Antimicrobial susceptibility testing is crucial when treating Finegoldia magna infections.

Finegoldia magna is an anaerobic gram-positive bacterium that can cause invasive human infections. Recently, a 52-year-old patient suffering from a periprosthetic joint infection (PJI) due to F. magna was treated with cefepime on hemodialysis; however, treatment failed due to relapse caused by antibiotic-resistant strains. Reports on the antimicrobial susceptibility of F. magna clinical isolates are rare. We collected 57 clinical F. magna isolates from Zurich, Switzerland, between September 2019 and July 2020 and tested their antimicrobial susceptibility to investigate the local resistance pattern. Antimicrobial susceptibility testing (AST) was evaluated for nine antibiotics (benzylpenicillin, amoxicillin/clavulanic acid, cefuroxime, cefepime, levofloxacin, rifampicin, metronidazole, doxycycline, and clindamycin) by E-test according to CLSI guidelines. All F. magna strains were susceptible to benzylpenicillin, amoxicillin/clavulanic acid, and metronidazole, while 75% to clindamycin. F. magna isolates showed MIC values lower than species-unrelated breakpoints for cefuroxime, levofloxacin, and cefepime in 93%, 56%, and 32% of the cases, respectively. MIC values for rifampicin and doxycycline were lower than locally determined ECOFFs in 98% and 72% of the cases, respectively. In summary, we recommend the use of benzylpenicillin, amoxicillin/clavulanic acid, or metronidazole without prior AST as first-line treatment option against F. magna PJI infections. If cefuroxime, cefepime, levofloxacin, rifampicin, doxycycline, or clindamycin are used, AST is mandatory.

Management and outcome of spinal implant-associated surgical site infections in patients with posterior instrumentation: analysis of 176 cases.

PURPOSE: The management of implant-associated surgical site infections (SSI) in patients with posterior instrumentation is challenging. Evidence regarding the most appropriate treatment and the need for removal of implants is equivocal. We sought to evaluate the management and outcome of such patients at our institution. METHODS: We searched our prospectively documented databases for eligible patients with posterior spinal instrumentation, excluding the cervical spine (January 2008-June 2018). Patient files were reviewed, demographic data and treatment details were recorded. Patient-reported outcome (PRO) was assessed with the Core Outcome Measures Index (COMI) preoperatively and postoperatively at 3 and 12 months. RESULTS: A total of 170 patients underwent 210 revisions for 176 SSIs. Two-thirds presented within four weeks (105/176, 59.7%, median 22.5d, 7d-11.1y). The most common pathogens were Staphylococcus aureus (n = 79/210, 37.6%) and Staphylococcus epidermidis (n = 56/210, 26.7%). Debridement and implant retention was performed in 135/210 (64.3%) revisions and partial replacement in 62/210 (29.5%). In 28/176 SSI (15.9%), persistent infection required multiple revisions (≤ 4). Surgery was followed by intravenous and oral antimicrobial treatment (10-12w). In 139/176 SSIs (79%) with ≥ 1y follow-up, infection was cured in 115/139 (82.7%); relapse occurred in 9 (relapse rate: 5.1%). Two patients (1.4%) died. COMI decreased significantly (8.2 ± 1.5 vs. 4.8 ± 2.9, p < 0.0001) over 12 months. 72.7% of patients were (very) satisfied with their care. CONCLUSION: Patients with SSI after posterior (thoraco-)lumbo(-sacral) instrumentation can be successfully treated in most cases with surgical and specific antibiotic treatment. An interdisciplinary approach is recommended. Loose implants should be replaced. In some cases, multiple revisions may be necessary. Patient outcomes were satisfactory.

The Impact of Surgical Strategy and Rifampin on Treatment Outcome in Cutibacterium Periprosthetic Joint Infections.

