Should We Use Rifampicin in Periprosthetic Joint Infections Caused by Staphylococci When the Implant Has Been Exchanged? A Multicenter Observational Cohort Study.

Background: Previous studies demonstrated the efficacy of a rifampicin-based regimen in the treatment of acute staphylococcal periprosthetic joint infections (PJIs) treated with surgical debridement. However, evidence is lacking to support the use of rifampicin in cases where the implant is exchanged during revision. Methods: We included all consecutive cases of staphylococcal PJIs treated from January 2013 to December 2018 with revision surgery in this international, retrospective, multicenter observational cohort study. PJI was defined according to the European Bone and Joint Infection Society diagnostic criteria. A relapse or reinfection during follow-up, the need for antibiotic suppressive therapy, the need for implant removal, and PJI-related death were defined as clinical failure. Cases without reimplantation or with follow-up <12 months were excluded. Results: A total of 375 cases were included in the final analysis, including 124 1-stage exchanges (33.1%) and 251 2-stage exchanges (66.9%). Of those, 101 cases failed (26.9%). There was no statistically significant difference in failure of patients receiving rifampicin (22.5%, 42/187) and those not receiving rifampicin (31.4%, 59/188; P = .051). A subanalysis of chronic PJIs treated by 2-stage exchange arthroplasty demonstrated a lower failure rate in cases treated with rifampicin (15%) compared with the no-rifampicin group (35.5%; P = .005). In this subgroup, the use of rifampicin and an antibiotic holiday of >2 weeks were independent predictors of clinical success (odds ratio [OR], 0.36; 95% CI, 0.15-0.88; and OR, 0.19; 95% CI, 0.04-0.90; respectively). Conclusions: Combination treatment with rifampicin increases treatment success in patients with chronic staphylococcal PJI treated with 2-stage exchange arthroplasty.

Risk factors for Gram-negative bacterial infection of cardiovascular implantable electronic devices: multicentre observational study (CarDINe Study).

BACKGROUND: Infections of cardiovascular implantable electronic devices (CIED) are mainly due to Gram-positive bacteria (GPB). Data about Gram-negative bacteria CIED (GNB-CIED) infections are limited. This study aimed to investigate risk factors, clinical and diagnostic characteristics, and outcome of patients with GNB-CIED. METHODS: A multicentre, international, retrospective, case-control-control study was performed on patients undergoing CIED implantation from 2015 to 2019 in 17 centres across Europe. For each patient diagnosed with GNB-CIED, one matching control with GPB-CIED infection and two matching controls without infection were selected. RESULTS: A total of 236 patients were enrolled: 59 with GNB-CIED infection, 59 with GPB-CIED infection and 118 without infection. No between-group differences were found regarding clinical presentation, diagnostic and therapeutic management. A trend toward a higher rate of fluorodeoxyglucose positron emission computed tomography (FDG PET/CT) positivity was observed among patients with GNB than in those with GPB-CIED infection (85.7% vs. 66.7%; P = 0.208). Risk factors for GNB-CIED infection were Charlson Comorbidity Index Score (relative risk reduction, RRR = 1.211; P = 0.011), obesity (RRR = 5.122; P = 0.008), ventricular-pacing ventricular-sensing inhibited-response pacemaker implantation (RRR = 3.027; P = 0.006) and right subclavian vein site of implantation (RRR = 5.014; P = 0.004). At 180-day survival analysis, GNB-CIED infection was associated with increased mortality risk (HR = 1.842; P = 0.067). CONCLUSIONS: Obesity, high number of comorbidities and right subclavian vein implantation site were associated with increased risk of GNB-CIED infection. A prompt therapeutic intervention that may be guided using FDG PET/CT is suggested in patients with GNB-CIED infection, considering the poorer outcome observed in this group.

Lethal Aeromonas veronii Sepsis in the Course of Medicinal Leech Therapy.

