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1.  Linezolid plus Rifampin as a Salvage Therapy in Prosthetic Joint Infections Treated without Removing the Implant▿ 
The aim of this study is to describe our experience with linezolid plus rifampin as a salvage therapy in prosthetic joint infections (PJIs) when other antibiotic regimens failed or were not tolerated. A total of 161 patients with a documented prosthetic joint infection were diagnosed with a PJI and prospectively followed up from January 2000 to April 2007. Clinical characteristics, inflammatory markers, microbiological and radiological data, and antibiotic treatment were recorded. After a 2-year follow-up, patients were classified as cured when the prosthesis was not removed, symptoms of infection disappeared, and inflammatory parameters were within the normal range. Any other outcome was considered a failure. The mean age of the entire cohort (n = 161) was 67 years. Ninety-five episodes were on a knee prosthesis (59%), and 66 were on a hip prosthesis (41%). A total of 49 patients received linezolid plus rifampin: 45 due to failure of the previous antibiotic regimen and 4 due to an adverse event associated with the prior antibiotics. In no case was the implant removed. The mean (standard deviation) duration of treatment was 80.2 (29.7) days. The success rate after 24 months of follow-up was 69.4% (34/49 patients). Three patients developed thrombocytopenia and 3 developed anemia; however, it was not necessary to stop linezolid. Linezolid plus rifampin is an alternative salvage therapy when the implant is not removed.
doi:10.1128/AAC.00352-11
PMCID: PMC3165328  PMID: 21690277
2.  Periprosthetic Infection Due to Resistant Staphylococci: Serious Problems on the Horizon 
Prosthetic joint infections (PJI) caused by methicillin-resistant staphylococci represent a major therapeutic challenge. We examined the effectiveness of surgical treatment in treating infection of total hip or knee arthroplasty caused by methicillin-resistant staphylococcal strains and the variables influencing treatment success. One hundred and twenty-seven patients were treated at our institution between 1999 and 2006. There were 58 men and 69 women, with an average age of 66 years. Patients were followed for a minimum of 2 years or until recurrence of infection. Débridement and retention of the prosthesis was performed in 35 patients and resection arthroplasty in 92. Débridement controlled the infection in only 37% of cases whereas two-stage exchange arthroplasty controlled the infection in 75% of hips and 60% of knees. Preexisting cardiac disease was associated with a higher likelihood of failure to control infection in all treatment groups. Antibiotic-resistant Staphylococci continue to compromise treatment outcome of prosthetic joint infections, especially in patients with medical comorbidities. New preventive and therapeutic strategies are needed.
Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-009-0857-z
PMCID: PMC2690767  PMID: 19408061
3.  Early prosthetic joint infections treated with debridement and implant retention 
Acta Orthopaedica  2012;83(3):227-232.
Background and purpose
Debridement and retention of the prosthesis is often attempted to treat early prosthetic joint infection (PJI). However, previous studies have found inconsistent results, with success rates ranging from 21% to 100%, and little has been written in the literature about hip function. We have therefore analyzed the clinical and functional outcome of early PJIs treated with this procedure.
Patients and methods
38 patients with early PJI after primary hip arthroplasty who were treated with debridement and retention of the implant between 1998 and 2005 were studied prospectively, with a median follow-up time of 4 (0.8–10) years. Early infection was defined as that which occurred within 4 weeks of index arthroplasty. The primary outcome measure was infection control. Functional outcome was assessed with the Harris hip score.
Results
27 of 38 patients were successfully treated, with no signs of infection or continued antibiotic treatment at the latest follow-up. Median Harris hip score was 86 (47–100) points. In 9 of the 11 patients for whom treatment failed, infection was successfully treated with 1-stage or 2-stage reimplantation or resection. Intraoperative cultures were positive in 36 hips, and the most frequently isolated organisms were Staphylococcus aureus and coagulase-negative staphylococci (CoNS). 15 infections were polymicrobial, and only 8 of them were successfully treated with debridement and retention of the implant.
Interpretation
Our data suggest that debridement and retention of the prosthesis is a reasonable treatment option in early PJI after primary hip arthroplasty, with satisfactory functional results.
doi:10.3109/17453674.2012.678801
PMCID: PMC3369146  PMID: 22489892
4.  Prosthetic joint-associated infections treated with DAIR (debridement, antibiotics, irrigation, and retention) 
Acta Orthopaedica  2013;84(4):380-386.
