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1.  Evaluation of a Genus- and Group-Specific Rapid PCR Assay Panel on Synovial Fluid for Diagnosis of Prosthetic Knee Infection 
Journal of Clinical Microbiology  2015;54(1):120-126.
We evaluated a genus- and group-specific PCR assay panel using 284 prosthetic knee synovial fluid samples collected from patients presenting to our institution with implant failure. Using the Musculoskeletal Infection Society diagnostic criteria, 88 and 196 samples were classified as showing prosthetic joint infection (PJI) and aseptic failure (AF), respectively. Sensitivities of the synovial fluid PCR panel and culture were 55.6% and 76.1% (P ≤ 0.001), respectively, and specificities were 91.8% and 97.4% (P = 0.016), respectively. Among the 70 subjects who had received antibiotics within the month preceding synovial fluid aspiration (48 of whom had PJI), PCR panel and synovial fluid culture sensitivities were 64.5% and 85.4%, respectively (P < 0.0001). In this group, the PCR panel detected Staphylococcus aureus in two culture-negative PJI cases. Overall, the evaluated molecular diagnostic tool had low sensitivity when applied to synovial fluid.
doi:10.1128/JCM.02302-15
PMCID: PMC4702737  PMID: 26537446
2.  Do Claims-based Comorbidities Adequately Capture Case Mix for Surgical Site Infections? 
Background
There is increasing interest in using administrative claims data for surveillance of surgical site infections in THAs and TKAs, but the performance of claims-based models for case-mix adjustment has not been well studied. Performance of claims-based models can be improved with the addition of clinical risk factors for surgical site infections.
Questions/purposes
We assessed (1) discrimination and calibration of claims-based risk-adjustment models for surgical site infections; and (2) the incremental value of adding clinical risk factors to claims-based risk-adjustment models for surgical site infections.
Patients and Methods
Our study included all THAs and TKAs performed at a large tertiary care hospital from January 1, 2002 to December 31, 2009 (total n = 20,171 procedures). Revision procedures for infections were excluded. Comorbidity data were ascertained through administrative records and classified by the Charlson comorbidity index. Clinical details were obtained from the institutional joint registry and patients’ electronic health records. Cox proportional hazards regression models were used to estimate the 1-year risk of surgical site infections with a robust sandwich covariance estimator to account for within-subject correlation of individuals with multiple surgeries. The performance of claims-based risk models with and without the inclusion of four clinical risk factors (morbid obesity, prior nonarthroplasties on the same joint, American Society of Anesthesiologists score, operative time) was assessed using measures of discrimination (C statistic, Somers’ Dxy rank correlation, and the Nagelkerke R2 index). Furthermore, calibrations of claims-based risk models with and without clinical factors were assessed graphically by plotting the smoothed trends between model predictions and empirical rates from Kaplan-Meier.
Results
Discrimination of the claims-based risk models was moderate for the THA (C statistic = 0.662, Dxy = 0.325, R2 = 0.028) and TKA (C statistic = 0.621, Dxy = 0.241, R2 = 0.017) cohorts. Inclusion of four clinical risk factors improved discrimination in both cohorts with significant improvement in the C statistic in the THA cohort (C statistic = 0.043; 95% CI, 0.012–0.074) and in the TKA cohort (C statistic = 0.027; 95% CI, 0.007–0.047). Visual inspection suggested that calibration of the claims-based risk models was adequate and comparable to that of models which included the four additional clinical factors.
Conclusions
Claims-based risk-adjustment models for surgical site infections in THA and TKA appear to be adequately calibrated but lack predictive discrimination, particularly with TKAs. The addition of clinical risk factors improves the discriminative ability of the models to a moderate degree; however, addition of clinical factors did not change calibrations, as the models showed reasonable degrees of calibration. When used in the clinical setting, the predictive performance of claims-based risk-adjustment models may be improved further with inclusion of additional clinical data elements.
doi:10.1007/s11999-014-4083-y
PMCID: PMC4385352  PMID: 25480123
4.  Systemic Inflammatory Markers and Aspiration Cell Count May Not Differentiate Bacterial From Fungal Prosthetic Infections 
Background
Fungal periprosthetic joint infections (PJIs) are rare. Fewer than 200 cases have been reported in the literature. The characteristics of systemic inflammatory markers and joint aspirate cell count analysis obtained in patients with fungal PJIs have not been fully assessed. The ability to diagnose involvement of fungal PJI preoperatively may optimize the surgical and medical management of these patients.
Questions/purposes
We determined whether preoperative systemic inflammatory markers and total synovial fluid leukocyte count and neutrophil percentage were different between patients with fungal and bacterial PJI.
Methods
We reviewed the medical records of 44 patients with culture-positive diagnosed fungal PJIs treated at our institution between January 1, 2002, and December 31, 2011, in this study. This represented 1.2% of the total 3822 PJIs treated at our institution during the study period. The mean values for C-reactive protein, erythrocyte sedimentation rate, leukocyte count, and neutrophil percentage of patients with purely fungal PJIs were compared to those of 59 patients with bacterial PJIs treated by one surgeon during the same time period.
