1040. Knee Explant Analysis (KnEA) Using PLG0206 in Periprosthetic Joint Infection (KnEA Study)

Abstract Background PLG0206 is a novel engineered cationic antimicrobial peptide being evaluated for treatment of prosthetic joint infections (PJI). This study evaluated the rapid bactericidal activity of PLG0206 to decrease biofilm and planktonic bacteria on ex vivo infected prosthesis following removal from patients with chronic PJI. Methods De-identified infected prosthetics were removed from nine patients with PJI, despite chronic suppressive oral antibiotics, during a 2-stage revision procedure. Removed prosthetics were then submersed ex vivo to an expected clinical exposure of PLG0206, 1 mg/mL, for ~15 minutes. Upon completion of the 15-minute exposure, the treated explant was placed into buffer and sonicated. The sonication solution was then plated for bacterial analysis including colony forming unit (CFU) enumeration. Remaining explanted implants from the same patient served as a control and was processed similarly but without exposure to PLG0206. Results As shown in the Table, both Gram-positive and Gram-negative bacteria were identified from removed prosthetics during a 2-stage revision procedure of chronic PJI. Eight of ten infected prosthetics treated ex vivo to PLG0206 1 mg/mL were sterilized (No. 1-5, 8-10). Of the two infected prosthetics that were not sterilized (No. 6 and 7), one was polymicrobial (No. 6) and the other was monomicrobial (No. 7). Collectively, infected prosthetics exposed to PLG0206 demonstrated a mean 4log10 reduction (range 2 to 7). Summary of culture and CFU log reduction among infected prosthetics exposed and not exposed to PLG0206 Table: Summary of culture and CFU log reduction among infected prosthetics exposed and not exposed to PLG0206 Conclusion Overall, these findings support the ongoing development of PLG0206 as a local irrigation solution at 1 mg/mL concentration in the wound cavity for 15 minutes in patients undergoing treatment of a PJI occurring after total knee arthroplasty. Disclosures David Huang, MD, PhD, Peptilogics (Employee) Nicholas Pachuda, DPM, Peptilogics (Employee) Despina Dobbins, BS, Peptilogics (Employee) Jonathan Steckbeck, PhD, Peptilogics (Employee) Kenneth Urish, MD, PhD, Peptilogics (Grant/Research Support)

Download Full-text

Bactericidal Action of Daptomycin against Stationary-Phase and Nondividing Staphylococcus aureus Cells

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00824-07 ◽

2007 ◽

Vol 51 (12) ◽

pp. 4255-4260 ◽

Cited By ~ 179

Author(s):

Carmela T. M. Mascio ◽

Jeff D. Alder ◽

Jared A. Silverman

Keyword(s):

Staphylococcus Aureus ◽

Stationary Phase ◽

Bactericidal Activity ◽

Direct Action ◽

Metabolic Inhibitor ◽

Log Reduction ◽

Joint Infections ◽

Prosthetic Joint ◽

Prosthetic Joint Infections ◽

Lipopeptide Antibiotic

ABSTRACT Most antibiotics with bactericidal activity require that the bacteria be actively dividing to produce rapid killing. However, in many infections, such as endocarditis, prosthetic joint infections, and infected embedded catheters, the bacteria divide slowly or not at all. Daptomycin is a lipopeptide antibiotic with a distinct mechanism of action that targets the cytoplasmic membrane of gram-positive organisms, including Staphylococcus aureus. Daptomycin is rapidly bactericidal against exponentially growing bacteria (a 3-log reduction in 60 min). The objectives of this study were to determine if daptomycin is bactericidal against nondividing S. aureus and to quantify the extent of the bactericidal activity. In high-inoculum methicillin-sensitive S. aureus cultures in stationary phase (1010 CFU/ml), daptomycin displayed concentration-dependent bactericidal activity, requiring 32 μg/ml to achieve a 3-log reduction. In a study comparing several antibiotics at 100 μg/ml, daptomycin demonstrated faster bactericidal activity than nafcillin, ciprofloxacin, gentamicin, and vancomycin. In experiments where bacterial cell growth was halted by the metabolic inhibitor carbonyl cyanide m-chlorophenylhydrazone or erythromycin, daptomycin (10 μg/ml) achieved the bactericidal end point (a 3-log reduction) within 2 h. In contrast, ciprofloxacin (10 μg/ml) did not produce bactericidal activity. Daptomycin (2 μg/ml) remained bactericidal against cold-arrested S. aureus, which was protected from the actions of ciprofloxacin and nafcillin. The data presented here suggest that, in contrast to that of other classes of antibiotics, the bactericidal activity of daptomycin does not require cell division or active metabolism, most likely as a consequence of its direct action on the bacterial membrane.

