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.

Establishment of a localized acute implant-associated Staphylococcus aureus bone infection model in sheep.

Orthopedic implant-associated bacterial infections with Staphylococcus aureus constitute a major clinical problem, and large pre-clinical animal models remain scarce. The aim of this study was to establish a standardized method of a localized, acute S. aureus bone infection in the presence of complex implanted devices in a sheep model. Four sheep underwent surgery receiving a complex implanted metallic device with a component stabilizing a bone defect created in the left tibial metaphysis, and an attached component placed in adjacent soft tissue. The bone defect was inoculated with S. aureus strain ATCC25293 (1 × 104 CFU). Twenty one days later, the surgery site was macroscopically evaluated, tissue samples and implants harvested for bacterial cell count quantification and tissue samples histologically analyzed. The animals exhibited clinical signs of localized infection (e.g. swelling, lameness, pain) but did not develop symptoms of sepsis. After euthanasia, macroscopic assessment revealed a localized bone and soft tissue infection at the surgery site. Histologically, an acute inflammation with neutrophils but also signs of bone destruction with necrosis was noted. An ovine model of a localized, acute S. aureus bone infection with complex implants was successfully established and could be used to test novel treatments against orthopedic implant-associated infections.

Deep surgical site infections following double-dose perioperative antibiotic prophylaxis in adult obese orthopedic patients.

BACKGROUND: Obesity is a risk factor for surgical site infections (SSI). Based on retrospective comparisons and pharmacology, many orthopedic centers have adopted weight- or body mass index (BMI)-related antibiotic prophylaxis. METHODS: Double-dose prophylaxis was introduced in March 2017 for patients weighting >80 kg. The period April 2014 to March 2017 ('before') was compared to the period March 2017 to June 2019 ('after') regarding the impact on deep SSIs. RESULTS: A total of 9318 surgeries 'before' were compared to 7455 interventions 'after' the introduction of double-dose prophylaxis. Baseline demographic characteristics (age, sex, BMI, American Society of Anesthesiologists score, and duration of surgery) were similar. In the period 'after', 3088 cases (3088/16 773; 18%) received double-dose prophylaxis. Overall, 82 deep SSIs were observed (0.5%). The pathogens were resistant to the standard cefuroxime prophylaxis in 30 cases (30/82; 37%). Excluding these prophylaxis-resistant cases and all of the five hematogenous SSIs, the remaining 47 SSIs (57%) could have been prevented by the preceding prophylaxis. Double-dosing of parenteral cefuroxime from 1.5 g to 3.0 g in obese patients did not reduce deep SSIs (hazard ratio 0.7, 95% confidence interval 0.3-1.6). In the direct group comparison among obese patients >80 kg, the double-dose prophylaxis equally failed to alter the SSI risk (3088/16 726 non-infections vs 8/47 SSI despite double-dose prophylaxis; Chi-square test, P = 0.78). CONCLUSIONS: In this single-center before-and-after study with almost 17 000 orthopedic surgeries in adult patients, systemic doubling of the perioperative antibiotic prophylaxis in obese patients clinically failed to reduce the overall deep SSI risk.

Cutibacterium avidum resists surgical skin antisepsis in the groin-a potential risk factor for periprosthetic joint infection: a quality control study.

BACKGROUND: The skin commensal Cutibacterium avidum has been recognized as an emerging pathogen for periprosthetic joint infections (PJI). One currently assumes that the early occurring PJIs are a consequence of skin commensals contaminating the peri-implant tissue during surgery. We addressed whether standard skin antisepsis with povidone-iodine/alcohol before total hip arthroplasty (THA) is effective to eliminate colonizing bacteria with focus on C. avidum. METHODS: In a single-center, prospective study, we screened all patients for skin colonizing C. avidum in the groin before THA. Only in the patients positive for C. avidum, we preoperatively repeated skin swabs after the first and third skin antisepsis and antibiotic prophylaxis. We also obtained dermis biopsies for microbiology and fluorescence in situ hybridization (FISH). RESULTS: Fifty-one out of 60 patients (85%) were colonized on the skin with various bacteria, in particular with C. avidum in 12 out of 60. Skin antisepsis eliminated C. avidum in eight of ten (20%) colonized patients undergoing THA. Deeper skin (dermis) biopsies were all culture negative, but FISH detected single positive ribosome-rich C. avidum in one case near sweat glands. CONCLUSION: Standard skin antisepsis was not effective to completely eliminate colonizing C. avidum on the skin in the groin of patients undergoing THA. Colonizing with C. avidum might pose an increased risk for PJI when considering a THA. Novel more effective antisepsis strategies are needed. Trial registration No clinical trial.

