Perichondritis and auricular cellulitis related to piercings as first manifestation of monkeypox.

INTRODUCTION: Pinna infections are usually due to Staphylococcus aureus infection. It is common for the patient to have had an earring in the area of infection. Monkeypox infection has gone from being an endemic infection to a worldwide health emergency. CASE SUMMARY: In this article we present five cases of monkeypox earring infection of the pinna and what common features we have seen that differentiate them from Staphylococcus aureus infection. DISCUSSION: Symptoms of monkeypox include general malaise, fever with uni- or bilateral lymphadenopathy, and then the appearance within one or two days of skin lesions, we want to alert he otolaryngologist and the medical society to the possibility the diagnostic possibility of monkeypox in patients with an auricular perichondritis.

Oral minocycline as systemic therapy for uncomplicated venous access device-related bloodstream infection with coagulase-negative staphylococci after allogeneic hematopoietic cell transplantation.

BACKGROUND: Venous access device-related bloodstream infection (VAD-BSI) with coagulase-negative staphylococci (CoNS) is a common complication after allogeneic hematopoietic cell transplantation (alloHCT). Standard systemic antimicrobial therapy for uncomplicated VAD-BSI with methicillin-resistant CoNS consists of intravenous (IV) vancomycin (vanco). This requires hospitalization, needs new competent venous access, exposes patients to potential toxicity (mainly renal) and increases the risk of commensal flora dysbiosis with selection of vanco-resistant enterococci. Combined with VAD management (removal or antibiotic locks), oral minocycline (mino) has been evaluated as an alternative systemic therapy for the treatment of uncomplicated VAD-BSIs with CoNS at our center, primarily when the reference treatment with IV vanco was not possible (renal failure or allergy) or when hospitalization was refused by patients. Here, we retrospectively report our single center experience with this mino-based approach. PATIENTS AND METHODS: From January 2012 to December 2020, 24 uncomplicated VAD-BSIs with CoNS in 23 alloHCT patients were treated with oral mino as systemic antibiotic therapy in combination with VAD management. VAD were implantable ports (n = 17), tunneled catheter (n = 1) or PIC-lines (n = 6). Staphylococci were S. epidermidis (n = 21) or S. haemolyticus (n = 3). Mino was administered with a loading dose of 200 mg followed by 100 mg BID for 7-14 days. For 8 VAD-BSIs, patients were initially treated with IV vanco for the first 1-3 days followed by oral mino, while 16 VAD-BSIs were treated with oral mino as the sole antimicrobial agent for systemic therapy. VAD management consisted of catheter removal (for tunneled catheters and PIC-lines, n = 7) or antibiotic locks with vanco (n = 15) or gentamicin (n = 2) administered at least 3 times a week for 14 days (for ports). RESULTS: Overall, clearance of bacteremia (as assessed by negativity for the same CoNS of surveillance peripheral blood cultures drawn between day+ 3 and +30 after initiation of systemic therapy) was achieved in all but 1 patient (with port) who had persistent bacteremia at day +9. No complication such as suppurative thrombophlebitis, endocarditis, distant foci of infection or BSI-related death was observed in any patient during the 3-month period after initiation of treatment. Regarding the 17 port-BSI cases for which VAD conservative strategy was attempted, failure of 3-month VAD preservation was documented in 7/17 cases and 3-month recurrence of VAD-BSI was observed in 3/17 cases (with 1 patient with cellulitis). Treatment with mino was well tolerated except for a mild skin rash in one patient. CONCLUSION: Further prospective studies are needed to evaluate efficacy and safety of this approach.

A pilot study of mitochondrial response to an in vivo prosthetic joint Staphylococcus aureus infection model.

Prosthetic joint infections (PJI) are associated with orthopaedic morbidity and mortality. Mitochondria, the "cell's powerhouses," are thought to play crucial roles in infection response and in increased risk of sepsis mortality. No current research discusses PJI's effect on mitochondrial function and a lack of understanding of immune-infection interactions potentially hinders patient care. The purpose of this pilot study was to evaluate the impact of simulated PJI on local tissue mitochondrial function. Using an established prosthetic implant-associated in vivo model, tissues were harvested from the surgical limb of a methicillin-sensitive Staphylococcus aureus implant-associated infection group (n = 6) and compared to a noninfected group (n = 6) at postoperative day (POD) 21. Using mitochondrial coupling assays, oxygen consumption rate and extracellular acidification rate were assessed in each group. Electron flow through mitochondrial complexes reflected group activity. Electron Paramagnetic Resonance (EPR) spectrometry measured the oxidizing potential of serum samples from infected versus noninfected groups. On POD21, colony-forming units per gram of tissue showed 5 × 109 in the infected group and 101 in the noninfected group (p < 0.0001). Maximal respiration and oxygen consumption due to adenosine triphosphate synthesis were significantly lower in isolated mitochondria from infected limbs (p = 0.04). Both groups had similar complex I, III, IV, and V activity (p > 0.1). Infected group EPR signal intensity reflecting reactive oxygen species levels was 1.31 ± 0.30 compared to 1.16 ± 0.28 (p = 0.73) in the noninfected group. This study highlights PJI's role in mammalian cell mitochondrial dysfunction and oxidative tissue damage, which can help develop interventions to combat PJI.