Download Full-text

Do Prosthetic Joint Infections Worsen the Functional Ambulatory Outcome of Patients with Joint Replacements? A Retrospective Matched Cohort Study

Antibiotics ◽

10.3390/antibiotics9120872 ◽

2020 ◽

Vol 9 (12) ◽

pp. 872

Author(s):

Isabel Mur ◽

Marcos Jordán ◽

Alba Rivera ◽

Virginia Pomar ◽

José Carlos González ◽

...

Keyword(s):

Cohort Study ◽

Joint Infection ◽

Assistive Device ◽

Matched Cohort ◽

Knee Prostheses ◽

Matched Cohort Study ◽

Joint Infections ◽

Prosthetic Joint ◽

Prosthetic Joint Infections ◽

Hip Arthroplasties

Objectives: To assess the effect on the functional ambulatory outcome of postoperative joint infection (PJI) cured at the first treatment attempt versus not developing PJI in patients with hip and knee prostheses. Methods: In a single-hospital retrospectively matched cohort study, each patient with PJI between 2007 and 2016 was matched on age, sex, type of prosthesis and year of implantation with two other patients with uninfected arthroplasties. The definition of a PJI cure included infection eradication, no further surgical procedures, no PJI-related mortality and no suppressive antibiotics. Functional ambulatory status evaluated one year after the last surgery was classified into four simple categories: able to walk without assistance, able to walk with one crutch, able to walk with two crutches, and unable to walk. Patients with total hip arthroplasties (THAs), total knee arthroplasties (TKAs) and partial hip arthroplasties (PHAs) were analysed separately. Results: A total of 109 PJI patients (38 TKA, 41 THA, 30 PHA) and 218 non-PJI patients were included. In a model adjusted for clinically relevant variables, PJI was associated with a higher risk of needing an assistive device for ambulation (vs. walking without aid) among THA (adjusted odds ratio (OR) 3.10, 95% confidence interval (95% CI) 1.26–7.57; p = 0.014) and TKA patients (OR 5.40, 95% CI 2.12–13.67; p < 0.001), and with requiring two crutches to walk or being unable to walk (vs. walking unaided or with one crutch) among PHA patients (OR 3.05, 95% CI 1.01–9.20; p = 0.047). Conclusions: Ambulatory outcome in patients with hip and knee prostheses with postoperative PJI is worse than in patients who do not have PJI.

Download Full-text

The Right Time to Safely Re-Evaluate Empirical Antimicrobial Treatment of Hip or Knee Prosthetic Joint Infections

Journal of Clinical Medicine ◽

10.3390/jcm8122113 ◽

2019 ◽

Vol 8 (12) ◽

pp. 2113 ◽

Cited By ~ 2

Author(s):

Deroche ◽

Bémer ◽

Valentin ◽

Jolivet-Gougeon ◽

Tandé ◽

...

