Septic Failure After One-Stage Exchange for Prosthetic Joint Infection of the Hip: Microbiological Implications.

BACKGROUND: The microbiological implications of septic failure after 1-stage exchange for prosthetic joint infection (PJI) of the hip remain unclear. METHODS: Information was gathered on comorbidities, previous procedures, preoperative and postoperative microbiology results, methods of detection, and antibiotic resistance patterns, for all patients, who developed septic failure after 1-stage exchange for PJI of the hip performed at our institution during 2001-2017. RESULTS: Seventy-seven patients were identified. Septic failure was diagnosed a mean of 1.7 (standard deviation 2.3, range 0-11.8) years later. Although the spectrum of microorganisms was similar to preoperative, in the majority of patients (55%), the initial microorganism(s) was (were) replaced by (a) totally different microorganism(s). Overall, there was a decrease in the number of polymicrobial PJIs. The number of patients with high virulent microorganisms decreased significantly from 52 to 36 (P = .034). The number of PJIs due to gram-negative pathogens remained similar (11 vs 14, P = .491). The number of rifampicin-resistant staphylococci, fluoroquinolone-resistant streptococci, enterococci, and fungi changed from 8 to 15, 0 to 2, 7 to 3, and 1 to 2, respectively, but these changes did not reach statistical significance. CONCLUSION: The majority of reinfections is caused by different infecting bacteria, hence it is essential to perform a new diagnostic workup and not base treatment decisions (solely) on historical cultures. We were furthermore unable to irrefutably prove that, from a microbiological point of view, septic failure after 1-stage exchange comes with increased challenges. Given the time interval to failure, we propose that a longer follow-up of these patients is needed, than previously suggested.

Periprosthetic joint infection caused by anaerobes. Retrospective analysis reveals no need for prolonged cultivation time if sensitive supplemented growth media are used.

BACKGROUND: In microbiological diagnosis of periprosthetic joint infection (PJI) culture media and incubation time are controversially discussed, especially if anaerobic bacteria are the causative agent. This study was conducted to demonstrate the influence of sensitive supplemented growth media on the duration of culturing anaerobes. METHODS: Twenty-five consecutive cases were included in this retrospective study. For definition of PJI, the criteria of the Musculoskeletal Infection Society (MSIS) were considered. Histopathological analysis was interpreted according to the classification by Krenn et al. The quantity and time to positivity of detected anaerobes were monitored. Furthermore, antimicrobial activity within the tissue and sonicate fluid was phenotypically tested. RESULTS: In all cases, even if the patients had received antibiotics before recovery, culture of anaerobes (Propionibacterium species, Finegoldia magna, Parvimonas micra and Robinsoniella peoriensis), both from tissue samples and prosthetic components, first became detectable in supplemented liver thioglycollate broth within six days (median: four days). CONCLUSION: Recommendations for prolonged cultivation for up to 14 days mostly aim at detection of anaerobes. Here we present a laboratory procedure that can shorten cultivation time considerably.

Limitations in the use of PSMγ, agr, RNAIII, and biofilm formation as biomarkers to define invasive Staphylococcus epidermidis from chronic biomedical device-associated infections.

Staphylococcus epidermidis is a common cause of biomedical device-associated infections. Agr is the major quorum sensing system in staphylococci and regulates virulence factors. Four agr-specificity groups exist in S. epidermidis, and chronic S. epidermidis infections are hypothesised to select for agr-negative phenotypes. Therefore, we investigated S. epidermidis strains from prosthetic joint- and catheter-associated infections to establish i) whether an infection selects for an agr-negative phenotype; ii) the importance of PSMγ and iii) if the agr-specificity group is infection dependent. S. epidermidis nasal isolates from healthy volunteers were used as controls. The distribution of agr-specificity groups was significantly different between infection and control episodes, but did not distinguish between the infection types. PSMγ secretion was used to determine agr-activity and HPLC analysis showed that 44% of prosthetic and 32% of catheter-associated episodes produced no PSMγ in comparison to 8% of the control strains. However, PSMγ expression did not always correlate with RNAIII up-regulation, indicating that PSMγ synthesis is likely influenced by additional post-transcriptional control. The data suggests chronic S. epidermidis infections favour agr-specificity group 1 but the results suggest that they do not select for an agr-negative phenotype. Further studies are required to explore the mechanisms underlying the selection and survival of these S. epidermidis phenotypes isolated from biomedical device-associated infections.

