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Background The use of adjunctive antibiotics directed against exotoxin production in Staphylococcus aureus bacteremia (SAB) is widespread, and it is recommended in many guidelines, but this is based on limited evidence. Existing guidelines are based on the theoretical premise of toxin suppression, as many strains of S. aureus produce toxins such as leukocidins (eg, Panton-Valentine leukocidin, toxic shock syndrome toxin 1, exfoliative toxins, and various enterotoxins). Many clinicians therefore believe that limiting exotoxin production release by S. aureus could reduce its virulence and improve clinical outcomes. Clindamycin, a protein synthesis inhibitor antibiotic, is commonly used for this purpose. We report the domain-specific protocol, embedded in a large adaptive, platform trial, seeking to definitively answer this question. Methods and Analysis The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a pragmatic, randomized, multicenter adaptive platform trial that aims to compare different SAB therapies, simultaneously, for 90-day mortality rates. The adjunctive treatment domain aims to test the effectiveness of adjunctive antibiotics, initially comparing clindamycin to no adjunctive antibiotic, but future adaptations may include other agents. Individuals will be randomized to receive either 5 days of adjunctive clindamycin (or lincomycin) or no adjunctive antibiotic therapy alongside standard-of-care antibiotics. Most participants with SAB (within 72 hours of index blood culture and with no contraindications) will be eligible to participate in this domain. Prespecified analyses are defined in the statistical appendix to the core protocol, and domain-specific secondary analyses will be adjusted for resistance to clindamycin, disease phenotype (complicated or uncomplicated SAB) and Panton-Valentine leukocidin–positive isolate. [ABSTRACT FROM AUTHOR]

Objective: Staphylococcus aureus is one of the leading causes of bacteremia in children. In this study, we aimed to evaluate our center’s experience on the etiology, management, and outcomes of pediatric Staphylococcus aureus bacteremia (SAB) with particular focus on transitioning to oral antibiotic therapy. Materials and Methods: This retrospective cohort study included children aged ≤ 19 years diagnosed with SAB over a 5-year period. The main outcome was poor clinical outcome related to SAB defined as (1) recurrence of SAB within 30 days after discontinuation of SAB treatment and (2) any-cause mortality within 30 days after detection of SAB. Results: Over a 5-year period, 88 SAB episodes of 76 unique patients were included. The most common source of SAB attributed to central line (n = 34), followed by osteoarticular (n = 24), infections. All patients received at least one day of intravenous (IV) antibiotics and treatment was switched to an oral agent in 45.5% of SAB episodes. Sources of SAB in the oral switch group were osteoarticular (n = 21), skin and soft tissue (n = 7), central line (n = 3), thrombophlebitis (n = 2), head and neck infection (n = 1), and unknown (n = 6). 30-day mortality and SAB recurrence within 30 days after initial treatment completion occurred in 3 and 5 SAB episodes, respectively. None of the patients in oral switch group had poor clinical outcomes. Conclusion: Our study results indicate that 30-day any-cause mortality and SAB-related mortality is low in children. Similar to growing adult literature, oral switch in SAB treatment was not associated with poor SAB outcomes in selected patients. [ABSTRACT FROM AUTHOR]

Background Staphylococcus aureus bacteremia (SAB) is a high-risk condition associated with high morbidity and mortality. In the presence of cardiac implantable electronic devices (CIEDs), SAB may cause or clinically indicate device infection. We aimed to estimate the 10-year absolute risk of SAB in adult Danish first-time CIED carriers. Secondary aims included identification of risk factors associated with SAB. Methods A registry-based study utilizing Danish nationwide registers and including consecutive Danish patients undergoing first CIED implantation between 2000 and 2020 was conducted. The primary outcome was first-time SAB after CIED implantation. Results A total of 87 257 patients with first CIED implantation in the study period were identified (median age, 75 years; 62.6% were male; median follow-up, 3.8 years). Patients with pacemakers (PMs) were older and with more noncardiovascular comorbidities compared to patients with implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy devices with or without defibrillator capacity (CRTs). In total, 1366 patients (1.6%) developed SAB. The 10-year absolute risk (95% confidence interval) of SAB was 2.0% (1.9%–2.1%) for PM, 2.6% (2.2%–3.1%) for ICD, and 3.7% (3.0%–4.5%) for CRT. A multivariable Cox analysis identified hemodialysis (hazard ratio [HR], 8.51), SAB before CIED (HR, 2.76), liver disease (HR, 2.35), and carrying a CRT device (HR, 1.68) among the covariates associated with increased risk of SAB. Conclusions The absolute risk of SAB in Danish CIED carriers increased with more advanced CIED systems. The risk was highest within the first 3 months after CIED implantation and increased with the presence of certain covariates including renal dialysis, SAB before CIED, male sex, and advancing age. [ABSTRACT FROM AUTHOR]

Background: We aimed to improve the prognosis, treatment, and management of Staphylococcus aureus bacteremia (SAB) by evaluating the association between adherence to quality indicators (QIs) and clinical outcomes in patients with their clinical outcomes. Methods: We retrospectively collected clinical and microbiological data on hospitalized patients with SAB from 14 hospitals (three with > 600, two with 401–600, five with 201–400, and four with ≤ 200 beds) in Japan from January to December 2022. The SAB management quality was evaluated using the SAB-QI score (ranging from 0 to 13 points), which consists of 13 QIs (grouped into five categories) based on previous literature. Results: Of the 4,448 positive blood culture episodes, 289 patients with SAB (6.5%) were enrolled. The SAB-QI scores ranged from 3 to 13, with a median score of 9 points. The SAB-QI score was highest in middle-sized hospitals with 401–600 beds. Adherence to each of the four QI categories (blood culture, echocardiography, source control, and antibiotic treatment) was significantly higher in survived cases than in fatal cases. Kaplan–Meier curves with log-rank tests demonstrated that higher adherence to SAB-QIs indicated a better prognosis. Logistic regression analysis revealed that age, methicillin resistance, multiple comorbidities (≥ 2), and low SAB-QI score were significantly associated with 30-day mortality in patients with SAB. Conclusions: Our study highlights that greater adherence to the SAB-QIs correlates with improved patient outcomes. Management of patients with SAB should follow these recommended indicators to maintain the quality of care, especially for patients with poor prognosticators. [ABSTRACT FROM AUTHOR]

Purpose: S. aureus bacteremia (SAB) is a common and severe infection with high mortality and morbidity. The clinical relevance of the finding of concurrent S. aureus bacteriuria (SABU) is debated. The goal of this study was to analyze whether a concurrent SABU is associated with complicated SAB, infective endocarditis (IE) and mortality. Methods: We conducted a retrospective cohort study, reviewing medical charts of all episodes of SAB in patients > 18 years in the region of Skåne, Sweden, between 1st of January and 31st of June 2020. Episodes where a concurrent urine culture was performed were included for analysis. An episode was considered as complicated SAB if there was either attributable mortality, recurrent infection, embolic stroke, or occurrence of a complicated focus of infection. Results: During the study period, there were 279 episodes of SAB. 154 episodes met the eligibility criteria, of whom 37 (24%) had concurrent SABU. In 78 episodes (51%), the patients had a complicated SAB. There was a significantly lower proportion of complicated SAB for episodes with concurrent SABU (32%), compared to episodes without concurrent SABU (56%), p-value 0.014. Moreover, in the cohort there were 11 episodes (7.1%) of IE and a 30 days mortality rate of 16%, with no difference between the groups with or without SABU. Conclusions: There is an association between concurrent SABU and a decreased risk for complicated SAB among patients with SAB. This study found no significant association between SABU and neither IE nor mortality for patients with SAB. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus bacteremia causes significant morbidity and mortality. Treatment of staphylococcal infections is hindered by widespread antibiotic resistance, and attempts to develop an S. aureus vaccine have failed. Improved S. aureus treatment and infection prevention options require a deeper understanding of the correlates of protective immunity. CD4+ T cells have been identified as key orchestrators in the defense against S. aureus, but uncertainties persist regarding the subset, polarity, and breadth of the memory CD4+ T-cell pool required for protection. Here, using a mouse model of systemic S. aureus infection, we discovered that the breadth of bacterium-specific memory CD4+ T-cell pool is a critical factor for protective immunity against invasive S. aureus infections. Seeding mice with a monoclonal bacterium-specific circulating memory CD4+ T-cell population failed to protect against systemic S. aureus infection; however, the introduction of a polyclonal and polyfunctional memory CD4+ T-cell pool significantly reduced the bacterial burden. Our findings support the development of a multi-epitope T-cell-based S. aureus vaccine, as a strategy to mitigate the severity of S. aureus bacteremia. [ABSTRACT FROM AUTHOR]

