Treatment of staphylococcal prosthetic joint infections with debridement, prosthesis retention and oral rifampicin and fusidic acid

There is growing evidence of the efficacy of treating early staphylococcal infections of prosthetic joints with surgical debridement and prosthesis retention, combined with oral antibiotic regimens that include rifampicin in combination with a fluoroquinolone. With rising rates of fluoroquinolone-resistant staphylococci, evidence concerning the efficacy of alternative combinations of antibiotics is required. Twenty patients with staphylococcal prosthetic joint infections who had been treated with surgical debridement and prosthesis retention, and a combination of rifampicin and fusidic acid were analysed. The mean duration of symptoms before initial debridement was 16 (range 2-75) days. The median time of follow-up was 32 (range 6-76) months. Treatment failure occurred in two patients. The cumulative risk of treatment failure after 1 year was 11.76% (95% CI 3.08-39.40%). Two patients had their treatment changed because of nausea. Ten of 11 patients with infections involving methicillin-resistant Staphylococcus aureus had successful outcomes. Debridement without prosthesis removal, in combination with rifampicin and fusidic acid treatment, was effective and should be considered for patients with early staphylococcal prosthetic joint infections, including those with infections involving fluoroquinolone-resistant organisms.     

Gram-negative prosthetic joint infection treated with debridement,prosthesis retention and antibiotic regimens including a fluoroquinolone

Information is required about treatment outcomes of Gram-negative prosthetic joint infections treated with prosthesis retention and surgical debridement, especially where biofilm-active antibiotics such as fluoroquinolones are used. The outcome of 17 consecutive patients with an early Gram-negative prosthetic joint infection who had been treated with prosthesis retention and surgical debridement was analysed. Enterobacteriaceae were isolated in 16 patients and infections were mixed with other organisms in 13 (76%) patients. The median joint age was 17 days and the median duration of symptoms before debridement was 7 days. All patients initially received intravenous β-lactam antibiotic therapy and 14 patients were then treated with oral ciprofloxacin. Treatment failure occurred in two patients over a median period of follow-up of 28 months. In only one patient was a relapsed Gram-negative infection responsible for the failure and this patient had not been treated with ciprofloxacin. The 2-year survival rate free of treatment failure was 94% (95% CI, 63–99%). Prosthesis retention with surgical debridement, in combination with antibiotic regimens including ciprofloxacin, was effective and should be considered for patients with early Gram-negative prosthetic joint infection.     

Use of rifampicin and ciprofloxacin combination therapy after surgical debridement in the treatment of early manifestation prosthetic joint infections

Prosthetic joint infections are difficult to eradicate, and antibiotic and surgical treatment strategies lack standardisation. The present study followed 29 patients (median age 72 years, median American Society of Anesthesia score of two) with early prosthetic joint infections. Treatment consisted of device retention, surgical debridement and therapy with rifampicin and ciprofloxacin for 3 months. This treatment regimen failed in five patients during the study, with a median observation period of 674 days. The results of this study confirm the findings of the only previous study on device retention with antibiotic treatment.     

Conservative medical therapy of prosthetic joint infections: retrospective analysis of an 8-year experience

Successful treatment of prosthetic joint infections often requires multiple surgical interventions and prolonged antimicrobial therapy. However, in certain situations, a surgical approach may not be in the best interest of the patient. A conservative approach was used to treat 34 patients with prosthetic joint infection between 1995 and 2003. Diagnosis of infection was based on clinical-microbiological evidence, confirmed by (99)Tc-labelled leukocyte scintigraphy, and involved 12 Staphylococcus aureus infections, nine Staphylococcus epidermidis infections, two Enterococcus faecalis infections, two mixed infections (S. aureus plus Pseudomonas aeruginosa; S. epidermidis plus E. faecalis), with the infecting pathogen being unidentified for nine patients. Most infections were treated initially with intravenous or intramuscular teicoplanin +/- ciprofloxacin or rifampicin, followed by oral ciprofloxacin or minocycline plus rifampicin. The mean duration of antimicrobial therapy was 41.2 weeks. Overall, only three patients did not respond to therapy, and infection was controlled in the remaining 31 patients. Among these, no relapse was observed in 17 patients during follow-up for 9-57 months; improvement with early (within 6 months of antibiotic discontinuation) or late relapse was observed in seven and three patients, respectively; two patients improved clinically, but continued to receive antibiotic therapy; and two patients whose condition improved initially were lost after a 6-month follow-up following discontinuation of antibiotics. No patient complained of side effects requiring discontinuation of antibiotic therapy. The study confirmed that suppression of infection, with salvage of the infected device in an acceptably functional state, can be achieved in selected cases.     