Successful antibiotic management of Staphylococcus epidermidis endophthalmitis after implantable collamer lens implantation.

PURPOSE: We report a case of successful medical management of endophthalmitis post implantable collamer lens (ICL) culture-positive of Staphylococcus epidermidis. OBSERVATIONS: A 18-year-old female presented with decreased visual acuity in the left eye 20 days after ICL implantation. A diagnosis of postoperative endophthalmitis was made based on examination and ultrasonography. A vitreous tap was taken, and intravitreal antibiotics (vancomycin 1 mg/0.1ml and ceftazidime 2 mg/0.1ml) were administered twice (every 72 h), and peribulbar injection of triamcinolone acetonide after four days of the second intravitreal injection. The vitreous culture was confirmed for Staphylococcus epidermidis. The endophthalmitis was resolved, and visual acuity improved from 6/20 to 12/20 on day 7 and 22/20 on day 38. This is the first successful medical resolution of Staphylococcus epidermidis endophthalmitis post ICL surgery without ICL explantation and vitrectomy in the V4c model. CONCLUSIONS AND IMPORTANCE: In antibiotic therapy, the excellent compliance and close follow-up of this endophthalmitis patient enabled careful postoperative surveillance on the effect of antibiotic therapy, avoiding the removal of the ICL or the loss of the integrity of the eye. The risk of potential infectious endophthalmitis post-ICL surgery should be fully emphasized during preoperative counseling.

Freezing nitrogen ethanol composite reduces periprosthetic infection caused by Staphylococcus aureus contaminated metal implants: An animal study.

BACKGROUND: Implant-associated infection remains a major complication of orthopedic surgery. The treatment of such infection is complicated by bacterial biofilm formation on the metal surfaces of implants. Biofilm surrounds and protects the bacteria against the organism's endogenous defense system and from external agents such as antibiotics and mechanical debridement. This study aims to evaluate whether freezing nitrogen ethanol composite (FNEC), the combination of liquid nitrogen and 95% ethanol in a 3 to 1 ratio, used frequently in bone tumor surgery, is capable of disinfecting Staphylococcus aureus contaminated implants. METHODS: The femurs of six New Zealand white rabbits were implanted with S. aureus-contaminated screws, half of which were treated with FNEC before implantation. The femurs were harvested 14 days after implantation. Histological analysis and TUNEL assay were conducted. The autoclaved screw, contaminated screw, and FNEC-treated contaminated screw were investigated using scanning electron microscopy to evaluate the biofilm structure. RESULTS: The FNEC-treated group had significantly lower relative C-reactive protein levels. An obvious periosteal reaction at the implant site was observed in all rabbits in the non-FNEC group but none was observed in the FNEC-treated group. The FNEC-treated group exhibited fewer empty lacunae, less inflammatory infiltration, and less bone necrosis. Immunohistochemical analysis showed no S. aureus in bone tissue from the FNEC-treated group. Scanning electron microscopy showed disruption of the biofilm on the contaminated screw treated with FNEC. CONCLUSION: FNEC showed potential in disinfecting S.aureus-contaminated implants. Further investigation is warranted, such as the effect on the implant-cement-bone interface, for FNEC to be used clinically in treating implant-associated infection.

Predictors of Reinfection in Prosthetic Joint Infections Following Two-Stage Reimplantation.

BACKGROUND: Two-stage reimplantation is an effective treatment for periprosthetic joint infection (PJI). Many factors are involved in the variable success of this procedure. The purpose of this study is to examine the relationship between patient risk factors, comorbidities, and the pathogen on reinfection rates following two-stage reimplantation. METHODS: We evaluated 158 patients treated for PJI from 2008-2019. Only patients who had completed a two-stage exchange were included. Patient demographics, comorbidities, laboratory values, time-to-reimplantation, pathogen, antibiotic sensitivities, host status, and reinfection rates were assessed. Multivariate analysis was performed to identify correlation between risk factors and reinfection. A P-value < .05 was considered statistically significant. RESULTS: 31 patients experienced a reinfection (19.6%). There was a statistically significant association between infection with Methicillin Sensitive Staphylococcus Aureus (MSSA) and reinfection (P = .046). Patients with a reinfection also had a significantly greater median serum C-reactive protein (CRP) level (12.65 g/dL) at the time of diagnosis compared to patients without a reinfection (5.0 g/dL) (P = .010). Median Erythrocyte Sedimentation Rate (ESR) (56 in no re-infection and 69 in re-infection) and time-to-reimplantation (101 days in no reinfection and 141 days in reinfection) demonstrated a trend toward an association with re-infection but were not statistically significant (P = .055 and P = .054 respectively). CONCLUSION: As the number of arthroplasties continue to rise, PJIs are increasing proportionately and represent a significant revision burden. Elevated C-reactive protein (CRP) levels and Methicillin Sensitive Staphylococcus aureus (MSSA) infection were strongly associated with failure of a two-stage reimplantation. While not statistically significant with our numbers, there were strong trends toward an association between elevated Erythrocyte Sedimentation Rate (ESR), longer time-to-reimplantation, and reinfection.