ABSTRACT Rapid and accurate identification of Staphylococcus aureus (SA) in blood culture specimens is crucial for timely clinical intervention. Traditional Gram staining methods, although widely accessible and cost-effective, exhibit variable sensitivities and specificities in the BACTEC system. We aimed to develop and validate the “STAPH score,” a novel semi-quantitative scoring system that integrates Gram stain morphology and time to positivity to differentiate SA from coagulase-negative staphylococci (CoNS) in blood cultures. We analyzed 148 blood culture specimens from septic patients. Each specimen was assessed independently by two examiners using Gram staining and the STAPH score, which assigns points based on five parameters: cluster size, time to positivity, aerobic enlargement, pint (three-dimensional appearance), and the presence of hemorrhage. Sensitivity and specificity were calculated for various cutoff points. Cohen’s kappa coefficient was used to assess inter-examiner agreement. Of the 148 specimens, 49 (33.1%) were identified as SA and 99 (66.9%) as CoNS. At a STAPH score cutoff of 3 points, the sensitivity was 93.9% (95% confidence interval [CI], 83.1%–98.7%) and specificity was 91.9% (95% CI, 84.7%–96.4%). The kappa coefficient at this cutoff was 0.67 (95% CI, 0.55–0.79). A STAPH score

Introduction Recommended duration of antibiotic treatment of Staphylococcus aureus bacteremia (SAB) is frequently based on distinguishing uncomplicated and complicated SAB, and several risk factors at the onset of infection have been proposed to define complicated SAB. Predictive values of risk factors for complicated SAB have not been validated, and consequences of their use on antibiotic prescriptions are unknown. Methods In a prospective cohort, patients with SAB were categorized as complicated or uncomplicated through adjudication (reference definition). Associations and predictive values of 9 risk factors were determined, compared with the reference definition, as was accuracy of Infectious Diseases Society of America (IDSA) criteria that include 4 risk factors, and the projected consequences of applying IDSA criteria on antibiotic use. Results Among 490 patients, 296 (60%) had complicated SAB. In multivariable analysis, persistent bacteremia (odds ratio [OR], 6.8; 95% confidence interval [CI], 3.9–12.0), community acquisition of SAB (OR, 2.9; 95% CI, 1.9–4.7) and presence of prosthetic material (OR, 2.3; 95% CI, 1.5–3.6) were associated with complicated SAB. Presence of any of the 4 risk factors in the IDSA definition of complicated SAB had a positive predictive value of 70.9% (95% CI, 65.5–75.9) and a negative predictive value of 57.5% (95% CI, 49.1–64.8). Compared with the reference, IDSA criteria yielded 24 (5%) false-negative and 90 (18%) false-positive classifications of complicated SAB. Median duration of antibiotic treatment of these 90 patients was 16 days (interquartile range, 14–19), all with favorable clinical outcome. Conclusions Risk factors have low to moderate predictive value to identify complicated SAB and their use may lead to unnecessary prolonged antibiotic use. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus bacteremia (SAB) is one of the most common serious bacterial infections worldwide. In this study, we demonstrated changes in SAB epidemiology in an Argentinean University Hospital during an 8-year period (2009–2016). A total of 326 S. aureus clinical isolates were recovered in three periods: P1: 2009–2010, P2: 2012–2014, and P3: 2015–2016. Among these, 127 were methicillin-resistant S. aureus (MRSA) and were characterized by phenotypic and molecular methods. We hereby report a significant decline in multiple drug resistance among MRSA isolates associated with an increase in SCCmec IV between the three periods. A diversity of MRSA-IV clones (mainly ST30-MRSA-IV, ST5-MRSA-IV, and ST8-MRSA-IV) replaced between 2009 and 2016 the previous prevalent MRSA clone causing bloodstream infections at this hospital (ST5-MRSA-I). MRSA population structure continued to diversify between P2 and P3. Notably, ST8-MRSA-IV-t008 related to USA300 was first detected during P2, and ST8-MRSA-IV together with ST30-MRSA-IV related to the Southwest Pacific clone were the more prevalent MRSA genotypes circulating during P3. [ABSTRACT FROM AUTHOR]

Abstract Background Empyema necessitans (EN) is a rare condition characterized by pleural infection with pus spreading into adjacent soft tissues. Although Mycobacterium tuberculosis and Actinomyces israelii are common causative agents, methicillin-resistant Staphylococcus aureus (MRSA) is relatively rare, but it is associated with high mortality in empyema cases. We aimed to report a unique case of EN caused by MRSA and present a literature review to better understand this rare condition. Case presentation A 69-year-old man with a history of right ureteral stone presented with fever and left anterior thoracic pain. A physical examination revealed redness and swelling in the left thoracic region. Imaging studies confirmed EN with fluid accumulation around the sternocostal joint of the left first rib. MRSA was identified from blood and pleural fluid cultures. The patient received antimicrobial therapy, and a chest tube was inserted for drainage. Despite initial improvement, vertebral osteomyelitis was diagnosed on day 17. The antimicrobials were subsequently terminated after 6 weeks, but vertebral osteomyelitis recurred, and treatment was resumed and completed on day 215. Conclusion EN caused by MRSA is rare, and the literature review revealed 14 cases from human sources. Positive blood cultures were observed in 40% of cases, and metastatic infections were present in 30% of cases. Osteomyelitis was the most common type of metastatic lesion. All the patients underwent drainage. Patients with MRSA-associated EN frequently develop disseminated lesions and should therefore be carefully examined. Moreover, appropriate treatment with antibiotics and drainage is necessary for a good prognosis. Although the prognosis appeared to be favorable in our review, publication bias and treatment challenges for metastatic infections should be considered.

Staphylococcus aureus bacteremia (SAB) is a common and serious condition, particularly among patients on long-term hemodialysis. A study conducted in Northern Australia found that the incidence of SAB was significantly lower during the wet season when patients received trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis after hemodialysis. However, there were limitations to the study, including its retrospective design and small sample size. While TMP-SMX has a broad spectrum of activity against various infections, it also has numerous adverse effects and concerns about increasing antimicrobial resistance. Further research is needed to determine the risks and benefits of using TMP-SMX as prophylaxis for SAB in high-risk populations. [Extracted from the article]