Results
The mean erythrocyte sedimentation rate values for fungal and bacterial PJIs were 40 mm/hour (95% CI: 30, 50 mm/hour) and 41 mm/hour (95% CI: 33, 49 mm/hour), respectively (p = 0.61). The mean C-reactive protein values for fungal and bacterial PJIs were 42 mg/L (95% CI: 22, 62 mg/L) and 65 mg/L (95% CI: 43, 88 mg/L), respectively (p = 0.42). The mean total nucleated leukocyte counts for fungal and bacterial PJIs were 11,928 (95% CI: 3906, 19,950) with 81% (95% CI: 75%, 88%) neutrophils and 36,901 (95% CI: 21,822, 51,921) with 73% (95% CI: 65%, 81%) neutrophils, respectively (leukocyte count: p = 0.19; neutrophil percentage: p = 0.55).
Conclusions
Early detection of fungal PJI is needed, but systemic inflammatory markers and synovial fluid cell count analyses from aspirations do not discriminate whether an infection may be of fungal origin.
Level of Evidence
Level IV, diagnostic study. See Instructions for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-014-3631-9
PMCID: PMC4182394  PMID: 24744131
5.  Incidence and Risk Factors of Prosthetic Joint Infection After Total Hip or Knee Replacement in Patients With Rheumatoid Arthritis 
Arthritis and rheumatism  2008;59(12):1713-1720.
Objective
Prosthetic joint infection is one of the most dreaded complications after total joint arthroplasty, a common procedure in patients with rheumatoid arthritis (RA). We conducted a study to evaluate potential risk factors of prosthetic joint infection and to clarify if RA is an independent predictor of this complication.
Methods
This study included all patients with RA who underwent total hip or knee replacement at the Mayo Clinic Rochester between January 1996 and June 2004. The association of potential risk factors with prosthetic joint infection was examined using Cox models. A matched cohort of patients with osteoarthritis (OA) was assembled to determine whether RA is an independent risk factor for prosthetic joint infection.
Results
We identified 462 patients with RA who underwent a total of 657 hip or knee replacements. Overall, 23 (3.7%) joint arthroplasties were complicated by an infection during a mean ± SD followup of 4.3 ± 2.4 years. Revision arthroplasty (hazard ratio [HR] 2.99, 95% confidence interval [95% CI] 1.02–8.75) and a previous prosthetic joint infection of the replaced joint (HR 5.49, 95% CI 1.87–16.14) were significant predictors of postoperative prosthetic joint infection. Comparison of RA patients with a matched cohort of OA patients identified an increased risk of prosthetic joint infections (HR 4.08, 95% CI 1.35–12.33) in patients with RA.
Conclusion
Patients with RA who undergo total hip or knee replacement are at increased risk of prosthetic joint infection, which is further increased in the setting of revision arthroplasty and a previous prosthetic joint infection. These findings highlight the importance of perioperative prophylactic measures and vigilance during the postoperative period.
doi:10.1002/art.24060
PMCID: PMC3923416  PMID: 19035425
6.  Genitourinary Procedures as Risk Factors for Prosthetic Hip or Knee Infection: A Hospital-Based Prospective Case-Control Study 
Open Forum Infectious Diseases  2015;2(3):ofv097.
Antibiotic prophylaxis during genitourinary procedures was not associated with a statistically significant reduction in risk for prosthetic joint infection in our study. Current policies for administering antibiotic prophylaxis to patients with prosthetic hip or knee arthroplasty undergoing genitourinary procedures should be reconsidered.
Background. The purpose of this study was to determine the risk of prosthetic joint infection (PJI) as a complication of routine genitourinary (GU) procedures in patients with total hip arthroplasty (THA) or total knee arthroplasty (TKA) and to study the impact of antibiotic prophylaxis administered prior to these procedures.
Methods. We conducted a prospective, single-center, case-control study between December 1, 2001 and May 31, 2006. Case patients were hospitalized with total hip or knee PJI. Control subjects underwent a THA or TKA and were hospitalized during the same period on the same orthopedic floor without a PJI. Data regarding demographic features and potential risk factors were collected. The outcome measure was the odds ratio (OR) of PJI after GU procedures performed within 2 years of admission.
Results. A total of 339 case patients and 339 control subjects were enrolled in the study. Of these, 52 cases (15%) and 55 controls (16%) had undergone a GU procedure in the preceding 2 years. There was no increased risk of PJI for patients undergoing a GU procedure with or without antibiotic prophylaxis (adjusted OR [aOR] = 1.0, 95% confidence interval [CI] = 0.2–4.5, P = .95 and aOR = 1.0, 95% CI = 0.6–1.7, P = .99, respectively). Results were similar in a subset of patients with a joint age less than 6 months, less than 1 year, or greater than 1 year.
Conclusions. Genitourinary procedures were not risk factors for subsequent PJI. The use of antibiotic prophylaxis before GU procedures did not decrease the risk of subsequent PJI in our study.
doi:10.1093/ofid/ofv097
PMCID: PMC4525011  PMID: 26258154
antibiotic prophylaxis; genitourinary procedures; prosthetic joint infection
7.  Rothia Bacteremia: a 10-Year Experience at Mayo Clinic, Rochester, Minnesota 
Journal of Clinical Microbiology  2014;52(9):3184-3189.