A patient with oral squamous cell carcinoma (OSCC) underwent complex surgical tumor therapy, including the reconstruction of soft tissues using a radial forearm flap. Due to venous congestion that could only partly be resolved by revision surgery, leech therapy was started on the second postoperative day. The patient developed pneumonia and sepsis and died as a result of septic shock, despite having received targeted broad-spectrum antibiotic therapy since day 5. Aeromonas spp. were cultured from both the patient's specimens and unused leeches. Biochemical identification and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) yielded inconsistent identification results. Finally, microbiological identification of Aeromonas spp. was performed via 16S rDNA sequencing and use of the basic local alignment search tool (BLAST), and strains from both the patient and the leeches were identified as Aeromonas veronii. Aeromonas spp. strains derived from the patient and leeches and independent laboratory strains were submitted to randomly amplified polymorphic DNA (RAPD) subtyping. RAPD of A. veronii strains from both sources revealed an identical pattern, strongly suggesting the transmission of A. veronii from the leeches to the patient. Physicians should be aware of the potential for severe lethal infections as a fatal side-effect of leech therapy in critically ill patients, which should be addressed using antibiotic prophylaxis.

Should all patients with a culture-negative periprosthetic joint infection be treated with antibiotics? : a multicentre observational study.

AIMS: The aim of this study was to analyze the prevalence of culture-negative periprosthetic joint infections (PJIs) when adequate methods of culture are used, and to evaluate the outcome in patients who were treated with antibiotics for a culture-negative PJI compared with those in whom antibiotics were withheld. METHODS: A multicentre observational study was undertaken: 1,553 acute and 1,556 chronic PJIs, diagnosed between 2013 and 2018, were retrospectively analyzed. Culture-negative PJIs were diagnosed according to the Muskuloskeletal Infection Society (MSIS), International Consensus Meeting (ICM), and European Bone and Joint Society (EBJIS) definitions. The primary outcome was recurrent infection, and the secondary outcome was removal of the prosthetic components for any indication, both during a follow-up period of two years. RESULTS: None of the acute PJIs and 70 of the chronic PJIs (4.7%) were culture-negative; a total of 36 culture-negative PJIs (51%) were treated with antibiotics, particularly those with histological signs of infection. After two years of follow-up, no recurrent infections occurred in patients in whom antibiotics were withheld. The requirement for removal of the components for any indication during follow-up was not significantly different in those who received antibiotics compared with those in whom antibiotics were withheld (7.1% vs 2.9%; p = 0.431). CONCLUSION: When adequate methods of culture are used, the incidence of culture-negative PJIs is low. In patients with culture-negative PJI, antibiotic treatment can probably be withheld if there are no histological signs of infection. In all other patients, diagnostic efforts should be made to identify the causative microorganism by means of serology or molecular techniques. Cite this article: Bone Joint J 2022;104-B(1):183-188.

Osteosynthesis-associated infection of the lower limbs by multidrug-resistant and extensively drug-resistant Gram-negative bacteria: a multicentre cohort study.

Purpose: The purpose of this study was the clinical and therapeutic assessment of lower-limb osteosynthesis-associated infection (OAI) by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), which have been poorly studied to date. Methods: A prospective multicentre observational study was conducted on behalf of ESGIAI (the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group on Implant-Associated Infections). Factors associated with remission of the infection were evaluated by multivariate and Cox regression analysis for a 24-month follow-up period. Results: Patients ( n = 57 ) had a history of trauma (87.7 %), tumour resection (7 %) and other bone lesions (5.3 %). Pathogens included Escherichia coli ( n = 16 ), Pseudomonas aeruginosa ( n = 14 ; XDR 50 %), Klebsiella spp. ( n = 7 ), Enterobacter spp. ( n = 9 ), Acinetobacter spp. ( n = 5 ), Proteus mirabilis ( n = 3 ), Serratia marcescens ( n = 2 ) and Stenotrophomonas maltophilia ( n = 1 ). The prevalence of ESBL (extended-spectrum ß -lactamase), fluoroquinolone and carbapenem resistance were 71.9 %, 59.6 % and 17.5 % respectively. Most patients ( n = 37 ; 64.9 %) were treated with a combination including carbapenems ( n = 32 ) and colistin ( n = 11 ) for a mean of 63.3 d. Implant retention with debridement occurred in early OAI (66.7 %), whereas the infected device was removed in late OAI (70.4 %) ( p = 0.008 ). OAI remission was achieved in 29 cases (50.9 %). The type of surgery, antimicrobial resistance and duration of treatment did not significantly influence the outcome. Independent predictors of the failure to eradicate OAI were age > 60  years (hazard ratio, HR, of 3.875; 95 % confidence interval, CI95 %, of 1.540-9.752; p = 0.004 ) and multiple surgeries for OAI (HR of 2.822; CI95 % of 1.144-6.963; p = 0.024 ). Conclusions: Only half of the MDR/XDR GNB OAI cases treated by antimicrobials and surgery had a successful outcome. Advanced age and multiple surgeries hampered the eradication of OAI. Optimal therapeutic options remain a challenge.