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.

Short postsurgical antibiotic therapy for spinal infections: protocol of prospective, randomized, unblinded, noninferiority trials (SASI trials).

BACKGROUND: There are several open scientific questions regarding the optimal antibiotic treatment of spinal infections (SIs) with or without an implant. The duration of postsurgical antibiotic therapy is debated. METHODS: We will perform two unblinded randomized controlled trials (RCTs). We hypothesize that shorter durations of systemic antibiotic therapy after surgery for SI are noninferior (10% margin, 80% power, α = 5%) to existing (long) treatment durations. The RCTs allocate the participants to two arms of 2 × 59 episodes each: 3 vs. 6 weeks of targeted postsurgical systemic antibiotic therapy for implant-free SIs or 6 vs. 12 weeks for implant-related SIs. This equals a total of 236 adult SI episodes (randomization scheme 1:1) with a minimal follow-up of 12 months. All participants receive concomitant multidisciplinary surgical, re-educational, internist, and infectious disease care. We will perform three interim analyses that are evaluated, in a blinded analysis, by an independent study data monitoring committee. Besides the primary outcome of remission, we will also assess adverse events of antibiotic therapy, changes of the patient's nutritional status, the influence of immune suppression, total costs, functional scores, and the timely evolution of the (surgical) wounds. We define infection as the presence of local signs of inflammation (pus, wound discharge, calor, and rubor) together with microbiological evidence of the same pathogen(s) in at least two intraoperative samples, and we define remission as the absence of clinical, laboratory, and/or radiological evidence of (former or new) infection. DISCUSSION: Provided that there is adequate surgical debridement, both RCTs will potentially enable prescription of less antibiotics during the therapy of SI, with potentially less adverse events and reduced overall costs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04048304. Registered on 5 August 2019. PROTOCOL VERSION: 2, 5 July 2019.

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.

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.

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.

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.

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.

Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera.

Prosthetic valve endocarditis (PVE) due to fast-growing nontuberculous mycobacteria (NTM) has been reported anecdotally. Reports of PVE with slowly growing NTM, however, are lacking. We present here one case of PVE and one case of bloodstream infection caused by Mycobacterium chimaera. Randomly amplified polymorphic DNA (RAPD)-PCR indicated a relatedness of the two M. chimaera strains. Both patients had heart surgery 2 years apart from each other. A nosocomial link was not detected.

A rare but severe pulmonary side effect of cetuximab in two patients.

Cetuximab is a monoclonal antibody that treats malignant disease by inhibiting epidermal growth factor receptor. Many common adverse events have been reported and include skin rashes, infusion reactions, gastrointestinal complaints and headache. Up to now, cetuximab-associated pulmonary toxicity has been rarely reported in the literature. The present report describes two cases with probable interstitial pneumonitis 5-6 weeks after commencing treatment with chemotherapy combined with cetuximab. One patient recovered and the second patient died due to gastrointestinal bleeding 3 weeks after an initial response to steroids.

Treatment strategies for periprosthetic infections after primary elbow arthroplasty.

BACKGROUND: The goal of this study was to investigate the outcome of different surgical procedures (debridement and retention vs 1- or 2-stage exchange) together with a well-defined antimicrobial regimen. MATERIALS AND METHODS: A total of 236 consecutive patients underwent 262 primary elbow arthroplasties between January 1994 and December 2007. We observed 20 episodes of periprosthetic infections in 19 patients and placed them into 3 groups according to the occurrence of infection after index surgery. A total of 9 early infections (<3 months), 1 delayed infection (3-24 months), and 10 late infections (>24 months) were observed. The treatment among those 3 groups was compared, and the outcome was assessed with a mean follow-up of 60.2 months. RESULTS: In the group with early infections (n = 9), 8 cases were treated by irrigation and debridement and 1 case was treated by a 2-stage exchange without recurrence of infection. The mean Mayo Elbow Performance Score improved from 48.3 points (range, 30-75 points) to 91.7 points (range, 85-100 points). The delayed infection was treated by 1-stage exchange without recurrence of infection. For late infections (n = 10), 3 cases presented recurrence of infection after debridement and irrigation, and the mean Mayo Elbow Performance Score remained nearly unchanged, from 60 points (range, 45-80 points) to 65 points (range, 50-80 points). Eradication of infection could be achieved by staged revision and in 3 cases by debridement. CONCLUSION: Both debridement with retention and staged reimplantation are highly successful for appropriate indications. Staged revisions are successful even against biofilm-active microorganisms, but a prosthesis-free interval of at least 3 months is recommended.