Rothia spp. are Gram-positive cocco-bacilli that cause a wide range of serious infections, especially in immunocompromised hosts. Risk factors for Rothia mucilaginosa (previously known as Stomatococcus mucilaginosus) bacteremia include prolonged and profound neutropenia, malignancy, and an indwelling vascular foreign body. Here, we describe 67 adults at the Mayo Clinic in Rochester, MN, from 2002 to 2012 with blood cultures positive for Rothia. Twenty-five of these patients had multiple positive blood cultures, indicating true clinical infection. Among these, 88% (22/25) were neutropenic, and 76% (19/25) had leukemia. Common sources of bacteremia were presumed gut translocation, mucositis, and catheter-related infection. One patient died with Rothia infection. Neutropenic patients were less likely to have a single positive blood culture than were nonneutropenic patients. Antimicrobial susceptibility testing was performed on 21% of the isolates. All of the tested isolates were susceptible to vancomycin and most beta-lactams; however, four of six tested isolates were resistant to oxacillin. There was no difference between the neutropenic and nonneutropenic patients in need of intensive care unit care, mortality, or attributable mortality.
doi:10.1128/JCM.01270-14
PMCID: PMC4313135  PMID: 24951810
8.  Long-Term Outcome of Pyogenic Vertebral Osteomyelitis: A Cohort Study of 260 Patients 
Open Forum Infectious Diseases  2014;1(3):ofu107.
Background
 The long-term outcome of patients with pyogenic vertebral osteomyelitis (PVO) has not been fully assessed.
Methods
 We conducted a retrospective cohort study to describe the long-term outcome of PVO and to assess risk factors for treatment failure in patients evaluated at our institution between 1994 and 2002. Patients were observed until July 1, 2013.
Results
 Two hundred sixty patients with PVO were included in this study. Twenty-seven percent (70) of patients developed their infection after an invasive spinal procedure. Staphylococcus aureus accounted for 40% (103) of infections. Forty-nine percent (128) of patients underwent spinal surgery as part of their initial therapy. The median duration of parenteral antimicrobial therapy was 42 days (interquartile range, 38–53). The estimated 2-, 5-, and 10-year cumulative probability of treatment failure-free survival was 72%, 69%, and 69%, respectively. Seventy-five percent of patients who developed treatment failure did so within 4.7 months of diagnosis. Residual neurological defects and persistent back pain were seen in 16% and 32% of patients, respectively. In a multivariate analysis, longer duration of symptoms before diagnosis and having an infection with S. aureus were associated with increased risk of treatment failure.
Conclusions
 Increasing duration of symptoms and infection with S. aureus were associated with treatment failure in patients with PVO. Most treatment failures occurred early after initiation of treatment. Pyogenic vertebral osteomyelitis is associated with a high 2-year failure rate. Persistent neurological deficits and back pain are common after therapy.
doi:10.1093/ofid/ofu107
PMCID: PMC4324221  PMID: 25734175
outcome; spondylodiscitis; treatment failure; vertebral osteomyelitis
9.  Prosthetic joint infection due to Salmonella species: a case series 
BMC Infectious Diseases  2014;14:633.
Background
Prosthetic joint infection (PJI) due to Salmonella is rare. Numerous outbreaks of Salmonella have been reported throughout the United States in the last decade. We reviewed and analyzed cases of Salmonella PJI seen at our institution.
Methods
The medical records of all patients diagnosed with a Salmonella PJI between 1969–2013 were reviewed. Patients were followed till death, treatment failure or loss to follow-up.
Results
Six patients of Salmonella PJI were identified during the 44 year study period. Five were male; median age was 63.5 years (range 52–76). Five patients were immunodeficient. Five had a total hip arthroplasty infection, while one had a total knee arthroplasty infection. Median prosthesis age at the time of diagnosis of first episode of Salmonella PJI was 5 years (range 4 months-9 years). Four presented with fever and constitutional signs within two weeks of symptom onset. Two patients each had gastrointestinal symptoms and Salmonella bacteremia. Salmonella enterica serovar Enteritidis was the most common organism isolated (4 patients). None were Salmonella enterica serovar Typhi. Initial management included aspiration and antimicrobial therapy only (3), debridement and component retention (1) and two-staged exchange (2). All four patients treated without resection failed treatment a median of 2.5 months (range 2–11) after diagnosis and required resection arthroplasty. All six patients who underwent prosthesis removal (and exchange or arthrodesis) had successful outcome with a median duration of follow-up of 11 years (range 4–21). Three of these received oral antimicrobial therapy for a median duration eight weeks (range 4–8) and three received parenteral antimicrobial therapy for a median duration of six weeks (range 4–6).
