Lower abdominal cyst complicated with suspected infection following INFIX internal fixation for pelvic fracture: a report of two rare cases.

BACKGROUND: The Internal Fixator (INFIX) is a popular method, known for its minimal invasiveness and short operation time, for treating anterior pelvic ring fractures. Studies have shown that postoperative complications may occur, including anterolateral femoral cutaneous nerve injury, the femoral nerve paralysis, and delayed fracture healing. These complications are believed to be related to surgical stimulation, an excessively long lateral end of the connecting rod, a small distance between the screw and bone surface, insufficient pre-bending of the connecting rod, and difficulties in fracture reduction. CASE PRESENTATION: We report two unique cases of lower abdominal pseudocyst complicated with suspected infection after INFIX treatment of pelvic fractures at our trauma center. Following surgical removal of the internal fixation, resolution of the cysts was observed in both patients, and subsequent postoperative follow-up revealed the absence of any residual sequelae. These cases have not been reported in previous literature reviews. DISCUSSION: The lower abdominal cysts, potentially arising from the dead space created during intraoperative placement of the INFIX rod, may increase infection risk. The etiology remains uncertain, despite the presence of abnormal inflammation markers in both cases, and staphylococcus aureus found in one. These cysts were confined to the lower abdomen, not involving the internal fixation, and hence, only the INFIX was removed. Postoperative oral cefazolin treatment was successful, with resolved pseudocysts and no subsequent discomfort. CONCLUSION: We report two unprecedented cases of post-INFIX abdominal cysts, with a suspected link to intraoperative dead space. Despite uncertain etiology, successful management involved INFIX removal and oral cefixime therapy. These findings necessitate further exploration into the causes and management of such complications.

Survivorship and Outcomes of 2-Stage Revision for Infected Total Hip Arthroplasty at a Mean of 7-Year Follow-Up.

BACKGROUND: Periprosthetic joint infection (PJI) continues to be one of the leading causes of failure following total hip arthroplasty (THA). The objectives of the study were to (1) determine the minimum 2-year infection-free survivorship of 2-stage revision THA, (2) determine the causative organisms for repeat 2-stage revision THA, and (3) characterize the results of failed 2-stage revisions and evaluate patient-reported outcome measures (PROMs). METHODS: A retrospective chart review was completed for patients who underwent 2-stage revision THA for PJI. Prospective data were collected on each patient, including demographics, causative organisms, complications, and type of reoperation. The PROMs, including Harris Hip Score, 12-item Short-Form Health Survey, and Western Ontario and McMaster Universities Osteoarthritis Index scores were obtained prior to 2-stage revision THA surgery and annually as part of standard clinical and radiographic follow-up. RESULTS: A total of 328 patients who underwent a 2-stage revision THA for a PJI were included in the study (mean age 67 years [range, 28 to 90], mean body mass index of 30.6 [range, 15 to 57]). The overall infection-free survivorship for 2-stage revision THA was 73.8% at a minimum of 2 years (range, 2 to 20). Overall, 194 (59.1%) patients who had successful infection eradication underwent a 2-revision THA only. The most common single organisms infected were Staphylococcus aureus (12.5%) and Staphylococcus epidermidis (11%). Higher reoperation rates were found in cases with methicillin-resistant Staphylococcus aureus and polymicrobial infections. All PROMs showed statistical improvement from preoperatively to the latest follow-up appointment. CONCLUSIONS: Two-stage revision THA is associated with a good success rate in the treatment of PJIs at mid-term to long-term follow-up. Polymicrobial and methicillin-resistant Staphylococcus aureus infections are poor prognostic factors, making the eradication of infection more difficult. The management of PJIs continues to be one of the most important orthopaedic challenges to treat.

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.

Increased Incidence of Methicillin-Resistant Staphylococcus aureus in Knee and Hip Prosthetic Joint Infection.