Very early infective endocarditis after transcatheter aortic valve replacement.

BACKGROUND: Scarce data exist about early infective endocarditis (IE) after trans-catheter aortic valve replacement (TAVR). OBJECTIVE: The objective was to evaluate the characteristics, management, and outcomes of very early (VE) IE (≤ 30 days) after TAVR. METHODS: This multicenter study included a total of 579 patients from the Infectious Endocarditis after TAVR International Registry who had the diagnosis of definite IE following TAVR. RESULTS: Ninety-one patients (15.7%) had VE-IE. Factors associated with VE-IE (vs. delayed IE (D-IE)) were female gender (p = 0.047), the use of self-expanding valves (p < 0.001), stroke (p = 0.019), and sepsis (p < 0.001) after TAVR. Staphylococcus aureus was the main pathogen among VE-IE patients (35.2% vs. 22.7% in the D-IE group, p = 0.012), and 31.2% of Staphylococcus aureus infections in the VE-IE group were methicillin-resistant (vs. 14.3% in the D-IE group, p = 0.001). The second-most common germ was enterococci (34.1% vs. 24.4% in D-IE cases, p = 0.05). VE-IE was associated with very high in-hospital (44%) and 1-year (54%) mortality rates. Acute renal failure following TAVR (p = 0.001) and the presence of a non-enterococci pathogen (p < 0.001) were associated with an increased risk of death. CONCLUSION: A significant proportion of IE episodes following TAVR occurs within a few weeks following the procedure and are associated with dismal outcomes. Some baseline and TAVR procedural factors were associated with VE-IE, and Staphylococcus aureus and enterococci were the main causative pathogens. These results may help to select the more appropriate antibiotic prophylaxis in TAVR procedures and guide the initial antibiotic therapy in those cases with a clinical suspicion of IE. Very early infective endocarditis after trans-catheter aortic valve replacement. VE-IE indicates very early infective endocarditis (≤30 days post TAVR). D-IE indicates delayed infective endocarditis.

Surgical Treatment of Patients With Infective Endocarditis After Transcatheter Aortic Valve Implantation.

BACKGROUND: The optimal treatment of patients developing infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is uncertain. OBJECTIVES: The goal of this study was to investigate the clinical characteristics and outcomes of patients with TAVI-IE treated with cardiac surgery and antibiotics (IE-CS) compared with patients treated with antibiotics alone (IE-AB). METHODS: Crude and inverse probability of treatment weighting analyses were applied for the treatment effect of cardiac surgery vs medical therapy on 1-year all-cause mortality in patients with definite TAVI-IE. The study used data from the Infectious Endocarditis after TAVI International Registry. RESULTS: Among 584 patients, 111 patients (19%) were treated with IE-CS and 473 patients (81%) with IE-AB. Compared with IE-AB, IE-CS was not associated with a lower in-hospital mortality (HRunadj: 0.85; 95% CI: 0.58-1.25) and 1-year all-cause mortality (HRunadj: 0.88; 95% CI: 0.64-1.22) in the crude cohort. After adjusting for selection and immortal time bias, IE-CS compared with IE-AB was also not associated with lower mortality rates for in-hospital mortality (HRadj: 0.92; 95% CI: 0.80-1.05) and 1-year all-cause mortality (HRadj: 0.95; 95% CI: 0.84-1.07). Results remained similar when patients with and without TAVI prosthesis involvement were analyzed separately. Predictors for in-hospital and 1-year all-cause mortality included logistic EuroSCORE I, Staphylococcus aureus, acute renal failure, persistent bacteremia, and septic shock. CONCLUSIONS: In this registry, the majority of patients with TAVI-IE were treated with antibiotics alone. Cardiac surgery was not associated with an improved all-cause in-hospital or 1-year mortality. The high mortality of patients with TAVI-IE was strongly linked to patients' characteristics, pathogen, and IE-related complications.

Preoperative Colonization With Staphylococcus Aureus in THA Is Associated With Increased Length of Stay.