Conclusions
The increase in Salmonella outbreaks does not seem to lead to increased Salmonella PJI. PJIs due to Salmonella remain rare, and the presentation is often acute with fever. It frequently occurs in immunocompromised patients. In our patient population, removal of prosthesis with or without reimplantation, along with 4–6 weeks of effective parenteral antimicrobial therapy was most often associated with successful eradication of infection.
doi:10.1186/s12879-014-0633-x
PMCID: PMC4258011  PMID: 25424009
Salmonella; Prosthetic joint infections; Arthroplasty
10.  Campylobacter Prosthetic Joint Infection 
Journal of Clinical Microbiology  2014;52(5):1771-1774.
A 75-year-old man was diagnosed with probable Campylobacter jejuni prosthetic knee infection after a diarrheal illness. Joint aspirate and operative cultures were negative, but PCR of prosthesis sonicate fluid was positive, as was stool culture. Nineteen additional cases of Campylobacter prosthetic joint infection reported in the literature are reviewed.
doi:10.1128/JCM.03572-13
PMCID: PMC3993679  PMID: 24523462
11.  Clinical Characteristics and Outcomes of Prosthetic Joint Infection Caused by Small Colony Variant Staphylococci 
mBio  2014;5(5):e01910-14.
ABSTRACT
Small colony variants (SCVs) are naturally occurring subpopulations of bacteria. The clinical characteristics and treatment outcomes of patients with prosthetic joint infection (PJI) caused by staphylococcal SCVs are unknown. This study was a retrospective series of 113 patients with staphylococcal PJI, with prospective testing of archived sonicate fluid samples. SCVs were defined using two-investigator review. Treatment failure was defined as (i) subsequent revision surgery for any reason, (ii) PJI after the index surgery, (iii) prosthesis nonreimplantation due to ongoing infection, or (iv) amputation of the affected limb. There were 38 subjects (34%) with SCVs and 75 (66%) with only normal-phenotype (NP) bacteria. Subjects with SCVs were more likely to have been on chronic antimicrobials prior to surgery (P = 0.048), have had prior surgery for PJI (P = 0.03), have had a longer duration of symptoms (P = 0.0003), and have had a longer time since joint implantation (P = 0.007), compared to those with only NP bacteria. Over a median follow-up of 30.6 months, 9 subjects (24%) with SCVs and 23 (32%) with only NP bacteria experienced treatment failure (P = 0.51). Subjects infected with Staphylococcus aureus were more likely to fail than were those infected with Staphylococcus epidermidis (hazard ratio [HR], 4.03; 95% confidence interval [CI], 1.80 to 9.04). While frequently identified in subjects with PJI and associated with several potential predisposing factors, SCVs were not associated with excess treatment failure compared to NP infections in this study, where they were primarily managed with two-stage arthroplasty exchange.
IMPORTANCE
Bacteria with the small colony variant (SCV) phenotype are described in small case series as causing persistent or relapsing infection, but there are insufficient data to suggest that they should be managed differently than infection with normal-phenotype bacteria. In an effort to investigate the clinical importance of this phenotype, we determined whether SCVs were present in biofilms dislodged from the surfaces of arthroplasties of patients with staphylococcal prosthetic joint infection and assessed the clinical outcomes associated with detection of SCVs. We found that prosthetic joint infection caused by SCV staphylococci was associated with a longer duration of symptoms and more prior treatment for infection but not with an increased rate of treatment failure, compared to infection caused by normal-phenotype staphylococci.
doi:10.1128/mBio.01910-14
PMCID: PMC4196237  PMID: 25271290
12.  Lack of Detection of Human Retrovirus-5 Proviral DNA in Synovial Tissue and Blood Specimens From Individuals With Rheumatoid Arthritis or Osteoarthritis 
Arthritis and rheumatism  2006;55(1):123-125.
Objective
Prior studies have suggested an association of human retrovirus 5 with rheumatoid arthritis. The purpose of this study was to determine if human retrovirus-5 proviral DNA is present in synovial tissue and blood specimens from patients with rheumatoid arthritis or osteoarthritis, or those without joint disease.
Methods
Synovial tissue and whole blood from 75 patients with rheumatoid arthritis, 75 patients with osteoarthritis, and 50 patients without a primary arthritis diagnosis were assayed by real-time quantitative polymerase chain reaction (PCR) using primers that amplify a 186-bp fragment of human retrovirus-5 proviral DNA.
Results
A total of 200 tissue specimens, 200 mononuclear cells, and 196 of 200 granulocyte specimens tested negative for human retrovirus-5 proviral DNA. No association between human retrovirus 5 and rheumatoid arthritis or osteoarthritis (P = 0.516) was identified. Granulocyte specimens from 4 patients, 2 with rheumatoid arthritis and 2 with osteoarthritis, yielded a low positive human retrovirus-5 proviral DNA signal (83–1,365 copies of human retrovirus-5 proviral DNA/ml blood).