Background and purpose
For prosthetic joint-associated infection (PJI), a regimen of debridement, antibiotics, irrigation, and retention of the prosthesis (DAIR) is generally accepted for acute infections. Various risk factors associated with treatment success have been described. The use of local antibiotic carriers (beads and sponges) is relatively unknown. We retrospectively analyzed risk factors in a cohort of patients from 3 hospitals, treated with DAIR for PJI.
Patients and methods
91 patients treated with DAIR for hip or knee PJI in 3 Dutch centers between 2004 and 2009 were retrospectively evaluated. The mean follow-up was 3 years. Treatment success was defined as absence of infection after 2 years, with retention of the prosthesis and without the use of suppressive antibiotics.
Results
60 patients (66%) were free of infection at follow-up. Factors associated with treatment failure were: a history of rheumatoid arthritis, late infection (> 2 years after arthroplasty), ESR at presentation above 60 mm/h, and infection caused by coagulase-negative Staphylococcus. Symptom duration of less than 1 week was associated with treatment success. The use of gentamicin sponges was statistically significantly higher in the success group, and the use of beads was higher in the failure group in the univariate analysis, but these differences did not reach significance in the logistic regression analysis. Less surgical procedures were performed in the group treated with sponges than in the group treated with beads.
Interpretation
In the presence of rheumatoid arthritis, duration of symptoms of more than 1 week, ESR above 60 mm/h, late infection (> 2 years after arthroplasty), and coagulase-negative Staphylococcus PJI, the chances of successful DAIR treatment decrease, and other treatment methods should be considered.
doi:10.3109/17453674.2013.823589
PMCID: PMC3768038  PMID: 23848215
5.  Outcome of Acute Prosthetic Joint Infections Due to Gram-Negative Bacilli Treated with Open Debridement and Retention of the Prosthesis▿  
Antimicrobial Agents and Chemotherapy  2009;53(11):4772-4777.
The aim of our study was to evaluate the outcome of acute prosthetic joint infections (PJIs) due to gram-negative bacilli (GNB) treated without implant removal. Patients with an acute PJI due to GNB diagnosed from 2000 to 2007 were prospectively registered. Demographics, comorbidity, type of implant, microbiology data, surgical treatment, antimicrobial therapy, and outcome were recorded. Classification and regression tree analysis, the Kaplan-Meier survival method, and the Cox regression model were applied. Forty-seven patients were included. The mean age was 70.7 years, and there were 15 hip prostheses and 32 knee prostheses. The median number of days from the time of arthroplasty was 20. The most frequent pathogens were members of the Enterobacteriaceae family in 41 cases and Pseudomonas spp. in 20 cases. Among the Enterobacteriaceae, 14 were resistant to ciprofloxacin, while all Pseudomonas aeruginosa isolates were susceptible to ciprofloxacin. The median durations of intravenous and oral antibiotic treatment were 14 and 64 days, respectively. A total of 35 (74.5%) patients were in remission after a median follow-up of 463 days (interquartile range, 344 to 704) days. By use of the Kaplan-Meier survival curve, a C-reactive protein (CRP) concentration of ≤15 mg/dl (P = 0.03) and receipt of a fluoroquinolone, when all GNB isolated were susceptible (P = 0.0009), were associated with a better outcome. By use of a Cox regression model, a CRP concentration of ≤15 mg/dl (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.05 to 12.5; P = 0.043) and receipt of a fluoroquinolone (OR, 9.09; 95% CI, 1.96 to 50; P = 0.005) were independently associated with better outcomes. Open debridement without removal of the implant had a success rate of 74.5%, and the factors associated with good prognosis were a CRP concentration at the time of diagnosis ≤15 mg/dl and treatment with a fluoroquinolone.
doi:10.1128/AAC.00188-09
PMCID: PMC2772308  PMID: 19687237
6.  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
7.  Periprosthetic Joint Infections 
Implantation of joint prostheses is becoming increasingly common, especially for the hip and knee. Infection is considered to be the most devastating of prosthesis-related complications, leading to prolonged hospitalization, repeated surgical intervention, and even definitive loss of the implant. The main risk factors to periprosthetic joint infections (PJIs) are advanced age, malnutrition, obesity, diabetes mellitus, HIV infection at an advanced stage, presence of distant infectious foci, and antecedents of arthroscopy or infection in previous arthroplasty. Joint prostheses can become infected through three different routes: direct implantation, hematogenic infection, and reactivation of latent infection. Gram-positive bacteria predominate in cases of PJI, mainly Staphylococcus aureus and Staphylococcus epidermidis. PJIs present characteristic signs that can be divided into acute and chronic manifestations. The main imaging method used in diagnosing joint prosthesis infections is X-ray. Computed tomography (CT) scan may assist in distinguishing between septic and aseptic loosening. Three-phase bone scintigraphy using technetium has high sensitivity, but low specificity. Positron emission tomography using fluorodeoxyglucose (FDG-PET) presents very divergent results in the literature. Definitive diagnosis of infection should be made by isolating the microorganism through cultures on material obtained from joint fluid puncturing, surgical wound secretions, surgical debridement procedures, or sonication fluid. Success in treating PJI depends on extensive surgical debridement and adequate and effective antibiotic therapy. Treatment in two stages using a spacer is recommended for most chronic infections in arthroplasty cases. Treatment in a single procedure is appropriate in carefully selected cases.