Background: Empyema necessitans (EN) is a rare condition characterized by pleural infection with pus spreading into adjacent soft tissues. Although Mycobacterium tuberculosis and Actinomyces israelii are common causative agents, methicillin-resistant Staphylococcus aureus (MRSA) is relatively rare, but it is associated with high mortality in empyema cases. We aimed to report a unique case of EN caused by MRSA and present a literature review to better understand this rare condition. Case presentation: A 69-year-old man with a history of right ureteral stone presented with fever and left anterior thoracic pain. A physical examination revealed redness and swelling in the left thoracic region. Imaging studies confirmed EN with fluid accumulation around the sternocostal joint of the left first rib. MRSA was identified from blood and pleural fluid cultures. The patient received antimicrobial therapy, and a chest tube was inserted for drainage. Despite initial improvement, vertebral osteomyelitis was diagnosed on day 17. The antimicrobials were subsequently terminated after 6 weeks, but vertebral osteomyelitis recurred, and treatment was resumed and completed on day 215. Conclusion: EN caused by MRSA is rare, and the literature review revealed 14 cases from human sources. Positive blood cultures were observed in 40% of cases, and metastatic infections were present in 30% of cases. Osteomyelitis was the most common type of metastatic lesion. All the patients underwent drainage. Patients with MRSA-associated EN frequently develop disseminated lesions and should therefore be carefully examined. Moreover, appropriate treatment with antibiotics and drainage is necessary for a good prognosis. Although the prognosis appeared to be favorable in our review, publication bias and treatment challenges for metastatic infections should be considered. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus bacteremia (SAB) carries a high risk for excess morbidity and mortality. Despite its prevalence, significant practice variation continues to permeate clinical management of this syndrome. Since the publication of the 2011 Infectious Diseases Society of America (IDSA) guidelines on management of methicillin-resistant Staphylococcus aureus infections, the field of SAB has evolved with the emergence of newer diagnostic strategies and therapeutic options. In this review, we seek to provide a comprehensive overview of the evaluation and management of SAB, with special focus on areas where the highest level of evidence is lacking to inform best practices. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus bacteremia causes significant morbidity and mortality. Treatment of staphylococcal infections is hindered by widespread antibiotic resistance, and attempts to develop an S. aureus vaccine have failed. Improved S. aureus treatment and infection prevention options require a deeper understanding of the correlates of protective immunity. CD4+ T cells have been identified as key orchestrators in the defense against S. aureus, but uncertainties persist regarding the subset, polarity, and breadth of the memory CD4+ T-cell pool required for protection. Here, using a mouse model of systemic S. aureus infection, we discovered that the breadth of bacterium-specific memory CD4+ T-cell pool is a critical factor for protective immunity against invasive S. aureus infections. Seeding mice with a monoclonal bacterium-specific circulating memory CD4+ T-cell population failed to protect against systemic S. aureus infection; however, the introduction of a polyclonal and polyfunctional memory CD4+ T-cell pool significantly reduced the bacterial burden. Our findings support the development of a multi-epitope T-cell-based S. aureus vaccine, as a strategy to mitigate the severity of S. aureus bacteremia.

Objectives: This paper aims to determine the Staphylococcus aureus bacteremia (SAB) in-hospital mortality rate and its associated risk factors during the COVID-19 pandemic. Methods: A total of 167 SAB samples were collected between March 2020 and March 2022 at a teaching hospital in Tehran, Iran. The patient's baseline data and antibiograms were collected. The outcome of the study was in-hospital mortality. Results: The overall in-hospital mortality rate was 41.9 %, with higher mortality observed in patients over 60 years old (P = 0.032), those with community-acquired Staphylococcus aureus bacteremia (P = 0.010), and those admitted to the ICU (P = 0.016). Antibiotic resistance profiles indicated a higher mortality in resistant S.aureus strains but only significant for ciprofloxacin (P = 0.001), methicillin (P = 0.047), and sulfamethoxazole (P = 0.023). Multivariate analysis identified age, sex, ICU admission, and the source of bacteremia as independent predictors of mortality, while COVID-19 coinfection and resistance to antibiotics were not found to be significant predictors. Conclusion: SAB remains a challenging infection that is amplified by the pandemic. Older age and ICU admission are significant mortality predictors. In settings with a high prevalence of MRSA, factors like age, sex, and quality of care outweigh pathogen-related factors such as antibiotic resistance.

Background Despite being the leading cause of mortality from bloodstream infections worldwide, little is known about regional variation in treatment practices for Staphylococcus aureus bacteremia (SAB). The aim of this study was to identify global variation in management, diagnostics, and definitions of SAB. Methods During a 20-day period in 2022, physicians throughout the world were surveyed on SAB treatment practices. The survey was distributed through listservs, e-mails, and social media. Results In total, 2031 physicians from 71 different countries on 6 continents (North America [701, 35%], Europe [573, 28%], Asia [409, 20%], Oceania [182, 9%], South America [124, 6%], and Africa [42, 2%]) completed the survey. Management-based responses differed significantly by continent for preferred treatment of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) bacteremia, use of adjunctive rifampin for prosthetic material infection, and use of oral antibiotics (P <.01 for all comparisons). The 18F-FDG PET/CT scans were most commonly used in Europe (94%) and least frequently used in Africa (13%) and North America (51%; P <.01). Although most respondents defined persistent SAB as 3 – 4 days of positive blood cultures, responses ranged from 2 days in 31% of European respondents to 7 days in 38% of Asian respondents (P <.01). Conclusions Large practice variations for SAB exist throughout the world, reflecting the paucity of high-quality data and the absence of an international standard of care for the management of SAB. [ABSTRACT FROM AUTHOR]

Background The Combination Antibiotic Therapy for Methicillin-Resistant Staphylococcus aureus (CAMERA2) trial ceased recruitment in July 2018, noting that a higher proportion of patients in the intervention arm (combination therapy) developed acute kidney injury (AKI) compared to the standard therapy (monotherapy) arm. We analyzed the long-term outcomes of participants in CAMERA2 to understand the impact of combination antibiotic therapy and AKI. Methods Trial sites obtained additional follow-up data. The primary outcome was all-cause mortality, censored at death or the date of last known follow-up. Secondary outcomes included kidney failure or a reduction in kidney function (a 40% reduction in estimated glomerular filtration rate to <60 mL/minute/1.73 m2). To determine independent predictors of mortality in this cohort, adjusted hazard ratios were calculated using a Cox proportional hazards regression model. Results This post hoc analysis included extended follow-up data for 260 patients. Overall, 123 of 260 (47%) of participants died, with a median population survival estimate of 3.4 years (235 deaths per 1000 person-years). Fifty-five patients died within 90 days after CAMERA2 trial randomization; another 68 deaths occurred after day 90. Using univariable Cox proportional hazards regression, mortality was not associated with either the assigned treatment arm in CAMERA2 (hazard ratio [HR], 0.84 [95% confidence interval [CI],.59–1.19]; P =.33) or experiencing an AKI (HR at 1 year, 1.04 [95% CI,.64–1.68]; P =.88). Conclusions In this cohort of patients hospitalized with methicillin-resistant S aureus bacteremia, we found no association between either treatment arm of the CAMERA2 trial or AKI (using CAMERA2 trial definition) and longer-term mortality. [ABSTRACT FROM AUTHOR]

Purpose: To assess the likelihood of occult infection in patients with clinically unsuspected orthopedic implants during Staphylococcus aureus bacteremia (SAB). Methods: In a retrospective study in two Dutch hospitals, we included all patients with SAB between 2013 and 2020 with one or more orthopedic implants in whom [18F]FDG-PET/CT was performed. The primary outcome was the percentage of patients who had an orthopedic implant-related infection by S. aureus. We also compared clinical parameters in patients with clinically suspected and unsuspected implants. Results: Fifty-five of 191 (29%) orthopedic implants in 118 SAB patients included had clinical signs of infection. Of all 136 unsuspected implants, 5 (3%, all arthroplasties), showed increased [18F]FDG uptake around the prosthesis on [18F]FDG-PET/CT. The clinical course of these patients without clinically overt infection or relapse of bacteremia during follow-up of a median of 48 months (range 0–48), however, argued against prosthetic joint infection. Conclusion: Although orthopedic implants are evidently a risk factor for metastatic infection during SAB, the absence of clinical symptoms obviate the need of additional investigations or prolonged antibiotic treatment. [ABSTRACT FROM AUTHOR]

Background Staphylococcus aureus bacteremia (SAB) disproportionately affects Black patients. The reasons for this disparity are unclear. Methods We evaluated a prospectively ascertained cohort of patients with SAB from 1995 to 2020. Clinical characteristics, bacterial genotypes, and outcome were compared among Black and White patients with SAB. Multivariable logistic regression models were used to determine factors independently associated with the outcomes. Results Among 3068 patients with SAB, 1107 (36%) were Black. Black patients were younger (median, 56 years vs 63 years; P <.001) and had higher rates of diabetes (47.5% vs 34.5%, P <.001), hemodialysis dependence (40.0% vs 7.3%, P <.001), and human immunodeficiency virus (6.4% vs 0.6%, P <.001). Black patients had higher rates of methicillin-resistant S. aureus (49.3% vs 44.9%, P =.020), including the USA300 hypervirulent clone (11.5% vs 8.4%, P =.007). White patients had higher rates of corticosteroid use (22.4% vs 15.8%, P <.0001) and surgery in the preceding 30 days (28.1% vs 18.7%, P <.001). Although the median Acute Physiology Score (APS) at the time of initial SAB diagnosis was significantly higher in Black patients (median APS, 9; interquartile range [IQR], 5–14 vs median APS, 7; IQR, 4–12; P <.001), race was not associated with 90-day mortality (risk ratio, 1.02; 95% confidence interval,.93–1.12), and rates of metastatic infection were lower among Black patients (37.2% vs 41.3% White, P =.029). Conclusions Despite differences in Black patients' higher APS on presentation and more risk factors, including a 5 times higher risk of hemodialysis dependence, 90-day mortality among Black and White patients with SAB was similar. [ABSTRACT FROM AUTHOR]