BACKGROUND: Cutibacterium species are common pathogens in periprosthetic joint infections (PJI). These infections are often treated with ß-lactams or clindamycin as monotherapy, or in combination with rifampin. Clinical evidence supporting the value of adding rifampin for treatment of Cutibacterium PJI is lacking. METHODS: In this multicenter retrospective study, we evaluated patients with Cutibacterium PJI and a minimal follow-up of 12 months. The primary endpoint was clinical success, defined by the absence of infection relapse or new infection. We used Fisher's exact tests and Cox proportional hazards models to analyze the effect of rifampin and other factors on clinical success after PJI. RESULTS: We included 187 patients (72.2% male, median age 67 years) with a median follow-up of 36 months. The surgical intervention was a 2-stage exchange in 95 (50.8%), 1-stage exchange in 51 (27.3%), debridement and implant retention (DAIR) in 34 (18.2%), and explantation without reimplantation in 7 (3.7%) patients. Rifampin was included in the antibiotic regimen in 81 (43.3%) cases. Infection relapse occurred in 28 (15.0%), and new infection in 13 (7.0%) cases. In the time-to-event analysis, DAIR (adjusted hazard ratio [HR] = 2.15, P = .03) and antibiotic treatment over 6 weeks (adjusted HR = 0.29, P = .0002) significantly influenced treatment failure. We observed a tentative evidence for a beneficial effect of adding rifampin to the antibiotic treatment-though not statistically significant for treatment failure (adjusted HR = 0.5, P = .07) and not for relapses (adjusted HR = 0.5, P = .10). CONCLUSIONS: We conclude that a rifampin combination is not markedly superior in Cutibacterium PJI, but a dedicated prospective multicenter study is needed.

Risk factor analysis for above-knee amputation in patients with periprosthetic joint infection of the knee: a case-control study.

BACKGROUND: Periprosthetic joint infection (PJI) is a severe complication following knee arthroplasty. Therapeutic strategies comprise a combination of surgical and antibiotic treatment modalities and aim to eradicate the infection. Sometimes control of the disease can only be attained by above-knee amputation (AKA). While a vast amount of literature exists illuminating predisposing factors for PJI, risk factors favoring the endpoint AKA in this context are sparsely known. METHODS: The purpose of this investigation was to delineate whether patients with PJI of the knee present specific risk factors for AKA. In a retrospective case-control study 11 cases of PJI treated with AKA were compared to 57 cases treated with limb salvage (LS). The minimum follow-up was 2 years. Comorbidities, signs and symptoms of the current infection, factors related to previous surgeries and the implant, microbiology, as well as therapy related factors were recorded. Comparative analysis was performed using student's t-test, chi-square test or Fisher's exact test. Binary differences were calculated using odds ratio (OR). Reoperation frequency was compared using Mann-Whitney U test. In-depth descriptive analysis of 11 amputees was carried out. RESULTS: A total of 68 cases aged 71 ± 11.2 years were examined, 11 of which underwent AKA and 57 had LS. Severe comorbidities (p = 0.009), alcohol abuse (p = 0.015), and preoperative anemia (p = 0.022) were more frequently associated with AKA. Preoperative anemia was found in all 11 amputees (100%) and in 33 of 57 LS patients (58%) with an average preoperative hemoglobin of 99.9 ± 15.1 g/dl compared to 118.2 ± 19.9 g/dl (p = 0.011). No other parameters differed significantly. AKA patients underwent a median of eight (range 2-24) reoperations, LS patients a median of five (range 2-15). CONCLUSION: Factors potentially influencing the outcome of knee PJI are diverse. The indication of AKA in this context remains a rarity and a case-by-case decision. Patient-intrinsic systemic factors such as alcohol abuse, severe comorbidities and preoperative anemia may elevate the individual risk for AKA in the setting of PJI. We recommend that anemia, being a condition well amenable to therapeutic measures, should be given special consideration in management of PJI patients. TRIAL REGISTRATION: This study was registered with Kantonale Ethikkommission Zürich, (BASEC-No. 2016-01048).

Factors affecting outcome in the treatment of streptococcal periprosthetic joint infections: results from a single-centre retrospective cohort study.