doi:10.1155/2013/542796
PMCID: PMC3760112  PMID: 24023542
8.  Oral rifampin plus ofloxacin for treatment of Staphylococcus-infected orthopedic implants. 
We examined the effectiveness and safety of the combination of rifampin plus ofloxacin given orally for treating prosthetic orthopedic implants infected with staphylococci. The prospective cohort study was conducted in a referral public hospital with ambulatory care services between 1985 and 1991. Consecutive patients from whom Staphylococcus organisms susceptible to the study drugs were isolated from their orthopedic implants and who had no contraindication to the treatment were eligible for the study. All patients were treated orally with rifampin, 900 mg/day, plus ofloxacin, 600 mg/day. Patients with hip prosthesis infection were treated for 6 months, with removal of any unstable prostheses after 5 months of treatment; patients with knee prosthesis infection were treated for 9 months, with removal of the prosthesis after 6 months of treatment; and patients with infected bone plates were treated for 6 months, with removal of the plate after 3 months of treatment, if necessary. Monthly clinical evaluations were conducted until the completion of the treatment and follow-up or telephone interviews were conducted at 6, 12, 24, 36, 48, and 60 months thereafter. Treatment failures were documented by clinical evaluation, sampling of the infected site for culture and antibiotic activity measurement, and fistulography, if possible. Cure was defined as the absence of clinical, biological, and radiological evidence of infection 6 months after the completion of treatment, treatment failure was defined as the absence of cure, and relapse was defined as the reappearance of infection caused by the same Staphylococcus isolate that caused the original infection, regardless of the timing of this secondary infection. Among 51 patients included in the study and evaluable for safety, 4 patients had side effects and were not evaluable for treatment effectiveness; the overall success rate was 74% among 47 patients, with a success rate of 81% for the hip prosthesis group, 69% for the knee prosthesis group, and 69% for the osteosynthesis device group. Eight treatment failures were relaxed to the isolation of a resistant bacterium. The combination of rifampin administered orally plus ofloxacin is a suitable alternative to the conventional long-term intravenous therapy for treatment of orthopedic implants infected with staphylococci.
PMCID: PMC187942  PMID: 8328772
9.  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
10.  2-stage revision recommended for treatment of fungal hip and knee prosthetic joint infections 
Acta Orthopaedica  2013;84(6):517-523.
Background and purpose
Fungal prosthetic joint infections are rare and difficult to treat. This systematic review was conducted to determine outcome and to give treatment recommendations.
Patients and methods
After an extensive search of the literature, 164 patients treated for fungal hip or knee prosthetic joint infection (PJI) were reviewed. This included 8 patients from our own institutions.
Results
Most patients presented with pain (78%) and swelling (65%). In 68% of the patients, 1 or more risk factors for fungal PJI were found. In 51% of the patients, radiographs showed signs of loosening of the arthroplasty. Candida species were cultured from most patients (88%). In 21% of all patients, fungal culture results were first considered to be contamination. There was co-infection with bacteria in 33% of the patients. For outcome analysis, 119 patients had an adequate follow-up of at least 2 years. Staged revision was the treatment performed most often, with the highest success rate (85%).
Interpretation
Fungal PJI resembles chronic bacterial PJI. For diagnosis, multiple samples and prolonged culturing are essential. Fungal species should be considered to be pathogens. Co-infection with bacteria should be treated with additional antibacterial agents.