Early prosthetic joint infection: outcomes with debridement and implant retention followed by antibiotic therapy

Recent expert reviews recommend a conservative surgical strategy – debridement and irrigation, antibiotics and implant retention (DAIR) – for most early post-surgical prosthetic joint infections (PJI). However, differences exist in published series regarding success rates with DAIR, and the size of most series is small. In this prospective multicenter cohort study of early PJI managed by DAIR, factors associated with failure of the DAIR were analyzed. Out of 139 early PJI, 117 cases managed with DAIR were studied For 67 patients (57.3%), infection was cured and the implant was salvaged with definite antimicrobial therapy. In 35 (29.9%) DAIR failed and removal of the prosthesis was necessary during follow-up. Finally, 15 patients (12.8%) needed chronic suppressive antimicrobial therapy due to suspected or confirmed persistent infection. Infections due to methicillin-resistant S. aureus (72.7% failed; p 0.05) and those treated at one of the hospitals (80.0% failed; p <0.05) had worse outcomes, but only this last variable was associated with treatment failure following multivariate analysis. Seventy-four per cent of patients who were successfully treated by DAIR and only 32.7% of the failures were able to walk without help or with one stick at the last follow-up visit (p <0.05). In conclusion, a substantial proportion of patients with an early PJI may be successfully treated with DAIR and definite antimicrobial therapy. In more than half of these, the infection can be cured. Since identification of factors associated with failure of DAIR is not simple, we recommend offering DAIR to most patients with early PJI.     

Gram-negative prosthetic joint infection: outcome of a debridement,antibiotics and implant retention approach. A large multicentre study

We aim to evaluate the epidemiology and outcome of gram-negative prosthetic joint infection (GN-PJI) treated with debridement, antibiotics and implant retention (DAIR), identify factors predictive of failure, and determine the impact of ciprofloxacin use on prognosis. We performed a retrospective, multicentre, observational study of GN-PJI diagnosed from 2003 through to 2010 in 16 Spanish hospitals. We define failure as persistence or reappearance of the inflammatory joint signs during follow-up, leading to unplanned surgery or repeat debridement >30 days from the index surgery related death, or suppressive antimicrobial therapy. Parameters predicting failure were analysed with a Cox regression model. A total of 242 patients (33% men; median age 76 years, interquartile range (IQR) 68–81) with 242 episodes of GN-PJI were studied. The implants included 150 (62%) hip, 85 (35%) knee, five (2%) shoulder and two (1%) elbow prostheses. There were 189 (78%) acute infections. Causative microorganisms were Enterobacteriaceae in 78%, Pseudomonas spp. in 20%, and other gram-negative bacilli in 2%. Overall, 19% of isolates were ciprofloxacin resistant. DAIR was used in 174 (72%) cases, with an overall success rate of 68%, which increased to 79% after a median of 25 months' follow-up in ciprofloxacin-susceptible GN-PJIs treated with ciprofloxacin. Ciprofloxacin treatment exhibited an independent protective effect (adjusted hazard ratio (aHR) 0.23; 95% CI, 0.13–0.40; p <0.001), whereas chronic renal impairment predicted failure (aHR, 2.56; 95% CI, 1.14–5.77; p 0.0232). Our results confirm a 79% success rate in ciprofloxacin-susceptible GN-PJI treated with debridement, ciprofloxacin and implant retention. New therapeutic strategies are needed for ciprofloxacin-resistant PJI.     

