Increased rate of enteric bacteria as cause of periprosthetic joint infections in patients with liver cirrhosis.

INTRODUCTION: Periprosthetic joint infections (PJI) are a major complication in joint-arthroplasty. Rifampicin is often used as an additional agent to treat PJI, because it penetrates bacterial biofilms. However, rifaximin, belonging to the same antibiotic class as rifampicin, is frequently used to prevent episodes of hepatic encephalopathy in patients with cirrhosis and may induce resistance to rifampicin. The aim of this study was to examine the microbial pattern of periprosthetic joint infections in cirrhotic patients and to test the hypothesis that intake of rifaximin increases the rate of resistance to rifampicin in periprosthetic joint infections. METHODS: A cohort of cirrhotic patients and PJI (n = 25) was analysed on the characteristics of bacterial isolates from sonication and tissue analysis. In a second step a subgroup analysis on the development of rifampicin resistant bacterial specimens, depending on the intake of rifaximin (8 rifaximin intake patients vs. 13 non rifaximin intake patients) was performed. RESULTS: Intestinal bacteria were found in 50% of the specimens, which was significantly more frequent than in a control cohort. By comparison of the single bacterial isolates, rifampicin resistance was detected in 69.2% (9/13) of the rifaximin-intake samples. In contrast, the non-rifaximin-intake isolates only were resistant to rifampicin in 22.2% (4/18) of the cases (p = 0.01). The odds ratio for developing a rifampicin-resistance through rifaximin intake was calculated as OR = 13.5. CONCLUSION: Periprosthetic joint infections have a high incidence of being caused by enteric bacteria in cirrhotic patients. Due to this change in microbial pattern and the innate resistance to rifampicin of most of gram-negative bacteria, the therapy with rifampicin should be carefully considered. The association between the use of rifaximin and developed resistance to rifampicin has a major impact on the treatment of PJI.

Outcome of repeated multi-stage arthroplasty with custom-made acetabular implants in patients with severe acetabular bone loss: a case series.

BACKGROUND: Failed reconstruction in cases of severe acetabular bone loss, with or without pelvic discontinuity, in revision total hip arthroplasty (rTHA) remains a great challenge in orthopaedic surgery. The aim of this study was to describe the outcome of a "second" rTHA with "custom-made acetabular components (CMACs)" after a previously failed reconstruction with CMACs. METHODS: 4 patients with severe acetabular bone loss (Paprosky Type IIIB), who required a second rTHA after a previously failed reconstruction with CMAC, due to prosthetic joint infection (PJI), were included in our retrospective study. All prostheses had been constructed on the basis of thin-layer computed-tomography scans of the pelvis. The second rTHA was considered unsuccessful in the event of PJI or aseptic loosening (AL) with need for renewed CMAC explantation. RESULTS: The treatment success rate after second rTHA with a CMAC was 50% (2 of 4). In the successful cases, the visual analogue scale (VAS) score and Harris Hip Score (HHS) after the second rTHA (VAS range 2-4; HHS range 45-58 points) did not differ from those after the first rTHA, before onset of symptoms (VAS: range 2-4; HHS: range 47-55 points). In the failed cases, the second CMACs needed to be explanted due to PJI, with renewed detection of previous pathogens. Patients with treatment failure of the second CMAC had required a higher number of revision surgeries after explantation of the first CMAC than patients with a successful outcome. CONCLUSIONS: In patients with severe acetabular bone loss and previously failed rTHA with CMACs, repeat rTHA with a CMAC may be a solid treatment option for patients with an "uncomplicated" multi-stage procedure, i.e., without persisting infection after explantation of the original CMAC. While the outcome in terms of clinical function does not appear negatively affected by such a "second attempt," the complication rate and risk of reinfection, nonetheless, is high.

Difficult-to-treat pathogens significantly reduce infection resolution in periprosthetic joint infections.

Periprosthetic joint infection (PJI) is a feared complication after arthroplasty. Our hypothesis was that PJI caused by difficult-to-treat (DTT) pathogens has a worse outcome compared with non-DTT PJI. Routine clinical data on 77 consecutive patients with confirmed PJI treated with 2-stage exchange arthroplasty were placed in DTT and non-DTT PJI groups and analyzed. The main outcome variable was that the patient was definitively free of infection after 2 years. We found definitive infection resolution in 31 patients in the DTT group (68.9%) and 28 patients (87.5%) in the non-DTT group (P < 0.05). The necessity for revision surgery until assumed resolution of infection was significantly more frequent in the DTT group with 4.72 ± 3.03 operations versus 2.41 ± 3.02 operations in the non-DTT group (P < 0.05). PJI caused by DTT bacteria is associated with significantly higher numbers of revision operations and significantly inferior definitive infection resolution.