We found no evidence that 1-stage revision, debridement, antibiotics, irrigation, and retention (DAIR) or antifungal therapy without surgical treatment adequately controls fungal PJI. Thus, staged revision should be the standard treatment for fungal PJI. After resection of the prosthesis, we recommend systemic antifungal treatment for at least 6 weeks—and until there are no clinical signs of infection and blood infection markers have normalized. Then reimplantation can be performed.
doi:10.3109/17453674.2013.859422
PMCID: PMC3851663  PMID: 24171675
11.  Pathogenic organisms in hip joint infections 
Infections of the hip joint are usually of bacterial etiology. Only rarely, an infectious arthritis is caused in this localization by viruses or fungi. Native joint infections of the hip are less common than infections after implantation of prosthetic devices. Difficulties in prosthetic joint infections are, (I) a higher age of patients, and, thus an associated presence of other medical risk factors, (II) often long courses of treatment regimes depending on the bacterium and its antibiotic resistance, (III) an increased mortality, and (IV) a high economic burden for removal and reimplantation of an infected prosthetic device. The pathogenic mechanisms responsible for articular infections are well studied only for some bacteria, e.g. Staphylococcus aureus, while others are only partially understood. Important known bacterial properties and microbiological characteristics of infection are the bacterial adhesion on the native joint or prosthetic material, the bacterial biofilm formation, the development of small colony variants (SCV) as sessile bacterial types and the increasing resistance to antibiotics.
PMCID: PMC2755118  PMID: 19834588
arthritis; bacteria; diagnosis; prosthesis; therapy
12.  Adjunctive Rifampin Is Crucial to Optimizing Daptomycin Efficacy against Rabbit Prosthetic Joint Infection Due to Methicillin-Resistant Staphylococcus aureus▿† 
Antimicrobial Agents and Chemotherapy  2011;55(10):4589-4593.
Daptomycin is an attractive option for treating prosthetic joint infection, but the 6-mg/kg of body weight/day dose was linked to clinical failure and emergence of resistance. Using a methicillin-resistant Staphylococcus aureus (MRSA) knee prosthesis infection in rabbits, we studied the efficacies of high-dose daptomycin (22 mg/kg given intravenously [i.v.] once daily [o.d.]; equivalent to 8 mg/kg/day in humans) or vancomycin (60 mg/kg given intramuscularly [i.m.] twice daily [b.i.d.]), both either alone or with adjunctive rifampin (10 mg/kg i.m. b.i.d.). After partial knee replacement with a silicone implant, 107 MRSA CFU was injected into the knees. Treatment started 7 days postinoculation and lasted 7 days. Positive cultures were screened for the emergence of mutant strains, defined as having 3-fold-increased MICs. Although in vivo mean log10 CFU/g of daptomycin-treated (4.23 ± 1.44; n = 12) or vancomycin-treated (4.63 ± 1.08; n = 12) crushed bone was significantly lower than that of controls (5.93 ± 1.15; n = 9) (P < 0.01), neither treatment sterilized bone (2/12 and 0/12 rabbits with sterile bone, respectively). Daptomycin mutant strains were found in 6/12, 3/12, and 2/9 daptomycin-treated, vancomycin-treated, and control rabbits, respectively; no resistant strains emerged (MIC was always <1 mg/liter). Adjunctive rifampin with daptomycin (1.47 ± 0.04 CFU/g of bone [detection threshold]; 11/11 sterile bones) or vancomycin (1.5 ± 0.12 CFU/g of bone; 6/8 sterile bones) was significantly more effective than monotherapy (P < 0.01) and prevented the emergence of daptomycin mutant strains. In this MRSA joint prosthesis infection model, combining rifampin with daptomycin was highly effective. Daptomycin mutant strains were isolated in vivo even without treatment, but adjunctive rifampin prevented this phenomenon, previously found after monotherapy in humans.
doi:10.1128/AAC.00675-11
PMCID: PMC3186998  PMID: 21825285
13.  Vancomycin-Rifampin Combination Therapy Has Enhanced Efficacy against an Experimental Staphylococcus aureus Prosthetic Joint Infection 
Antimicrobial Agents and Chemotherapy  2013;57(10):5080-5086.
Treatment of prosthetic joint infections often involves a two-stage exchange, with implant removal and antibiotic spacer placement followed by systemic antibiotic therapy and delayed reimplantation. However, if antibiotic therapy can be improved, one-stage exchange or implant retention may be more feasible, thereby decreasing morbidity and preserving function. In this study, a mouse model of prosthetic joint infection was used in which Staphylococcus aureus was inoculated into a knee joint containing a surgically placed metallic implant extending from the femur. This model was used to evaluate whether combination therapy of vancomycin plus rifampin has increased efficacy compared with vancomycin alone against these infections. On postoperative day 7, vancomycin with or without rifampin was administered for 6 weeks with implant retention. In vivo bioluminescence imaging, ex vivo CFU enumeration, X-ray imaging, and histologic analysis were carried out. We found that there was a marked therapeutic benefit when vancomycin was combined with rifampin compared with vancomycin alone. Taken together, our results suggest that the mouse model used could serve as a valuable in vivo preclinical model system to evaluate and compare efficacies of antibiotics and combinatory therapy for prosthetic joint infections before more extensive studies are carried out in human subjects.