BACKGROUND: Staphylococcus aureus is a common organism implicated in prosthetic joint infection after THA and TKA, prompting preoperative culturing and decolonization to reduce infection rates. It is unknown whether colonization is associated with other noninfectious outcomes of THA or TKA. QUESTIONS/PURPOSES: (1) What is the association between preoperative S. aureus colonization (methicillin-sensitive S. aureus [MSSA] and methicillin-resistant S. aureus [MRSA]) and the noninfectious outcomes (discharge destination, length of stay, Hip/Knee Disability and Osteoarthritis Outcome Score [HOOS/KOOS] pain score, HOOS/KOOS physical function score, 90-day readmission, and 1-year reoperation) of THA and TKA? (2) What factors are associated with colonization with S. aureus ? METHODS: Between July 2015 and March 2019, 8078 patients underwent primary THA in a single healthcare system, and 17% (1382) were excluded because they were not tested preoperatively for S. aureus nasal colonization, leaving 6696 patients in the THA cohort. Between June 2015 and March 2019, 9434 patients underwent primary TKA, and 12% (1123) were excluded because they were not tested for S. aureus colonization preoperatively, leaving 8311 patients in the TKA cohort. The goal of the institution's standardized care pathways is to test all THA and TKA patients preoperatively for S. aureus nasal colonization; the reason the excluded patients were not tested could not be determined. Per institutional protocols, all patients were given chlorhexidine gluconate skin wipes to use on the day before and the day of surgery, and patients with positive S. aureus cultures were instructed to use mupirocin nasal ointment twice daily for 3 to 5 days preoperatively. Adherence to these interventions was not tracked, and patients were not rescreened to test for S. aureus control. The minimum follow-up time for each outcome and the percentage of the cohort lost for each was: for discharge destination, until discharge (0 patients lost); for length of stay, until discharge (0.06% [4 of 6696] lost in the THA group and 0.01% [1 of 8311] lost in the TKA group); for HOOS/KOOS pain score, 1 year (26% [1734 of 6696] lost in the THA group and 24% [2000 of 8311] lost in the TKA group); for HOOS/KOOS physical function, 1 year (33% [2193 of 6696] lost in the THA group and 28% [2334 of 8311] lost in the TKA group); for 90-day readmission, 90 days (0.06% [4 of 6696] lost in the THA group and 0.01% [1 of 8311] lost in the TKA group); and for 1-year reoperation, 1 year (30% [1984 of 6696] lost in the THA group and 30% [2475 of 8311] lost in the TKA group). Logistic regression models were constructed to test for associations between MSSA or MRSA and nonhome discharge, length of stay greater than 1 day, improvement in the HOOS/KOOS pain subscale (≥ the minimum clinically important difference), HOOS/KOOS physical function short form (≥ minimum clinically important difference), 90-day readmission, and 1-year reoperation. We adjusted for patient-related and hospital-related factors, such as patient age and hospital site. Variable significance was assessed using the likelihood ratio test with a significance level of p < 0.05. To assess factors associated with S. aureus colonization, we constructed a logistic regression model with the same risk factors. RESULTS: Among the THA cohort, after controlling for potentially confounding variables such as patient age, smoking status, and BMI, S. aureus colonization was associated with length of stay greater than 1 day (MSSA: odds ratio 1.32 [95% CI 1.08 to 1.60]; MRSA: OR 1.88 [95% CI 1.24 to 2.85]; variable p < 0.001 by likelihood ratio test) but not the other outcomes of THA. Male sex (OR 1.26 [95% CI 1.09 to 1.45]; p = 0.001) and BMI (OR 1.02 for a one-unit increase over median BMI [95% CI 1.01 to 1.03]; p = 0.003) were patient-related factors associated with S. aureus colonization, whereas factors associated with a lower odds were older age (OR 0.99 [95% CI 0.98 to 0.99]; p < 0.001) and Black race compared with White race (OR 0.64 [95% CI 0.50 to 0.82]; p < 0.001). Among the TKA cohort, S. aureus colonization was associated with 90-day readmission (MSSA: OR 1.00 [95% CI 0.99 to 1.01]; MRSA: OR 1.01 [95% CI 1.00 to 1.01]; variable p = 0.007 by likelihood ratio test). Male sex (OR 1.19 [95% CI 1.05 to 1.34]; p = 0.006) was associated with S. aureus colonization, whereas factors associated with a lower odds of colonization were older age (OR 0.99 [95% CI 0.98 to 0.99]; p < 0.001), Veterans RAND-12 mental component score (OR 0.99 [95% CI 0.99 to 1.00]; p = 0.027), Black race compared with White race (OR 0.70 [95% CI 0.57 to 0.85]; p < 0.001), and being a former smoker (OR 0.86 [95% CI 0.75 to 0.97]; p = 0.016) or current smoker (OR 0.70 [95% CI 0.55 to 0.90]; p = 0.005) compared with those who never smoked. CONCLUSION: After controlling for the variables we explored, S. aureus colonization was associated with increased length of stay after THA and 90-day readmission after TKA, despite preoperative decolonization. Given that there is little causal biological link between colonization and these outcomes, the association is likely confounded but may be a proxy for undetermined social or biological factors, which may alert the surgeon to pay increased attention to outcomes in patients who test positive. Further study of the association of S. aureus colonization and increased length of stay after THA and readmission after TKA may be warranted to determine what the confounding variables are, which may be best accomplished using large cohorts or registry data. LEVEL OF EVIDENCE: Level III, therapeutic study.