Algorithm to Diagnose Delayed and Late PJI: Role of Joint Aspiration.

Total Joint Arthroplasty (TJA) continues to gain acceptance as the standard of care for the treatment of severe degenerative joint disease, and is considered one of the most successful surgical interventions in the history of medicine. A devastating complication after TJA is infection. Periprosthetic joint infection (PJI), represents one of the major causes of failure and remains a significant challenge facing orthopaedics today. PJI usually requires additional surgery including revision of the implants, fusion or amputations causing tremendous patient suffering but also a heavy health economics burden. PJI is at the origin of around 20-25 % of total knee arthroplasty (Bozic et al. 2010; de Gorter et al. 2015; Sundberg et al. 2015) and 12-15 % of total hip arthroplasty (Bozic et al. 2009; Garellick et al. 2014; de Gorter et al. 2015) failures.

A Standardized Regimen for the Treatment of Acute Postoperative Infections and Acute Hematogenous Infections Associated With Hip and Knee Arthroplasties.

BACKGROUND: Papers concerning the treatment of periprosthetic infections and acute hematogenous infections often concern inhomogeneous treatment concepts or low numbers of patients; this results in inconsistent rates of treatment success. METHODS: Thirty-nine patients with early periprosthetic infections and 28 patients with acute hematogenous infections were treated with a homogeneous concept and followed with a mean period of 41.8 (24-132) months in order to investigate the success rate and influencing factors. All patients were treated with open surgical debridement, a revision of all removable components and irrigation with an antiseptic solution (octinedine). All patients received a systemic vancomycin/rifampicin antibiotic therapy until the microorganism causing the infection could be identified; a specific antibiotic therapy then followed until the end of the sixth week. RESULTS: This unified treatment regimen resulted in an overall success rate of 71.6%, an 82.1% success for early infections and 57.1% for acute hematogenous infections. Variables that influenced the recurrence of an infection were the timespan between revision and first appearance of symptoms (<2 days), the number of previous operations, the American Society of Anesthesiologists classification, and nicotine abuse. CONCLUSION: It appears that, in cases of early postoperative infection, a reproducibly high rate of success in retaining an implant can be achieved with this specific therapy regime if surgical intervention can be carried out within 2 days of first symptoms.

Robinsoniella peoriensis, originally isolated from swine manure, and early periprosthetic hip infection: Case report and review of the literature.

We report on the first case of a periprosthetic joint infection with the anaerobic spore-forming Gram-positive rod Robinsoniella peoriensis as the causative agent. The bacterium was first isolated from a swine manure storage pit and has so far rarely been associated with human infections.

Lyophilized allogeneic bone tissue as an antibiotic carrier.

The rising number of primary joint replacements worldwide causes an increase of revision surgery of endoprostheses due bacterial infection. Revision surgery using non-cemented implants seems beneficial for the long-term outcome and the use of antibiotic-impregnated bone grafts might control the infection and give a good support for the implant. In this study we evaluated the release of antibiotics from fresh-frozen and lyophilized allogeneic bone grafts. Lyophilized bone chips and fresh frozen bone chips were mixed with gentamicin sulphate, gentamicin palmitate, vancomycin, calcium carbonate/calcium sulphate impregnated with gentamicin sulphate, and calcium carbonate/calcium sulphate bone substitute material impregnated with vancomycin. The efficacy of each preparation was measured by drug release tests and bacterial susceptibility using B. subtilis, S. aureus and methicillin-resistant Staphylococcus aureus. The release of gentamicin from lyophilized bone was similar to the release rate from fresh frozen bone during all the experimental time. That fact might be related to the similar porosity and microstructure of the bone chips. The release of gentamicin from lyophilized and fresh frozen bone was high in the first and second day, decreasing and keeping a low rate until the end of the second week. Depending on the surgical strategy either polymethylmethacrylate or allogeneic bone are able to deliver sufficient concentrations of gentamicin to achieve bacterial inhibition within two weeks after surgery. In case of uncemented revision of joint replacements allogeneic bone is able to deliver therapeutic doses of gentamicin and peak levels immediately after implantation during a fortnight. The use of lyophilized and fresh frozen bone allografts as antibiotic carriers is recommended for prophylaxis of bone infection.

Effects of polysaccharide intercellular adhesin (PIA) in an ex vivo model of whole blood killing and in prosthetic joint infection (PJI): A role for C5a.