PURPOSE: To report and analyse factors affecting the outcome of streptococcal periprosthetic joint infections (PJIs). METHODS: A retrospective analysis of consecutive streptococcal PJIs was performed. Musculoskeletal Infection Society 2013 criteria were used. Outcome was compared with a prospective PJI cohort from the same institution. RESULTS: The most common isolated streptococcal species was Streptococcus dysgalactiae (9/22, 41%) among 22 patients included. Surgical treatment consisted of DAIR (debridement, antibiotics, irrigation and retention) in 12 (55%), one-stage revision arthroplasty in one (4%), two-stage revision arthroplasty in eight (37%) and implant removal in one (4%) patient. An infection free-outcome was achieved in 15 cases (68%), whilst seven (32%) patients failed initial revision and relapsed with the same pathogen, from which six were treated with DAIR and one with one-stage revision arthroplasty. No failures were observed in patients who received a two-stage revision. Failure rates did not differ in the cases treated with rifampin (1/5) from those without 6/17 (p = 0.55). There was no correlation between the length of antibiotic treatment and relapse (p = 0.723). In all failures, a persistent distant infection focus was identified at the time of relapse. Compared with our prospective PJI cohort, relapse rates were significantly higher 32% vs 12% (p < 0.05). CONCLUSION: No correlation with the use of rifampin or length of antibiotic treatment was found. No failures were observed in patients who received a two-stage revision, which may be the surgical treatment of choice. A distant persisting infection focus could be the reason for PJI relapse with recurrent hematogenous seeding in the joint.

Development of a Novel and Rapid Antibody-Based Diagnostic for Chronic Staphylococcus aureus Infections Based on Biofilm Antigens.

Prosthetic joint infections are difficult to diagnose and treat due to biofilm formation by the causative pathogens. Pathogen identification relies on microbial culture that requires days to weeks, and in the case of chronic biofilm infections, lacks sensitivity. Diagnosis of infection is often delayed past the point of effective treatment such that only the removal of the implant is curative. Early diagnosis of an infection based on antibody detection might lead to less invasive, early interventions. Our study examined antibody-based assays against the Staphylococcus aureus biofilm-upregulated antigens SAOCOL0486 (a lipoprotein), glucosaminidase (a domain of SACOL1062), and SACOL0688 (the manganese transporter MntC) for detection of chronic S. aureus infection. We evaluated these antigens by enzyme-linked immunosorbent assay (ELISA) using sera from naive rabbits and rabbits with S. aureus-mediated osteomyelitis, and then we validated a proof of concept for the lateral flow assay (LFA). The SACOL0688 LFA demonstrated 100% specificity and 100% sensitivity. We demonstrated the clinical diagnostic utility of the SACOL0688 antigen using synovial fluid (SF) from humans with orthopedic implant infections. Elevated antibody levels to SACOL0688 in clinical SF specimens correlated with 91% sensitivity and 100% specificity for the diagnosis of S. aureus infection by ELISA. We found measuring antibodies levels to SACOL0688 in SF using ELISA or LFA provides a tool for the sensitive and specific diagnosis of S. aureus prosthetic joint infection. Development of the LFA diagnostic modality is a desirable, cost-effective option, potentially providing rapid readout in minutes for chronic biofilm infections.

Alpha-defensin lateral flow test does not appear to be useful in predicting shoulder periprosthetic joint infections.

PURPOSE: Periprosthetic joint infections (PJIs) remain a challenging complication after shoulder arthroplasty. The antimicrobial peptide α-defensin has been proposed as a new synovial fluid biomarker in diagnosing PJIs. To date, only little data are available on the diagnostic accuracy of α-defensin in shoulder PJIs; thus, we aimed to evaluate its diagnostic value in a cohort of patients with a suspected shoulder PJI. METHODS: Between June 2016 and June 2018, we prospectively enrolled patients with a diagnostic shoulder aspiration due to painful shoulder arthroplasty or planned revision surgery. PJI diagnostics were performed according to the Musculoskeletal Infection Society (MSIS) criteria. All patients with an antibiotic therapy within two  weeks before enrollment, insufficient amount of synovial aspirate, or bloody aspiration were excluded. α-Defensin was measured in the synovial fluid using the α-defensin lateral flow (ADLF) test (Synovasure®). RESULTS: Out of 60 patients, we could include 29 (59% female) patients with a mean age of 70 (range, 50-92) years. A shoulder PJI was detected in five cases (Staphylococcus aureus, n = 2; Staphylococcus epidermidis, n = 2; Cutibacterium acnes, n = 1). The ADLF test was positive in seven out of 29 cases. According to the MSIS criteria, the ADLF test was false-negative in two patients and false-positive in four patients, resulting in sensitivity, specificity, and positive and negative predictive value of 60%, 83%, 43%, and 91%, respectively. The overall accuracy was 79%. CONCLUSION: The ALDF test does not appear to be useful in predicting shoulder PJIs but may be used as an additional diagnostic factor in rejecting these infections.