Timing of implant-removal in late acute periprosthetic joint infection: A multicenter observational study.

OBJECTIVES: We evaluated the treatment outcome in late acute (LA) periprosthetic joint infections (PJI) treated with debridement and implant retention (DAIR) versus implant removal. METHODS: In a large multicenter study, LA PJIs of the hip and knee were retrospectively evaluated. Failure was defined as: PJI related death, prosthesis removal or the need for suppressive antibiotic therapy. LA PJI was defined as acute symptoms <3 weeks in patients more than 3 months after the index surgery and with a history of normal joint function. RESULTS: 445 patients were included, comprising 340 cases treated with DAIR and 105 cases treated with implant removal (19% one-stage revision (n = 20), 74.3% two-stage revision (n = 78) and 6.7% definitive implant removal (n = 7). Overall failure in patients treated with DAIR was 45.0% (153/340) compared to 24.8% (26/105) for implant removal (p < 0.001). Difference in failure rate remained after 1:1 propensity-score matching. A preoperative CRIME80-score ≥3 (OR 2.9), PJI caused by S. aureus (OR 1.8) and implant retention (OR 3.1) were independent predictors for failure in the multivariate analysis. CONCLUSION: DAIR is a viable surgical treatment for most patients with LA PJI, but implant removal should be considered in a subset of patients, especially in those with a CRIME80-score ≥3.

Multidrug-resistant and extensively drug-resistant Gram-negative prosthetic joint infections: Role of surgery and impact of colistin administration.

Factors influencing treatment outcome of patients with Gram-negative bacterial (GNB) multidrug-resistant (MDR) and extensively drug-resistant (XDR) prosthetic joint infection (PJIs) were analysed. Data were collected (2000-2015) by 18 centres. Treatment success was analysed by surgery type for PJI, resistance (MDR/XDR) and antimicrobials (colistin/non-colistin) using logistic regression and survival analyses. A total of 131 patients (mean age 73.0 years, 35.9% male, 58.8% with co-morbidities) with MDR (n = 108) or XDR (n = 23) GNB PJI were assessed. The most common pathogens were Escherichia coli (33.6%), Pseudomonas aeruginosa (25.2%), Klebsiella pneumoniae (21.4%) and Enterobacter cloacae (17.6%). Pseudomonas aeruginosa predominated in XDR cases. Isolates were carbapenem-resistant (n = 12), fluoroquinolone-resistant (n = 63) and ESBL-producers (n = 94). Treatment outcome was worse in XDR versus MDR cases (P = 0.018). Success rates did not differ for colistin versus non-colistin in XDR cases (P = 0.657), but colistin was less successful in MDR cases (P = 0.018). Debridement, antibiotics and implant retention (DAIR) (n = 67) was associated with higher failure rates versus non-DAIR (n = 64) (OR = 3.57, 95% CI 1.68-7.58; P < 0.001). Superiority of non-DAIR was confirmed by Kaplan-Meir analysis (HR = 0.36, 95% CI 0.20-0.67) and remained unchangeable by time of infection (early/late), antimicrobial resistance (MDR/XDR) and antimicrobials (colistin/non-colistin) (Breslow-Day, P = 0.737). DAIR is associated with higher failure rates even in early MDR/XDR GNB PJIs versus implant removal. Colistin should be preserved for XDR cases as it is detrimental in MDR infections.

Clinical outcome and risk factors for failure in late acute prosthetic joint infections treated with debridement and implant retention.