doi:10.1128/AAC.00702-13
PMCID: PMC3811477  PMID: 23917317
14.  Prosthetic Joint Infection in Patients with Rheumatoid Arthritis: An Outcome Analysis Compared with Controls 
PLoS ONE  2013;8(8):e71666.
Background
Patients with rheumatoid arthritis (RA) have been shown to have an increased susceptibility to the development of prosthetic joint infection (PJI) after hip or knee replacement. However, little information is available on the demographic data, outcome of treatment and prognostic factors in RA patients when compared to those in non-RA patients.
Methods/Principal Findings
We performed a retrospective cohort analysis of all cases of PJI that were treated at our institution between 2002 and 2008. Of 346 episodes of PJI during the study period, 46 (13.3%) occurred in patients with RA. Compared to the non-RA cohort, RA patients with PJI were female predominant (74% vs 27%, p<0.001), younger (median age, 51 vs 63 years, p<0.001) and developed infection earlier (median joint age, 72 vs 128 days, p<0.001). The 2-year survival rate free of treatment failure was lower in RA patients with PJI episodes either treated with débridement (22% vs 52%, p = 0.002) or two-stage exchange (78% vs 95%, p = 0.004). A longer duration of symptoms before débridement surgery (median, 11 vs 5 days, p = 0.015), and absence of antibiotics in bone cement for two-stage exchange (relative risk, 8.0; p = 0.02) were associated with treatment failure in patients with RA.
Discussion
The outcome of PJI in RA patients was generally worse than that in non-RA patients. Risk of treatment failure increased in the setting of delayed débridement and two-stage exchange without the use of antibiotic-impregnated bone cement. These findings highlight the importance of vigilant monitoring and aggressive treatment for PJI in RA patients.
doi:10.1371/journal.pone.0071666
PMCID: PMC3753295  PMID: 23990969
15.  Randomized Controlled Trial of the Safety and Efficacy of Daptomycin versus Standard-of-Care Therapy for Management of Patients with Osteomyelitis Associated with Prosthetic Devices Undergoing Two-Stage Revision Arthroplasty 
Antimicrobial Agents and Chemotherapy  2012;56(11):5626-5632.
The prevalence of Staphylococcus aureus causing prosthetic joint infection (PJI) supports investigation of higher doses of daptomycin in the management of PJI. This was a prospective, randomized controlled trial studying safety and efficacy of daptomycin (6 and 8 mg/kg of body weight) compared with standard-of-care therapy for PJI. This open-label study randomized 75 patients undergoing 2-stage revision arthroplasty to daptomycin at 6 or 8 mg/kg or a comparator (vancomycin, teicoplanin, or semisynthetic penicillin). After prosthesis removal, patients received 6 weeks of antibiotic treatment and a 2- to 6-week antibiotic-free period before implantation of a new prosthesis. Test of cure (TOC) was within 1 to 2 weeks after reimplantation. The primary objective was evaluation of creatine phosphokinase (CPK) levels. Secondary objectives were clinical efficacy and microbiological assessments. Of 73 CPK safety population patients, CPK elevation of >500 U/liter occurred in 4 of 25 (16.0%) (daptomycin, 6 mg/kg) and 5 of 23 (21.7%) (daptomycin, 8 mg/kg) daptomycin-treated patients and 2 of 25 (8.0%) comparator patients. Adverse-event rates were similar among daptomycin and comparator groups. Among modified intent-to-treat patients at TOC, clinical success rates were 14 of 24 (58.3%) for 6 mg/kg daptomycin, 14 of 23 (60.9%) for 8 mg/kg daptomycin, and 8 of 21 (38.1%) for the comparator. Overall microbiological success at TOC was 12 of 24 (50.0%) for 6 mg/kg daptomycin, 12 of 23 (52.2%) for 8 mg/kg daptomycin, and 8 of 21 (38.1%) for comparator patients. In conclusion, daptomycin at 6 and 8 mg/kg given for up to 6 weeks was safe and appeared to be effective in managing staphylococcal PJI using a 2-stage revision arthroplasty technique in a total of 49 patients.