Non-traumatic mediastinal abscesses are very rare in children; we can classify them into 2 types: descending mediastinitis (or mediastinitis by extension or by contiguity) complicating an otorhinolaryngological or esophageal etiology and mediastinitis generated by direct blood inoculation in a context of a septicemia or primary mediastinitis which is exceptional. We describe a case of right pleuropulmonary staphylococcal disease with bilateral mediastinal localization in a previously healthy 9-month-old infant. It was revealed by sepsis with severe respiratory distress. The germ was isolated from the pleural puncture fluid. A thoracic computed tomography was indicated due to a widening mediastinum noted on chest X-ray in addition to pleuropulmonary involvement. Thoracic computed tomography revealed a huge bilateral mediastinal abscess which was curbed thanks to right pleural drainage with adapted antibiotic therapy. Other investigations did not show any immune abnormalities in this infant. Mediastinitis represents a diagnostic and therapeutic emergency; those that are secondary to direct blood or lymphatic dissemination even very rare; should be considered in any context of severe sepsis including staphylococcus or streptococcus pneumonia. Since 1985 only 11 cases of such mediastinal abscesses have been reported. [ABSTRACT FROM AUTHOR]

The current duration of therapy in patients with Staphylococcus aureus bacteremia (SAB) is based on differentiating complicated from uncomplicated disease. While this approach allows clinicians and investigators to group SAB patients into broadly similar clinical categories, it fails to account for the intrinsic heterogeneity of SAB. This is due in part to the fact that risk factors for metastatic infection and confirmed metastatic infection are considered as equivalent in most scoring systems. In this viewpoint, we propose a two-step system of categorizing patients with SAB. Initially, patients with SAB would be categorized as 'high risk' or 'low risk' for metastatic infection based upon an initial set of diagnostic procedures. In the second step, patients identified as 'high-risk' would undergo additional diagnostic evaluation. The results of this stepwise diagnostic evaluation would define a 'final clinical diagnosis' to inform an individualized final treatment plan. [ABSTRACT FROM AUTHOR]

Background Staphylococcus aureus bacteremia (SAB) can be community-acquired or healthcare-associated, and prior small studies have suggested that this mode of acquisition impacts the subsequent prevalence of infective endocarditis (IE) and patient outcomes. Methods First-time SAB was identified from 2010 to 2018 using Danish nationwide registries and categorized into community-acquired (no healthcare contact within 30 days) or healthcare-associated (SAB >48 hours of hospital admission, hospitalization within 30 days, or outpatient hemodialysis). Prevalence of IE (defined from hospital codes) was compared between groups using multivariable adjusted logistic regression analysis. One-year mortality of S aureus IE (SAIE) was compared between groups using multivariable adjusted Cox proportional hazard analysis. Results We identified 5549 patients with community-acquired SAB and 7491 with healthcare-associated SAB. The prevalence of IE was 12.1% for community-acquired and 6.6% for healthcare-associated SAB. Community-acquired SAB was associated with a higher odds of IE as compared with healthcare-associated SAB (odds ratio, 2.12 [95% confidence interval {CI}, 1.86–2.41]). No difference in mortality was observed with 0–40 days of follow-up for community-acquired SAIE as compared with healthcare-associated SAIE (HR, 1.07 [95% CI,.83–1.37]), while with 41–365 days of follow-up, community-acquired SAIE was associated with a lower mortality (HR, 0.71 [95% CI,.53–.95]). Conclusions Community-acquired SAB was associated with twice the odds for IE, as compared with healthcare-associated SAB. We identified no significant difference in short-term mortality between community-acquired and healthcare-associated SAIE. Beyond 40 days of survival, community-acquired SAIE was associated with a lower mortality. [ABSTRACT FROM AUTHOR]

BackgroundStaphylococcus aureus bacteremia complicated with non-traumatic mediastinal abscess rarely occurs in children. Herein, we report a case of S. aureus bacteremia in a previously healthy 15-month-old boy, which was complicated with a non-traumatic mediastinal abscess, followed by recovery without surgeryCase presentationA previously healthy 15-month-old boy presented to the hospital with a high fever, accompanied by chills, lethargy, tachycardia, tachypnea, and slight cough. Contrast-enhanced computerized tomography revealed mediastinal abscess and blood culture analysis showed the presence of S. aureus which was methicillin-susceptible. With prompt initiation of antibiotic treatment, with appropriate duration, the patient successfully recovered without surgical drainage upon discharge.ConclusionsStaphylococcus aureus bacteremia complicated with non-traumatic mediastinal abscess is rare in children, and early recognition and appropriate management are essential for a successful outcome.

This retrospective cohort study was performed to compare clinical outcomes between patients with Staphylococcus aureus bacteremia who received an early versus late infectious disease consultation. Early consultation resulted in significantly greater adherence to quality care indicators and shorter hospital stays. [ABSTRACT FROM AUTHOR]

Background Infectious diseases (ID) and antimicrobial stewardship (AS) improve Staphylococcus aureus bacteremia (SAB) outcomes. However, many small community hospitals (SCHs) lack on-site access to these services, and it is not known if ID telehealth (IDt) offers the same benefit for SAB. We evaluated the impact of an integrated IDt service on SAB outcomes in 16 SCHs. Methods An IDt service offering IDt physician consultation plus IDt pharmacist surveillance was implemented in October 2016. Patients treated for SAB in 16 SCHs between January 2009 and August 2019 were identified for review. We compared SAB bundle adherence and outcomes between patients with and without an IDt consult (IDt group and control group, respectively). Results A total of 423 patients met inclusion criteria: 157 in the IDt group and 266 in the control group. Baseline characteristics were similar between groups. Among patients completing their admission at an SCH, IDt consultation increased SAB bundle adherence (79% vs 23%; odds ratio [OR], 16.9; 95% CI, 9.2–31.0). Thirty-day mortality and 90-day SAB recurrence favored the IDt group, but the differences were not statistically significant (5% vs 9%; P =.2; and 2% vs 6%; P =.09; respectively). IDt consultation significantly decreased 30-day SAB-related readmissions (9% vs 17%; P =.045) and increased length of stay (median [IQR], 5 [5–8] days vs 5 [3–7] days; P =.04). In a subgroup of SAB patients with a controllable source, IDt appeared to have a mortality benefit (2% vs 9%; OR, 0.12; 95% CI, 0.01–0.98). Conclusions An integrated ID/AS telehealth service improved SAB management and outcomes at 16 SCHs. These findings provide important insights for other IDt programs. [ABSTRACT FROM AUTHOR]

A positive follow-up blood culture for methicillin-resistant Staphylococcus aureus (MRSA) while on seemingly appropriate therapy is a common and ominous development. However, the definition and management of persistent MRSA bacteremia is unstandardized. In this Opinion Paper, we identify the presence of bacteremia for > 1 calendar day as a "worry point" that should trigger an intensive diagnostic evaluation to identify metastatic infection sites. Next, we define the duration of MRSA bacteremia that likely constitutes antibiotic failure and outline a potential management algorithm for such patients. Finally, we propose pragmatic clinical trial designs to test treatment strategies for persistent MRSA bacteremia. [ABSTRACT FROM AUTHOR]

Objectives: Consultation with infectious disease specialists is associated with reduced patient mortality in the care of patients with Staphylococcus aureus bacteremia (SAB) through appropriate management of complications including infective endocarditis. This study aimed to determine the rates of confirmation of a negative blood culture, implementation of echocardiography, and administration of appropriate antibiotics in patients with SAB at a university hospital in Japan that provides general internal medicine and not an infectious disease consultation service., Methods: We conducted a retrospective cohort study at Dokkyo Medical University Hospital in Japan. Patients eligible for inclusion in the study were ≥20 years of age with ≥1 positive blood culture for S. aureus identified in a clinical microbiology laboratory. The primary outcome was the proportion of patients with confirmation of a negative blood culture, implementation of echocardiography, and administration of appropriate antimicrobial agents., Results: A total of 109 patients with SAB were included in the analysis. Follow-up blood cultures were collected in 91 patients and negative results were documented in 88 patients. Follow-up blood culture collection was performed within 4 days of the initial blood culture collection in 49 patients. Echocardiography was performed appropriately in 40 patients. Appropriate antibiotic therapy was administered in 36 patients., Conclusions: Quality-of-care indicators were more commonly implemented in patients with SAB who received general internal medicine consultation than in those who did not., Competing Interests: YD reports grants from Entasis and Shionogi that were paid to his institution; consulting fees from GSK, Meiji Seika Pharma, Shionogi, Gilead, FujiFilm, and bioMérieux that were paid directly to him; and speaker payments from MSD, Shionogi, and Gilead. The other authors declare no conflicts of interest. The funding source had no role in the design, practice, or analysis of this study.