Clearance of Staphylococcus aureus from In Vivo Models of Chronic Infection by Immunization Requires Both Planktonic and Biofilm Antigens.

Staphylococcus aureus is a causative agent of chronic biofilm-associated infections that are recalcitrant to resolution by the immune system or antibiotics. To combat these infections, an antistaphylococcal, biofilm-specific quadrivalent vaccine against an osteomyelitis model in rabbits has previously been developed and shown to be effective at eliminating biofilm-embedded bacterial populations. However, the addition of antibiotics was required to eradicate remaining planktonic populations. In this study, a planktonic upregulated antigen was combined with the quadrivalent vaccine to remove the need for antibiotic therapy. Immunization with this pentavalent vaccine followed by intraperitoneal challenge of BALB/c mice with S. aureus resulted in 16.7% and 91.7% mortality in pentavalent vaccine and control groups, respectively (P < 0.001). Complete bacterial elimination was found in 66.7% of the pentavalent cohort, while only 8.3% of the control animals cleared the infection (P < 0.05). Further protective efficacy was observed in immunized rabbits following intramedullary challenge with S. aureus, where 62.5% of the pentavalent cohort completely cleared the infection, versus none of the control animals (P < 0.05). Passive immunization of BALB/c mice with serum IgG against the vaccine antigens prior to intraperitoneal challenge with S. aureus prevented mortality in 100% of mice and eliminated bacteria in 33.3% of the challenged mice. These results demonstrate that targeting both the planktonic and biofilm stages with the pentavalent vaccine or the IgG elicited by immunization can effectively protect against S. aureus infection.

Francisella tularensis Periprosthetic Joint Infections Diagnosed with Growth in Cultures.

Tularemia caused by Francisella tularensis is a zoonotic infection of the Northern Hemisphere that mainly affects the skin, lymph nodes, bloodstream, and lungs. Other manifestations of tularemia are very rare, especially those with musculoskeletal involvement. Presenting in 2016, we diagnosed two cases of periprosthetic knee joint infections (PJI) caused by Francisella tularensis in Europe (one in Switzerland and one in the Czech Republic). We found only two other PJI cases in the literature, another knee PJI diagnosed 1999 in Ontario, Canada, and one hip PJI in Illinois, USA, in 2017. Diagnosis was made in all cases by positive microbiological cultures after 3, 4, 7, and 12 days. All were successfully treated, two cases by exchange of the prosthesis, one with debridement and retention, and one with repeated aspiration of the synovial fluid only. Antibiotic treatment was given between 3 weeks and 12 months with either ciprofloxacin-rifampin or with doxycycline alone or doxycycline in combination with gentamicin. Zoonotic infections should be considered in periprosthetic infections in particular in culture-negative PJIs with a positive histology or highly elevated leukocyte levels in synovial aspiration. Here, we recommend prolonging cultivation time up to 14 days, performing specific PCR tests, and/or conducting epidemiologically appropriate serological tests for zoonotic infections, including that for F. tularensis.

Meningitis and epididymitis caused by Toscana virus infection imported to Switzerland diagnosed by metagenomic sequencing: a case report.

BACKGROUND: We report a rare case of Toscana virus infection imported into Switzerland in a 23-year old man who travelled to Imperia (Italy) 10 days before onset of symptoms. Symptoms included both meningitis and as well epididymitis. This is only the fourth case of Toscana virus reported in Switzerland. CASE PRESENTATION: The patient presented with lymphocytic meningitis and scrotal pain due to epididymitis. Meningitis was initially treated with ceftriaxone. Herpes simplex, tick-borne encephalitis, enterovirus, measles, mumps, rubella and Treponema pallidum were excluded with specific polymerase chain reaction (PCR) or serology. In support of routine diagnostic PCR and serology assays, unbiased viral metagenomic sequencing was performed of cerebrospinal fluid and serum. Toscana virus infection was identified in cerebrospinal fluid and the full coding sequence could be obtained. Specific PCR in cerebrospinal fluid and blood and serology with Immunoglobulin (Ig) M and IgG against Toscana virus confirmed our diagnosis. Neurological symptoms recovered spontaneously after 5 days. CONCLUSIONS: This case of Toscana virus infection highlights the benefits of unbiased metagenomic sequencing to support routine diagnostics in rare or unexpected viral infections. With increasing travel histories of patients, physicians should be aware of imported Toscana virus as the agent for viral meningitis and meningoencephalitis.