BACKGROUND: A major complication of using medical devices is the development of biofilm-associated infection caused by Staphylococcus epidermidis where polysaccharide intercellular adhesin (PIA) is a major mechanism of biofilm accumulation. PIA affects innate and humoral immunity in isolated cells and animal models. Few studies have examined these effects in prosthetic joint infection (PJI). METHODS: This study used ex vivo whole blood modelling in controls together with matched-serum and staphylococcal isolates from patients with PJI. RESULTS: Whole blood killing of PIA positive S. epidermidis and its isogenic negative mutant was identical. Differences were unmasked in immunosuppressed whole blood pre-treated with dexamethasone where PIA positive bacteria showed a more resistant phenotype. PIA expression was identified in three unique patterns associated with bacteria and leukocytes, implicating a soluble form of PIA. Purified PIA reduced whole blood killing while increasing C5a levels. In clinically relevant staphylococcal isolates and serum samples from PJI patients; firstly complement C5a was increased 3-fold compared to controls; secondly, the C5a levels were significantly higher in serum from PJI patients whose isolates preferentially formed PIA-associated biofilms. CONCLUSIONS: These data demonstrate for the first time that the biological effects of PIA are mediated through C5a in patients with PJI.

High rate of infection control with one-stage revision of septic knee prostheses excluding MRSA and MRSE.

BACKGROUND: The rate of infection control for one-stage revision of infected knee arthroplasties is unclear as are the factors influencing infection control. Such factors include duration of infection and the type of infected prosthesis. QUESTIONS/PURPOSES: We therefore determined: (1) the rate of infection control with one-stage revision of septic knee prostheses, (2) the clinical knee scores that can be achieved, (3) whether the duration of infection or the type of prosthesis influence the level of infection control, and (4) whether different types of prostheses influence the knee scores. METHODS: We retrospectively reviewed prospectively collected data from 63 patients who underwent one-stage revisions of septic knee endoprostheses (six unicondylar, 37 primary total knee replacement prostheses, and 20 hinged knee endoprostheses) between 2004 and 2006. All were treated locally and systemically with microorganism-specific antibiotics. For this study we excluded patients with Methicillin-resistant Staphylococcus aureus and Methicillin-resistant Staphylococcus epidermidis or unknown microorganisms. The patients were examined for infection every 3 months and Oxford and Knee Society scores were assessed at the same time. The minimum followup was 24 months (mean followup, 36 months; range, 24-70 months). RESULTS: None of the patients with replacement unicondylar and primary total knee replacement prostheses had recurrence of infection. Three of the 20 patients with the hinged infected knee prostheses had recurrences; these three patients had chronic infections and had undergone two to three revision operations during at least a 5-year period. The likelihood of infection control was influenced by the duration of infection. The mean Knee Society knee score 24 months after surgery was 72 points (range, 20-98 points), the Knee Society function score was 71 points (range, 10-100 points), and the Oxford-12 knee score was 27 points (range, 13-44 points). CONCLUSIONS: One-stage revision of septic knee prostheses achieved an infection control rate of 95% and higher knee scores than reported for two-stage revisions. Higher rates of recurrent infection appeared to be associated with long-term chronic infections of hinged prostheses.

Improved treatment strategies can result in better outcomes following one-stage exchange surgery for MRSA periprosthetic joint infection.

Introduction. Periprosthetic joint infections caused by methicillin-resistant Staphylococcus aureus (MRSA-PJIs) are rare, with only a few studies reporting the treatment outcomes and even fewer reporting outcomes with one-stage exchange.Aim. This study aims to analyse the outcomes of one-stage exchange in the management of MRSA-PJIs.Methodology. Patients with MRSA-PJI of the hip and knee, who were treated with a one-stage exchange between 2001 and 2018 were enrolled in this study. The final cohort comprised of 29 patients, which included 23 hips and six knees. The mean follow-up was 5.3 years (1-9 years). Reinfection and complications rates after the one-stage exchange were analysed.Results. Overall infection control could be achieved in 93.1 % (27 out of 29 patients). The overall revision rate was 31.0% (9 patients), with three patients requiring an in-hospital revision (10.3 %). Six patients had to be revised after hospital discharge (20.7 %). Of the two reinfections, one had a growth of MRSA while the other was of methicillin-sensitive Staphyloccocus epidermidis.Conclusion. One-stage exchange surgery using current techniques could improve surgical outcomes with excellent results in the management of MRSA-PJIs.