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication of knee and hip arthroplasty. Past literature has shown that gram-positive bacteria are commonly responsible for these infections, although limited research exists studying the changes in the microbial profile of PJIs over time. This study sought to analyze the incidence and trends of pathogens responsible for PJI over three decades. METHODS: This is a multi-institutional retrospective review of patients who had a knee or hip PJI from 1990 to 2020. Patients with a known causative organism were included and those with insufficient culture sensitivity data were excluded. There were 731 eligible joint infections from 715 patients identified. Organisms were divided into multiple categories based on genus/species and 5-year increments were used to analyze the study period. The Cochran-Armitage trend tests were used to evaluate linear trends in microbial profile over time and a P-value <.05 was considered statistically significant. RESULTS: There was a statistically significant positive linear trend in the incidence of methicillin-resistant Staphylococcus aureus over time (P = .0088) as well as a statistically significant negative linear trend in the incidence of coagulase-negative staphylococci over time (P = .0018). There was no statistical significance between organism and affected joint (knee/hip). CONCLUSION: The incidence of methicillin-resistant Staphylococcus aureus PJI is increasing over time, whereas, coagulase-negative staphylococci PJI is decreasing, paralleling the global trend of antibiotic resistance. Identifying these trends may help with the prevention and treatment of PJI through methods such as remodeling perioperative protocols, modifying prophylactic/empiric antimicrobial approaches, or transitioning to alternative therapeutic strategies.

Disrupted tongue microbiota and detection of nonindigenous bacteria on the day of allogeneic hematopoietic stem cell transplantation.

Disruption of the intestinal microbiota caused by intensive chemotherapy, irradiation and antibiotics can result in development of severe gut graft-versus-host disease and infectious complications, leading to poorer outcomes among allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Although the oral cavity is also densely colonized by indigenous microorganisms, the bacterial composition in allo-HSCT recipients remains unclear. We determined the tongue microbiota composition of 45 patients with hematological disorders on the day of transplantation and compared them to 164 community-dwelling adults. The V1-V2 regions of the 16S rRNA gene sequences demonstrated that the allo-HSCT recipients had less diverse and distinct microbiota from that of community-dwelling adults. The full-length 16S rRNA gene sequences identified 146 bacterial taxa in the microbiota of allo-HSCT recipients, of which 34 bacterial taxa did not correspond to bacteria primarily inhabiting the oral cavity deposited in the expanded Human Oral Microbiome Database. Notably, the detection of Staphylococcus haemolyticus and/or Ralstonia pickettii was significantly associated with a higher risk of mortality during the follow-up period. These results demonstrate that the oral cavity of allo-HSCT recipients is colonized by a disrupted microbiota on the day of transplantation and suggest that detection of specific nonindigenous taxa could be a predictor of transplant outcome.

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.

Tacrolimus Impairs Kupffer Cell Capacity to Control Bacteremia: Why Transplant Recipients Are Susceptible to Infection.

BACKGROUND AND AIMS: Kupffer cells (KCs) are the resident intravascular phagocyte population of the liver and critical to the capture and killing of bacteria. Calcineurin/nuclear factor of activated T cells (NFAT) inhibitors (CNIs) such as tacrolimus are used to prevent rejection in solid organ transplant recipients. Although their effect on lymphocytes has been studied extensively, there are limited experimental data about if and how CNIs shape innate immunity, and whether this contributes to the higher rates of infection observed in patients taking CNIs. APPROACH AND RESULTS: Here, we investigated the impact of tacrolimus treatment on innate immunity and, more specifically, on the capability of Kupffer cells (KCs) to fight infections. Retrospective analysis of data of >2,700 liver transplant recipients showed that taking calcineurin inhibitors such as tacrolimus significantly increased the likelihood of Staphylococcus aureus infection. Using a mouse model of acute methicillin-resistant S. aureus (MRSA) bacteremia, most bacteria were sequestered in the liver and we found that bacteria were more likely to disseminate and kill the host in tacrolimus-treated mice. Using imaging, we unveiled the mechanism underlying this observation: the reduced capability of KCs to capture, phagocytose, and destroy bacteria in tacrolimus-treated animals. Furthermore, in a gene expression analysis of infected KCs, the triggering receptor expressed on myeloid cells 1 (TREM1) pathway was the one with the most significant down-regulation after tacrolimus treatment. TREM1 inhibition likewise inhibited KC bacteria capture. TREM1 levels on neutrophils as well as the overall neutrophil response after infection were unaffected by tacrolimus treatment. CONCLUSIONS: Our results indicate that tacrolimus treatment has a significant impact directly on KCs and on TREM1, thereby compromising their capacity to fend off infections.

Sustained Coinfections with Staphylococcus aureus and Pseudomonas aeruginosa in Cystic Fibrosis.