Association of Cutibacterium avidum Colonization in the Groin With Obesity: A Potential Risk Factor for Hip Periprosthetic Joint Infection.

Background: An increase in the incidence of hip periprosthetic joint infections caused by Cutibacterium avidum has recently been detected after hip arthroplasty with an anterior surgical approach. We raised the question of whether skin colonization with C. avidum differs between the anterior and the lateral thigh as areas of surgical incision fields. Methods: Between February and June 2017, we analyzed skin scrapings from the groin and the anterior and lateral thigh in patients undergoing a primary hip arthroplasty. We anaerobically cultured plated swab samples for Cutibacterium spp. for ≥7 days. Univariate logistic regression analysis was used to explore associations between body mass index (BMI) and colonization rate at different sites. Results: Twenty-one of 65 patients (32.3%) were colonized with C. avidum at any site, mainly at the groin (n = 16; 24.6%), which was significantly higher at the anterior (n = 5; 7.7%; P = .009) or lateral (n = 6; 9.2%; P = .02) thigh. Patients colonized with C. avidum did not differ from noncolonized patients in age or sex, but their BMIs were significantly higher (30.1 vs 25.6 kg/m2, respectively; P = .02). Furthermore, increased BMI was associated with colonization at the groin (odds ratio per unit BMI increase, 1.15; 95% confidence interval; 1.03-1.29; P = .01). Conclusions: The groin, rather than the anterior thigh, showed colonization for C. avidum in obese patients. Further studies are needed to evaluate current skin disinfection and draping protocols for hip arthroplasty, particularly in obese patients.

Propionibacterium avidum: A Virulent Pathogen Causing Hip Periprosthetic Joint Infection.

Background: Propionibacteria are important members of the human skin microbiota, but are also opportunistic pathogens associated with periprosthetic joint infection (PJI). While the role of Propionibacterium acnes in PJI has been widely described, insight into the capacity of Propionibacterium avidum to cause PJI is limited. Methods: An unusual cluster of 4 hip PJIs caused by P. avidum in one orthopedic center in 2015 prompted us to retrospectively identify and analyze clinical data related to previous P. avidum PJI cases (1997-2015). We also characterized the hemolytic and biofilm-producing capacity of our 4 clinical P. avidum strains isolated in 2015, and investigated their phylogenetic relationships by whole-genome sequencing. Results: We retrospectively identified 13 P. avidum PJIs, with the majority being hip-related infections (n = 11). Preoperative synovial fluid cultures were P. avidum positive in 63.6% of cases. Six of 12 patients (50%) with available case histories were treated with an exchange of the prosthesis. In all but 1 of the 6 patients treated with debridement-retention of the prosthesis, treatment failed, thus requiring a 2-stage revision. The isolated P. avidum strains showed a more pronounced hemolytic activity, but a similar biofilm-forming ability when compared to P. acnes. Whole-genome sequencing identified 2 phylogenetic clusters highly related to P. avidum PJI strains isolated in Sweden. Conclusions: We describe the largest series of P. avidum PJI predominantly located in the hip. Phylogenetic similarity of our P. avidum strains to PJI strains isolated elsewhere suggests that these invasive lineages may be common.

Perioperative Antibiotic Prophylaxis Has No Effect on Time to Positivity and Proportion of Positive Samples: a Cohort Study of 64 Cutibacterium acnes Bone and Joint Infections.

If a bone or joint infection is suspected, perioperative antibiotic prophylaxis is frequently withheld until intraoperative microbiological sampling has been performed. This practice builds upon the hypothesis that perioperative antibiotics could render culture results negative and thus impede tailored antibiotic treatment of infections. We aimed to assess the influence of antibiotic prophylaxis within 30 to 60 min before surgery on time to positivity of microbiological samples and on proportion of positive samples in Cutibacterium acnes bone and joint infections. Patients with at least one sample positive for C. acnes between January 2005 and December 2015 were included and classified as having an "infection" if at least 2 samples were positive; otherwise they were considered to have a sample "contamination." Kaplan-Meier curves were used to illustrate time to culture positivity. We found 64 cases with a C. acnes infection and 46 classified as having a C. acnes contamination. Application of perioperative prophylaxis significantly differed between the infection and contamination groups (72.8% versus 55.8%; P < 0.001). Within the infection group, we found no difference in time to positivity between those who had or had not received a perioperative prophylaxis (7.07 days; 95% confidence interval [CI], 6.4 to 7.7, versus 7.11 days; 95% CI, 6.8 to 7.5; P = 0.3). Also, there was no association between the proportion of sample positivity and the application of perioperative prophylaxis (71.6% versus 65.9%; P = 0.39). Since perioperative prophylaxis did not negatively influence the microbiological yield in C. acnes infections, antibiotic prophylaxis can be routinely given to avoid surgical site infections.

