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

Introduction The aim of this study was firstly to investigate the prevalence of icaABCD-operon which codes the production of the polysaccharide intracellular adhesin(PIA), responsible for biofilm production, in a collection of clinically significant staphylococci isolated from orthopaedic infections and secondly to assess the relationship between biofilm production and the presence or not of ica-operon.

First Step – Material & Methods Between 1/2003 and 12/2005 200 CoNS were isolated from orthopaedic patients associated with soft tissue and bone infections(group I) and 200 CoNS from blood cultures of hospitalized patients from different wards of the same Hospital(group II). Identification was carried out by Gram-stain, catalase and coagulase tests and the API Staph System. Detection of icaADBC genes was performed by PCR. Production of biofilm was tested by the method of Christensen.

Results In group I, 62(31.37%) carried the entire ica-operon; from these isolates biofilm formation was detected in 35(17.5%). 5 isolates, despite biofilm production, did not carry any gene of ica-operon. In group II, 70(35.5%) carried entire the ica-operon; biofilm formation was detected in 37(18.5%) of these isolates. 3 S. capitis, 1 S. epidermidis and 1 S. hominis carried only the icaADB, icaA and icaB genes respectively.

Second Step – Material & Methods Based on the observation of PIA-production only in (50%) of ica(+) CoNS, 20 S. epidermidis isolates recovered from clinical specimens (pus) of orthopaedic patients and belonging to distinct PFGE clones, were selected on the basis of the presence of the entire ica operon. Nevertheless, only 10 of them produced biofilm. Nucleotide sequence analysis of ica-operon was carried out in all isolates; expression of icaADBC genes was also tested by RT-PCR.

Results Sequencing analysis revealed that all isolates carried an intact ica-operon, without point mutations. Concerning icaADBC mRNA production, all genes of ica-operon were expressed in biofilm-producing isolates, whereas in the no-biofilm producing strains the icaA and icaC genes were not expressed, while a faint expression was observed for the icaB and icaD genes.

Discussion Biofilm-forming capacities of CoNS from orthopaedic infections was not significantly greater than those from other infections (p> 0,05). The capacity of ica-operon(+) staphylococcal isolates to form biofilm seems to be dependent on the expression of ica-genes, specifically of icaA and icaC. The inability of ica(+) isolates to produce biofilm emphasizes that some unknown mechanisms influence icaADBC expression. Finally, the recognition of biofilm-producing CoNS without carrying any gene of ica operon underlined the existence of unidentified also mechanisms controlling biofilm production, apart from icaADBC expression.

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

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

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

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

Introduction: The aim of study was to evaluate the prevalence of microbiological isolates obtained from patients admitted to a 308-bed university-affiliated adult and children orthopaedic hospital of northern Italy (with more than 16.000 admissions per year), during a three year period (2000–2002), and, to analyze modifications during this period with regard to the prevalence of methicillin-resistant staphylococci strains. Material and Methods: A retrospective study was conducted using laboratory records from 2000 to 2002 (2003 in progress) concerning bacterial and yeast isolates from all specimens sent to microbiological laboratory for culture. The specimens came from 8 surgical, 1 intensive care, 1 oncologie and 1 physiotherapy wards and included samples taken at surgical intervention, as like as at patient bed. Antimicrobial susceptibility testing results were also collected. All data were stored in an electronic database for statistical analysis. Results: Between 2000 and 2002 a total of 8302 clinical specimens have been cultured and they yielded to 2978 isolates from 2653 positive samples. The prevalence of positive cultures form 24.8% in 2000 to 36.7% in 2002 and the isolated organisms are shown in table 1. Gram positive bacteria represent more than 70% of isolates and staphylococci are the most common organism (almost 50%). Staphylococcus epidermidis and other coagulase-negative staphylococci prevalence raised during the period 2000–2002 (respectively 25.4% to 33.4%, and 3.3% to 6.5%). Methicillin resistance rate resulted, 27.1% to 34.9% for Staphylococcus aureus, 37.6% to 28% for Staphylococcus epidermidis, and 33.3% to 42.1% for other coagulase-negative staphylococci. No difference in methicillin sensitivity was found between staphylococci isolated from surgical sites and other samples (urine, blood, sputum, throat swab). Conclusions: Knowledge of the local epidemiology of pathogens in a surgical/orthopaedic hospital is . critical. in formulating . policies. on infection control. Amongst these rules the choice of antibiotic prophylaxis should be taken after analysis of bacteria prevalence and their antibiotic sensitivity