doi:10.1128/AAC.00038-12
PMCID: PMC3486533  PMID: 22908174
16.  Patients with Prosthetic Joint Infection on IV Antibiotics are at High Risk for Readmission 
Due to the rise in prosthetic joint implantations, prosthetic joint infections (PJI) are increasing. Most PJI are treated outside the hospital setting via community-based parenteral antiinfective therapy (CoPAT) after initial surgical management, although little is reported about the short-term complications of CoPAT. We therefore ascertained the numbers of unanticipated readmissions, unplanned surgeries, and CoPAT complications within 12 weeks of hospital discharge in patients with PJI on CoPAT. We retrospectively reviewed the charts of 74 patients with PJI. Twenty-seven (73% of readmitted patients) were for unanticipated reasons within 12 weeks of hospital discharge; 16 (43% of readmitted) underwent an unplanned surgery. Nine patients (12% of total cohort) had CoPAT-related adverse events. Our data suggest patients with PJI on CoPAT represent a complex cohort that needs to be monitored closely for complications early after hospital discharge.
Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-009-0825-7
PMCID: PMC2690761  PMID: 19381747
17.  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
18.  One hundred and twelve infected arthroplasties treated with ‘DAIR’ (debridement, antibiotics and implant retention): antibiotic duration and outcome 
Objectives
We describe treatment failure rates by antibiotic duration for prosthetic joint infection (PJI) managed with debridement, antibiotics and implant retention (DAIR).
Methods
We retrospectively collected data from all the cases of PJI that were managed with DAIR over a 5 year period. Surgical debridement, microbiological sampling, early intravenous antibiotics and prolonged oral follow-on antibiotics were used.
Results
One hundred and twelve cases of PJI were identified. Twenty infections (18%) recurred during a mean follow-up of 2.3 years. The mean duration of antibiotic use was 1.5 years. Failure was more common after arthroscopic debridement, for previously revised joints and for Staphylococcus aureus infection. There were 12 failures after stopping antibiotics and 8 while on antibiotics [hazard ratio (HR) = 4.3, 95% confidence interval (CI) 1.4–12.8, P = 0.01]. However, during the first 3 months of follow-up, there were eight failures after stopping antibiotics and two while on antibiotics (HR = 7.0, 95% CI 1.5–33, P = 0.015). The duration of antibiotic therapy prior to stopping did not predict outcome.
Conclusions
PJI may be managed by DAIR. The risk of failure with this strategy rises after stopping oral antibiotics, but lengthening antibiotic therapy may simply postpone, rather than prevent, failure.
doi:10.1093/jac/dkp107
PMCID: PMC2680346  PMID: 19336454
prosthetic; infection; management
19.  Ambulatory Treatment of Multidrug-Resistant Staphylococcus-Infected Orthopedic Implants with High-Dose Oral Co-trimoxazole (Trimethoprim-Sulfamethoxazole) 
Antimicrobial Agents and Chemotherapy  1998;42(12):3086-3091.
We examined the effectiveness and safety of high-dose oral co-trimoxazole (trimethoprim-sulfamethoxazole) for the treatment of orthopedic implants infected with multidrug-resistant Staphylococcus species. The prospective study was conducted between 1989 and 1997 in a university medical center with ambulatory-care services. Patients eligible for the study consisted of those from whom multidrug-resistant Staphylococcus spp. organisms susceptible only to glycopeptides and co-trimoxazole were isolated from their orthopedic implants and for whom there was no contraindication to the treatment. All patients were treated orally with high-dose co-trimoxazole (trimethoprim, 20 mg/kg of body weight/day; sulfamethoxazole, 100 mg/kg/day). Patients with prosthetic hip infections were treated for 6 months, with removal of any unstable prosthesis after 5 months of treatment; patients with prosthetic knee infections were treated for 9 months, with removal of any unstable prosthesis after 6 months of treatment; and patients with infected osteosynthetic devices were treated for 6 months, with removal of the device after 3 months of treatment, if necessary. Monthly clinical evaluations were conducted until the completion of the treatment, and follow-up examinations were conducted regularly for up to 6 years. The overall treatment success rate was 66.7% (26 of 39 patients), with success rates of 62.5% for patients with prosthetic knee infections, 50% for those with prosthetic hip infections, and 78.9% for those with other device infections. Seventeen of the 28 (60.7%) patients who did not have any orthopedic material removed were cured. Eight patients stopped the treatment because of side effects, and one patient was not compliant. In three patients treatment failed because of the appearance of a resistant bacterium. Long-term oral ambulatory treatment with co-trimoxazole appears to be an effective alternative to the conventional medicosurgical treatment of chronic multidrug-resistant Staphylococcus-infected orthopedic implants which includes long-term intravenous antibiotic therapy combined with surgical debridement and removal of foreign material or its subsequent one- or two-stage replacement.