Comparative outcomes of combined corticosteroid and remdesivir therapy with corticosteroid monotherapy in ventilated COVID-19 patients.

Remdesivir (RDV) reduces time to clinical improvement in hospitalized COVID -19 patients requiring supplemental oxygen. Dexamethasone improves survival in those requiring oxygen support. Data is lacking on the efficacy of combination therapy in patients on mechanical ventilation. We analyzed for comparative outcomes between Corticosteroid (CS) therapy with combined Corticosteroid and Remdesivir (CS-RDV) therapy. We conducted an observational cohort study of patients aged 18 to 90 with COVID-19 requiring ventilatory support using TriNetX (COVID-19 Research Network) between January 20, 2020, and February 9, 2021. We compared patients who received at least 48 hours of CS-RDV combination therapy to CS monotherapy. The primary outcome was 28-day all-cause mortality rates in propensity-matched (PSM) cohorts. Secondary outcomes were Length of Stay (LOS), Secondary Bacterial Infections (SBI), and MRSA (Methicillin-Resistant Staphylococcus aureus), and Pseudomonas infections. We used univariate and multivariate Cox proportional hazards models and stratified log-rank tests. Of 388 patients included, 91 (23.5%) received CS-RDV therapy, and 297 (76.5%) received CS monotherapy. After propensity score matching, with 74 patients in each cohort, all-cause mortality was 36.4% and 29.7% in the CS-RDV and CS therapy, respectively (P = 0.38). We used a Kaplan-Meier with a log-rank test on follow up period (P = 0.23), and a Hazards Ratio model (P = 0.26). SBI incidence was higher in the CS group (13.5% vs. 35.1%, P = 0.02) with a similar LOS (13.4 days vs. 13.4 days, P = 1.00) and similar incidence of MRSA/Pseudomonas infections (13.5% vs. 13.5%, P = 1.00) in both the groups. Therefore, CS-RDV therapy is non-inferior to CS therapy in reducing 28-day all-cause in-hospital mortality but associated with a significant decrease in the incidence of SBI in critically ill COVID-19 patients.

Staphylococcus aureus Bacteremia Among Patients Receiving Maintenance Hemodialysis: Trends in Clinical Characteristics and Outcomes.

RATIONALE & OBJECTIVE: Staphylococcus aureus (Saureus) bacteremia (SAB) is associated with morbidity and mortality in patients receiving maintenance hemodialysis (HD). We evaluated changes in clinical and bacterial characteristics, and their associations with clinical outcomes with SAB in this population over a 21-year period. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 453 hospitalized, non-neutropenic adults receiving maintenance HD who developed monomicrobial SAB between 1995 and 2015. EXPOSURE: Clinical characteristics and bacterial genotype. OUTCOME: All-cause and SAB-attributable mortality, persistent bacteremia, and metastatic complications. ANALYTICAL APPROACH: Proportions of participants experiencing each outcome were calculated overall and by calendar year. Secular trends were estimated using binomial risk regression, a generalized linear model with the log link function for a binomial outcome. Associations with outcomes were estimated using logistic regression. RESULTS: Over the 21-year study period, patients receiving maintenance HD experienced significant increases in age- and diabetes-adjusted SAB-attributable mortality (0.45% [95% CI, 0.36%-0.46%] per year), persistent bacteremia (0.86% [95% CI, 0.14%-1.55%] per year), metastatic complications (0.84% [95% CI, 0.11%-1.56%] per year), and infection with the virulent Saureus clone USA300 (1.47% [95% CI, 0.33%-2.52%] per year). Over time, the suspected source of SAB was less likely to be a central venous catheter (-1.32% [95% CI, -2.05 to-0.56%] per year) or arteriovenous graft (-1.08% [95% CI, -1.54 to-0.56] per year), and more likely to be a nonvascular access source (1.89% [95% CI, 1.29%-2.43%] per year). Patients with a nonvascular access suspected source of infection were more likely to die as a result of their S aureus infection (OR, 3.20 [95% CI, 1.36-7.55]). The increase in USA300 infections may have contributed to the observed increase in persistent bacteremia (OR, 2.96 [95% CI, 1.12-7.83]) but did not explain the observed increases in SAB-attributable mortality (OR, 0.83 [95% CI, 0.19-3.61]) or metastatic complications (OR, 1.34 [95% CI, 0.53-3.41]). LIMITATIONS: Single-center, inpatient cohort. CONCLUSIONS: The clinical and molecular epidemiology of SAB in patients receiving maintenance HD has changed over time, with an increase in SAB-attributable mortality and morbidity despite a decline in catheter-related infections.

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.

Intra-wound vancomycin powder for the eradication of periprosthetic joint infection after debridement and implant exchange: experimental study in a rat model.