Keyword(s):

Joint Infection ◽

Antimicrobial Treatment ◽

Microbiological Diagnosis ◽

Joint Infections ◽

Time To Positivity ◽

Prosthetic Joint ◽

Prosthetic Joint Infections ◽

Two Samples ◽

The Right ◽

Polymicrobial Infections

Currently, no guideline provides recommendations on the duration of empirical antimicrobial treatment (EAT) in prosthetic joint infection (PJI). The aim of our study was to describe the time to growth of bacteria involved in PJI, rendering possible decreased duration of EAT. Based on a French multicentre prospective cohort study, culture data from patients with confirmed hip or knee PJI were analysed. For each patient, five samples were processed. Time to positivity was defined as the first positive medium in at least one sample for virulent pathogens and as the first positive medium in at least two samples for commensals. Definitive diagnosis of polymicrobial infections was considered the day the last bacteria were identified. Among the 183 PJIs, including 28 polymicrobial infections, microbiological diagnosis was carried out between Day 1 (D1) and D5 for 96.7% of cases. There was no difference in the average time to positivity between acute and chronic PJI (p = 0.8871). Microbiological diagnosis was given earlier for monomicrobial than for polymicrobial infections (p = 0.0034). When an optimized culture of peroperative samples was carried out, almost all cases of PJI were diagnosed within five days, including polymicrobial infections. EAT can be re-evaluated at D5 according to microbiological documentation.

Download Full-text

Is Gram staining still useful in prosthetic joint infections?

Journal of Bone and Joint Infection ◽

10.7150/jbji.31312 ◽

2019 ◽

Vol 4 (2) ◽

pp. 56-59 ◽

Cited By ~ 1

Author(s):

Marjan Wouthuyzen-Bakker ◽

Noam Shohat ◽

Marine Sebillotte ◽

Cédric Arvieux ◽

Javad Parvizi ◽

...

Keyword(s):

Revision Surgery ◽

Joint Infection ◽

Individual Case ◽

Gram Stain ◽

Reactive Protein ◽

Joint Infections ◽

Gram Staining ◽

Causative Microorganism ◽

Prosthetic Joint ◽

Prosthetic Joint Infections

Abstract. Introduction: Staphylococcus aureus is an independent risk factor for DAIR failure in patients with a late acute prosthetic joint infection (PJI). Therefore, identifying the causative microorganism in an acute setting may help to decide if revision surgery should be chosen as a first surgical approach in patients with additional risk factors for DAIR failure. The aim of our study was to determine the sensitivity of Gram staining in late acute S. aureus PJI.Material and methods: We retrospectively evaluated all consecutive patients between 2005-2015 who were diagnosed with late acute PJI due to S. aureus. Late acute PJI was defined as the development of acute symptoms and signs of PJI, at least three months after the index surgery. Symptoms existing for more than three weeks were excluded from the analysis. Gram staining was evaluated solely for synovial fluid.Results: A total of 52 cases were included in the analysis. Gram staining was positive with Gram positive cocci in clusters in 31 cases (59.6%). Patients with a C-reactive protein (CRP) > 150 mg/L at clinical presentation had a significantly higher rate of a positive Gram stain (30/39, 77%) compared to patients with a CRP ≤ 150 mg/L (4/10, 40%) (p=0.02). A positive Gram stain was not related to a higher failure rate (60.6% versus 57.9%, p 0.85).Conclusion: Gram staining may be a useful diagnostic tool in late acute PJI to identify S. aureus PJI. Whether a positive Gram stain should lead to revision surgery instead of DAIR should be determined per individual case.

Download Full-text

Prosthetic Joint Infections

10.1093/med/9780199976805.003.0048 ◽

2016 ◽

Author(s):

David Mabey ◽

Hasan E. Baydoun ◽

Jamil D. Bayram

Keyword(s):

Antimicrobial Prophylaxis ◽

Joint Infection ◽

Treatment Options ◽

Joint Fluid ◽

Care Providers ◽

Joint Replacement Surgery ◽

Fluid Analysis ◽

Joint Infections ◽

Prosthetic Joint ◽

Prosthetic Joint Infections

Prosthetic joint infection (PJI), a complication of joint replacement surgery, presents with fever, joint pain, erythema, effusion, and joint loosening. Many advances have decreased the risk of infection, such as the use of perioperative antimicrobial prophylaxis and intraoperative laminar airflow. Joint fluid analysis should be pursued by the orthopedic surgeons; primary and acute care providers should consult the definitive care team and refer these patients for admission. Organisms causing prosthetic joint infections often grow in biofilms, which make them difficult to treat. Surgical treatment options include one or two-stage prosthesis exchange, debridement with retention of the prosthesis, resection arthroplasty, arthrodesis, or amputation. Antibiotic therapy should be guided by intraoperative cultures and selected in consultation with the infectious disease service.