Rapid and accurate identification of Staphylococcus aureus (SA) in blood culture specimens is crucial for timely clinical intervention. Traditional Gram staining methods, although widely accessible and cost-effective, exhibit variable sensitivities and specificities in the BACTEC system. We aimed to develop and validate the "STAPH score," a novel semi-quantitative scoring system that integrates Gram stain morphology and time to positivity to differentiate SA from coagulase-negative staphylococci (CoNS) in blood cultures. We analyzed 148 blood culture specimens from septic patients. Each specimen was assessed independently by two examiners using Gram staining and the STAPH score, which assigns points based on five parameters: cluster size, time to positivity, aerobic enlargement, pint (three-dimensional appearance), and the presence of hemorrhage. Sensitivity and specificity were calculated for various cutoff points. Cohen's kappa coefficient was used to assess inter-examiner agreement. Of the 148 specimens, 49 (33.1%) were identified as SA and 99 (66.9%) as CoNS. At a STAPH score cutoff of 3 points, the sensitivity was 93.9% (95% confidence interval [CI], 83.1%-98.7%) and specificity was 91.9% (95% CI, 84.7%-96.4%). The kappa coefficient at this cutoff was 0.67 (95% CI, 0.55-0.79). A STAPH score <3 effectively ruled out SA with 100% sensitivity, whereas a score of 5 confirmed SA with 100% specificity. The STAPH score is a reliable and efficient tool for the rapid identification of SA in blood cultures within the BACTEC system. By combining Gram staining observations with time to positivity, this method enhances diagnostic accuracy, reduces subjectivity, and supports timely clinical decision-making.IMPORTANCEThe rapid and accurate identification of Staphylococcus aureus (SA) in blood cultures is vital for timely and appropriate clinical intervention. This study introduces the "STAPH score," a novel semi-quantitative scoring system that combines Gram stain morphology and time to positivity. By providing a reliable and efficient method to differentiate SA from coagulase-negative staphylococci, the STAPH score enhances diagnostic accuracy and reduces subjectivity in microscopic examinations. This score, applicable within the BACTEC system, addresses the limitations of traditional Gram staining methods and expensive molecular techniques. The implementation of the STAPH score in clinical practice can lead to faster diagnosis, improved patient outcomes, and optimized antimicrobial therapy. This method is particularly valuable in resource-limited settings where advanced diagnostic tools may not be available., Competing Interests: The authors declare no conflict of interest.

Background: We conducted a systematic review of randomized controlled trials (RCTs) to generate more precise estimates of the efficacy and safety of oral versus intravenous antibiotic therapy for S. aureus bacteremia or endocarditis., Methods: MEDLINE, EMBASE, the Cochrane Library, and Web of Science database were searched through February 21st, 2024. RCTs were included if they compared oral versus intravenous antibiotic therapy for S. aureus bacteremia or endocarditis, and appropriately reported outcomes for each group. Risk of bias was assessed using the revised Cochrane tool for assessing risk of bias in randomized trials. Heterogeneity between studies was evaluated with the Cochran's Q-statistic and I2 test. Treatment effects were summarized with pooled risk ratios using a random effects model meta-analysis. (PROSPERO CRD42024481512)., Results: Only four RCTs met criteria for inclusion in meta-analysis. Among participants assessed for treatment failure, there was no difference between the oral and intravenous therapy groups (RR 0.99; 95% CI, 0.63-1.57; I2 = 0%). There was also no significant difference in adverse events between oral and intravenous therapy groups (RR 0.65; 95% CI, 0.07-5.94; I2 = 74%); however, the confidence interval is wide, and heterogeneity was high., Conclusions: In this systematic review of RCTs comparing oral to intravenous antibiotic therapy for S. aureus bacteremia or endocarditis, few studies met eligibility criteria for inclusion. Meta-analysis of these studies suggests that transitioning from intravenous to oral therapy is likely effective in a subgroup of carefully selected patients. Additional randomized trials are necessary before transition to oral therapy can be routinely recommended., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Sequence type 72 (ST72) is the predominant community-associated methicillin-resistant Staphylococcus aureus (MRSA) genotype in Korea. With an increasing prevalence of the ST72 S. aureus lineage, regardless of methicillin resistance, it is crucial to understand the clinical and microbiological characteristics of ST72 methicillin-susceptible S. aureus (MSSA) as well as ST72 MRSA., Materials and Methods: In this retrospective cohort study, data from patients with S. aureus bacteremia (SAB) who were admitted to a tertiary hospital in Korea from March 2007 to December 2018 were collected. Multilocus sequence typing was used to identify ST72 isolates. The clinical and microbiological characteristics of ST72 MSSA were compared with those of ST72 MRSA among patients infected with SAB., Results: Among the 442 SAB patients with ST72, 157 (35.5%) were infected with MSSA and 285 (64.5%) were infected with MRSA. There was a significant increase in the proportion of ST72 MSSA in both the community and hospital settings. Compared to ST72 MRSA, ST72 MSSA isolates were less likely to have multidrug resistance. The main infection foci, infection severity, and duration of bacteremia did not differ significantly between the two groups. The 90-day recurrence rate was significantly lower in the MSSA group (2.5% vs. 8.4%, P =0.03), while the 90-day mortality rate was comparable (28.0% vs. 23.9%, P =0.40)., Conclusion: ST72 MSSA had similar clinical features as ST72 MRSA in terms of infection site, severity, and 90-day mortality. Despite exhibiting lower levels of antibiotic resistance, ST72 MSSA has increased in the hospital environment concurrently with ST72 MRSA., (© 2024 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, The Korean Society for AIDS, and Korean Society of Pediatric Infectious Diseases.)

Background In patients with Staphylococcus aureus bacteremia (SAB), endocarditis evaluation includes transthoracic echocardiography (TTE) and, in patients at increased risk of endocarditis, subsequent transesophageal echocardiography (TEE). Whether performing TTE before TEE influences clinicians' decision making has not been well studied in patients deemed to warrant TEE. Methods In this retrospective case series, we studied clinician behavior at a large Veterans Affairs medical center regarding the care of adult patients diagnosed with SAB who completed both TTE and TEE (n  = 206 episodes of SAB). The timing of key patient management decisions was compared to the timing of the patient's TTE and TEE. It was inferred whether each management decision could have been informed by TTE alone versus TTE plus subsequent TEE. Management decisions included the following: documentation of antibiotic treatment duration, initiation of synergistic antibiotics, consultation of relevant specialists, ordering of relevant imaging studies, and performance of valve surgery or cardiac device explanation. Results The primary outcome (any of the above 5 management decisions taking place) occurred after completion of TTE but before TEE in 13 SAB episodes (6.3%). The primary outcome occurred after completion of both TTE and TEE in 178 SAB episodes (86.4%). Documentation of antibiotic treatment duration accounted for the large majority of observed management decisions. Conclusions Among patients with SAB who are deemed to warrant TEE for endocarditis evaluation, TTE results alone rarely prompt clinical management decisions. [ABSTRACT FROM AUTHOR]

Patients with heart valve prosthesis (HVP) and Staphylococcus aureus bacteremia (SAB) are at risk for endocarditis. In this retrospective, population-based cohort study of 134 patients with SAB and HVP, 97 patients (72%) were diagnosed with possible endocarditis. Despite that most patients with possible endocarditis received short antibiotic treatment, only 3 patients suffered recurrent SAB. [ABSTRACT FROM AUTHOR]

Abstract Background Appendicitis is one of the most frequently encountered conditions at the emergency department. Distinction is made between complicated and uncomplicated appendicitis. Complicated appendicitis may cause serious intra-abdominal infection, bacteremia, or sepsis. Emergency health providers should be highly alert to any early signs indicating such complications. Case presentation We present the case of a healthy young male with a gangrenous appendicitis, who received antibiotics and underwent appendectomy. Blood cultures showed unequivocal Staphylococcus aureus and concomitant Klebsiella pneumoniae bacteremia requiring prolonged antibiotic treatment and further diagnostic evaluation. Conclusions Although rare, appendicitis can cause Staphylococcus aureus and Klebsiella pneumoniae bacteremia with extensive implications for workup and antibiotic management. Our case stresses the importance of obtaining cultures in patients with suspicion of bacteremia given its consequences for clinical management.

