S. Aureus Bacteremia Research Articles

Risk Factors for Persistent Staphylococcus aureus Bacteremia in Children.

Staphylococcus aureus is a leading cause of pediatric bacteremia. Persistent S. aureus bacteremia (SAB) is associated with increased morbidity and mortality in adults and children. Risk factors for S. aureus bacteremia have been well established, but there is a limited understanding of the factors that contribute to the development of persistent SAB in children. This is a single-center retrospective secondary analysis of a prospective observational study of pediatric patients hospitalized with S. aureus infection over a 3.5-year period at a large, quaternary, children's hospital. Two hundred fifty-nine children with confirmed S. aureus infection were enrolled in the study. Sixty-five of these were found to have bacteremia, with 28 (43%) developing persistent bacteremia. Patients with persistent SAB were culture-positive for a median of 3.5 days compared with 1 day for those without (P ≤ 0.001). Children with persistent SAB were more likely to have an identified osteoarticular source of infection (93%, n = 26 vs. 62%, n = 23; P = 0.008) and had a shorter median duration to culture positivity than those without persistent SAB (16 hours vs. 20 hours; P ≤ 0.001). In addition, children with persistent SAB had higher median values of presenting erythrocyte sedimentation rate, peak erythrocyte sedimentation rate, presenting C-reactive protein and peak C-reactive protein. Not surprisingly, hospital length of stay was longer in children with persistent SAB compared with those without. These findings suggest that a shorter time to culture positivity, osteoarticular infection, and higher presenting and peak values for select inflammatory markers are potential risk factors for persistent SAB in children.

A Machine Learning-Based Risk Score for Prediction of Infective Endocarditis Among Patients With Staphylococcus aureus Bacteremia-The SABIER Score.

Early risk assessment is needed to stratify Staphylococcus aureus infective endocarditis (SA-IE) risk among patients with S. aureus bacteremia (SAB) to guide clinical management. The objective of the current study was to develop a novel risk score that is independent of subjective clinical judgment and can be used early, at the time of blood culture positivity. We conducted a retrospective big data analysis from territory-wide electronic data and included hospitalized patients with SAB between 2009 and 2019. We applied a random forest risk scoring model to select variables from an array of parameters, according to the statistical importance in predicting SA-IE outcome. The data were divided into derivation and validation cohorts. The areas under the curve of the receiver operating characteristic (AUCROCs) were determined. We identified 15 741 SAB patients, among them 658 (4.18%) had SA-IE. The AUCROC was 0.74 (95%CI 0.70-0.76), with a negative predictive value of 0.980 (95%CI 0.977-0.983). The four most discriminatory features were age, history of infective endocarditis, valvular heart disease, and community onset. We developed a novel risk score with performance comparable with existing scores, which can be used at the time of SAB and prior to subjective clinical judgment.

Female Sex and Mortality in Patients with Staphylococcus aureus Bacteremia

Staphylococcus aureus is the leading cause of death due to bacterial bloodstream infection. Female sex has been identified as a risk factor for mortality in S aureus bacteremia (SAB) in some studies, but not in others. To determine whether female sex is associated with increased mortality risk in SAB. MEDLINE, Embase, and Web of Science were searched from inception to April 26, 2023. Included studies met the following criteria: (1) randomized or observational studies evaluating adults with SAB, (2) included 200 or more patients, (3) reported mortality at or before 90 days following SAB, and (4) reported mortality stratified by sex. Studies on specific subpopulations (eg, dialysis, intensive care units, cancer patients) and studies that included patients with bacteremia by various microorganisms that did not report SAB-specific data were excluded. Data extraction and quality assessment were performed by 1 reviewer and verified by a second reviewer. Risk of bias and quality were assessed with the Newcastle-Ottawa Quality Assessment Scale. Mortality data were combined as odds ratios (ORs). Mortality at or before 90-day following SAB, stratified by sex. From 5339 studies retrieved, 89 were included (132 582 patients; 50 258 female [37.9%], 82 324 male [62.1%]). Unadjusted mortality data were available from 81 studies (109 828 patients) and showed increased mortality in female patients compared with male patients (pooled OR, 1.12; 95% CI, 1.06-1.18). Adjusted mortality data accounting for additional patient characteristics and treatment variables were available from 32 studies (95 469 patients) and revealed a similarly increased mortality risk in female relative to male patients (pooled adjusted OR, 1.18; 95% CI, 1.11-1.27). No evidence of publication bias was encountered. In this systematic review and meta-analysis, female patients with SAB had higher mortality risk than males in both unadjusted and adjusted analyses. Further research is needed to study the potential underlying mechanisms.