Corynebacterium Species Rarely Cause Orthopedic Infections.

Corynebacterium spp. are rarely considered pathogens, but data on Corynebacterium spp. as a cause of orthopedic infections are sparse. Therefore, we asked how often Corynebacterium spp. caused an infection in a defined cohort of orthopedic patients with a positive culture. In addition, we aimed to determine the species variety and the susceptibility of isolated strains to define potential treatment strategies. We retrospectively assessed all bone and joint samples that were collected between 2006 and 2015 from an orthopedic ward and that were positive for Corynebacterium spp. by culture. The isolates were considered relevant to an infection if the same Corynebacterium sp. was present in at least two samples. We found 97 orthopedic cases with isolation of Corynebacterium spp. (128 positive samples). These were mainly Corynebacterium tuberculostearicum (n = 26), Corynebacterium amycolatum (n = 17), Corynebacterium striatum (n = 13), and Corynebacterium afermentans (n = 11). Compared to the species found in a cohort of patients with positive blood cultures hospitalized in nonorthopedic wards, we found significantly more C. striatum- and C. tuberculostearicum-positive cases but no C. jeikeium-positive cases in our orthopedic cohort. Only 16 out of 66 cases (24.2%) with an available diagnostic set of at least two samples had an infection. Antibiotic susceptibility testing (AST) showed various susceptibility results for all antibiotics except vancomycin and linezolid, to which 100% of the isolates were susceptible. The rates of susceptibility of corynebacteria isolated from orthopedic samples and of isolates from blood cultures were comparable. In conclusion, our study results confirmed that a Corynebacterium sp. is most often isolated as a contaminant in a cohort of orthopedic patients. AST is necessary to define the optimal treatment in orthopedic infections.

Staged Revision With Antibiotic Spacers for Shoulder Prosthetic Joint Infections Yields High Infection Control.

BACKGROUND: The treatment of periprosthetic joint infection (PJI) of the shoulder with two-stage revision arthroplasty using an antibiotic-loaded cement spacer is established strategy, but there is sparse information regarding the likelihood of infection control and restoration of shoulder. QUESTIONS/PURPOSE: (1) What is the likelihood of infection control after two-stage revision using an antibiotic cement spacer for patients with PJI of the shoulder? (2) What are the improvements in Constant and Murley scores at 2 years after these staged revisions? PATIENTS AND METHODS: Between 2000 and 2013, we treated 48 patients with PJI of the shoulder using two-stage revision including an antibiotic-containing cement spacer during the first stage. Of those, 38 (79%) were available for review at a minimum of 24 months (mean, 52 ± 34 months). Ten patients (21%) were excluded because they were deceased (n = 3), moved abroad (n = 4), or refused followup (n = 3), leaving 38 for analysis in this retrospective study. During the first stage, removal of the prosthesis, débridement, and implantation of a gentamicin and vancomycin-filled cement spacer were performed by four different surgeons followed by antibiotic therapy (2 weeks intravenous plus 10 weeks oral). For the second stage, we generally tried a reverse total shoulder arthroplasty (RTSA; n = 26). In case of severe glenoid destruction, hemiarthroplasty (HA; n = 8) was used as a salvage option. In 14 patients the cement spacer was left in place because the patients refused further surgery or were not operable owing to medical reasons. The primary outcome included the proportion of patients achieving infection control 2 years after the second-stage procedure after implantation of the cement spacer. Infection control was determined as the absence of the Musculoskeletal Infection Society PJI criteria. The clinical outcome assessed with the Constant and Murley scores served as the secondary outcome parameter. A subgroup (RTSA; HA, spacer retention) analysis of the Constant and Murley scores was performed. RESULTS: Successful infection control was achieved in 36 of 38 patients (95%). Patients who underwent treatment with a cement spacer had increased Constant and Murley scores at latest followup compared with their pretreatment scores (mean ± SD, 27 ± 19 versus 43 ± 20; mean difference, 17; 95% CI, 10-24; p = 0.001). For patients who underwent staged treatment followed by second-stage RTSA (n = 23), the Constant and Murley scores increased (mean ± SD, 31 ± 20 versus 51 ± 20; mean difference, 20; 95% CI, 11-30; p = 0.001). The Constant and Murley scores did not improve in patients who underwent HA (mean ± SD, 22 ±15 versus 24 ± 90; mean difference, 3; 95% CI, -10 to 16; p = 0.509) or who retained the spacer (mean ± SD, 18 ±12 versus 35 ±10; mean difference, 19; 95% CI, -5 to 44; p = 0.093). CONCLUSION: Revision arthroplasty using an antibiotic-loaded cement spacer provided successful infection control in patients with periprosthetic shoulder infections in this small, retrospective series. Functional improvement was obtained after reimplantation of a reverse total shoulder prosthesis but was not seen after HA and cement spacer; however, baseline differences among patient groups very likely contributed to these differences, and they should not be attributed to implant selection alone. LEVEL OF EVIDENCE: Level III, therapeutic study.