Conclusion
Contrary to prior reports, we did not find an association between human retrovirus 5 and rheumatoid arthritis or osteoarthritis using a real-time PCR assay. Our findings are consistent with the recent finding that human retrovirus 5 is actually rabbit endogenous retrovirus H.
doi:10.1002/art.21690
PMCID: PMC1464419  PMID: 16463423
Human retrovirus-5; Rheumatoid arthritis; Osteoarthritis
13.  Implant sonication for the diagnosis of prosthetic elbow infection 
Background
Periprosthetic infection is a potentially devastating complication of elbow arthroplasty, associated with formation of microbial biofilm on the implant surface. The definitive microbiologic diagnosis of periprosthetic infection after elbow arthroplasty may be difficult to establish. Our study aim was to compare the diagnostic accuracy of conventional periprosthetic tissue culture and culture of fluid derived from vortexing and bath sonication of the explanted hardware (a biofilm-sampling strategy).
Materials and methods
Patients undergoing revision elbow arthroplasty at our institution between July 2007 and July 2010, from each of whom 2 or more periprosthetic tissue cultures and 1 implant sonicate culture were obtained, were studied. A standardized definition of orthopedic implant—associated infection was applied.
Results
We identified 27 subjects with aseptic failure and 9 with prosthetic elbow infection. Rheumatoid arthritis was the most common underlying disorder. The Coonrad-Morrey prosthesis was the most common type of implant used. The sensitivities of implant sonicate and periprosthetic tissue culture were 89% and 55%, respectively (P = .18), and the specificities were 100% and 93%, respectively (P = .16). Coagulase-negative staphylococci (n = 7) and Staphylococcus aureus (n = 2) were isolated in cases of infection.
Conclusion
Culture of the implant by sonication is at least as sensitive as periprosthetic tissue culture to detect prosthetic elbow infection.
Level of evidence
Level I, Diagnostic Study.
doi:10.1016/j.jse.2011.06.016
PMCID: PMC3910532  PMID: 22078323
Prosthetic joint infection; elbow prosthesis; implant; sonication; biofilm; periprosthetic tissue
14.  Rapid Molecular Microbiologic Diagnosis of Prosthetic Joint Infection 
Journal of Clinical Microbiology  2013;51(7):2280-2287.
We previously showed that culture of samples obtained by prosthesis vortexing and sonication was more sensitive than tissue culture for prosthetic joint infection (PJI) diagnosis. Despite improved sensitivity, culture-negative cases remained; furthermore, culture has a long turnaround time. We designed a genus-/group-specific rapid PCR assay panel targeting PJI bacteria and applied it to samples obtained by vortexing and sonicating explanted hip and knee prostheses, and we compared the results to those with sonicate fluid and periprosthetic tissue culture obtained at revision or resection arthroplasty. We studied 434 subjects with knee (n = 272) or hip (n = 162) prostheses; using a standardized definition, 144 had PJI. Sensitivities of tissue culture, of sonicate fluid culture, and of PCR were 70.1, 72.9, and 77.1%, respectively. Specificities were 97.9, 98.3, and 97.9%, respectively. Sonicate fluid PCR was more sensitive than tissue culture (P = 0.04). PCR of prosthesis sonication samples is more sensitive than tissue culture for the microbiologic diagnosis of prosthetic hip and knee infection and provides same-day PJI diagnosis with definition of microbiology. The high assay specificity suggests that typical PJI bacteria may not cause aseptic implant failure.
doi:10.1128/JCM.00335-13
PMCID: PMC3697690  PMID: 23658273
15.  INCIDENCE, SECULAR TRENDS AND OUTCOMES OF PROSTHETIC JOINT INFECTION (PJI): A POPULATION BASED STUDY, OLMSTED COUNTY, MINNESOTA, 1969 – 2007 
Context
The epidemiology of prosthetic joint infection (PJI) in a population based cohort has not been studied in the United States.
Objectives
To provide an accurate assessment of the true incidence, secular trends, clinical manifestations, microbiology and treatment outcomes of PJI in a population based cohort.
Design
Historical cohort study
Setting
Olmsted County, Minnesota, United States of America.
Participants
Residents who underwent total knee arthroplasty (TKA) or total hip arthroplasty (THA) between 1/ 1/ 1969 and 12/ 31/ 2007.
Methods
Incidence rates and trends in PJI were assessed using the Kaplan Meier method and log-rank test, as were treatment outcomes among PJI cases.
Results
7375 THA or TKA were implanted in residents of Olmsted County during the study period. Seventy five discrete joints in 70 individuals developed PJI, during a mean(+/− SD) follow up of 6.8 (+/− 6.1) years. The cumulative incidence of PJI was 0.5%, 0.8% and 1.4% after 1, 5 and 10 years following arthroplasty, respectively. Overall, the rate of survival free of clinical failure after treatment of PJI was 76.8 % ( 95% CI: 64.3 – 85.2) and 65.2 % ( 95% CI: 33.1 – 76.2) at 3 years and 5 years, respectively. The incidence and treatment outcomes did not significantly differ by decade of implantation, patient age at implantation, gender or joint location.
Conclusions
The incidence of PJI is relatively low in a population based cohort, and is a function of age of the prosthesis. Incidence trends and outcomes have not significantly changed over the past forty years.
doi:10.1086/668421
PMCID: PMC3602045  PMID: 23143357
16.  Effect of Continuous Venovenous Hemofiltration Dose on Achievement of Adequate Vancomycin Trough Concentrations 
Antimicrobial Agents and Chemotherapy  2012;56(12):6181-6185.