Clinical and Microbiological Characteristics of ST72 Methicillin-Susceptible Staphylococcus aureus: Comparison with ST72 Methicillin-Resistant S. aureus.

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. 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. 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). 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.

Short-term versus usual-term antibiotic treatment for uncomplicated Staphylococcus aureus bacteremia: a systematic review and meta-analysis.

Uncomplicated Staphylococcus aureus bacteremia remains a leading cause of morbidity and mortality in hospitalized patients. Current guidelines recommend a minimum of 14 days of treatment. To evaluate the efficacy and safety of short versus usual antibiotic therapy in adults with uncomplicated S. aureus bacteremia (SAB). We developed a search strategy to identify systematic review and meta-analysis of non-randomized studies (NRS), comparing short versus usual or long antibiotic regimens for uncomplicated SAB in MEDLINE, Embase, and the Cochrane Register up to June 2023. The risk of bias was assessed using the ROBINS I tool. The meta-analysis was performed using Review Manager software with a random effect model. Six NRS with a total of 1700 patients were included. No significant differences were found when comparing short versus prolonged antibiotic therapy as defined by the authors for 90-day mortality [odds ratio (OR): 1.09; 95% confidence interval (CI): 0.82-1.46, p: 0.55; I2 = 0%] or 90-day recurrence or relapse of bacteremia [OR: 0.72; 95% CI: 0.31-1.68, p: 0.45; I2 = 26%]. Sensitivity analysis showed similar results when comparing a predefined duration of <14 days versus ⩾14 days and when excluding the only study with a high risk of bias. Shorter-duration regimens could be considered as an alternative option for uncomplicated SAB in low-risk cases. However, based on a small number of studies with significant methodological limitations and risk of bias, the benefits and harms of shorter regimens should be analyzed with caution. Randomized clinical trials are needed to determine the best approach regarding the optimal duration of therapy.

2532. Pharmacokinetic-Pharmacodynamic Analyses for Ceftobiprole Efficacy Based on Phase 3 Data from Patients with Staphylococcus aureus Bacteremia

2532. Pharmacokinetic-Pharmacodynamic Analyses for Ceftobiprole Efficacy Based on Phase 3 Data from Patients with <i>Staphylococcus aureus</i> Bacteremia

Early Oral Antibiotic Switch in Staphylococcus aureus Bacteraemia: The Staphylococcus aureus Network Adaptive Platform (SNAP) Trial Early Oral Switch Protocol.

Staphylococcus aureus bloodstream infection (bacteremia) is traditionally treated with at least 2 weeks of intravenous (IV) antibiotics in adults, 3-7 days in children, and often longer for those with complicated disease. The current practice of treating S. aureus bacteremia (SAB) with prolonged IV antibiotics (rather than oral antibiotics) is based on historical observational research and expert opinion. Prolonged IV antibiotic therapy has significant disadvantages for patients and healthcare systems, and there is growing interest in whether a switch to oral antibiotics following an initial period of IV therapy is a safe alternative for clinically stable patients. The early oral switch (EOS) domain of the S. aureus Network Adaptive Platform (SNAP) trial will assess early switch to oral antibiotics compared with continued IV treatment in clinically stable patients with SAB. The primary endpoint is 90-day all-cause mortality. Hospitalised SAB patients are assessed at platform day 7 ±2 (uncomplicated SAB) and day 14 ±2 (complicated SAB) to determine their eligibility for randomization to EOS (intervention) or continued IV treatment (current standard of care). Recruitment is occurring in the EOS domain of the SNAP trial. As of August 2023, 21% of all SNAP participants had been randomized to the EOS domain, a total of 264 participants across 77 centers, with an aim to recruit at least 1000 participants. We describe challenges and facilitators to enrolment in this domain to aid those planning similar trials.