Detection of methicillin-resistant coagulase-negative staphylococci harboring the class A mec complex by MALDI-TOF mass spectrometry.

The aim of this study was to test the identification of methicillin resistance in coagulase-negative staphylococci by routine matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). SCCmec cassettes of type II, III and VIII encode a small peptide called PSM-mec in the vicinity of mecA. It is visible at m/z 2415 during MALDI-TOF MS of whole cells of Staphylococcus aureus. In view of the fact that psm-mec has been identified in methicillin-resistant coagulase-negative staphylococci, we evaluated a collection of clinical coagulase-negative staphylococci, that contained 77.03% of methicillin-resistant isolates, for the presence of the structural gene encoding PSM-mec and the appearance of the corresponding signal during mass spectroscopy. In MALDI-TOF MS spectra, 89.65% of the strains that harbored the gene yielded the correct signal, corresponding to a sensitivity of 0.897 and a specificity of 1.0. However, regarding detection of methicillin resistance, i. e. considering all resistant strains as positive regardless of the presence of the gene, the overall sensitivity of the test decreased to 0.285, due to the fact that only 29.43% of all resistant isolates contained psm-mec. In conclusion, the presence of the signal in MALDI-TOF MS quickly indicates methicillin-resistance in coagulase-negative staphylococci but its absence does not indicate susceptibility to methicillin.

Activity of ceftobiprole against Staphylococcus spec. isolates derived from foreign body associated infections.

Antibiotic therapy is essential in foreign body associated infections. The treatment regime should aim at high tissue concentrations, high bioavailability, high biofilm penetration and good tolerance. We investigated whether the new cephalosporin ceftobiprole is active against clinical isolates from musculoskeletal foreign body associated infections. One hundred ninety-six staphylococci isolates (coagulase negative staphylococci and Staphylococcus aureus) derived from foreign body associated infections were tested towards susceptibility to ceftobiprole, using a test strip assay and broth microdilution. The MIC for all strains S. aureus indicated susceptibility to ceftobiprole. The MIC of only two strains of coagulase negative staphylococci was above 2 mg/L. Our results show that ceftobiprole might be considered as an off-label treatment option in foreign body associated infections.

Novel Diagnostics in Revision Arthroplasty: Implant Sonication and Multiplex Polymerase Chain Reaction.

In orthopedic patients, foreign body-associated infections, especially periprosthetic joint infections (PJIs), are a devastating complication of arthroplasty. Infection requires complex treatment, may result in long hospitalization and causes considerable costs. Multiple surgical revisions can be necessary in these patients, with a loss in function as well as in quality of life. The routine preoperative diagnostics include blood examination for C-reactive protein (CRP) and other biomarkers, as well as joint aspirate analysis for cell count, differentiation, and culture. Intraoperative specimens for histology and microbiology are also standard procedure. The microbiological examination of removed implants with sonication, in combination with the implementation of molecular biology techniques in microbiology, represent two novel techniques currently employed to enhance the differential diagnostics of PJI. We present here the step-wise procedure of analyzing joint aspirate and sonication fluid, using a cartridge-based multiplex polymerase chain reaction (PCR) system. Results were matched against conventional cultures and consensus criteria for PJI. Conventional microbiological cultures from tissue biopsies, joint aspirate and sonication fluid showed a sensitivity of 66.7%, 66.7%, and 88.9%, respectively, and a specificity of 82.3%, 54.6%, and 61.5%, respectively. The PCR diagnostic of the sonication fluid and the joint fluid showed a sensitivity of 50.0% and 55.6%, respectively, and both a specificity of 100.0%. Both PCR diagnostics combined had a sensitivity of 66.7% and a specificity of 100.0%. The multiplex PCR therefore presents a rapid diagnostic tool with moderate sensitivity but high specificity in diagnosing PJI.

Successful Therapy of a Multidrug-Resistant Extended-Spectrum ß-Lactamase-Producing and Fluoroquinolone-Resistant Salmonella enterica Subspecies enterica Serovar Typhi Infection Using Combination Therapy of Meropenem and Fosfomycin.