The vancomycin dose necessary for the achievement of target serum trough concentrations during continuous venovenous hemofiltration (CVVH) remains to be elucidated. This was a retrospective cohort study of critically ill adults at a tertiary medical center on concurrent CVVH and vancomycin between 2006 and 2010 with a steady-state vancomycin trough concentration. The 87 included patients were grouped according to low (≤30 ml/kg/h; n = 10) or high (>30 ml/kg/h; n = 77) CVVH hemofiltration rate (HFR) for analysis. Vancomycin goal trough achievement occurred in only 32 (37%) patients. The primary endpoint of trough attainment significantly differed between HFR subgroups: 90% versus 30% in low- and high-HFR individuals, respectively (P < 0.001). Patients with subtherapeutic trough concentrations had a median (interquartile range) HFR of 40 ml/kg/h (range, 37 to 47 ml/kg/h) compared to 36 ml/kg/h (range, 30 to 39 ml/kg/h) in those who achieved the trough goal. Irrespective of goal trough, an inverse correlation existed between HFR and serum vancomycin concentration (r = −0.423; P < 0.001). In the subgroup of 14 methicillin-resistant Staphylococcus aureus (MRSA) patients, trough achievement was similar to the aggregate cohort (36%). Mortality at 28 days was unrelated to trough achievement in both the overall sample (P = 0.516) and in culture-positive MRSA patients (P = 0.396). Critically ill patients undergoing CVVH therapy may experience clinically significant reductions in goal vancomycin troughs. The results of the present study justify prospective evaluations in this population to determine the optimal vancomycin dosing strategy for attainment of goal trough concentrations.
doi:10.1128/AAC.00459-12
PMCID: PMC3497205  PMID: 22985887
17.  Prosthetic Joint Infection Diagnosis Using Broad-Range PCR of Biofilms Dislodged from Knee and Hip Arthroplasty Surfaces Using Sonication 
Journal of Clinical Microbiology  2012;50(11):3501-3508.
Periprosthetic tissue and/or synovial fluid PCR has been previously studied for prosthetic joint infection (PJI) diagnosis; however, few studies have assessed the utility of PCR on biofilms dislodged from the surface of explanted arthroplasties using vortexing and sonication (i.e., sonicate fluid PCR). We compared sonicate fluid 16S rRNA gene real-time PCR and sequencing to culture of synovial fluid, tissue, and sonicate fluid for the microbiologic diagnosis of PJI. PCR sequences generating mixed chromatograms were decatenated using RipSeq Mixed. We studied sonicate fluids from 135 and 231 subjects with PJI and aseptic failure, respectively. Synovial fluid, tissue, and sonicate fluid culture and sonicate fluid PCR had similar sensitivities (64.7, 70.4, 72.6, and 70.4%, respectively; P > 0.05) and specificities (96.9, 98.7, 98.3, and 97.8%, respectively; P > 0.05). Combining sonicate fluid culture and PCR, the sensitivity was higher (78.5%, P < 0.05) than those of individual tests, with similar specificity (97.0%). Thirteen subjects had positive sonicate fluid culture but negative PCR, and 11 had negative sonicate fluid culture but positive PCR (among which 7 had prior use of antimicrobials). Broad-range PCR and culture of sonicate fluid have equivalent performance for PJI diagnosis.
doi:10.1128/JCM.00834-12
PMCID: PMC3486250  PMID: 22895042
18.  Increased risk of prosthetic joint infection associated with esophago-gastro-duodenoscopy with biopsy 
Acta Orthopaedica  2013;84(1):82-86.
Background
There are no prospective data regarding the risk of prosthetic joint infection following routine gastrointestinal endoscopic procedures. We wanted to determine the risk of prosthetic hip or knee infection following gastrointestinal endoscopic procedures in patients with joint arthroplasty.
Methods
We conducted a prospective, single-center, case-control study at a single, tertiary-care referral center. Cases were defined as adult patients hospitalized for prosthetic joint infection of the hip or knee between December 1, 2001 and May 31, 2006. Controls were adult patients with hip or knee arthroplasties but without a diagnosis of joint infection, hospitalized during the same time period at the same orthopedic hospital. The main outcome measure was the odds ratio (OR) of prosthetic joint infection after gastrointestinal endoscopic procedures performed within 2 years before admission.
Results
339 cases and 339 controls were included in the study. Of these, 70 cases (21%) cases and 82 controls (24%) had undergone a gastrointestinal endoscopic procedure in the preceding 2 years. Among gastrointestinal procedures that were assessed, esophago-gastro-duodenoscopy (EGD) with biopsy was associated with an increased risk of prosthetic joint infection (OR = 3, 95% CI: 1.1–7). In a multivariable analysis adjusting for sex, age, joint age, immunosuppression, BMI, presence of wound drain, prior arthroplasty, malignancy, ASA score, and prothrombin time, the OR for infection after EGD with biopsy was 4 (95% CI: 1.5–10).