Staphylococcus aureus Bacteremia in the Pediatric Emergency Department and Predictors of Poor Outcome.

Staphylococcus aureus has become the leading cause of bacteremia among previously healthy children older than 5 years. We aimed to describe the infants presenting to pediatric emergency departments and diagnosed with S. aureus bacteremia (SAB) and identify predictors (clinical and laboratory variables) of poor outcome (complications, sequelae or death). We performed an observational study and subanalysis of a multicenter prospective registry, including every patient under the age of 18 years with a positive blood culture obtained at any of the 22 participating Spanish pediatric emergency departments between 2011 and 2016. We considered chronic diseases, immunosuppressive treatment and the presence of mechanical devices as risk factors for SAB. Of the 229 patients with SAB, 176 (76.9%) were previously healthy, 192 (83.8%) had a normal pediatric assessment triangle and 158 (69.0%) had an associated focal infection (mainly osteoarticular infection, skin and soft tissue infection and pneumonia). Fifty-three patients (23.1%) had 1 or more risk factors for SAB. Thirty-one (13.5%) presented a poor outcome, including 4 deaths (1.7%). A poor outcome was more common in patients with SAB risk factors [odds ratio (OR): 7.0; 95% CI: 3.2-15.4], abnormal PAT (OR: 5.9; 95% CI: 2.6-13.3), elevated procalcitonin (OR: 1.2; 95% CI: 1.05-1.3) and C-reactive protein, the latter being the only independent predictor of poor outcome (OR: 1.01; 95% CI: 1.01-1.02). Overall, children with SAB are previously healthy, appear well, and have an associated focal infection. One out of 7 had a poor outcome, with C-reactive protein being the only predictor identified.

Characteristics and outcomes in adult patients with Staphylococcus lugdunensis bacteremia compared to patients with Staphylococcus epidermidis and Staphylococcus aureus bacteremia: a retrospective study in a 16-year period at the university hospital, Japan

BackgroundStaphyococcus lugudnensis (S. lugdunensis) is one of coagulase-negative Staphylococcus species with a potential to cause invasive infections. Few studies have evaluated the characteristics and outcomes of patients with S. lugdunensis bacteremia (SLB) compared with those of patients with Staphylococcus epidermidis (S. epidermidis) and Staphylococcus aureus (S. aureus) bacteremia.MethodsWe performed a single-center retrospective case–control study of patients aged ≥ 18 who had SLB with at least two sets of positive blood cultures at the Kyoto University Hospital, Japan, from January 2005 to June 2022. Patients who had S. epidermidis bacteremia (SEB) with at least two sets of positive blood cultures and those who had S. aureus bacteremia (SAB) with at least one set of positive blood cultures were randomly selected in a 1:5:5 (SLB:SEB:SAB) ratio.ResultsA total of 22 patients with SLB, 110 patients with SEB, and 110 patients with SAB were included. The proportions of infective endocarditis (IE) and metastatic infections were statistically higher in the SLB group than in the SEB group (14% vs. 2%, p < 0.01 and 18% vs. 5%, p 0.02, respectively) and were not significantly different between the SLB and SAB groups (14% vs. 5%, p 0.16 and 18% vs. 16%, p 0.78, respectively). The seven-day mortality was higher in the SLB group than in the SEB group (9% vs. 1%, p 0.02) and similar between the SLB and SAB groups (9% vs. 7%, p 0.77).ConclusionsThe clinical course and outcome of SLB were worse than those of SEB and similar to those of SAB. Appropriate evaluation and treatment for SAB may be warranted in patients with SLB.

Conventional Hospitalization versus Sequential Outpatient Parenteral Antibiotic Therapy for Staphylococcus aureus Bacteremia: Post-Hoc Analysis of a Multicenter Observational Cohort.

