 86.4%; CA: 95.7%), and to vancomycin plus cefotaxime 93.3% (HA: 90.9%; CA: 95.7%). In 14 cases, empiric antibiosis was adjusted based on the results of the antibiogram. Conclusions. Antibiotic resistance of CA SD pathogens differed significantly from HA SD. The identification of the pathogen and the analysis of its susceptibility guides the antibiotic therapy. Vancomycin in combination with a carbapenem, broad-spectrum cephalosporin, or fluoroquinolone may be appropriate for empiric treatment of HA SD

Aim. There is an ongoing controversy whether the observed benefit of infection risk reduction by ALBC outweighs the risk of possible antimicrobial resistance development. Methods. The scientific & clinical literature in PubMed, Medline and Embase has been systematically reviewed with the keywords “antibiotic resistance”, “antibiotic loaded bone cement”, “local antibiotics”, “bacterial colonization” and “joint infection”. In total 28 relevant publications were found with the majority of them reporting laboratory results. Only 7 papers focused on clinical septic situations & patient data. Results. Although rare as consequence of the initially high drug concentrations in situ, experimental and clinical studies demonstrated survival of resistant bacteria on ALBC with subsequent bacterial re-colonisation of the biomaterial. This was most notable for coagulase-negative staphylococci (CoNS). Bacterial survival in presence of ALBC represents a selection process of already pre-existing high-level resistant mutants and not antibiotic resistance induction. The use of antibiotic combinations with gentamicin in bone cement is associated with a markedly lower risk of survival of resistant bacteria. This is particularly important in patients at high infection risks and in septic revision cases. There is no clinical evidence for a widespread increase of clinically important gentamicin resistancies in the orthopaedic ward because of routine use of ALBC. On an individual basis, the benefit of a lower infection probability with combined systemic & local antibiotic application should outweigh the risk of selecting pre-existing resistant bacteria. Each prevented infection case means that a complex and extended antibiotic therapy with risk of antibiotic resistance development over time has been avoided for a patient. In those cases where pre-existing resistant bacteria have survived the prophylactic exposure to antibiotics in bone cement, they remain in vast majority still susceptible to the clinically important antibiotics used for treatment of prosthetic joint infections. Conclusions. The benefit of a lower infection probability with ALBC should outweigh the risk of selecting resistant bacteria against the particular antibiotic used in bone cement. A trend towards broad resistance development which may complicate treatment of infection cases was not found

Aims. Current antibiotic treatment strategies for prosthetic joint infection (PJI) are based mostly on observational retrospective studies. High-quality data from prospective cohorts using identical treatment strategies may improve current clinical practice. We developed a regional network of collaborating hospitals and established a uniform treatment protocol. Data from all patients diagnosed with a PJI are prospectively registered in a an online database. With this quality registry we aim to study the outcome of antibiotic and surgical strategies while adhering to a pre-established treatment protocol. Methods. A working group of orthopaedic surgeons, infectious disease specialists and microbiologists was established. The working group reached consensus on definition of PJI and a uniform treatment protocol, based on current guidelines and expert-based clinical experience. A website was built to communicate information to colleagues and patients (. www.protheseinfectie.nl. ). In each participating hospital weekly multidisciplinary meetings were started to discuss all PJI cases. All patients are included in an online quality registry and followed for at least two years. We aim to enroll >600 patients with a knee or hip PJI. Research will focus on the duration of antibiotic treatment, antibiotic suppressive therapy and comparison of different oral antibiotic treatment strategies in relation to successful treatment outcomes. Results. Currently, four regional hospitals are included in the partnership. Multidisciplinary meetings have lowered the threshold to discuss patients, and the adherence to the PJI treatment protocol has improved steadily. Complicated cases are discussed between colleagues from collaborating centers. The collaboration has been perceived as very successful by the participating hospitals. Since 2015, over 300 patients have been included, of whom 52% were male. In 26%, PJI occurred after revision surgery. Staphylococcus aureus was involved in 25% of cases, coagulase-negative Staphylococci in 23%, Streptococci in 13% and Gram-negative micro-organisms in 15%. Conclusions. In this project, collaboration between different medical specialties through multidisciplinary meetings was the key to the improvement of patient care The regional collaborative project led to the implementation of a uniform treatment protocol for PJI. With this prospective project we aim to improve patient care by providing evidence for optimal antibiotic and surgical strategies for PJI. Ideally, countries should have hospital networks and a uniform method of data collection to make it easy to share data for scientific research

Aim. This study aims to describe our department experience with single stage revision (SSR) for chronic prosthetic-joint infection (PJI) after total hip arthroplasty (THA) between 2005 and 2014 and to analyze success rates and morbidity results of patients submitted to SSR for infected THA according to pathogen. Method. We retrospectively reviewed our 10 years of results (2005–2014) of patients submitted to SSR of the hip combined with IV and oral antibiotic therapy for treatment of chronic PJI (at least 4 weeks of symptoms), with a minimum follow-up of four years (n=26). Patients were characterized for demographic data, comorbidities, identified germ and antibiotic therapy applied (empiric and/or targeted). Outcomes analyzed were re-intervention rate (infection-related or aseptic), success rate (clinical and laboratory assessment), length of stay, morbidity and mortality outcomes. Results. In this period, 26 single-stage revisions for chronic PJI of the hip were performed. Patients average age was 72 years (range 44–82). Ten patients were women. The average time of follow up was 69 months (range 4 to 12 years). The most commonly isolated bacteria were coagulase-negative Staphylococci (30%), methicillin-resistant Staphylococcus aureus (MRSA) (18%) and methicillin-sensitive Staphylococcus aureus (15%). It wasn't possible to identify the germ in 19% of the patients and other 23% were polymicrobial. Targeted antibiotic therapy was administered to 73% of patients and the most used targeted antibiotics were Vancomycin (53%), Linezolid (32%) and Rifampicin (21%). Mean length of stay was 25 days. In the follow-up period, 9 patients (35%) required a re-intervention for infection relapse. Two patients (8%) needed surgery because of persistent instability. During the follow-up period, the infection-free survival was 65% (33% for MRSA; 82% for coagulase-negative Staphylococci) and the surgery-free survival was 62%. Six patients (23%) died during the follow-up, all due to other medical conditions not related to hip infection. Conclusions. Our experience suggests that SSR is associated with good outcomes and low re-intervention rate, except in the case of infection due to MRSA. In this last group, the results were significantly poorer, what leads to suggest that a two-stage revision may be a better option. The potential advantages of a SSR include good rates of infection eradication, a decrease in surgical morbidity and mortality as well as a decrease in healthcare and global economic costs. As such, a one-stage aggressive surgical attitude in addition to targeted antibiotherapy seems to be a suitable solution in selected patients