Interpretation
EGD with biopsy was associated with an increased risk of prosthetic joint infection in patients with hip or knee arthroplasties. This association will need to be confirmed in other epidemiological studies and adequately powered prospective clinical trials prior to recommending antibiotic prophylaxis in these patients.
doi:10.3109/17453674.2013.769079
PMCID: PMC3584609  PMID: 23350577
19.  Reinfection after two-stage revision for periprosthetic infection of total knee arthroplasty 
International Orthopaedics  2011;36(1):65-71.
Purpose
Limited data exist regarding the long-term results or risk factors for failure after two-stage reimplantation for periprosthetic knee infection. The purpose of this retrospective review was to investigate infection-free implant survival and identify variables associated with reinfection after this procedure. Furthermore, a staging system was evaluated as a possible prognostic tool for patients undergoing two-stage reimplantation of infected total knee arthroplasty (TKA).
Methods
In this level II, retrospective prognostic study, 368 patients with infected TKA treated with a two-stage revision protocol at our institution between 1998 and 2006 were reviewed. Patients who developed recurrent infection and an equal number of patients randomly selected for the control group were analysed for risk factors associated with treatment failure.
Results
At the most recent follow-up, 58 (15.8%) patients had developed reinfection after the two-stage reimplantation. The median time to reinfection was 1,303 days (3.6 years), with follow-up time ranging from six to 2,853 days (7.8 years). The strongest positive predictors of treatment failure included chronic lymphoedema [hazard ratio (HR) = 2.28, 95% confidence interval (CI) 1.16–4.48; p = 0.02),and revision between resection and definitive reimplantation (HR = 2.13, 95% CI 1.20–3.79; p = 0.01, whereas patients treated with intravenously administered Cefazolin had a significant reduction in recurrent infection rate (HR = 0.48, 95% CI 0.25–0.90; p = 0.02).
Conclusions
Our findings should be of help in counselling patients regarding their prognosis when faced with two-stage exchange for infected TKA and provide a basis for future comparisons.
doi:10.1007/s00264-011-1267-x
PMCID: PMC3251662  PMID: 21553042
20.  Practical Considerations in the Use of Outpatient Antimicrobial Therapy for Musculoskeletal Infections 
Mayo Clinic Proceedings  2012;87(1):98-105.
Successful treatment of many musculoskeletal infections often requires an extended course of outpatient antimicrobial therapy, much of which is administered parenterally outside the hospital under the guidance of an infectious disease specialist. Delivery of outpatient parenteral antimicrobial therapy (OPAT) may occur in physicians' offices, ambulatory infusion centers, or hospital clinics but most frequently is done in patients' homes, often by the patients themselves. In this article, we outline the essential elements of outpatient antimicrobial therapy for musculoskeletal infections with particular emphasis on OPAT, including patient selection and evaluation; antimicrobial administration, including the route, duration, and complications of central venous access; and clinical and laboratory monitoring of antimicrobial therapy. We believe that primary care physicians, orthopedists, and infectious disease specialists caring for patients with musculoskeletal infections should become familiar with the use of, indications for, and complications of OPAT.
doi:10.1016/j.mayocp.2011.11.005
PMCID: PMC3498104  PMID: 22212975
21.  Antimicrobial Prophylaxis in Adults 
Mayo Clinic Proceedings  2011;86(7):686-701.
Antimicrobial prophylaxis is commonly used by clinicians for the prevention of numerous infectious diseases, including herpes simplex infection, rheumatic fever, recurrent cellulitis, meningococcal disease, recurrent uncomplicated urinary tract infections in women, spontaneous bacterial peritonitis in patients with cirrhosis, influenza, infective endocarditis, pertussis, and acute necrotizing pancreatitis, as well as infections associated with open fractures, recent prosthetic joint placement, and bite wounds. Perioperative antimicrobial prophylaxis is recommended for various surgical procedures to prevent surgical site infections. Optimal antimicrobial agents for prophylaxis should be bactericidal, nontoxic, inexpensive, and active against the typical pathogens that can cause surgical site infection postoperatively. To maximize its effectiveness, intravenous perioperative prophylaxis should be administered within 30 to 60 minutes before the surgical incision. Antimicrobial prophylaxis should be of short duration to decrease toxicity and antimicrobial resistance and to reduce cost.
doi:10.4065/mcp.2011.0012
PMCID: PMC3127564  PMID: 21719623
22.  Prior Use of Antimicrobial Therapy is a Risk Factor for Culture-negative Prosthetic Joint Infection 
Background
Clinical characteristics and control of the infection of patients with culture-negative (CN) prosthetic joint infection (PJI) have not been well assessed. Prior use of antimicrobial therapy has been speculated but not proven as a risk factor for CNPJI.
Questions/purposes
We therefore determined whether prior use of antimicrobial therapy, prior PJI, and postoperative wound healing complications were associated with CN PJI.
Methods
We performed a retrospective case-control study of 135 patients with CN PJI treated between January 1, 1985, and December 31, 2000 matched with 135 patients with culture-positive (CP) PJIs (control patients) during the study period. The time to failure of therapy compared between cases and control patients using a Kaplan-Meier analysis.