OBJECTIVES: Debridement, antibiotics and implant retention (DAIR) is the recommended treatment for all acute prosthetic joint infections (PJI), but its efficacy in patients with late acute (LA) PJI is not well described. METHODS: Patients diagnosed with LA PJI between 2005 and 2015 were retrospectively evaluated. LA PJI was defined as the development of acute symptoms (≤ 3 weeks) occurring ≥ 3 months after arthroplasty. Failure was defined as: (i) the need for implant removal, (ii) infection related death, (iii) the need for suppressive antibiotic therapy and/or (iv) relapse or reinfection during follow-up. RESULTS: 340 patients from 27 centers were included. The overall failure rate was 45.0% (153/340). Failure was dominated by Staphylococcus aureus PJI (54.7%, 76/139). Significant independent preoperative risk factors for failure according to the multivariate analysis were: fracture as indication for the prosthesis (odds ratio (OR) 5.4), rheumatoid arthritis (OR 5.1), age above 80 years (OR 2.6), male gender (OR 2.0) and C-reactive protein > 150 mg/L (OR 2.0). Exchanging the mobile components during DAIR was the strongest predictor for treatment success (OR 0.35). CONCLUSION: LA PJIs have a high failure rate. Treatment strategies should be individualized according to patients' age, comorbidity, clinical presentation and microorganism causing the infection.

Prevalence of Propionibacterium acnes in the glenohumeral compared with the subacromial space in primary shoulder arthroscopies.

HYPOTHESIS: We hypothesized that the prevalence of Propionibacterium acnes in patients undergoing primary shoulder arthroscopy is equal in the glenohumeral space compared with the subacromial space. METHODS: Patients aged 18 years or older with shoulder arthroscopies were included. The exclusion criteria were prior shoulder operations, complete rotator cuff tears, systemic inflammatory diseases, tumors, shoulder injections within 6 months of surgery, and antibiotic therapy within 14 days preoperatively. After standardized skin disinfection with Kodan Tinktur Forte Gefärbt, a skin swab was taken at the posterior portal. Arthroscopy was performed without cannulas, prospectively randomized to start either in the glenohumeral space or in the subacromial space, with direct harvesting of a soft-tissue biopsy specimen. Sample cultivation was conducted according to standardized criteria for bone and joint aspirate samples and incubated for 14 days. Matrix-assisted laser desorption-ionization time-of-flight spectrometry was used for specimen identification in positive culture results. RESULTS: The study prospectively included 115 consecutive patients with normal C-reactive protein levels prior to surgery (54.8% men; mean age, 47.2 ± 14.6 years). P acnes was detected on the skin after disinfection in 36.5% of patients, in the glenohumeral space in 18.9%, and in the subacromial space in 3.5% (P = .016). CONCLUSION: The prevalence of P acnes is significantly higher in the glenohumeral space compared with the subacromial space in primary shoulder arthroscopies. The results do not confirm the contamination theory but also cannot clarify whether P acnes is a commensal or enters the joint hematologically or even lymphatically or via an unknown pathway. Despite standardized surgical skin disinfection, P acnes can be detected in skin swab samples in more than one-third of patients.

Methicillin-resistant Staphylococcus aureus Screening PCR adapted to locally emerging variants-Evaluation of novel SCCmec primers.

Infections with multi-resistant bacteria, such as Methicillin-resistant Staphylococcus aureus (MRSA), represent a world-wide health-care problem. The original MRSA Screening TaqMan PCR was based on the detection of the SCCmec-orfX-junction as described by the group of Huletsky in 2004. In the recent years, this assay increasingly failed to detect new MRSA variants in swab specimens. In this work, we analyzed the usefulness of 17 additional SCCmec primers to increase PCR sensitivity by testing 290 collected samples with negative PCR results and positive MRSA culture in a retrospective analysis, and 380 samples of the daily routine diagnostics. Sequencing of the PCR products revealed that locally new MRSA variants became detectable by nine of these forward primers. Four primers were solely responsible for the detection of 85.4% (117/123) of the PCR products: F13 (n=76), F11 (n=6), F14 (n=15) and F25 (n=8). These four primers were integrated in the Screening PCR and the novel primer collection was validated by testing 71 MRSA isolates, which covered SCCmec types I to VI, 50 MSSA isolates and 100 swab specimens. The sensitivity of MRSA Screening PCR increased from 93% to 98.6% without affecting the detection of the common MRSA strains. Phylogenetic analysis of the PCR products suggests that the adapted MRSA Screening PCR is able to detect SCCmec types I-X, including CA- and LA-MRSA variants by the SCCmec primers F11 and F25.