We report a traveler who acquired a Salmonella enterica subspecies enterica serovar Typhi strain with resistance against ß-lactams, cephalosporins (extended-spectrum ß-lactamase-producing type SHV-12), and quinolones (plasmid-mediated quinolone resistance gene qnrB7). After clinical deterioration using meropenem monotherapy, treatment success was achieved after commencement of fosfomycin in conjunction with high-dose meropenem. The case illustrates clinical challenges of multidrug-resistant S. Typhi.

Comparison of bacterial growth in sonication fluid cultures with periprosthetic membranes and with cultures of biopsies for diagnosing periprosthetic joint infection.

Total joint arthroplasty is a common operation worldwide with infection rates between 1% and 3%. In cases of suspected periprosthetic joint infection, it is very challenging to rule out the causative microorganisms. In this study, we compared the appearance of periprosthetic membranes with the microbiological results obtained from cultures of sonication fluid and the correlation between classical microbiological cultures and cultures of sonication fluid. The results confirmed a strong correlation of bacterial growth in sonication fluid cultures with bacterial growth in classical microbiological cultures. Most importantly, however, our study documented a highly significant correlation of periprosthetic membranes typical for periprosthetic joint infection (PJI) with bacterial growth in sonication fluid. Sonication fluid cultures yielded a better sensitivity than tissue cultures (72.34-60.87%). These 3 methods are useful tools in diagnosing PJIs, and even more, sonication fluid cultures should be included in the diagnostic path of PJI.

Unyvero i60 implant and tissue infection (ITI) multiplex PCR system in diagnosing periprosthetic joint infection.

Periprosthetic joint infection (PJI) is one of the most challenging complications in orthopedic surgery. In cases of suspected periprosthetic joint infection several diagnostic methods are available. In this study we investigated the performance of the newly available Unyvero i60 implant and tissue infection (ITI) multiplex PCR System. 62 specimens from 31 patients with suspected PJI or aseptic loosening of a painful joint arthoplasty were included in this study. Besides the established diagnostic procedures we included a commercial multiplex PCR detection system for diagnosis of PJI. The PCR results obtained from analysis of sonication and synovial fluids (62 specimens) showed a sensitivity of 66.7%, a specificity of 100%, a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 68.4% when compared to cultural methods. Notably, cultures from sonication fluid displayed a sensitivity of 88.9%, a specificity of 61.5%, a PPV of 76.2% and a NPV of 80.0% when compared to tissue cultures. In conclusion, multiplex PCR is an additional - rapid - method for diagnosing PJI. Positive results with the PCR assay used in this study were always confirmed by subsequent matching culture positivity. However, apart from the time saved the nucleic acid amplification technique did not yield additional information than that obtained from microbiological cultures.

Polymicrobial infections reduce the cure rate in prosthetic joint infections: outcome analysis with two-stage exchange and follow-up ≥two years.

PURPOSE: Prosthetic joint infections (PJI) are a serious and challenging complication after total joint arthroplasty. According to the literature, most PJI are monomicrobial infections caused by gram-positive cocci. The number of polymicrobial PJI might be underrepresented in the literature and only limited data are available regarding the outcome of polymicrobial PJI. Our hypothesis was that polymicrobial PJI are associated with a reduced cure rate compared with monomicrobial PJI. METHODS: Routine clinical data were collected and analysed retrospectively as anonymised, aggregated data. A total of 77 consecutive patients with 77 confirmed PJI and proven infectious organism of the hip and knee joint treated within a two-stage exchange concept and a follow-up ≥ two years were investigated. Detection of the infectious organism was based on multiple microbiological cultures taken intra-operatively. Superficial wound swabs or swabs from sinus tracts were not taken into account. Data were grouped into polymicrobial and monomicrobial PJI. The main outcome variable was "definitively free of infection after two years" as published. Second, we considered several variables as potential confounders or as risk factors. RESULTS: A total of 42 men and 35 women with 46 infected total hip arthroplasties and 31 infected total knee arthroplasties were evaluated. In 37 (46.6 %) of our 77 patients a polymicrobial PJI could be detected. We found a significant association between polymicrobial PJI and the outcome parameter definitively free of infection after two years with an odds ratio (OR) of 0.3 [95 % confidence interval (CI) 0.1-1.0]. The rate of patients graded as definitively free of infection after two years was 67.6 % for polymicrobial infections vs. 87.5 % for monomicrobial infections. The American Society of Anesthesiologists (ASA) score (OR 0.4, 95 % CI 0.2-1.0, p = 0.062) was identified as a borderline significant covariable. CONCLUSIONS: Our data suggest that polymicrobial PJI might be underrepresented in the current literature. Additionally, the presence of multiple infectious organisms is associated with a reduced rate after two years with 67.6 vs 87.5 % for monomicrobial infections. Special attention and extra care should be considered for these patients.