Background: Antibiotic-loaded spacers and cement nails are commonly used in patients undergoing a two-stage implant exchange procedure for treatment of prosthetic joint infection (PJI). During re-implantation 2–6 weeks after implant removal, tissue specimens are collected to document successful eradication of infection. However, these specimens have limited sensitivity, especially in patients receiving antimicrobial treatment. We investigated the value of sonication of removed spacers and cement nails. Methods: We prospectively included patients in whom a spacer or cement nail was removed from January 2007 through April 2009 during a two-stage exchange procedure. The removed temporary device was sonicated in a container with Ringer’s solution in an ultrasound bath for 5 min at 40 kHz (as described in . NEJM. 2007. ;. 357. :. 654. ). The resulting sonication fluid was cultured aerobically and anaerobically for 10 days. In parallel, > 2 tissue samples were collected for conventional cultures on blood agar plates and enrichment broth. PJI was defined as visible purulence, acute inflammation on histopathology, sinus tract or significant microbial growth in tissue or implant sonication cultures. Results: In this ongoing study, 28 spacers and 10 cement nails from patients with confirmed PJI were included (median age 75 y; range 49–86 y). All devices were impregnated with antibiotics (gentamicin and/or vancomycin) and were placed in the hip (n=21), knee (n=9) or shoulder joint region (n=7). At the time of explantation, the following pathogens were isolated: coagulase-negative staphylococci (n=19), Staphylococcus aureus (n=7), Streptococcus agalactiae (n=3), Propionibacterium acnes (n=5) and mixed infection (n=4). All patients received systemic antibiotics for a median of 19 days (range 11–42 days) before removal of the spacer/nail. At the time of re-implantation, tissue cultures were negative in all 38 patients, whereas sonication cultures showed growth of Propionibacterium acnes in 2 of 38 patients (5%) with a hip and shoulder spacer, both in significant numbers (150 and 550 colonies/ml sonication fluid, respectively). These organisms were probably present as mixed infection already at the time of explantation, but were missed due to overgrowth due to another organism (S. aureus in one patient and coagulase-negative staphylococci in another). Both patients were not initially treated for the Propionibacterium acnes infection, but the treatment was given after re-implantation. Conclusion: Sonication of removed spacers is a suitable approach to identify persistent infection in patients with a two-stage exchange. Sonication may replace the current standard approach consisting of multiple tissue specimens in order to document successful eradication of infection

Introduction. Management of periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is a challenging task. Antibiotic management remains elusive due to differences in epidemiology and resistance between countries and reports. Increasing resistance of bacteria is a concern. The aim of this study was to investigate the development of antibiotic resistance of main causative bacteria in a single center. Methods. A retrospective review of all revision TKA between 2006 and 2018 in a tertiary referral center was performed. Included were cases meeting the consensus criteria for PJI with at least two positive cultures. Three chronological groups were created using a two-step cluster analysis. Results. In 129 cases of PJI there were 161 different bacteria identified by growth in culture. Of all bacteria 76.4% were gram positive, 23.6% were gram negative. Coagulase-negative Staphylococci (CNS) were diagnosed in 46.6% cultures, followed by Staphylococcus aureus in 19.8% of cultures. Overall antibiotic resistance (p=0.454) and Staphylococcus aureus resistance (p=0.788) have not increased during the study period. CNS resistance to teicoplanin (4% to 44%; p<0.001), fosfomycin (16% to 44%, p=0.016) and tetracycline (0% to 28%, p=0.014) increased significantly. Vancomycin had an 84.4% overall sensitivity and 100% CNS sensitivity and remained the most effective agent. Conclusion. The increasing resistance to several antibiotics over a little more than a decade is concerning. This study suggests that referral centres should continuously monitor obtained cultures as this has significant implications for both prophylactic treatment in primary as well as empirical antibiotic treatment in PJI. Resistance profiles may differ between centres and are subject to dynamic changes