Rationale: Staphylococcus aureus and Pseudomonas aeruginosa often infect the airways in cystic fibrosis (CF). Because registry studies show higher prevalence of P. aeruginosa versus S. aureus in older patients with CF, a common assumption is that P. aeruginosa replaces S. aureus over time. In vitro, P. aeruginosa can outgrow and kill S. aureus. However, it is unknown how rapidly P. aeruginosa replaces S. aureus in patients with CF.Methods: We studied a longitudinal cohort of children and adults with CF who had quantitative sputum cultures. We determined the abundance of P. aeruginosa and S. aureus in cfu/ml. We determined the duration and persistence of infections and measured longitudinal changes in culture positivity and abundance for each organism.Measurements and Main Results: Between 2004 and 2017, 134 patients had ≥10 quantitative cultures, with median observation time of 10.15 years. One hundred twenty-four patients had at least one positive culture for P. aeruginosa, and 123 had at least one positive culture for S. aureus. Both species had median abundance of >106 cfu/ml. Culture abundance was stable over time for both organisms. There was an increase in the prevalence of S. aureus/P. aeruginosa coinfection but no decrease in S. aureus prevalence within individuals over time.Conclusions: S. aureus and P. aeruginosa are abundant in CF sputum cultures. Contrary to common assumption, we found no pattern of replacement of S. aureus by P. aeruginosa. Many patients with CF have durable long-term coinfection with these organisms. New strategies are needed to prevent and treat these 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.

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.

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.

Anti-PD-L1 Therapy Does Not Improve Survival in a Murine Model of Lethal Staphylococcus aureus Pneumonia.

BACKGROUND: Staphylococcus aureus (SA) bacterial pneumonia is a common cause of sepsis in intensive care units. Immune checkpoint inhibitors (CPIs) that target programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have been proposed for the treatment of sepsis. However, in our systematic review of sepsis preclinical models, none of the models examined CPIs in pneumonia. METHODS: Mice were inoculated intratracheally with vehicle control, low dose (LD)- or high dose (HD)-SA. Immune cell recruitment and checkpoint molecule expression were examined at 4, 24, and 48 hours after infection. Infected animals, treated with control or anti-PD-L1 antibodies, were assessed for survival, bacterial burden, lung immunophenotypes, and mediator production. RESULTS: LD-SA and HD-SA produced lethality of 15% and 70%, respectively, by 168 hours. At 24 hours, LD-infected animals exhibited increased lung monocyte PD-L1 expression (P = .0002) but lower bacterial counts (P = .0002) compared with HD animals. By 48 hours, either infection induced lung neutrophil and macrophage PD-L1 expression (P < .0001). Anti-PD-L1 treatment at the time of infection and at 24 hours following infection with low to high doses of SA reduced PD-L1 detection but did not affect survival or bacterial clearance. CONCLUSIONS: Anti-PD-L1 therapy did not alter survival in this pneumonia model. Preclinical studies of additional common pathogens and septic foci are needed.

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.

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.

Fatal sepsis associated with a storage container leak permitting platelet contamination with environmental bacteria after pathogen reduction.

BACKGROUND: Pathogen reduction technology and enhanced bacterial culture screening promise to significantly reduce the risk of transfusion-associated septic reactions due to contaminated platelets. Recent reports suggest that these interventions lack efficacy for post-collection and processing contamination with environmental organisms if the storage bag integrity is compromised. CASE REPORT: We report a fatal septic transfusion reaction in a 63-year-old patient with chronic kidney and liver disease who received a pathogen reduced platelet transfusion in anticipation of surgery. METHODS: The residual platelet concentrate was cultured, with the detected microorganisms undergoing 16S genotype sequencing. Separate pathogen reduction studies were performed on the recovered bacteria, including assessment for amotosalen photoproducts. The storage container was subjected to pressure testing and microscopic examination. Environmental culture screening was performed at the hospital. RESULTS: Gram negative rods were detected in the platelet unit and cultures of both platelet component and the patient's blood grew Acinetobacter baumannii complex, Leclercia adecarboxylata and Staphylococcus saprophyticus. These strains were effectively inactivated with >7.2, 7.7, and >7.1 log10 kill, respectively. The platelet storage container revealed a leak visible only on pressure testing. Hospital environmental cultures were negative and the contamination source is unknown. A. baumannii complex and S. saprophyticus 16S genotyping sequences were identical to those implicated in a previously reported septic reaction. CONCLUSION: Findings are compatible with post-processing environmental contamination of a pathogen reduced platelet concentrate via a non-visible, acquired storage container leak. Efforts are warranted to actively prevent damage to, and detect defects in, platelet storage containers, and to store and transport components in clean environments.

