Successful Identification of Pathogens by Polymerase Chain Reaction (PCR)-Based Electron Spray Ionization Time-of-Flight Mass Spectrometry (ESI-TOF-MS) in Culture-Negative Periprosthetic Joint Infection

Jacovides, Christina; Melton-Kreft, Rachael; Adeli, Bahar; Hozack, Bryan A.; Ehrlich, Garth D.; Parvızı, Javad

doi:10.2106/jbjs.l.00210

Cited by 133 publications

(118 citation statements)

References 34 publications

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“…Moreover, peptidoglycan, a PAMP produced by both Gram-negative and Gram-positive bacteria, exists in synovial tissue from patients with osteoarthritis and rheumatoid arthritis [16,96] and, therefore, likely exists in periprosthetic tissue of patients with aseptic loosening. One potential source of PAMPs during aseptic loosening is the bacteria present in the biofilms found on many loose implants despite the absence of clinical signs of infection [21,47,54,74,76,107,109]. Patients with inflammatory arthritis, especially those receiving anti-TNF-a therapies, may be especially at risk for formation of these bacterial biofilms [95].…”

Section: Toll-like Receptorsmentioning

confidence: 99%

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Greenfield

2014

Clin Orthop Relat Res

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Background Overwhelming evidence supports the concept that wear particles are the primary initiator of aseptic loosening of orthopaedic implants. It is likely, however, that other factors modulate the biologic response to wear particles. This review focuses on three potential other factors: genetic susceptibility, Toll-like receptors (TLRs), and bacterial pathogen-associated molecular patterns (PAMPs). Where Are We Now? Considerable evidence is emerging that both genetic susceptibility and TLR activation are important factors that modulate the biologic response to wear particles, but it remains controversial whether bacterial PAMPs also do so. Where Do We Need to Go? Detailed understanding of the roles of these other factors may lead to identification of novel therapeutic targets for patients with aseptic loosening. How Do We Get There? Highest priority should be given to polymorphism replication studies with large numbers of patients and studies to replicate the reported correlation between bacterial biofilms and the severity of aseptic loosening.

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Section: Toll-like Receptorsmentioning

confidence: 99%

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Greenfield

2014

Clin Orthop Relat Res

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“…Using standard procedures, the infection rates for revision knee arthroplasties are around 10%, with a 7 to 12% false-negative rate, even in cases in which gross infections are present (19). When more rigorous techniques are used to detect infection, Ͼ50% of the retrieved implants are found to have bacterial contaminants, suggesting that antibiotic prophylaxis has limited success (20).In this study, we sought to determine if the prophylactic antibiotics, commonly CFZ, present in synovial fluid are able to prevent bacterial contamination. Based on our recent studies showing that bacterial clumping in synovial fluid dominates its phenotype, we hypothesized that even these high levels of the bactericidal antibiotic CFZ would not be able to eradicate a Staphylococcus aureus challenge.…”

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confidence: 99%

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confidence: 99%

Staphylococcal Persistence Due to Biofilm Formation in Synovial Fluid Containing Prophylactic Cefazolin

Dastgheyb

Hammoud

Ketonis

et al. 2015

Antimicrob Agents Chemother

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Antibiotic prophylaxis is standard for patients undergoing surgical procedures, yet despite the wide use of antibiotics, breakthrough infections still occur. In the setting of total joint arthroplasty, such infections can be devastating. Recent findings have shown that synovial fluid causes marked staphylococcal aggregation, which can confer antibiotic insensitivity. We therefore asked in this study whether clinical samples of synovial fluid that contain preoperative prophylactic antibiotics can successfully eradicate a bacterial challenge by pertinent bacterial species. This study demonstrates that preoperative prophylaxis with cefazolin results in high antibiotic levels. Furthermore, we show that even with antibiotic concentrations that far exceed the expected bactericidal levels, Staphylococcus aureus bacteria added to the synovial fluid samples are not eradicated and are able to colonize model implant surfaces, i.e., titanium pins. Based on these studies, we suggest that current prophylactic antibiotic choices, despite high penetration into the synovial fluid, may need to be reexamined.I nfection remains a major concern with orthopedic procedures, although infection rates are generally Ͻ1% (1). Because of the high prophylactic antibiotic levels within synovial fluid, the use of minimally invasive techniques, and short surgical times, infection rates remain low. However, with increasing numbers of total knee arthroplasties, infections are projected to exceed 60,000 to 70,000 cases in the United States by 2020 (2, 3). When hardware, such as a prosthesis, is present, infection is recalcitrant to antibiotic treatment. Once established, infection can cause prolonged disability, multiple operations, and increased health care costs (3, 4). According to the WHO, patients with a surgical site infection have twice the mortality rate, are twice as likely to spend time in an intensive care unit, and are five times more likely to be readmitted to the hospital than uninfected patients (5).To avoid the establishment of infection, antibiotic prophylaxis has become the standard of care (6, 7). For orthopedic procedures, cefazolin (CFZ), which is bactericidal for staphylococci, streptococci, and Escherichia coli (8, 9), is commonly used in the absence of a penicillin allergy (10). Alternative prophylactic antibiotics include fusidic acid, cloxacillin (11), cefixime (12), vancomycin, and gentamicin (13). Interestingly, synovial fluid has been suggested to possess antibacterial properties (14-16) that are attributed to hyaluronic acid within the synovial fluid (17), the induction of bactericidal/permeability-increasing protein (15), or unknown compounds, including antimicrobial peptides, within the synovial fluid (14). We recently reported that this ostensible decrease in bacterial numbers, which is perceived to be an "antibacterial" effect, is actually due to the clumping of bacteria within synovial fluid, which masks the true microbial load levels (18).The recognition of this behavior also helps to elucidate the difficulties ...