Download Full-text

Handling of Doubtful WBC Scintigraphies in Patients with Suspected Prosthetic Joint Infections

Journal of Clinical Medicine ◽

10.3390/jcm9124031 ◽

2020 ◽

Vol 9 (12) ◽

pp. 4031

Author(s):

Chiara Lauri ◽

Giancarlo Lauretti ◽

Filippo Galli ◽

Giuseppe Campagna ◽

Simone Tetti ◽

...

Keyword(s):

Visual Analysis ◽

Joint Infection ◽

White Blood Cells ◽

Final Diagnosis ◽

Joint Infections ◽

Prosthetic Joint ◽

Prosthetic Joint Infections ◽

Significant Difference ◽

Sensitivity Specificity

Despite the application of EANM recommendations for radiolabelled white-blood-cells (WBC) scintigraphy, some cases still remain doubtful based only on visual analysis. The aim of this study was to investigate the role of semi-quantitative analysis and bone marrow scan (BMS) in solving doubtful cases. We retrospectively evaluated all [99mTc]HMPAO-WBC scintigraphies performed, in the last 7 years, for a suspected monolateral prosthetic joint infection (PJI). In doubtful cases, we used five different thresholds of increase of target-to-background (T/B) ratio, between delayed and late images, as criteria of positivity (5%, 10%, 15%, 20% and 30%). BMS were also analysed and sensitivity, specificity and accuracy of different methods were calculated according to final diagnosis. The sensitivity, specificity and accuracy were, respectively, 77.8%, 43.8% and 53.0% for the cut-off at 5%; 72.2%, 66.7% and 68.2% for the cut-off at 10%; 66.7%, 75.0% and 72.7% for the cut-off at 15%; 66.7%, 85.4% and 80.3% for the cut-off at 20%; 33.3%, 93.8% and 77.3% for the cut-off at 30%. BMS provided a significantly higher diagnostic performance than 5%, 10% and 15% thresholds. Conversely, we did not observe any statistically significant difference between BMS and the cut-off of more than 20%. Therefore, doubtful cases should be analysed semi-quantitatively. An increase in T/B ratio of more than 20% between delayed and late images, should be considered as a criterion of positivity, thus avoiding BMS.

Download Full-text

Periprosthetic Joint Infections: Clinical and Bench Research

The Scientific World JOURNAL ◽

10.1155/2013/549091 ◽

2013 ◽

Vol 2013 ◽

pp. 1-17 ◽

Cited By ~ 15

Author(s):

Laurence Legout ◽

Eric Senneville

Keyword(s):

Prosthetic Joint Infection ◽

Joint Infection ◽

Diagnostic Methods ◽

High Morbidity ◽

Substantial Cost ◽

Prosthetic Infection ◽

Joint Infections ◽

Prosthetic Joint ◽

Prosthetic Joint Infections ◽

Definition Of

Prosthetic joint infection is a devastating complication with high morbidity and substantial cost. The incidence is low but probably underestimated. Despite a significant basic and clinical research in this field, many questions concerning the definition of prosthetic infection as well the diagnosis and the management of these infections remained unanswered. We review the current literature about the new diagnostic methods, the management and the prevention of prosthetic joint infections.

Download Full-text

Prosthetic Joint Infection Due to Histoplasma capsulatum Complicating a Total Knee Arthroplasty

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx118 ◽

2017 ◽

Vol 4 (3) ◽

Cited By ~ 2

Author(s):

Cima Nowbakht ◽

Katherine Garrity ◽

Nicholas Webber ◽

Jairo Eraso ◽

Luis Ostrosky-Zeichner

Keyword(s):

Total Knee Arthroplasty ◽

Prosthetic Joint Infection ◽

Histoplasma Capsulatum ◽

Joint Infection ◽

Stage Management ◽

Joint Infections ◽

Prosthetic Joint ◽

Prosthetic Joint Infections ◽

Oral Itraconazole ◽

Total Knee

Abstract Histoplasmosis is a common pathogen but rarely reported in prosthetic joint infections. We present a case of Histoplasmosis capsulatum prosthetic joint infection along with a literature review revealing no guidelines or consensus on surgical and antifungal management. We chose the 2-stage management with an antifungal spacer and systemic oral itraconazole.