BACKGROUND: Intra-wound vancomycin powder (VP) has been used in clinical practice to prevent periprosthetic joint infection (PJI) after primary knee/hip arthroplasty. The role of intra-wound VP in the setting of debridement and implant exchange after PJI remains undefined. This study aimed to explore the efficacy and safety of intra-wound VP in the control of methicillin-resistant S. aureus (MRSA) infection after debridement and implant exchange. METHODS: PJI modeling by knee prosthesis implantation and MRSA inoculation, debridement and implant exchange were performed in Wistar rats successively to mimic the one-stage exchange arthroplasty of PJI patients. Two weeks of systemic vancomycin (SV) or/and intraoperative intra-wound VP of single dosage were applied after revision surgery. RESULTS: No post-surgery deaths, incision complications and signs of drug toxicity were observed. The microbial counts of SV or intra-wound VP group were significantly reduced compared with the control group, while bacteria were still detected on the bone, soft-tissue and prosthesis. The elimination of bacterial counts, along with improvement of tissue inflammation and serum inflammatory markers, were observed in the rats with SV plus intra-wound VP. Serum levels of vancomycin in all groups were lower than that of causing nephrotoxicity, while no statistic difference was observed in the serum biochemical marker among the groups. CONCLUSIONS: Intra-wound VP is effective after debridement and implant exchange in our current rat PJI model. Neither SV nor intra-wound VP alone could eradicate the bacteria within a two-weeks treatment course, while SV plus intra-wound VP could eliminate the MRSA infection, without notable hepatic or renal toxicity and any incision complications.

Two-stage reconstruction of infected Charcot foot using internal fixation : a promising functional limb salvage technique.

AIMS: In our unit, we adopt a two-stage surgical reconstruction approach using internal fixation for the management of infected Charcot foot deformity. We evaluate our experience with this functional limb salvage method. METHODS: We conducted a retrospective analysis of prospectively collected data of all patients with infected Charcot foot deformity who underwent two-stage reconstruction with internal fixation between July 2011 and November 2019, with a minimum of 12 months' follow-up. RESULTS: We identified 23 feet in 22 patients with a mean age of 56.7 years (33 to 70). The mean postoperative follow-up period was 44.7 months (14 to 99). Limb salvage was achieved in all patients. At one-year follow-up, all ulcers have healed and independent full weightbearing mobilization was achieved in all but one patient. Seven patients developed new mechanical skin breakdown; all went on to heal following further interventions. Fusion of the hindfoot was achieved in 15 of 18 feet (83.3%). Midfoot fusion was achieved in nine of 15 patients (60%) and six had stable and painless fibrous nonunion. Hardware failure occurred in five feet, all with broken dorsomedial locking plate. Six patients required further surgery, two underwent revision surgery for infected nonunion, two for removal of metalwork and exostectomy, and two for dynamization of the hindfoot nail. CONCLUSION: Two-stage reconstruction of the infected and deformed Charcot foot using internal fixation and following the principle of 'long-segment, rigid and durable internal fixation, with optimal bone opposition and local antibiotic elusion' is a good form of treatment provided a multidisciplinary care plan is delivered. Cite this article: Bone Joint J 2021;103-B(10):1611-1618.

Characteristics of infective endocarditis in a cancer population.

BACKGROUND: Infective endocarditis (IE) is more common in patients with cancer as compared with the general population. Due to an immunocompromised state, the need for invasive procedures, hypercoagulability and the presence of indwelling catheters, patients with cancer are particularly predisposed to the development of IE. OBJECTIVES: Limited information exists about IE in patients with cancer. We aimed to evaluate the characteristics of patients with cancer and IE at our tertiary care centre, including a comparison of the microorganisms implicated and their association with mortality. METHODS: A retrospective chart review of patients with cancer who had echocardiography for suspicion of endocarditis was conducted. A total of 56 patients with a confirmed diagnosis of cancer and endocarditis, based on the modified Duke criteria, were included in the study. Baseline demographics, risk factors for developing IE, echocardiography findings, microbiology and mortality data were analysed. RESULTS: Following the findings of vegetations by echocardiography, the median survival time was 8.5 months. Staphylococcus aureus was the most common organism identified as causing endocarditis. The mitral and aortic valves were the most commonly involved sites of endocarditis. Patients with S. aureus endocarditis (SAE) had a significantly poorer survival when compared with patients without SAE (p=0.0217) over the 12-month period from diagnosis of endocarditis. CONCLUSIONS: Overall survival of patients with cancer and endocarditis is poor, with a worse outcome in patients with SAE.

Comparison of Naturally Occurring vs. Experimental Infection of Staphylococcus aureus Septicemia in Laying Hens in Two Different Age Groups.