High level methicillin resistance correlates with reduced Staphylococcus aureus endothelial cell damage.

There has been controversy about the intrinsic virulence of methicillin-resistant Staphylococcus aureus (MRSA) as compared to methicillin-susceptible S. aureus (MSSA). To address this discrepancy, the intrinsic virulence of 42 MRSA and 40 MSSA clinical isolates was assessed by testing endothelial cell (EC) damage, a surrogate marker for virulence in blood stream infections. Since these clinical isolates represent a heterogeneous group, well characterized S. aureus laboratory strains with SCCmec loss- and gain-of-function mutations were used in addition. The clinical MRSA isolates carrying typical hospital acquired SCCmec types (I, II or III) induced significantly less damage (47.8%) as compared to isolates with other SCCmec types (62.3%, p=0.03) and MSSA isolates (64.2%, p<0.01). There was a strong inverse correlation between high-level oxacillin resistance and low EC damage induction (R2=0.4464, p<0.001). High-level oxacillin resistant strains (MIC >32µ/ml) grew significantly slower as compared to isolates with low-level resistance (p=0.047). The level of EC damage positively correlated with α- and δ-toxin production (p<0.0001 and p<0.05, respectively) but not with ß-toxin production. Invasive MRSA isolates (n=21, 56.3%) were significantly less cytotoxic as compared to invasive MSSA isolates (n=20, 68.0%, p<0.05). There was no difference between EC damage induced by superficial versus invasive isolates in either MRSA or MSSA strains. Our data suggest that the intrinsic virulence of MRSA is similar or even reduced as compared to MSSA strains but is linked to the level of methicillin resistance.

Optimal Length of Cultivation Time for Isolation of Propionibacterium acnes in Suspected Bone and Joint Infections Is More than 7 Days.

Diagnosis of Propionibacterium acnes bone and joint infection is challenging due to the long cultivation time of up to 14 days. We retrospectively studied whether reducing the cultivation time to 7 days allows accurate diagnosis without losing sensitivity. We identified patients with at least one positive P. acnes sample between 2005 and 2015 and grouped them into "infection" and "no infection." An infection was defined when at least two samples from the same case were positive. Clinical and microbiological data, including time to positivity for different cultivation methods, were recorded. We found 70 cases of proven P. acnes infection with a significant faster median time to positivity of 6 days (range, 2 to 11 days) compared to 9 days in 47 cases with P. acnes identified as a contamination (P < 0.0001). In 15 of 70 (21.4%) patients with an infection, tissue samples were positive after day 7 and in 6 patients (8.6%) after day 10 when a blind subculture of the thioglycolate broth was performed. The highest sensitivity was detected for thioglycolate broth (66.3%) and the best positive predictive values for anaerobic agar plates (96.5%). A prolonged transportation time from the operating theater to the microbiological laboratory did not influence time to positivity of P. acnes growth. By reducing the cultivation time to 7 days, false-negative diagnoses would increase by 21.4%; thus, we recommend that biopsy specimens from bone and joint infections be cultivated to detect P. acnes for 10 days with a blind subculture at the end.

Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery.