Download Full-text

Micromonas micros Infection of a Prosthetic Hip Joint: A Case Report and Review of the Literature

Case Reports in Infectious Diseases ◽

10.1155/2021/9042790 ◽

2021 ◽

Vol 2021 ◽

pp. 1-5

Author(s):

Abhimanyu Aggarwal ◽

Durane Walker

Keyword(s):

Antibiotic Prophylaxis ◽

Hip Joint ◽

Joint Infection ◽

Dental Procedure ◽

Joint Infections ◽

Prosthetic Joints ◽

Prosthetic Joint ◽

Dental Procedures ◽

Prosthetic Joint Infections ◽

Hematogenous Seeding

Micromonas micros is an oral anaerobic Gram-positive coccus and is a commensal of the mouth, and it is rarely isolated in prosthetic joint infections (PJIs) and even less frequently related to a preceding dental procedure with eventual hematogenous seeding of the prosthetic joint. Here, we present a case of a 56-year-old male with a prosthetic hip joint who developed Micromonas micros prosthetic hip joint infection with symptoms starting a few days after a dental procedure and not having received periprocedural antibiotic prophylaxis. He recovered well with surgical intervention and antimicrobial therapy. We conducted a literature review of prosthetic hip joint infections caused by Micromonas micros as well as briefly discuss current guidelines on antibiotic prophylaxis in patients with prosthetic joints undergoing dental procedures and some knowledge gaps.

Download Full-text

Brucella Melitensis Review of the Human Infection Case

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2006.3203 ◽

2006 ◽

Vol 6 (1) ◽

pp. 15-18 ◽

Cited By ~ 6

Author(s):

Šukrija Zvizdić ◽

Dževad Čengić ◽

Maja Bratić ◽

Snježana Mehanić ◽

Fikret Pinjo ◽

...

Keyword(s):

Brucella Melitensis ◽

Diagnostic Yield ◽

Joint Infection ◽

Human Infection ◽

Optimal Treatment ◽

Joint Aspiration ◽

Joint Infections ◽

Prosthetic Joint ◽

Prosthetic Joint Infections ◽

Endemic Areas

Brucella spp. prosthetic joint infections are infrequently reported in the literature, particularly in returning travellers, and optimal treatment is unknown.METHOD:We describe a prosthetic joint infection (PJI) caused by Brucella melitensis in a traveller returning to the UK from Thailand, which we believe to be the first detailed report of brucellosis in a traveller returning from this area. The 23 patients with Brucella-related PJI reported in the literature are summarised, together with our case.RESULTS:The diagnosis of Brucella-related PJI is difficult to make; only 30% of blood cultures and 75% of joint aspiration cultures were positive in the reported cases. Culture of intraoperative samples provides the best diagnostic yield. In the absence of radiological evidence of joint loosening, combination antimicrobial therapy alone may be appropriate treatment in the first instance; this was successful in 6/7 [86%] of patients, though small numbers of patients and the likelihood of reporting bias warrant caution in drawing any firm conclusions about optimal treatment. Aerosolisation of synovial fluid during joint aspiration procedures and nosocomial infection has been described.CONCLUSIONS:Brucella-related PJI should be considered in the differential of travellers returning from endemic areas with PJI, including Thailand. Personal protective equipment including fit tested filtering face piece-3 (FFP3) mask or equivalent is recommended for personnel carrying out joint aspiration when brucellosis is suspected. Travellers can reduce the risk of brucellosis by avoiding unpasteurised dairy products and animal contact (particularly on farms and abattoirs) in endemic areas and should be counselled regarding these risks as part of their pre-travel assessment.

Download Full-text