Actinomyces neuii subsp. neuii Associated with periprosthetic infection in total hip arthroplasty as causative agent.

Actinomyces neuii has until now not been described as a pathogen associated with periprosthetic infection in total joint replacement. The case presented here suggests that A. neuii subsp. neuii is a causative pathogen. The discussion and review of the literature indicate the impact that detection of Actinomyces species could have.

Two-stage cementless revision of infected hip endoprostheses.

UNLABELLED: Cementless two-stage revision of infected total hip prostheses lacks the possibility of local antibiotic protection of the implant at the time of reimplantation, which leads to the concern that this protocol may not sufficiently eradicate periprosthetic infection. Moreover, early implant loosening as much as 18% and stem subsidence as much as 30% have been reported. To determine whether a cementless revision could eradicate infection and achieve sufficient implant stability, we prospectively followed 36 patients with two-stage revisions for septic hip prostheses. We used a uniform protocol of a 6-week spacer interval, specific local and systemic antibiotic therapies, and cementless modular revision stems. The minimum followup was 24 months (mean, 35 months; range, 24-60 months). In one patient, the spacer was changed when the C-reactive protein value failed to normalize after 6 weeks, and the reimplantation was performed after an additional 6 weeks. No infections recurred. There was no implant loosening and a 94% bone-ingrowth fixation of stems. Subsidence occurred in two patients. The Harris hip score increased from a preoperative mean of 41 to 90 at 12 months after reimplantation and later. Using cementless prostheses in two-stage revisions of periprosthetic infections of the hip in combination with a specific local and systemic antibiotic therapy seems to eradicate infection and provide implant stability. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Prolonged bacterial culture to identify late periprosthetic joint infection: a promising strategy.

BACKGROUND: The value of microbiological culture to diagnose late periprosthetic infection is limited, especially because standard methods may fail to detect biofilm-forming sessile or other fastidious bacteria. There is no agreement on the appropriate cultivation period, although this period is a crucial factor. This study was designed to assess the duration of culture that is necessary for reliable detection. PATIENTS AND METHODS: Ten periprosthetic tissue specimens each were obtained during revision from 284 patients with suspected late hip or knee arthroplasty infection. Five samples were examined by microbiological culture over a 14-day period, and 5 were subjected to histologic analysis. To define infection, a pre-established algorithm was used; this included detection of indistinguishable organisms in >/=2 tissue samples or growth in 1 tissue sample and a positive result of histologic analysis (>5 neutrophils in at least 10 high-power fields). The time to detection of organisms was monitored. RESULTS: Infection was diagnosed in 110 patients. After 7 days (the longest incubation period most frequently reported), the detection rate via culture was merely 73.6%. Organisms indicating infection were found for up to 13 days. "Early"-detected species (mostly staphylococci) emerged predominantly during the first week, whereas "late"-detected agents (mostly Propionibacterium species) were detected mainly during the second week. In both populations, an unequivocal correlation between the number of culture-positive tissue samples and positive results of histologic analysis was noted, which corroborated the evidence that true infections were detected over the entire cultivation period. CONCLUSIONS: Prolonged microbiological culture for 2 weeks is promising because it yields signs of periprosthetic infection in a significant proportion of patients that would otherwise remain unidentified.

The Accuracy of the Alpha Defensin Lateral Flow Device for Diagnosis of Periprosthetic Joint Infection: Comparison with a Gold Standard.