Results
The use of prior antimicrobial therapy and postoperative wound drainage after index arthroplasty were associated with increased odds of PJI being culture-negative (odds ratio, 4.7; 95% CI, 2.8–8.1 and odds ratio, 3.5; 95% CI, 1.5–8.1, respectively). The percent (± SE) cumulative incidence free of treatment failure at 2 years followup was similar for CN and CP PJI: 75% (± 4%) and 79% (± 4%), respectively.
Conclusions
Prior antimicrobial therapy and postoperative wound drainage were associated with an increased risk of negative cultures among patients with PJI. Physicians should critically evaluate the need for antimicrobial therapy before establishing a microbiologic diagnosis of PJI in patients with suspected PJI.
Level of Evidence
Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-010-1338-0
PMCID: PMC2895855  PMID: 20401555
23.  Laboratory and Clinical Characteristics of Staphylococcus lugdunensis Prosthetic Joint Infections▿  
Journal of Clinical Microbiology  2010;48(5):1600-1603.
Staphylococcus lugdunensis is a coagulase-negative staphylococcus that has several similarities to Staphylococcus aureus. S. lugdunensis is increasingly being recognized as a cause of prosthetic joint infection (PJI). The goal of the present retrospective cohort study was to determine the laboratory and clinical characteristics of S. lugdunensis PJIs seen at the Mayo Clinic in Rochester, MN, between 1 January 1998 and 31 December 2007. Kaplan-Meier survival methods and Wilcoxon sum-rank analysis were used to determine the cumulative incidence of treatment success and assess subset comparisons. There were 28 episodes of S. lugdunensis PJIs in 22 patients; half of those patients were females. Twenty-five episodes (89%) involved the prosthetic knee, while 3 (11%) involved the hip. Nine patients (32%) had an underlying urogenital abnormality. Among the 28 isolates in this study tested by agar dilution, 24 of 28 (86%) were oxacillin susceptible. Twenty of the 21 tested isolates (95%) lacked mecA, and 6 (27%) of the 22 isolates tested produced β-lactamase. The median durations of parenteral β-lactam therapy and vancomycin therapy were 38 days (range, 23 to 42 days) and 39 days (range, 12 to 60 days), respectively. The cumulative incidences of freedom from treatment failure (standard deviations) at 2 years were 92% (±7%) and 76% (±12%) for episodes treated with a parenteral β-lactam and vancomycin, respectively (P = 0.015). S. lugdunensis is increasingly being recognized as a cause of PJIs. The majority of the isolates lacked mecA. Episodes treated with a parenteral β-lactam antibiotic appear to have a more favorable outcome than those treated with parenteral vancomycin.
doi:10.1128/JCM.01769-09
PMCID: PMC2863876  PMID: 20181900
25.  C-Reactive Protein, Erythrocyte Sedimentation Rate and Orthopedic Implant Infection 
PLoS ONE  2010;5(2):e9358.
Background
C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) have been shown to be useful for diagnosis of prosthetic hip and knee infection. Little information is available on CRP and ESR in patients undergoing revision or resection of shoulder arthroplasties or spine implants.
Methods/Results
We analyzed preoperative CRP and ESR in 636 subjects who underwent knee (n = 297), hip (n = 221) or shoulder (n = 64) arthroplasty, or spine implant (n = 54) removal. A standardized definition of orthopedic implant-associated infection was applied. Receiver operating curve analysis was used to determine ideal cutoff values for differentiating infected from non-infected cases. ESR was significantly different in subjects with aseptic failure infection of knee (median 11 and 53.5 mm/h, respectively, p = <0.0001) and hip (median 11 and 30 mm/h, respectively, p = <0.0001) arthroplasties and spine implants (median 10 and 48.5 mm/h, respectively, p = 0.0033), but not shoulder arthroplasties (median 10 and 9 mm/h, respectively, p = 0.9883). Optimized ESR cutoffs for knee, hip and shoulder arthroplasties and spine implants were 19, 13, 26, and 45 mm/h, respectively. Using these cutoffs, sensitivity and specificity to detect infection were 89 and 74% for knee, 82 and 60% for hip, and 32 and 93% for shoulder arthroplasties, and 57 and 90% for spine implants. CRP was significantly different in subjects with aseptic failure and infection of knee (median 4 and 51 mg/l, respectively, p<0.0001), hip (median 3 and 18 mg/l, respectively, p<0.0001), and shoulder (median 3 and 10 mg/l, respectively, p = 0.01) arthroplasties, and spine implants (median 3 and 20 mg/l, respectively, p = 0.0011). Optimized CRP cutoffs for knee, hip, and shoulder arthroplasties, and spine implants were 14.5, 10.3, 7, and 4.6 mg/l, respectively. Using these cutoffs, sensitivity and specificity to detect infection were 79 and 88% for knee, 74 and 79% for hip, and 63 and 73% for shoulder arthroplasties, and 79 and 68% for spine implants.
Conclusion
CRP and ESR have poor sensitivity for the diagnosis of shoulder implant infection. A CRP of 4.6 mg/l had a sensitivity of 79 and a specificity of 68% to detect infection of spine implants.
doi:10.1371/journal.pone.0009358
PMCID: PMC2825262  PMID: 20179760

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