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“…In addition, in our meta-analysis, there were 80 false-negative results from 12 studies. Most of the included studies explained that the false-negative resulted from the patient receiving antibiotics previous to sampling (3,(5)(6)(7)(8)(11)(12)(13)(14)(15).…”

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confidence: 99%

PCR-Based Diagnosis of Prosthetic Joint Infection

Zhai

et al. 2013

J Clin Microbiol

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bWe performed a meta-analysis to evaluate use of PCR assays for diagnosis of prosthetic joint infection (PJI). The pooled sensitivity and specificity were 0.86 (95% confidence interval [CI], 0.77 to 0.92) and 0.91 (CI, 0.81 to 0.96), respectively. Subgroup analyses showed that use of tissue samples may improve sensitivity, and quantitative PCR and sonication of prostheses fluid may improve specificity. The results showed that PCR is reliable and accurate for detection of PJI.P rosthetic joint infection (PJI) is one of the most common complications of total joint arthroplasty, with an incidence of 1 to 12%, and it always has catastrophic consequences (1, 2). The distinction between PJI and other causes of joint failure, such as aseptic loosening, is frequently difficult and still challenging. Several studies have assessed the diagnostic value of PCR techniques for diagnosing PJI. However, the true diagnostic capabilities of PCR assays remain controversial. Therefore, the aim of our study was to perform a meta-analysis to evaluate the detection validity of PCR in the diagnosis of PJI.We searched MEDLINE, EMBASE, and OVID for articles that were published between January 1990 and February 2013, using the following medical subject headings (MeSH) or free text words: (i) joint prosthesis, prosthesis infection, septic loosening, aseptic loosening, replacement, or arthroplasty and (ii) PCR. We also manually searched the reference lists of eligible studies and review articles. Our reviewers independently evaluated the selected studies using the following inclusion criteria: (i) the study reported the accuracy of PCR for the diagnosis of joint infection in comparison with visible purulence of joint aspirate or surgical site, presence of a sinus tract (fistula) communicating with the prosthesis, acute inflammation in histopathology sections of periprosthetic tissue, or simultaneously obtained microbiologic cultures from at least two periprosthetic tissue samples (the reference standard); (ii) sufficient data were reported to allow us to calculate the truepositive (TP), false-negative (FN), false-positive (FP), and truenegative (TN) values; (iii) the study reported evaluations of at least 10 patients, from which data could be extracted using our standardized data collection form (X. Qu and Z. Zhai). Discrepancies were resolved by discussion with other investigators and by consulting the original articles (Huiwu Li and K. Dai). We estimated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) of summary receiver operating characteristic (ROC) curves to evaluate the capability of PCR assays for diagnosing PJI. We performed meta-regression and subgroup analyses to assess potential heterogeneity, and we constructed Deeks' funnel plot asymmetry test to evaluate potential publication bias. All of the statistical analyses were undertaken using STATA version 11 (StataCorp, College Station, TX).Our research yielded 2,024 primary st...

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Successful Identification of Pathogens by Polymerase Chain Reaction (PCR)-Based Electron Spray Ionization Time-of-Flight Mass Spectrometry (ESI-TOF-MS) in Culture-Negative Periprosthetic Joint Infection

Abstract: Javad, "Successful identification of pathogens by polymerase chain reaction (PCR)-based electron spray ionization time-of-flight mass spectrometry (ESI-TOF-MS) in culture-negative periprosthetic joint infection." (2012). Rothman Institute. Paper 22.

Cited by 133 publications

References 34 publications

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Staphylococcal Persistence Due to Biofilm Formation in Synovial Fluid Containing Prophylactic Cefazolin

PCR-Based Diagnosis of Prosthetic Joint Infection

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