Early administration of proper antibiotics is considered to improve the clinical outcomes of Staphylococcus aureus bacteremia (SAB), but routine clinical antimicrobial susceptibility testing takes an additional 24 h after species identification. Recent studies elucidated matrix-assisted laser desorption/ionization time-of-flight mass spectra to discriminate methicillin-resistant strains (MRSA) or even incorporated with machine learning (ML) techniques. However, no universally applicable mass peaks were revealed, which means that the discrimination model might need to be established or calibrated by local strains' data. Here, a clinically feasible workflow was provided. We collected mass spectra from SAB patients over an 8-month duration and preprocessed by binning with reference peaks. Machine learning models were trained and tested by samples independently of the first six months and the following two months, respectively. The ML models were optimized by genetic algorithm (GA). The accuracy, sensitivity, specificity, and AUC of the independent testing of the best model, i.e., SVM, under the optimal parameters were 87%, 75%, 95%, and 87%, respectively. In summary, almost all resistant results were truly resistant, implying that physicians might escalate antibiotics for MRSA 24 h earlier. This report presents an attainable method for clinical laboratories to build an MRSA model and boost the performance using their local data. [ABSTRACT FROM AUTHOR]

Background Staphylococcus aureus bacteremia (SAB) is in 10% to 20% of cases complicated by infective endocarditis. Clinical prediction scores may select patients with SAB at highest risk for endocarditis, improving the diagnostic process of endocarditis. We compared the accuracy of the Prediction Of Staphylococcus aureus Infective endocarditiseTime to positivity, Iv drug use, Vascular phenomena, preExisting heart condition (POSITIVE), Predicting Risk of Endocarditis Using a Clinical Tool (PREDICT), and VIRSTA scores for classifying the likelihood of endocarditis in patients with SAB. Methods Between August 2017 and September 2019, we enrolled consecutive adult patients with SAB in a prospective cohort study in 7 hospitals in the Netherlands. Using the modified Duke Criteria for definite endocarditis as reference standard, sensitivity, specificity, negative predictive (NPV), and positive predictive values were determined for the POSITIVE, PREDICT, and VIRSTA scores. An NPV of at least 98% was considered safe for excluding endocarditis. Results Of 477 SAB patients enrolled, 33% had community-acquired SAB, 8% had a prosthetic valve, and 11% a cardiac implantable electronic device. Echocardiography was performed in 87% of patients, and 42% received transesophageal echocardiography (TEE). Eighty-seven (18.2%) had definite endocarditis. Sensitivity was 77.6% (65.8%–86.9%), 85.1% (75.8%–91.8%), and 98.9% (95.7%–100%) for the POSITIVE (n = 362), PREDICT, and VIRSTA scores, respectively. NPVs were 92.5% (87.9%–95.8%), 94.5% (90.7%–97.0%), and 99.3% (94.9%–100%). For the POSITIVE, PREDICT, and VIRSTA scores, 44.5%, 50.7%, and 70.9% of patients with SAB, respectively, were classified as at high risk for endocarditis. Conclusions Only the VIRSTA score had an NPV of at least 98%, but at the expense of a high number of patients classified as high risk and thus requiring TEE. Clinical Trials Registration Netherlands Trial Register code 6669. [ABSTRACT FROM AUTHOR]

Purpose: [18F]FDG-PET/CT scanning can help detect metastatic infectious foci and reduce mortality in patients with Staphylococcus aureus bacteremia (SAB), but it is unknown if patients with SAB and an indication for prolonged treatment because of possible endovascular, orthopaedic implant, or other metastatic infection still need [18F]FDG-PET/CT. Methods: In a retrospective single-center cohort study, we included all consecutive adult patients with SAB between 2013 and 2020 if an [18F]FDG-PET/CT scan was performed and antibiotic treatment was planned for ≥ 6 weeks prior to [18F]FDG-PET/CT. We aimed to identify patients for whom treatment was adjusted due to the results of [18F]FDG-PET/CT, and assessed concordance of [18F]FDG-PET/CT and clinical diagnosis for infected prosthetic material. Results: Among 132 patients included, the original treatment plan was changed after [18F]FDG-PET/CT in 22 patients (16.7%), in the majority (n = 20) due to diagnosing or rejecting endovascular (graft) infection. Antibiotic treatment modifications were shortening in 2, iv-oral switch in 3, extension in 13, and addition of rifampicin in 4 patients. Ninety additional metastatic foci based on [18F]FDG-PET/CT results were found in 69/132 patients (52.3%). [18F]FDG-PET/CT suggested vascular graft infection in 7/14 patients who lacked clinical signs of infection, but showed no infection of prosthetic joints or osteosynthesis material in eight patients who lacked clinical signs of such an infection. Conclusion: [18F]FDG-PET/CT can help refine treatment for SAB in patients with clinically suspected endovascular infection or vascular grafts, even if 6 weeks treatment is already indicated, but can be safely omitted in other patients who are clinically stable. [ABSTRACT FROM AUTHOR]

Objectives: Most Japanese hospitals need to keep to higher Staphylococcus aureus bacteremia (SAB) quality-of-care indicators (QCIs) and create strategies that can maximize the effect of these QCIs with only a small number of infectious disease specialists. This study aimed to evaluate the clinical outcomes of patients with SAB before and after the enhancement of the mandatory infectious disease consultations (IDCs). Methods: This retrospective study was conducted at a tertiary care hospital in Japan. The primary outcome was the 30-day mortality between each period. A generalized structural equation model was employed to examine the effect of the mandatory IDC enhancement on 30-day mortality among patients with SAB. Results: A total of 114 patients with SAB were analyzed. The 30-day all-cause mortality differed significantly between the two periods (17.3% vs. 4.8%, P = 0.02). Age, three-QCI point ≥ 1, and Pitt bacteremia score ≥ 3 were the significant risk factors for 30-day mortality. The intervention was also significantly associated with improved adherence to QCIs. Conclusion: Mandatory IDCs for SAB improved 30-day mortality and adherence to QCIs after the intervention. In Japan, improving the quality of management in patients with SAB should be an important target.

Background: Treatment optimization for serious infections, such as Staphylococcus aureus bacteremia (SAB), is a challenge for antimicrobial stewardship teams. Currently, SAB guidelines recommend a completely intravenous therapy (CIT). Objectives: The objective of the study was to analyze the usefulness and safety of oral sequential therapy (OST) in SAB. Patients and methods: We conducted a retrospective, observational study in a tertiary teaching hospital in Spain. The inclusion criteria were complicated and non-complicated monomicrobial SAB and an adequate duration of therapy, with patients classified into OST or CIT. The primary endpoint was the 90-day recurrence of S. aureus infection. We also analyzed the mortality, the length of the hospital stay, and the duration of the intravenous antibiotic administration. Results: Of a total of 201 patients with SAB, 125 (62%) underwent OST. The most commonly administered oral antibiotic was trimethoprim-sulfamethoxazole (66% of patients). Of those administered OST, 43% had complicated bacteremia (most with an osteoarticular source of infection), and 6% had an intravascular device. The 90-day recurrence rate was 4%, with no differences between the two groups. The duration of the therapy (22 [16–28] vs. 13 days [8–17] for CIT and OST, respectively; p < 0.001) and the hospital stay (36 [27–71] vs. 18 days [13–29] for CIT and OST, respectively; p < 0.001) were shorter for OST. MRSA was related with mortality (OR 4.4, 95% CI [1.67−11.37]; p = 0.003). Conclusions: OST for properly selected patients with SAB could be a safe therapeutic option and can reduce their use of CIT and their hospital stay.