Antibiotic susceptibility among Staphylococcus epidermidis isolated from prosthetic joint infections,with focus on doxycycline

In recent years, coagulase‐negative staphylococci such as Staphylococcus epidermidis have gained importance as nosocomial pathogens, especially in immunocompromised patients and prosthetic joint infections (PJIs). These infections are often long lasting and difficult to treat due to the production of bacterial biofilm and the transformation of the bacteria into a stationary growth phase. Rifampicin is able to penetrate the biofilm, but to reduce the risk of development of rifampicin resistance it should be used in combination with an additional antibiotic. In this study we used Etest to investigate the antimicrobial susceptibility of 134 clinical isolates of S. epidermidis obtained from PJIs to six oral antibiotics: doxycycline, rifampicin, linezolid, fusidic acid, clindamycin, and ciprofloxacin. We also performed synergy testing on doxycycline in combination with each of the remaining antibiotics. Ninety‐three (69%) of the 134 isolates were susceptible to doxycycline, 94/134 (70%) to rifampicin, 56/134 (42%) to clindamycin, 25/134 (19%) to ciprofloxacin, 81/134 (60%) to fusidic acid, and 100% to linezolid. Thirty‐two (80%) of the 40 isolates not fully susceptible to rifampicin were susceptible to doxycycline. Doxycycline in combination with each of the other investigated antibiotics exerted an additive effect on nearly half of the isolates, with the exception of clindamycin, which displayed an even higher percentage of additive effect (69%). To conclude, as the majority of the S. epidermidis isolates were susceptible to doxycycline, this antimicrobial agent may provide a potential alternative for combination therapy together with rifampicin.     

Cost analysis of debridement and retention for management of prosthetic joint infection

Prosthetic joint infection remains one of the most devastating complications of arthroplasty. Debridement and retention of the prosthesis is an attractive management option in carefully selected patients. Despite this, there are no data investigating the cost of this management modality for prosthetic joint infections. The aim of this case–control study was to calculate the cost associated with debridement and retention for management of prosthetic joint infection compared with primary joint replacement surgery without prosthetic joint infection. From 1 January 2008 to 30 June 2010, there were 21 prosthetic joint infections matched to 42 control patients. Controls were matched to cases according to the arthroplasty site, age and sex. Cases had a greater number of unplanned readmissions (100% vs. 7.1%; p <0.001), more additional surgery (3.3 vs. 0.07; p <0.001) and longer total bed days (31.6 vs. 7.9 days; p <0.001). In addition they had more inpatient, outpatient and emergency department visits (p <0.001, respectively). For patients with prosthetic joint infection the total cost, including index operation and costs of management of the prosthetic joint infection, was 3.1 times the cost of primary arthoplasty; the mean cost for cases was Australian dollars (AUD) $69 414 (±29 869) compared with $22 085 (±8147) (p <0.001). The demand for arthroplasty continues to grow and with that, the number of prosthetic joint infections will also increase, placing significant burden on the health system. Our study adds significantly to the growing body of evidence highlighting the substantial costs associated with prosthetic joint infection.     

Microbiological diagnosis of prosthetic joint infections: a prospective evaluation of four bacterial culture media in the routine laboratory

The diagnosis of prosthetic joint infection (PJI) in the routine microbiology laboratory is labour-intensive, but semi-automated methods may be appropriate. We prospectively compared four microbiological culture methods on samples taken at prosthetic joint revision surgery. Automated BACTEC blood culture bottles and cooked meat enrichment broth were the most sensitive methods (87% and 83%, respectively, as compared with fastidious anaerobic broth (57%) and direct plates (39%)); all were highly specific (97–100%). To our knowledge, this is the first prospective study aimed at comparing culture methods in routine use in UK clinical laboratories for the diagnosis of PJI.     