Indwelling catheterization, renal stones, and hydronephrosis are risk factors for symptomatic Staphylococcus aureus-related urinary tract infection.

PURPOSE: Staphylococcus aureus is a relatively uncommon causative agent of urinary tract infection (UTI). However, the clinical features of S. aureus-related UTI are unclear. Thus, we aimed to clarify how patients with S. aureus bacteriuria develop UTI and determine the features and clinical risk factors of symptomatic S. aureus-related UTI. METHODS: We performed a retrospective study of patients at the Hiroshima University Hospital for whom S. aureus had been isolated from urine culture from January 2010 to December 2017. The characteristics (age, sex, body mass index, indwelling catheterization, renal stones, hydronephrosis, anticancer drug use, diabetes mellitus, steroid use, serum albumin, antibiotic use in the past 1 month, estimated glomerular filtration rate, benign prostate hyperplasia, and neurogenic bladder) of patients with UTI and those without UTI were compared, and the risk factors for S. aureus-related UTI were identified by multiple logistic regression model. RESULTS: A total of 286 patients with S. aureus bacteriuria were analyzed; 33 patients developed UTI. The causative pathogens were methicillin-sensitive S. aureus and methicillin-resistant S. aureus (MRSA) in 14 and 19 patients, respectively, who developed UTI. This study demonstrated that indwelling catheterization, hydronephrosis, and renal stones are significantly associated with S. aureus-related UTI (p = 0.01, odds ratio = 3.1; and p < 0.01, odds ratio = 7.0; and p = 0.02, odds ratio = 1.2; respectively) and hypoalbuminemia in MRSA-related UTI (p < 0.01). CONCLUSION: Paying attention to risk factors, specifically indwelling catheterization, renal stones, and hydronephrosis, will be an effective strategy for prevention of S. aureus-related UTI with persistent staphylococcal bacteriuria.

Prognostic value of pro-adrenomedullin and copeptin in acute infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is a life-threatening disease whose prognosis is often difficult to predict based on clinical data. Biomarkers have been shown to favorably affect disease management in a number of cardiac disorders. Aims of this retrospective study were to assess the prognostic role of procalcitonin (PCT), pro-adrenomedullin (pro-ADM) and copeptin in IE and their relation with disease characteristics and the traditional biomarker C-reactive protein (CRP). METHODS: We studied 196 patients with definite IE. Clinical, laboratory and echocardiography parameters were analyzed, with a focus on co-morbidities. PCT, pro-ADM and copeptin were measured on stored plasma samples obtained on admission during the acute phase of the disease. RESULTS: Pro-ADM and copeptin were significantly higher in older patients and associated with prior chronic kidney disease. Pro-ADM was an independent predictor of hospital mortality (OR 3.29 [95%C.I. 1.04-11.5]; p = 0.042) whilst copeptin independently predicted 1-year mortality (OR 2.55 [95%C.I. 1.18-5.54]; p = 0.017). A high PCT value was strictly tied with S. aureus etiology (p = 0.001). CRP was the only biomarker associated with embolic events (p = 0.003). CONCLUSIONS: Different biomarkers correlate with distinct IE outcomes. Pro-ADM and copeptin may signal a worse prognosis of IE on admission to the hospital and could be used to identify patients who need more aggressive treatment. CRP remains a low-cost marker of embolic risk. A high PCT value should suggest S. aureus etiology.

Cavitary pulmonary disease in a patient on dialysis.

A 24-year-old man on maintenance hemodialysis presented with bilateral cavitary consolidations and methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia following ulceration of the skin over his arteriovenous (AV) fistula cannulation site. A diagnosis of septic pulmonary embolism was made, which presumptively originated from a localized MSSA infection of his AV access. He had an excellent response to a 28-day course of cloxacillin, with the resolution of the pulmonary lesions.

Staphylococcus aureus ventilator-associated pneumonia in patients with COVID-19: clinical features and potential inference with lung dysbiosis.