Background: Antimicrobial stewardship (AMS) programs aim to secure the rational prescription of antibiotics through implementing department- or hospital-level activities. Infectious disease (ID) specialists improve the quality of care and outcomes in infection patients predominantly by individual consultations and patient-level interventions. While hospital AMS programs are established to various extents in Germany, ID specialist services are rarely available in this country. In the ID ROLL OUT study, we will implement and evaluate hospital-level AMS tools with and without ID specialist services in secondary and tertiary care hospitals. We aim to identify means to comprehensively and sustainably improve the quality of care of patients with infectious diseases. Methods: This project is a clustered, two-armed intervention study, which will be conducted in ten secondary and tertiary (non-university) care hospitals in Germany. The intervention groups are stratified by key characteristics of the hospitals. We will compare two interventional strategies: implementation of AMS teams and implementation of AMS teams combined with the activities of ID specialists (AMS + IDS). Planned Outcomes: The primary outcome is the quality of care as measured in changes in a Staphylococcus aureus bacteremia (SAB) score (as an indicator of difficult-to-treat infections) and a community-acquired pneumonia (CAP) score (as an indicator of common infections) compared to a baseline pre-interventional period. Our secondary outcomes comprise patient- and hospital-level outcomes, such as the quality and frequency of antibiotic treatment, in-hospital mortality, duration of hospitalization, and C. difficile incidence (associated diarrhea episodes). The study may provide urgently needed key information for the aspired advancement of ID care in Germany. Trial Registration: DRKS00023710 (registered on 9th April 2021). [ABSTRACT FROM AUTHOR]

Objective: Bacteremia is the presence of bacteria in the bloodstream. The objective of this study was to determine the relationship between low socioeconomic status (SES) and the epidemiology, process of care, and outcomes of patients with Staphylococcus aureus bacteremia (SAB). Methods: We conducted a multicenter, retrospective, cohort study that evaluated adult patients with SAB in 3 Los Angeles County hospitals from July 15, 2012, through May 31, 2018. We determined SES (low SES, intermediate SES, and high SES) for each patient and compared sociodemographic and epidemiologic characteristics, management of care received by patients with SAB (ie, process of care), and outcomes. We used a Cox proportional hazards model to determine predictors of 30-day mortality for each SES group. Results: Of 915 patients included in the sample, 369 (40%) were in the low-SES group, 294 (32%) in the intermediate-SES group, and 252 (28%) in the high-SES group. Most significant predictors of 30-day mortality in the Cox proportional hazards model were admission to an intensive care unit (hazard ratio [HR] = 9.04; 95% CI, 4.26-19.14), Pitt bacteremia score ≥4 indicating critical illness (HR = 4.30; 95% CI, 2.49-7.44), having ≥3 comorbidities (HR = 2.05; 95% CI, 1.09-3.85), and advanced age (HR = 1.03; 95% CI, 1.01-1.05). Distance between home and admitting hospital affected mortality only in the low-SES group (HR = 1.02; 95% CI, 1.00-1.02). Conclusions: SES did not independently affect the outcome of SAB; however, the farther the patient's residence from the hospital, the greater the negative effect on survival in a low-SES population. Our findings underscore the need to develop multipronged, targeted public health efforts for populations that have transportation barriers to health care. [ABSTRACT FROM AUTHOR]

Introduction: Outcomes from Staphylococcus aureus bacteremia (SAB) in solid organ transplant (SOT) recipients are poorly understood. Methods: This is a prospective cohort study comparing the bacterial genotype and clinical outcomes of SAB among SOT and non‐transplant (non‐SOT) recipients from 2005 to 2019. Each subject's initial S. aureus bloodstream isolate was genotyped using spa typing and assigned to a clonal complex. Results: A total of 103 SOT and 1783 non‐SOT recipients with SAB were included. Bacterial genotype did not differ significantly between SOT and non‐SOT recipients (p =.4673), including the proportion of SAB caused by USA300 (13.2% vs. 16.0%, p =.2680). Transplant status was not significantly associated with 90‐day mortality (18.4% vs. 29.5%; adjusted odds ratio [aOR] 0.74; 95% confidence interval [CI]: 0.44, 1.25), but was associated with increased risk for septic shock (50.0% vs. 21.8%; aOR 2.31; 95% CI: 1.48, 3.61) and acute respiratory distress syndrome (21.4% vs. 13.7%; aOR 2.03; 95% CI: 1.22, 3.37), and a significantly lower risk of metastatic complications (33.0% vs. 45.5%; aOR 0.49; 95% CI: 0.32, 0.76). No association was found between bacterial genotype and 90‐day mortality (p =.6222) or septic shock (p =.5080) in SOT recipients with SAB. Conclusions: SOT recipients with SAB do not experience greater mortality than non‐SOT recipients. The genotype of S. aureus bloodstream isolates in SOT recipients is similar to that of non‐SOT recipients, and does not appear to be an important determinant of outcome in SOT recipients with SAB. [ABSTRACT FROM AUTHOR]

Background Staphylococcus aureus bacteremia (SAB) is uniquely characterized by focal pyogenic complications that might not be apparent clinically. We investigated the benefit of adding fluorodeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) in the workup of patients with SAB. Methods In a matched-cohort study patients with SAB (intervention group) were prospectively recruited to undergo FDG-PET/CT 7–14 days after diagnosis. Treatment was directed by FDG-PET/CT findings. Clinical outcomes were compared with a control group of patients with SAB who had not undergone FDG-PET/CT, matched by age, Charlson score, methicillin susceptibility, and survival duration to FDG-PET/CT. The primary outcome was 90-day mortality. Residual confounding was controlled through regression analyses. Results During the study period 149 patients with 151 separate episodes of SAB underwent FDG-PET/CT and were compared with 150 matched patients with 151 SAB episodes. Patients in the intervention group acquired infections more frequently in the community and had less frequently solid malignancies and more frequently high-risk SAB. Ninety-day mortality in the intervention group was significantly lower than in the control group (21/151 [13.9%] vs 43/151 [28.5%], P  = .002). The difference remained significant in a subgroup analysis of patients with community-onset infections without malignancy and among patients with low-risk SAB. Controlling for other risk factors for mortality, FDG-PET/CT performance among all patients was independently associated with lower mortality (OR,.39; 95% CI,.18–.84). Patients in the intervention group had longer duration of treatment and more focus control procedures performed compared with the control group. Conclusions FDG-PET/CT in patients with SAB seems to improve survival through guidance of treatment duration and co-interventions. [ABSTRACT FROM AUTHOR]

Abstract Background Persistent bacteremia occurs in at least 30% of patients with Staphylococcus aureus bloodstream infection (SAB) and may be attributable to a dysregulated host immune response. Neutrophils interact with a variety of S. aureus microbial factors, including lipoteichoic acid (LTA), to activate phagocytic function in a concentration-dependent manner. Antibiotics have been shown to exert both direct antimicrobial action as well as immunomodulatory effects. In this study, we compared the effects of different anti-staphylococcal antibiotics on LTA-mediated immune activation of neutrophils. Methods Neutrophils obtained from healthy volunteers were exposed to two levels of LTA (1 and 10 μg/ml) with or without addition of antibiotics from different pharmacologic classes (vancomycin, daptomycin, ceftaroline). Neutrophil function was assessed by examining phagocytic response, activation (CD11b, CD62L expression), Toll-like receptor-2 expression, cell survival and apoptosis, and CXCL8 release. Results Differential LTA-mediated antibiotic effects on neutrophil function were observed primarily at the high LTA exposure level. Ceftaroline in the presence of 10 μg/ml LTA had the most prominent effects on phagocytosis and CD11b and CD62L expression, with trends towards increased neutrophil survival and preservation of CXCL8 release when compared to daptomycin and vancomycin with the latter significantly dampening PMN CXCL8 release. Conclusions Select antimicrobial agents, such as ceftaroline, exert immunostimulatory effects on neutrophils exposed to S. aureus LTA, which when confirmed in vivo, could be leveraged for its dual immunomodulatory and antibacterial actions for the treatment of persistent SAB mediated by a dysregulated host response.