Acute haematogenous prosthetic joint infection: prospective evaluation of medical and surgical management

The optimum treatment for prosthetic joint infections has not been clearly defined. We report our experience of the management of acute haematogenous prosthetic joint infection (AHPJI) in patients during a 3-year prospective study in nine Spanish hospitals. Fifty patients, of whom 30 (60%) were female, with a median age of 76 years, were diagnosed with AHPJI. The median infection-free period following joint replacement was 4.9 years. Symptoms were acute in all cases. A distant previous infection and/or bacteraemia were identified in 48%. The aetiology was as follows: Staphylococcus aureus, 19; Streptococcus spp., 14; Gram-negative bacilli, 12; anaerobes, two; and mixed infections, three. Thirty-four (68%) patients were treated with a conservative surgical approach (CSA) with implant retention, and 16 had prosthesis removal. At 2-year follow-up, 24 (48%) were cured, seven (14%) had relapsed, seven (14%) had died, five (10%) had persistent infection, five had re-infection, and two had an unknown evolution. Overall, the treatment failure rates were 57.8% in staphylococcal infections and 14.3% in streptococcal infections. There were no failures in patients with Gram-negative bacillary. By multivariate analysis, CSA was the only factor independently associated with treatment failure (OR 11.6; 95% CI 1.29–104.8). We were unable to identify any factors predicting treatment failure in CSA patients, although a Gram-negative bacillary aetiology was a protective factor. These data suggest that although conservative surgery was the only factor independently associated with treatment failure, it could be the first therapeutic choice for the management of Gram-negative bacillary and streptococcal AHPJI, and for some cases with acute S. aureus infections.     

Antibiotic susceptibility among Staphylococcus epidermidis isolated from prosthetic joint infections with special focus on rifampicin and variability of the rpoB gene

Staphylococcus epidermidis is the most important pathogen in infections related to implanted foreign materials, especially prosthetic joint infections (PJIs). The aim of this study was to investigate the antimicrobial activities of 16 antibiotics against S. epidermidis isolated from PJIs, with special focus on rifampicin and rpoB variability. Ninety-one per cent of the isolates were multiresistant (i.e. resistant to members of more than three classes of antibiotics). Thirty-nine per cent were resistant to rifampicin, associated with one or two single-nucleotide polymorphisms (SNPs) in rpoB . Using IsoSensitest agar with supplements, 61% were resistant to oxacillin, and using Mueller–Hinton II agar with supplement, 84% were resistant. Using the Etest, 58% were resistant to cefoxitin, and using the disk diffusion test, 91% were resistant. The mecA gene was detected in 85% of the isolates. Regarding recently available antibiotics, all isolates were susceptible to tigecycline and linezolid, and 97% were susceptible to daptomycin. In addition, two novel antibiotics, dalbavancin and ceftobiprole, were tested, although not yet available for routine use. The MIC₅₀ and MIC₉₀ values of these novel antibiotics were 0.032 and 0.047 mg/L and 0.5 and 1.5 mg/L, respectively. Among the other antibiotics, the rates of resistance varied between 0% (vancomycin) and 82% (trimethoprim–sulphamethoxazole). S. epidermidis strains causing PJIs often show multiresistance, including resistance to rifampicin, which is mainly caused by one or two SNPs. Some of the newer antimicrobial agents may provide alternatives for monotherapy or combination therapy with rifampicin. Detection of mecA is necessary before initiating treatment of infections due to S. epidermidis when it displays intermediate susceptibility to cefoxitin.     

Characteristics of prosthetic joint infections due to Enterococcus sp. and predictors of failure: a multi-national study

The objective of this study was to review the characteristics and outcome of prosthetic joint infections (PJI) due to Enterococcus sp. collected in 18 hospitals from six European countries. Patients with a PJI due to Enterococcus sp. diagnosed between January 1999 and July 2012 were retrospectively reviewed. Relevant information about demographics, comorbidity, clinical characteristics, microbiological data, surgical treatment and outcome was registered. Univariable and multivariable analyses were performed. A total of 203 patients met the inclusion criteria. The mean (SD) was 70.4 (13.6) years. In 59 patients the infection was diagnosed within the first 30 days (29.1%) from arthroplasty, in 44 (21.7%) between 31 and 90 days, in 54 (26.6%) between 91 days and 2 years and in 43 (21%) after 2 years. Enterococcus faecalis was isolated in 176 cases (89%). In 107 (54%) patients the infection was polymicrobial. Any comorbidity (OR 2.53, 95% CI 1.18–5.40, p 0.01), and fever (OR 2.65, 95% CI 1.23–5.69, p 0.01) were independently associated with failure. The only factor associated with remission was infections diagnosed later than 2 years (OR 0.25, 95% CI 0.09–0.71, p 0.009). In conclusion, prosthetic joint infections due to Enterococcus sp. were diagnosed within the first 2 years from arthroplasty in >70% of the patients, almost 50% had at least one comorbidity and infections were frequently polymicrobial (54%). The global failure rate was 44% and patients with comorbidities, fever, and diagnosed within the first 2 years from arthroplasty had a poor prognosis.     