BACKGROUND: Hospitalized patients with COVID-19 admitted to the intensive care unit (ICU) and requiring mechanical ventilation are at risk of ventilator-associated bacterial infections secondary to SARS-CoV-2 infection. Our study aimed to investigate clinical features of Staphylococcus aureus ventilator-associated pneumonia (SA-VAP) and, if bronchoalveolar lavage samples were available, lung bacterial community features in ICU patients with or without COVID-19. METHODS: We prospectively included hospitalized patients with COVID-19 across two medical ICUs of the Fondazione Policlinico Universitario A. Gemelli IRCCS (Rome, Italy), who developed SA-VAP between 20 March 2020 and 30 October 2020 (thereafter referred to as cases). After 1:2 matching based on the simplified acute physiology score II (SAPS II) and the sequential organ failure assessment (SOFA) score, cases were compared with SA-VAP patients without COVID-19 (controls). Clinical, microbiological, and lung microbiota data were analyzed. RESULTS: We studied two groups of patients (40 COVID-19 and 80 non-COVID-19). COVID-19 patients had a higher rate of late-onset (87.5% versus 63.8%; p = 0.01), methicillin-resistant (65.0% vs 27.5%; p < 0.01) or bacteremic (47.5% vs 6.3%; p < 0.01) infections compared with non-COVID-19 patients. No statistically significant differences between the patient groups were observed in ICU mortality (p = 0.12), clinical cure (p = 0.20) and microbiological eradication (p = 0.31). On multivariable logistic regression analysis, SAPS II and initial inappropriate antimicrobial therapy were independently associated with ICU mortality. Then, lung microbiota characterization in 10 COVID-19 and 16 non-COVID-19 patients revealed that the overall microbial community composition was significantly different between the patient groups (unweighted UniFrac distance, R2 0.15349; p < 0.01). Species diversity was lower in COVID-19 than in non COVID-19 patients (94.4 ± 44.9 vs 152.5 ± 41.8; p < 0.01). Interestingly, we found that S. aureus (log2 fold change, 29.5), Streptococcus anginosus subspecies anginosus (log2 fold change, 24.9), and Olsenella (log2 fold change, 25.7) were significantly enriched in the COVID-19 group compared to the non-COVID-19 group of SA-VAP patients. CONCLUSIONS: In our study population, COVID-19 seemed to significantly affect microbiological and clinical features of SA-VAP as well as to be associated with a peculiar lung microbiota composition.

Clinical Characteristics and Risk Factors for Mortality due to Bloodstream Infection of Unknown Origin in Hemodialysis Patients: A Single-Center, Retrospective Study.

INTRODUCTION: Hemodialysis patients are at a high risk of bloodstream infection (BSI). The risk factors for BSI-associated mortality, especially of unknown origin, remain uncertain. BSI of unknown origin is highly prevalent and related to high mortality. The present study aimed to investigate the clinical and microbiological characteristics of BSI and risk factors for BSI-associated mortality, including BSI of unknown origin, in hemodialysis patients. METHODS: This study was a single-center, retrospective study conducted from August 2012 to July 2019 in hemodialysis patients with BSI at Kawashima Hospital. Data related to demographics, clinical parameters, BSI sources, causative microorganisms, and initial treatments were collected from the medical records. The predictors for mortality associated with BSI were evaluated by logistic regression. RESULTS: Among 174 patients, 55 (30.9%) had the infection from unknown origin. The most frequent bacterium was Staphylococcus aureus. Low serum albumin level was an independent predictor of mortality due to BSI (odds ratio [OR]: 0.28, 95% confidence interval [CI]: 0.13-0.59). A lower serum albumin level (≤2.5 g/dL) was associated with poorer mortality. Methicillin-resistant Staphylococcus aureus (MRSA) was independently associated with mortality due to BSI of unknown origin (OR: 6.20, 95% CI: 1.04-37.1); 87.5% cases with BSI of unknown origin due to MRSA were not initially administrated anti-MRSA antibiotics, and in such patients, the mortality rate was 85.7%. CONCLUSIONS: Serum albumin level of 2.5 g/dL is a cutoff value, which could predict the mortality due to BSI in hemodialysis patients. Considering the high mortality rate of MRSA-associated BSI of unknown origin, wherein no focus of infection was identified in the present study, initial empiric treatment should be considered for MRSA-associated BSI of unknown origin.