We report a case of incipient systemic lupus erythematosus (SLE) that rapidly progressed to complete atrioventricular block (cAVB). A 20-year-old man was admitted with facial erythema, painless oral aphtha, polyarthritis, and myalgia of each extremity. On admission, he developed first-degree atrioventricular block, pericarditis, pleuritis, renal failure, hemophagocytic lymphohistiocytosis, neurophychiatric SLE (left cerebellar infarction), and Staphylococcus aureus bacteremia. He was subsequently diagnosed with SLE based on several positive findings on immunological tests (including positive for antinuclear antibody). Despite immediate glucocorticoid pulse therapy and plasma exchange (PE) along with antibiotic, he developed cAVB that required temporary pacing on day 2. Because it was thought that hypercytokinemia exacerbated pericarditis, which progressed to myocarditis and cAVB, we decided to PE and cytokine-adsorbing therapy with AN69ST-continuous hemodiafiltration (CHDF). Other than renal failure, his organ dysfunctions improved with the multidisciplinary therapy. CAVB improved and temporary pacing was no longer required on day 11. Even a first-degree atrioventricular block can rapidly progress to cAVB; therefore, strict attention to electrocardiogram is necessary in severe SLE cases. When presenting with organ dysfunctions caused by hypercytokinemia such as severe SLE cases or SLE with severe infection cases, use of the combination of PE and AN69ST-CHDF might be beneficial.

Kamal Hamed, Tatiana Wiktorowicz, Maziar Assadi Gehr Basilea Pharmaceutica International Ltd., Basel, SwitzerlandCorrespondence: Kamal HamedBasilea Pharmaceutica International Ltd., Grenzacherstrasse 487, Basel 4005, SwitzerlandTel +41 61 567 1588Fax +41 61 606 1216Email kamal.hamed@basilea.comPurpose: Drug-induced immune hemolytic anemia (DIIHA) is a rare but serious adverse event associated with a number of drugs, including second- and third-generation cephalosporins. A positive direct antiglobulin test (DAT) is a reliable finding in DIIHA, but positive results without evidence of hemolysis can occur, particularly in hospitalized patients. There have been no reports of hemolytic anemia in four previous Phase 3 trials or from post-marketing surveillance of the advanced-generation, broad-spectrum cephalosporin, ceftobiprole. The aim of this analysis was to review the incidence of positive DAT results and any evidence of hemolytic anemia from three recent Phase 3 trials of ceftobiprole.Patients and Methods: Patients were enrolled in three Phase 3 randomized controlled trials: 94 pediatric patients with pneumonia received ceftobiprole in the BPR-PIP-002 trial; 335 adults with acute bacterial skin and skin structure infections received ceftobiprole in the TARGET trial; and 201 adults with Staphylococcus aureus bacteremia have been randomized 1:1 to ceftobiprole or daptomycin ± aztreonam in the ongoing ERADICATE trial. In all three trials, DAT results were obtained at baseline, and follow-up tests were performed either at the test of cure (TOC) visit (BPR-PIP-002), end-of-treatment (EOT) visit (TARGET), or both EOT and post-treatment Day 70 visits (ERADICATE).Results: In the BPR-PIP-002 trial, five patients (all ceftobiprole treated) had a documented negative DAT result at baseline followed by a positive result at the TOC visit. One patient in the ongoing, blinded ERADICATE trial had a positive DAT result at both baseline and EOT. Results from other laboratory investigations showed no evidence of hemolytic anemia in these patients. No positive DAT results were reported in the TARGET trial.Conclusion: No evidence of hemolytic anemia associated with ceftobiprole was observed in either adults or children across several indications in this analysis of three large Phase 3 trials.Keywords: DIIHA, direct antiglobulin test, hemolysis, pneumonia, ABSSSIs, Staphylococcus aureus bacteremia

Purpose: Septic thrombosis often complicates Staphylococcus aureus bacteremia (SAB) in patients with a central venous catheter. Currently there is no reference standard for diagnosis. We describe the diagnostic value of [18F]FDG-PET/CT imaging in a patient cohort and the potential contribution of quantitative measurements in detecting septic thrombosis. Methods: We selected patients with catheter-related SAB from our institutional database (2013–2020). The contribution of [18F]FDG-PET/CT on clinical diagnosis of septic thrombosis was evaluated. Standardized Uptake Values (SUV) were measured and compared with a composite reference standard (clinical signs, initial [18F]FDG-PET/CT result, Multidisciplinary Team (MDT) meeting outcome) to identify a cut-off value for detecting septic thrombosis. Results: We identified 93 patients with a catheter-related SAB. Quantitative measurements were possible for 43/56 patients in whom a [18F]FDG-PET/CT scan was performed. Septic thrombosis was clinically diagnosed in 30% (13/43) of the cases. In 85% of these cases, significant [18F]FDG-PET/CT uptake at the site of the thrombus was the deciding factor for diagnosis of septic thrombosis during the MDT meeting. All mean SUV’s of thrombotic lesions were higher in patients with clinically proven septic thrombosis compared to patients in whom this diagnosis was rejected (p

Staphylococcus aureus ( S. aureus ), an opportunistic Gram-positive bacterium, is notorious for causing a plethora of clinical diseases. While it does not typically infect healthy skin, S. aureus infections are prevalent in both community-acquired and hospital-acquired settings. Rheumatoid arthritis (RA), a chronic autoimmune disease characterized by joint inflammation and progressive bone erosion, can be managed medically and, in moderate to severe cases, surgically through arthroplasty. Complications of arthroplasty include wound infection, blood clots, stiffness, and infection around the prosthesis. Prosthetic joint infections (PJIs) are a rare complication of arthroplasty, commonly caused by aerobic Gram-positive bacteria. These infections can lead to bacteremia, precipitating a cascade of adverse clinical sequelae. This report aims to explore the etiology of delayed-onset PJIs, the underlying pathophysiology of this condition leading to bacteremia, the complications of S. aureus bacteremia, and the management strategies employed to treat PJIs and complicated cases of S. aureus bacteremia resulting from PJIs., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Holder et al.)

We discuss a case where the blood cultures of a patient with clinical chorioamnionitis and elevated D-dimer levels enabled early diagnosis of infective endocarditis. A 31-year-old female with a 39-week pregnancy presented to the obstetrics department with a fever. Cardiotocography revealed fetal tachycardia and severe late deceleration. Preoperative examinations revealed a leukocyte count of 15,900/μL and D-dimer levels of 86.2 μg/mL. She was diagnosed with a non-reassuring fetal status due to clinical chorioamnionitis; accordingly, an emergency cesarean section was performed. Imaging studies ruled out the possibility of a thromboembolism. Subsequent maternal blood cultures were positive for Staphylococcus aureus . Echocardiography revealed vegetation on the aortic valve, leading to a diagnosis of infective endocarditis. Blood cultures can be useful in evaluating for sepsis in cases of clinical chorioamnionitis with elevated D-dimer levels as they may facilitate early diagnosis of infective endocarditis during pregnancy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Yamano et al.)

Background: Appendicitis is one of the most frequently encountered conditions at the emergency department. Distinction is made between complicated and uncomplicated appendicitis. Complicated appendicitis may cause serious intra-abdominal infection, bacteremia, or sepsis. Emergency health providers should be highly alert to any early signs indicating such complications. Case presentation: We present the case of a healthy young male with a gangrenous appendicitis, who received antibiotics and underwent appendectomy. Blood cultures showed unequivocal Staphylococcus aureus and concomitant Klebsiella pneumoniae bacteremia requiring prolonged antibiotic treatment and further diagnostic evaluation. Conclusions: Although rare, appendicitis can cause Staphylococcus aureus and Klebsiella pneumoniae bacteremia with extensive implications for workup and antibiotic management. Our case stresses the importance of obtaining cultures in patients with suspicion of bacteremia given its consequences for clinical management. [ABSTRACT FROM AUTHOR]