PMCID: PMC106003  PMID: 9835495
20.  The Diagnosis of Periprosthetic Infection 
Periprosthetic infection (PJI) is the most serious joint replacement complication, occurring in 0.8-1.9% of knee arthroplasties and 0.3-1.7% of hip arthroplasties. A definition of PJI was proposed in the November 2011 issue of the journal Clinical Orthopedics and Related Research. The presence of a fistula or of local inflammatory signs is indicative of PJI, but in many cases local pain is the only symptom. In the absence of underlying inflammatory conditions, C-reactive protein measurement is the most useful preoperative blood test for detecting infection associated with a prosthetic joint. The most useful preoperative diagnostic test is the aspiration of synovial joint fluid to obtain a total and differential cell count and culture. Intraoperative frozen sections of periprosthetic tissues produce excellent accuracy in predicting a diagnosis of PJI but only moderate accuracy in ruling out the diagnosis. In this process, obtaining a quality sample is the first step, and determines the quality of microbiological results. Specimens for culture should be obtained prior to the initiation of antibiotic treatment. Sonication of a removed implant may increase the culture yield. Plain radiography has low sensitivity and low specificity for detecting infection associated with a prosthetic joint. Computed tomography and magnetic resonance imaging may be useful in the evaluation of complex cases, but metal inserts interfere with these tests, and abnormalities may be non-specific. Labelled-leucocyte imaging (e.g., leucocytes labelled with indium-111) combined with bone marrow imaging with the use of technetium-99m–labelled sulphur colloid is considered the imaging test of choice when imaging is necessary.
doi:10.2174/1874325001307010178
PMCID: PMC3722546  PMID: 23898349
Diagnosis; periprosthetic infection; joint replacement; hip; knee.
21.  A Superficial Swab Culture is Useful for Microbiologic Diagnosis in Acute Prosthetic Joint Infections 
The literature documents poor concordance between superficial swab and intraoperative tissue cultures in chronic prosthetic joint infections but is less clear in acute postsurgical prosthetic joint infections. We evaluated the relationship between superficial swab and deep intraoperative cultures in 56 patients with acute postsurgical prosthetic joint infections from June 2003 to June 2007; patients receiving antibiotics were excluded. There were 30 hip and 26 knee prostheses. A superficial sample of the wound drainage was taken at admission and three deep samples were obtained during open débridement. Concordance was defined when at least one of the microorganisms isolated in the superficial samples also was found in the deep samples. The analysis also was performed according to the type of microorganism: Staphylococcus aureus, gram-negative bacilli, or other gram-positive microorganisms. Concordance between superficial and deep samples was 80.3% (45 of 56). The sensitivity, specificity, and positive and negative predictive values of superficial cultures to predict the microorganism isolated in deep cultures varied depending on the type of microorganism: 93.7%, 100%, 100%, and 97.5% for S. aureus; 90%, 91.6%, 85.7%, and 94.3% for gram-negative bacilli; and 50%, 75%, 60%, and 66.7% for other gram-positive microorganisms. We therefore believe the superficial swab culture is useful in identifying the etiologic microorganism of acute prosthetic joint infections, especially when S. aureus or gram-negative bacilli were identified.
Level of Evidence: Level II, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-008-0553-4
PMCID: PMC2628497  PMID: 18850254
22.  Remission after treatment of osteoarticular infections due to Pseudomonas aeruginosa versus Staphylococcus aureus: a case-controlled study 
International Orthopaedics  2011;36(5):1065-1071.
Purpose
Osteoarticular infections due to methicillin-susceptible Staphylococcus aureus (MSSA) or its methicillin-resistant variant (MRSA) are feared due to treatment failures. According to clinical experience, Pseudomonas aeruginosa may reveal less long-term remission than S. aureus.
Methods
A case-controlled study comparing outcomes of osteoarticular infections due to P. aeruginosa vs S. aureus was performed at Geneva University Hospitals.