BACKGROUND: Alpha defensin is a new biomarker that has been shown to have a very high accuracy to rule out periprosthetic joint infection. Recently, a new rapid lateral flow version of the alpha defensin test was developed and introduced to detect high levels of alpha defensin in synovial fluid quickly and with ease. We conducted a single-center prospective clinical study to compare the results of the Synovasure Alpha Defensin Test with those of the Musculoskeletal Infection Society (MSIS) criteria, which are considered to be the gold standard for diagnosing periprosthetic joint infection. METHODS: A total of 223 consecutive patients with pain after total hip arthroplasty or total knee arthroplasty were enrolled into the study. In all patients, blood C-reactive protein was measured and joint aspirations were performed. From the synovial fluid, a leukocyte cell count with granulocyte percentage, microbiology cultures, and leukocyte esterase tests were carried out according to the recommendation of the MSIS for diagnosing periprosthetic joint infection. Concurrently, the Synovasure Alpha Defensin Test with a lateral flow device was performed from the aspirate. In the final clinical and statistical evaluation, 191 subjects with 195 joint aspirations (96 hips and 99 knees) were included. According to the MSIS criteria, there were 119 joints with an aseptic revision and 76 joints with periprosthetic joint infection. RESULTS: After statistical analysis, the overall sensitivity of the Synovasure Alpha Defensin Test was 92.1% (95% confidence interval [CI], 83.6% to 97.1%), the specificity was 100% (95% CI, 97.0% to 100%), the positive predictive value was 100% (95% CI, 94.9% to 100%), and the negative predictive value was 95.2% (95% CI, 89.9% to 98.2%). The overall accuracy of the Synovasure test was 96.9% (95% CI, 93.4% to 98.9%), 189 of 195 cases. CONCLUSIONS: Our results suggest that the Synovasure periprosthetic joint infection test has a very high accuracy in diagnosing periprosthetic infections after total hip arthroplasty or total knee arthroplasty. Although the Synovasure Alpha Defensin Test does not provide information on the identity of the infectious pathogen, the test does have an important role in recognizing periprosthetic joint infection early and enables surgeons to start proper therapy without delay. LEVEL OF EVIDENCE: Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.

Polysaccharide intercellular adhesin or protein factors in biofilm accumulation of Staphylococcus epidermidis and Staphylococcus aureus isolated from prosthetic hip and knee joint infections.

Nosocomial staphylococcal foreign-body infections related to biofilm formation are a serious threat, demanding new therapeutic and preventive strategies. As the use of biofilm-associated factors as vaccines is critically restricted by their prevalence in natural staphylococcal populations we studied the distribution of genes involved in biofilm formation, the biofilm phenotype and production of polysaccharide intercellular adhesin (PIA) in clonally independent Staphylococcus aureus and Staphylococcus epidermidis strains isolated from prosthetic joint infections after total hip or total knee arthroplasty. Biofilm formation was detected in all S. aureus and 69.2% of S. epidermidis strains. Importantly, 27% of biofilm-positive S. epidermidis produced PIA-independent biofilms, in part mediated by the accumulation associated protein (Aap). Protein-dependent biofilms were exclusively found in S. epidermidis strains from total hip arthroplasty (THA). In S. aureus PIA and proteins act cooperatively in biofilm formation regardless of the infection site. PIA and protein factors like Aap are of differential importance for the pathogenesis of S. epidermidis in prosthetic joint infections (PJI) after THA and total knee arthroplasty (TKA), implicating that icaADBC cannot serve as a general virulence marker in this species. In S. aureus biofilm formation proteins are of overall importance and future work should focus on the identification of functionally active molecules.

Are There Benefits In Early Diagnosis Of Prosthetic Joint Infection With Multiplex Polymerase Chain Reaction?

Purpose Identification of bacteria and susceptibility are fundamental in periprosthetic joint infection (PJI). Especially in the case of systemic inflammatory response syndrome (SIRS) rapid detection of pathogens is essential for proper therapy. Bacterial cultures are time consuming. The polymerase chain reaction (PCR) is a non-culture molecular method and is able to rapidly identify pathogens and their resistance genes. Multiplex PCR (mPCR) can amplify several different DNA sequences simultaneously. The aim of this study was to show the value of mPCR for early diagnosis of PJI. Methods 60 patients undergoing total hip or knee revisions were recruited in this prospective single-centre-study. Three groups were created: 26 patients with aseptic loosening (negative control), 26 patients with chronic PJI, and 8 patients with acute PJI/SIRS. We compared the results of joint aspirates obtained intraoperatively investigated by mPCR with the microbiology results of tissue specimens. Results The overall sensitivity of mPCR was 78.8% (95% CI, 61.1 - 91.0%), the specificity was 100% (95% CI, 87.2 - 100%), the negative predictive value was 79.4% (95% CI, 62.1 - 91.3%), the positive predictive value was 100% (95% CI, 86.8 - 100%), and the overall accuracy was 88.3% (95% CI, 77.4 - 95.2%). The overall accuracy in acute infections/SIRS (87.5%) was greater than in late chronic PJI (76.9%). In PJI the mPCR was able to provide the results within 5 hours whereas the mean time for cultures was 6.4 days. Conclusions Multiplex PCR is a reliable diagnostic tool in PJI management, especially in acute cases complicated with SIRS. Early diagnosis within several hours is possible, targeted antibiotic treatment can be started promptly.