In April and November of 2018, multiple commercial laying hen flocks within the same company presented with a sharp increase in mortality and drop in egg production that persisted for several days. These flocks showed striking necropsy lesions consistent with systemic infection and responded to antimicrobial treatment in the feed. Staphylococcus aureus (SA) was the most frequently isolated organism from multiple tissues including comb and wattle lesions, lungs, liver, ovary, spleen, and bone marrow. Given such an uncommon presentation of SA, which is known as a secondary opportunistic pathogen, a challenge study was conducted to evaluate its role in these disease outbreaks. In the present study, laying hens of two ages (22 and 96 wk) were inoculated with SA via three routes: oral gavage, subcutaneous (SC) injection, and intravenous (IV) injection. Both young and old hens in the IV group showed a significant increase in body temperature and drop in body weight; however, the clinical signs observed in the naturally occurring outbreaks were not present. SA was reisolated at multiple time points postchallenge from all challenge groups except the negative control group. While the SC group showed localized necrosis at the injection site, microscopic changes were different from changes observed in birds from the natural outbreaks. Despite observed initial differences in route and age, the SA challenge strain was not capable of reproducing the disease on its own. The results of this study indicate that SA may have played a role in the increased mortality, clinical signs, and necropsy lesions reported with the naturally occurring outbreaks. However, SA should still be considered as a secondary opportunistic pathogen. Other factors that could have caused the initial insult are stress, immunosuppression, or other primary infectious agents. The results of this study may aid veterinary diagnosticians, clinicians, and all poultry professionals to include SA in their differentials list as a secondary opportunistic pathogen in similar cases. This is an uncommon presentation and further field observations and clinical studies are needed to better elucidate the pathogenesis of this disease, which will in turn help to prevent future outbreaks.

Reporte de caso­Comparación de la septicemia por presentación natura o por infección natural por Staphylococcus aureus en gallinas de postura de dos grupos diferentes de edades. En abril y noviembre del 2018, múltiples parvadas comerciales de gallinas de postura dentro de la misma empresa presentaron un marcado aumento en la mortalidad y una caída en la producción de huevo que persistió durante varios días. Estas parvadas mostraron marcadas lesiones a la necropsia compatibles con una infección sistémica y respondieron al tratamiento antimicrobiano en el alimento. El organismo que se aisló con mayor frecuencia de múltiples tejidos fue Staphylococcus aureus (SA), incluyendo lesiones de cresta y barbillas, pulmones, hígado, ovario, bazo y médula ósea. Dada una presentación tan poco común de S. aureus, que se conoce como un patógeno oportunista secundario, se realizó un estudio de desafío para evaluar su papel en estos brotes de enfermedades. En el presente estudio, se inocularon con Staphylococcus aureus gallinas de postura de dos edades (22 y 96 semanas) a través de tres vías: sonda oral, inyección subcutánea (SC) e inyección intravenosa (IV). Tanto las gallinas jóvenes como las de mayor edad del grupo IV mostraron un aumento significativo de la temperatura corporal y una disminución del peso corporal; sin embargo, los signos clínicos observados en los brotes naturales no estaban presentes. Se aisló S. aureus en varios momentos posteriores al desafío de todos los grupos desafiados, excepto el grupo de control negativo. Si bien el grupo inoculado por inyección subcutánea mostraron necrosis localizada en el sitio de la inyección, los cambios microscópicos fueron diferentes de los cambios observados en las aves de los brotes naturales. A pesar de las diferencias iniciales observadas en la ruta y en la edad, la cepa de desafío de S. aureus no fue capaz de reproducir la enfermedad por sí sola. Los resultados de este estudio indican que S. aureus pudo haber jugado un papel en el aumento de la mortalidad, los signos clínicos y las lesiones a la necropsia reportadas con los brotes de origen natural. Sin embargo, se debe considerar S. aureus como un patógeno oportunista secundario. Otros factores que podrían haber causado el daño inicial son el estrés, la inmunosupresión u otros agentes infecciosos primarios. Los resultados de este estudio pueden ayudar a los patólogos veterinarios, clínicos y todos los profesionales avícolas para incluir S. aureus en su lista de diferenciales como patógeno oportunista secundario en casos similares. Esta es una presentación poco común y se necesitan más observaciones de campo y estudios clínicos para dilucidar mejor la patogénesis de esta enfermedad, lo que a su vez ayudará a prevenir futuros brotes.

A murine Staphylococcus aureus fracture-related infection model characterised by fracture non-union, staphylococcal abscess communities and myeloid-derived suppressor cells.