Results
A total of 111 S. aureus (including 37 MRSA) and 20 P. aeruginosa osteoarticular infections were analysed in 131 patients: arthroplasties (n = 38), fracture fixation devices (n = 56), native joint arthritis (n = 7) and osteomyelitis without implant (n = 30). The median active follow-up time was 4 years. The patients underwent a median number of two surgical interventions for P. aeruginosa infections compared to two for S. aureus (two for MRSA), while the median duration of antibiotic treatment was 87 days for P. aeruginosa and 46 days for S. aureus infections (58 days for MRSA) (all p > 0.05). Overall, Pseudomonas-infected patients tended towards a lower remission rate than those infected with S. aureus (12/20 vs 88/111; p = 0.06). This was similar when P. aeruginosa was compared with MRSA alone (12/20 vs 30/37; p = 0.08). In multivariate logistic regression analyses adjusting for case mix, odds ratios (OR) for remission were as follows: P. aeruginosa vs S. aureus [OR 0.4, 95% confidence interval (CI) 0.1–1.2], number of surgical interventions (OR 0.6, 95% CI 0.5–1.0) and duration of antibiotic treatment (OR 1.0, 95% CI 1.0–1.0).
Conclusions
Despite a similar number of surgical interventions and longer antibiotic treatment, osteoarticular infections due to P. aeruginosa tended towards a lower remission rate than infections due to S. aureus in general or MRSA in particular.
doi:10.1007/s00264-011-1366-8
PMCID: PMC3337090  PMID: 21983903
Medicine & Public Health; Orthopedics
23.  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
24.  Rifampin Combination Therapy for Nonmycobacterial Infections 
Clinical Microbiology Reviews  2010;23(1):14-34.
Summary: The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant Staphylococcus aureus (MRSA), has resulted in the increased use of rifampin combination therapy. The data supporting rifampin combination therapy in nonmycobacterial infections are limited by a lack of significantly controlled clinical studies. Therefore, its current use is based upon in vitro or in vivo data or retrospective case series, all with major limitations. A prominent observation from this review is that rifampin combination therapy appears to have improved treatment outcomes in cases in which there is a low organism burden, such as biofilm infections, but is less effective when effective surgery to obtain source control is not performed. The clinical data support rifampin combination therapy for the treatment of prosthetic joint infections due to methicillin-sensitive S. aureus (MSSA) after extensive debridement and for the treatment of prosthetic heart valve infections due to coagulase-negative staphylococci. Importantly, rifampin-vancomycin combination therapy has not shown any benefit over vancomycin monotherapy against MRSA infections either clinically or experimentally. Rifampin combination therapy with daptomycin, fusidic acid, and linezolid needs further exploration for these severe MRSA infections. Lastly, an assessment of the risk-benefits is needed before the addition of rifampin to other antimicrobials is considered to avoid drug interactions or other drug toxicities.
doi:10.1128/CMR.00034-09
PMCID: PMC2806656  PMID: 20065324
25.  Blood Culture Flasks for Culturing Synovial Fluid in Prosthetic Joint Infections 
Background
Identifying the etiologic microorganism is essential to guide antimicrobial therapy in prosthetic joint infection.
Questions/purpose
We (1) compared the frequency of positive cultures with synovial fluid inoculated in blood culture flasks (SF) with those of periprosthetic tissues or swabs in traditional cultures from patients with acute and chronic prosthetic joint infections (PJI) and (2) determined the sensitivity, specificity, and predictive values of the three methods.
Patients and Methods
We retrospectively reviewed 87 patients with PJIs (54 knees, 33 hips) and 63 patients with aseptic loosening (34 knees, 29 hips). Two SF, periprosthetic tissue, and swab samples were taken for culture in all 150 patients except for 14 in whom only one SF fluid sample was obtained. Synovial fluid was inoculated in blood culture flasks and periprosthetic tissue and swab samples in standard media. Positive cultures were identified with standard biochemical procedures.
Results
SF samples were positive in 78 of 87 infected cases (90%), periprosthetic tissue samples were positive in 71 (82%), and swab samples were positive in 59 (68%). SF, periprosthetic tissue, and swab samples were positive more frequently in acute than in chronic infections (96% versus 82% for SF, 87% versus 74% for periprosthetic tissue, and 87% versus 44% for swabs). The sensitivity, specificity, and positive and negative predictive values of SF were 91, 100, 100, and 93 for acute infections and 79, 100, 100, and 88 for chronic infections, respectively.
Conclusions
SF samples cultured in flasks had higher sensitivity, specificity, and positive and negative predictive values for diagnosis of PJI when compared with standard tissue and swab samples. The usefulness of all samples was less in chronic than in acute infections.
Level of Evidence
Level II, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-010-1254-3
PMCID: PMC2895826  PMID: 20162386

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