Technetium-99m-labeled annexin V imaging for detecting prosthetic joint infection in a rabbit model

Accurate and timely diagnosis of prosthetic joint infection is essential to initiate early treatment and achieve a favorable outcome.In this study,we used a rabbit model to assess the feasibility of technetium-99m-labeled annexin V for detecting prosthetic joint infection.Right knee arthroplasty was performed on 24 New Zealand rabbits.After surgery,methicillin-susceptible Staphylococcus aureus was intra-articularly injected to create a model of prosthetic joint infection(the infected group,n = 12).Rabbits in the control group were injected with sterile saline(n=12).Seven and 21 days after surgery,technetium-99m-labeled annexin V imaging was performed in 6 rabbits of each group.Images were acquired 1 and 4 hours after injection of technetium-99 mlabeled annexin V(150 MBq).The operated-to-normal-knee activity ratios were calculated for quantitative analysis.Seven days after surgery,increased technetium-99m-labeled annexin V uptake was observed in all cases.However,at 21 days a notable decrease was found in the control group,but not in the infected group.The operated-to-normal-knee activity ratios of the infected group were 1.84 ± 0.29 in the early phase and 2.19 ±0.34 in the delay phase,both of which were significantly higher than those of the control group(P=0.03 and P=0.02).The receiver operator characteristic curve analysis showed that the operated-to-normal-knee activity ratios of the delay phase at 21 days was the best indicator,with an accuracy of 80%.In conclusion,technetium-99m-labeled annexin V imaging could effectively distinguish an infected prosthetic joint from an uninfected prosthetic joint in a rabbit model.     

Diagnosis of prosthetic joint infection by beadmill processing of a periprosthetic specimen

We report a microbiological process for the documentation of prosthetic joint infection (PJI). Intraoperative periprosthetic tissue samples from 92 consecutive patients undergoing revision surgery for PJI were submitted to mechanized beadmill processing: specimens were aseptically collected in polypropylene vials, filled with sterile water and glass beads and submitted to mechanized agitation with a beadmill. The documentation rate of PJI following culture on solid and liquid media was 83.7% and the contamination rate 8.7%. Final documentation was obtained after overnight culture for 51.9% of cases and with 7 days of broth culture for all documented cases.     

Sequence types of Staphylococcus epidermidis associated with prosthetic joint infections are not present in the laminar airflow during prosthetic joint surgery

Molecular characterization of Staphylococcus epidermidis isolates from prosthetic joint infections (PJIs) has demonstrated a predominance of healthcare‐associated multi‐drug resistant sequence types (ST2 and ST215). How, and when, patients acquire these nosocomial STs is not known. The aim was to investigate if sequence types of S. epidermidis associated with PJIs are found in the air during prosthetic joint surgery. Air sampling was undertaken during 17 hip/knee arthroplasties performed in operating theaters equipped with mobile laminar airflow units in a 500‐bed hospital in central Sweden. Species identification was performed using MALDI‐TOF MS and 16S rRNA gene analysis. Isolates identified as S. epidermidis were further characterized by MLST and antibiotic susceptibility testing. Seven hundred and thirty‐five isolates were available for species identification. Micrococcus spp. (n = 303) and coagulase‐negative staphylococci (n = 217) constituted the majority of the isolates. Thirty‐two isolates of S. epidermidis were found. S. epidermidis isolates demonstrated a high level of allelic diversity with 18 different sequence types, but neither ST2 nor ST215 was found. Commensals with low pathogenic potential dominated among the airborne microorganisms in the operating field during prosthetic joint surgery. Nosocomial sequence types of S. epidermidis associated with PJIs were not found, and other routes of inoculation are therefore of interest in future studies.     