A fracture-related infection (FRI) is a serious complication that can occur after surgical fixation of bone fractures. Affected patients may encounter delayed healing and functional limitations. Although it is well established that Staphylococcus aureus (S. aureus) is the main causative pathogen of an FRI, the pathophysiology of an S. aureus-induced FRI is not well characterised over time. Therefore, an experimental study in mice comparing S. aureus-inoculated and non-inoculated groups was performed that particularly focused on staphylococcal abscess communities (SACs) and host cellular response. C57Bl/6N female mice received a double osteotomy of the femur, which was stabilised using a titanium 6-hole MouseFix locking plate and four screws. Animals were either S. aureus-inoculated or non-inoculated and euthanised between 1 and 28 d post-surgery. Histopathological evaluation showed normal bone healing for non-inoculated mice, whereas inoculated mice had no fracture consolidation and severe osteolysis. Within the bone marrow of inoculated mice, SACs were observed from 7 d, which increased in size and number over time. A fibrin pseudocapsule enclosed the SACs, which were surrounded by many Ly6G+ neutrophils with some Ly6C+ monocytes and F4/80+ macrophages, the majority of which were viable. The abscesses were encapsulated by fibrin(ogen), collagen and myofibroblasts, with regulatory T cells and M2 macrophages at the periphery. Only bone marrow monocytes and neutrophils of inoculated mice displayed functional suppression of T cells, indicative of myeloid-derived suppressor cells. The present study revealed that an FRI in mice is persistent over time and associated with osteolysis, SAC formation and an immunosuppressive environment.

Pharmacokinetics and pharmacodynamics of antibiotics in cystic fibrosis: a narrative review.

Cystic fibrosis affects several organs, predisposing patients to severe bacterial respiratory infections, including those caused by methicillin-resistant Staphylococcus aureus. Cystic fibrosis is also associated with a wide spectrum of pathological changes that can significantly affect the absorption, distribution, metabolism, and/or elimination of several drugs, including antibacterial agents. Therefore, awareness of the pharmacokinetic derangements in patients with cystic fibrosis is mandatory for the optimisation of antibiotic therapy. This review discusses the basic principles of pharmacokinetics and the pathophysiology of the pharmacokinetics changes associated with cystic fibrosis; it also provides an update of available data for the most widely used antibiotics. Evidence accumulated in the last few years has clearly shown that a significant number of cystic fibrosis patients treated with conventional dosing schemes have sub-therapeutic antibiotic concentrations, increasing their risk of therapeutic failure and/or the emergence of resistant pathogens. Some proposals to optimise antibiotic therapies in this clinical setting based on therapeutic drug monitoring are also discussed.

Coagulase negative Staphylococcus bacteremia in hematopoietic stem cell transplant recipients: Clinical features and molecular characterization.

The purpose of our study was to investigate the epidemiology of coagulase negative staphylococci (CoNS) responsible for bacteremia in hematopoietic stem cell transplant (HSCT) recipients and to determine the prevalence and the genetic background of methicillin resistance. The prevalence of CoNS bacteremia was 7.4% (54/728), higher in allograft (10.7%) than in autograft (4.7%) recipients. A sepsis or a septic shock were observed in 9% of cases. No deaths were attributable to CoNS bacteremia. The methicillin resistance rate was 81%. All MR-CoNS, harbored mecA gene and 90% were typeable with SCCmec typing using PCR amplification. The SCCmec type IV was the most frequent (44%). Clonal dissemination of MR- Staphylococcus epidermidis strains was limited. Our study showed a low prevalence and favorable outcome of CoNS bacteremia in HSCT recipients with limited clonal diffusion. However, they were associated with a significant rate of severe infections and a high rate of methicillin resistance, mediated by SCCmec IV element in most cases.

Platelet Deficiency Represents a Modifiable Risk Factor for Periprosthetic Joint Infection in a Preclinical Mouse Model.

BACKGROUND: Well known for their hemostatic function, platelets are increasingly becoming recognized as important immunomodulators. The purpose of the present study was to assess the impact of platelet depletion on antimicrobial host defense in a mouse model of periprosthetic joint infection (PJI). METHODS: Thrombocytopenia (TCP) was induced in C57BL/6 mice with use of a selective antibody against platelet CD41 (anti-CD41). Whole blood from pre-treated mice was incubated with Staphylococcus aureus to assess antimicrobial efficacy with use of bioluminescent imaging, quantitative histological staining, and colony forming unit (CFU) quantification. In parallel, untreated heterologous platelets were added to TCP blood to assess potential rescue of antimicrobial efficacy. In vivo, TCP and control mice underwent placement of a titanium implant in the femur inoculated with bioluminescent Xen36 S. aureus. Longitudinal bioluminescent imaging was performed postoperatively to quantify the evolution of bacterial burden, which was confirmed via assessment of S. aureus CFUs on the implant and in peri-implant tissue on postoperative day (POD) 28. RESULTS: Anti-CD41 treatment resulted in significant dose-dependent reductions in platelet count. Ex vivo, platelet-depleted whole blood demonstrated significantly less bacterial reduction than control blood. These outcomes were reversed with the addition of untreated rescue platelets. In vivo, infection burden was significantly higher in TCP mice and was inversely correlated with preoperative platelet count (r2 = 0.63, p = 0.037). Likewise, CFU quantification on POD28 was associated with increased bacterial proliferation and severity of periprosthetic infection in TCP mice compared with controls. CONCLUSIONS: Thrombocytopenia resulted in an increased bacterial burden both ex vivo and in vivo in a mouse model of PJI. CLINICAL RELEVANCE: In orthopaedic patients, deficiencies in platelet quantity or function represent an easily modifiable risk factor for PJI.