Rapid brain death caused by a cerebellar abscess with Fusobacterium nucleatum in a young man with drug abuse: a case report.

BACKGROUND: Fusobacterium nucleatum is a strict anaerobic microorganism that causes disease entities such as periodontal and soft tissue abscesses, pulmonary and intraabdominal infections and very rarely intracerebral infections. CASE PRESENTATION: Here, we report the rare case of a previously healthy 25-year-old German man with a cerebellar abscess caused by Fusobacterium nucleatum that resulted in rapid brain death. Toxicological screening showed positivity for amphetamines and cannabis. The diagnosis was obtained by polymerase chain reaction amplification of bacterial deoxyribonucleic acid in cerebrospinal fluid. CONCLUSIONS: In drug users clinicians should think about rare causes of brain abscesses/meningitis. Early diagnosis is necessary and justifies the use of molecular techniques.

Evidence of MRSE on a gentamicin and vancomycin impregnated polymethyl-methacrylate (PMMA) bone cement spacer after two-stage exchange arthroplasty due to periprosthetic joint infection of the knee.

BACKGROUND: Periprosthetic joint infections (PJI) are often treated by two stage exchange with the use of an antibiotic impregnated spacer. Most of the two-stage exchange algorithms recommend the implantation of an antibiotic-impregnated spacer during the first stage for a period of 2-24 weeks before reimplantation of the new prosthesis. For the spacer to have a therapeutic effect, the local antibiotic concentration must be greater than the minimal inhibition concentration (MIC) against the pathogens causing the PJI. It must remain so for the entire spacer period, otherwise recurrence of infection or resistances might occur. The question as to whether a sufficient concentration of antibiotics in vivo is reached for the entire spacer period has not been answered satisfactorily. CASE PRESENTATION: We here present a case of a histologically confirmed chronic PJI 20 month after primary arthroplasty. The primary knee arthroplasty was performed due to osteoarthritis of the joint. Initial assessment did not detect a causative pathogen, and two stage exchange with a vancomycin-gentamycin impregnated spacer was performed. At the time of reimplantation, sonication of the explanted spacer revealed a multi-resistant strain of staphylococcus epidermidis on the device and in the joint. Adaption of the therapy and prolonged treatment successfully eradicated the infection. CONCLUSION: According to the authors' knowledge, the case presented here confirms for the first time the surface contamination (proven through sonication) of a vancomycin-/gentamicin- impregnated Vancogenx®-spacer with a MRSE after ten weeks of implantation.This case study demonstrates the difficulties still associated with the diagnostics of PJI and the published different two stage treatment regimes with the use of antibiotic impregnated spacers.

Detection of Pantoea agglomerans in hip prosthetic infection by sonication of the removed prosthesis: the first reported case.

Pantoea agglomerans is a rare isolate in orthopaedic patients. We describe the first case of an acute hip prosthetic joint infection (PJI) caused by Pantoea agglomerans. The microorganism was detected after sonication of the removed hip endoprosthesis.

The immunosuppressant mycophenolate mofetil attenuates neuronal damage after excitotoxic injury in hippocampal slice cultures.

In this study we investigated whether treatment with the immunosuppressant mycophenolate mofetil (MMF) has beneficial effects on neuronal damage after excitotoxic injury. Organotypic hippocampal slice culture (OHSC), lesioned by the application of N-methyl-d-aspartate (NMDA) after 6 days in vitro, showed an improved preservation of the hippocampal cytoarchitecture after continuous treatment with MMF for 3 further days (10 or 100 micro g/mL). Treatment with NMDA and MMF (100 microg/mL) reduced the number of damaged propidium iodide (PI)+ neurons by 50.7% and the number of microglial cells by 52%. Continuous treatment of lesioned OHSCs with MMF for 3 days almost abrogated the glial proliferative response, reflected by the 91.5% reduction in the number of bromo-desoxy-uridine (BrdU)-labelled microglial cells and astrocytes. Microglial cells in MMF-treated OHSCs contained fragmented nuclei, indicating apoptotic cell death, an effect which was also found in isolated microglial cells treated with MMF. The beneficial effect of MMF on neuronal survival apparently does not reflect a direct antiexcitotoxic effect, as short-term treatment of OHSCs with NMDA and MMF for 4 h did not reduce the number of PI+ neurons. In conclusion, MMF inhibits proliferation and activation of microglia and astrocytes and protects neurons after excitotoxic injury.