AIMS: We identified 10 patients with disseminated Mycobacterium chimaera infections subsequent to open-heart surgery at three European Hospitals. Infections originated from the heater-cooler unit of the heart-lung machine. Here we describe clinical aspects and treatment course of this novel clinical entity. METHODS AND RESULTS: Interdisciplinary care and follow-up of all patients was documented by the study team. Patients' characteristics, clinical manifestations, microbiological findings, and therapeutic measures including surgical reinterventions were reviewed and treatment outcomes are described. The 10 patients comprise a 1-year-old child and nine adults with a median age of 61 years (range 36-76 years). The median duration from cardiac surgery to diagnosis was 21 (range 5-40) months. All patients had prosthetic material-associated infections with either prosthetic valve endocarditis, aortic graft infection, myocarditis, or infection of the prosthetic material following banding of the pulmonary artery. Extracardiac manifestations preceded cardiovascular disease in some cases. Despite targeted antimicrobial therapy, M. chimaera infection required cardiosurgical reinterventions in eight patients. Six out of 10 patients experienced breakthrough infections, of which four were fatal. Three patients are in a post-treatment monitoring period. CONCLUSION: Healthcare-associated infections due to M. chimaera occurred in patients subsequent to cardiac surgery with extracorporeal circulation and implantation of prosthetic material. Infections became clinically apparent after a time lag of months to years. Mycobacterium chimaera infections are easily missed by routine bacterial diagnostics and outcome is poor despite long-term antimycobacterial therapy, probably because biofilm formation hinders eradication of pathogens.

Propionibacterium acnes: from commensal to opportunistic biofilm-associated implant pathogen.

Propionibacterium acnes is known primarily as a skin commensal. However, it can present as an opportunistic pathogen via bacterial seeding to cause invasive infections such as implant-associated infections. These infections have gained more attention due to improved diagnostic procedures, such as sonication of explanted foreign materials and prolonged cultivation time of up to 14 days for periprosthetic biopsy specimens, and improved molecular methods, such as broad-range 16S rRNA gene PCR. Implant-associated infections caused by P. acnes are most often described for shoulder prosthetic joint infections as well as cerebrovascular shunt infections, fibrosis of breast implants, and infections of cardiovascular devices. P. acnes causes disease through a number of virulence factors, such as biofilm formation. P. acnes is highly susceptible to a wide range of antibiotics, including beta-lactams, quinolones, clindamycin, and rifampin, although resistance to clindamycin is increasing. Treatment requires a combination of surgery and a prolonged antibiotic treatment regimen to successfully eliminate the remaining bacteria. Most authors suggest a course of 3 to 6 months of antibiotic treatment, including 2 to 6 weeks of intravenous treatment with a beta-lactam. While recently reported data showed a good efficacy of rifampin against P. acnes biofilms, prospective, randomized, controlled studies are needed to confirm evidence for combination treatment with rifampin, as has been performed for staphylococcal implant-associated infections.

Prolonged Outbreak of Mycobacterium chimaera Infection After Open-Chest Heart Surgery.

BACKGROUND: Invasive Mycobacterium chimaera infections were diagnosed in 2012 in 2 heart surgery patients on extracorporeal circulation. We launched an outbreak investigation to identify the source and extent of the potential outbreak and to implement preventive measures. METHODS: We collected water samples from operating theaters, intensive care units, and wards, including air samples from operating theaters. Mycobacterium chimaera strains were characterized by randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Case detection was performed based on archived histopathology samples and M. chimaera isolates since 2006, and the patient population at risk was prospectively surveyed. RESULTS: We identified 6 male patients aged between 49 and 64 years with prosthetic valve endocarditis or vascular graft infection due to M. chimaera, which became clinically manifest with a latency of between 1.5 and 3.6 years after surgery. Mycobacterium chimaera was isolated from cardiac tissue specimens, blood cultures, or other biopsy specimens. We were able also to culture M. chimaera from water circuits of heater-cooler units connected to the cardiopulmonary bypass, and air samples collected when the units were in use. RAPD-PCR demonstrated identical patterns among M. chimaera strains from heater-cooler unit water circuits and air samples, and strains in 2 patient clusters. CONCLUSIONS: The epidemiological and microbiological features of this prolonged outbreak provided evidence for the airborne transmission of M. chimaera from contaminated heater-cooler unit water tanks to patients during open-heart surgery.