A Novel Staphylococcal Cassette Chromosome mec Type XI Primer for Detection of mecC-Harboring Methicillin-Resistant Staphylococcus aureus Directly from Screening Specimens.

Methicillin-resistant Staphylococcus aureus (MRSA) screening using real-time PCR has decreased in sensitivity due to the emergence of variant staphylococcal cassette chromosome mec element (SCCmec) types. We have designed and validated a novel SCCmec XI primer, which enables for the first time the rapid detection of mecC-harboring MRSA directly from nasopharyngeal swabs without prior cultivation.

Evaluation of an interdisciplinary therapy algorithm in patients with prosthetic joint infections.

PURPOSE: Current concepts in the treatment of prosthetic joint infections include prosthetic retention and exchange strategies according to published recommendations. A useful algorithm should fit for each type of prosthetic joint infection, even the most complicated situations. We present the outcome of 147 patients with prosthetic joint infections of the hip or the knee joint in an unselected population in clinical routine. METHODS: Between November 2006 and November 2009, 147 consecutive patients with prosthetic joint infections of the hip or knee were treated according to an algorithm based on the concept published by Zimmerli et al. in 2004. Causative organism, duration of infection, patient comorbidities, surgical treatment, antibiotic treatment, and outcome of treatment were analysed retrospectively. According to the criteria duration of infection, stability of prosthesis, local and systemic risk factors, and susceptibility of the causative pathogen, patients were treated either with debridement and retention or a long-interval two-stage procedure. RESULTS: A pathogen could be detected in 82.8% of the patients, gram-positive cocci being most common. Twenty-seven patients were treated with debridement and retention and 120 were treated with a two-stage procedure. In 68 cases difficult-to-treat pathogens could be detected, a polymicrobial infection was found in 51 patients. Definitely free of infection were 71.6% after a two-stage procedure, and 70.4% after debridement and retention. CONCLUSIONS: Our data indicates that the applied algorithm is suitable to be applied as a day-to-day routine, and we confirmed that published results from the literature can be reproduced in an inhomogeneous patient cohort.

Longitudinal study of the molecular epidemiology of methicillin-resistant Staphylococcus aureus at a university hospital.

Surveillance for methicillin-resistant Staphylococcus aureus (MRSA) at the University Hospital of Heidelberg revealed an increase in the numbers of newly detected MRSA isolates in recent years. We conducted a study to assess the dynamics of the changes in the MRSA population. Pulsed-field gel electrophoresis (PFGE) typing of MRSA isolates from all patients at the University Hospital of Heidelberg collected between 1993 and 2004 was performed. The microbiology database contained 1,807 entries for newly detected MRSA isolates from 1,301 patients. A total of 1,252 isolates were available for PFGE typing. The isolates could be classified into 109 different PFGE types. Most PFGE types (n=70) were detected less than five times and showed no evidence of transmission (sporadic strains). They accounted for 8.7% of all isolates, with few variations in frequency over the time. Thirty-seven PFGE types were clustered by time of detection, and transmission of the strains was likely (local epidemic strains). A total of 37.3% of the isolates belonged to this group of strains. The remaining 54.0% of the isolates belonged to only two further PFGE types (endemic strains). One endemic strain accounted for 5.0% of all isolates in 1994 and 68.2% in 2004. A second endemic strain was detected in 1.1% of all isolates in 1998 but in 12.4% in 2004. Statistical analysis of the associations between the kind of strain (sporadic, local epidemic, or endemic) and the patients' characteristics revealed a significant association for age and mode of acquisition. The remarkable increase in the rate of MRSA detection at the University Hospital of Heidelberg is mainly due to the dissemination of two different strains. Infection control measures seemed sufficient to prevent further transmission of some but not all of the strains.