Prosthetic joint infection due to Lysobacter thermophilus diagnosed by 16S rRNA gene sequencing

We report the first case of prosthetic joint infection caused by Lysobacter thermophilus which was identified by 16S rRNA gene sequencing. Removal of prosthesis followed by antibiotic treatment resulted in good clinical outcome. This case illustrates the use of molecular diagnostics to detect uncommon organisms in suspected prosthetic infections.     

Diagnosis of knee prosthetic joint infection; aspiration and biopsy

BackgroundProsthetic joint infection (PJI) is a significant cause of morbidity and mortality following knee replacement surgery. The diagnosis can be challenging and is based on a combination of clinical suspicion, radiographic findings and also biochemical/ microbiological investigations. Our Aim was to review the role of aspiration and biopsy in the diagnosis of PJI in Total Knee Arthroplasty (TKA).Method/resultsAspirated synovial fluid should be analysed by direct culture, via blood culture bottles, EDTA bottles for cell count and ‘point of care’ testing such as leucocyte esterase or alpha defensin. Synovial WCC and PMN cell percentage are important steps in diagnosis of both acute and chronic PJI. A minimum of 5 deep samples using a 5 clean instrument technique should be obtained and sent for tissue culture done either blind or arthroscopic. Formal fluoroscopic guided interface biopsy has also been described with excellent results. In a recent series of 86 TKRs preoperative arthroscopic biopsy group had a sensitivity of 100%, specificity of 94.7%, positive predictive value of 87.4% and a negative predictive value of 100%.ConclusionIn the presence of clinical suspicion with raised biomarkers, it is recommended that aspiration +/- biopsy with synovial fluid testing is performed. Direct culture and cell count are recommended. ‘Point of care tests’ such as Leucocyte Esterase testing should be considered. Duration of culture, including pathogen and host factors, should be discussed with a local microbiology/ID department in the context of a formal multi-disciplinary team.     

保留假体清创治疗人工关节置换后的急性感染

文题释义：保留假体清创：是用于治疗关节置换后感染的一种方法,主要应用于早期治疗,对于感染的关节只是进行垫片或者内衬的更换,清除关节腔内感染及疑似感染的组织,不取出假体,对患者来说是一种痛苦小、花费少的治疗方法。人工全膝关节置换：用于治疗重度关节磨损、严重关节畸形的患者,用金属假体代替股骨关节面和胫骨关节面并在关节面之间加聚乙烯衬垫,是近代发展非常快的手术,解决了患者膝关节疼痛,纠正了力线,提高了患者生活质量。背景：与翻修手术比较,保留假体清创治疗假体周围感染具有创伤小、耗时短、花费低等优势,但是关于保留假体清创的适应证和围术期管理还存在争议。目的：综述清创保留假体手术应用于假体周围感染的术前适应证、术中操作及术后抗生素应用。方法：英文文献检索PubMed、Web ofScience、Embase、The Cochrane Library数据库,年限为2000至2018年,检索关键词为“total kneearthroplasty、periprostheticjoint infection、Diagnose、treatment”。中文文献检索中国知网、万方数据库,检索年限为2000至2018年,检索关键词为“关节置换术、术后感染、保留假体清创术”。筛选相关文献,统计文献保留假体治疗关节置换后感染的成功率,总结最为准确的诊断标准及治疗最有效的方法经验。结果与结论：目前关于关节置换后感染的诊断国际上没有统一的标准,有很多组织提出了一些共识和指南,其中Parvizi等综合其他共识和指南提出了新的假体周围感染诊断标准,其敏感性和特异性都较高,得到了大多数人的认可。保留假体清创适用于稳定且固定良好的假体、症状持续时间短、软组织良好且无窦道形成的患者。术中应该彻底清除感染坏死组织及疑似感染的组织,碘伏水浸泡半小时,更换新的垫片,清创完全后对重新消毒铺巾更换一套新的手术工具。术后应根据培养结果联合应用敏感的抗生素,院外口服利福平4个月。保留假体清创是治疗早期急性关节置换后感染的最佳方法,具有患者痛苦小、花费少、接受度高、避免翻修等优势。ORCID: 0000-0002-2784-1542(徐长波)中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程