It is not known whether sequential outpatient parenteral antimicrobial (OPAT) is as safe and effective as conventional hospitalization in patients with S. aureus bacteremia (SAB). A post-hoc analysis of the comparative effectiveness of conventional hospitalization versus sequential OPAT was performed in two prospective Spanish cohorts of patients with S. aureus bacteremia. The PROBAC cohort is a national, multicenter, prospective observational cohort of patients diagnosed in 22 Spanish hospitals between October 2016 and March 2017. The DOMUS OPAT cohort is a prospective observational cohort including patients from two university hospitals in Seville, Spain from 2012 to 2021. Multivariate regression was performed, including a propensity score (PS) for receiving OPAT, stratified analysis according to PS quartiles, and matched pair analyses based on PS. Four hundred and thirteen patients were included in the analysis: 150 in sequential OPAT and 263 in the full hospitalization therapy group. In multivariate analysis, including PS and center effect as covariates, 60-day treatment failure was lower in the OPAT group than in the full hospitalization group (p &lt; 0.001; OR 0.275, 95%CI 0.129-0.584). In the PS-based matched analyses, sequential treatment under OPAT was not associated with higher 60-day treatment failure (p = 0.253; adjusted OR 0.660; % CI 0.324-1.345). OPAT is a safe and effective alternative to conventional in-patient therapy for completion of treatment in well-selected patients with SAB, mainly those associated with a low-risk source and without end-stage kidney disease.

Anti-Alpha-Toxin Antibody Responses and Clinical Outcomes of Staphylococcus aureus Bacteremia.

Alpha-toxin (AT), a major virulence factor of Staphylococcus aureus, is an important immunotherapeutic target to prevent or treat invasive S. aureus infections. Previous studies have suggested that anti-AT antibodies (Abs) may have a protective role against S. aureus bacteremia (SAB), but their function remains unclear. Therefore, we aimed to investigate the association between serum anti-AT Ab levels and clinical outcomes of SAB. Patients from a prospective SAB cohort at a tertiary-care medical center (n = 51) were enrolled in the study from July 2016 to January 2019. Patients without symptoms or signs of infection were enrolled as controls (n = 100). Blood samples were collected before the onset of SAB and at 2- and 4-weeks post-bacteremia. Anti-AT immunoglobin G (IgG) levels were measured using an enzyme-linked immunosorbent assay. All clinical S. aureus isolates were tested for the presence of hla using polymerase chain reaction. Anti-AT IgG levels in patients with SAB before the onset of bacteremia did not differ significantly from those in non-infectious controls. Pre-bacteremic anti-AT IgG levels tended to be lower in patients with worse clinical outcomes (7-day mortality, persistent bacteremia, metastatic infection, septic shock), although the differences were not statistically significant. Patients who needed intensive care unit care had significantly lower anti-AT IgG levels at 2 weeks post-bacteremia (P = 0.020). The study findings suggest that lower anti-AT Ab responses before and during SAB, reflective of immune dysfunction, are associated with more severe clinical presentations of infection.

2234. Clinical Significance of Staphylococcus aureus Bacteriuria without Bacteremia

Abstract Background Staphylococcus aureus urinary tract infection (UTI) is uncommon. Staphylococcus aureus bacteriuria (SABU) can occur in patients with urinary tract instrumentation, urinary calculi, or S. aureus bacteremia (SAB) and is associated with development of invasive diseases and death. Thus, SABU is often treated with a prolonged course of antimicrobial therapy similar to SAB. However, little is known about the significance of SABU in patients without SAB and recent urinary tract instrumentation. Methods We conducted a retrospective study of patients with SABU in the Veterans Affairs (VA) system nation-wide from 2017 to 2019. Patients with concomitant SAB, recent history of urinary tract instrumentation, or overt urologic abnormalities were excluded. The primary outcome was development of invasive S. aureus infections or death within 12 months. The secondary outcome was recurrent SABU within 12 months. Results 133 patients met the inclusion criteria. 102 patients (76%) received antimicrobial treatment for SABU. The duration of treatment ranged from 3-30 (mean = 8.5) days. Compared with the non-treated group, patients treated with antimicrobials had significantly more urinary tract symptoms (p = 0.0001), microscopic pyuria (p = 0.002), and hematuria (p = 0.035). Of those treated, 11 (7.3%) died within 12 months of SABU compared to 4 patients (13%) who did not receive treatment (p = 0.749). Three percent of patients from both groups (n = 3 vs 1) developed invasive S. aureus infections within 12 months (p = 1.00). 16% of patients in the treatment group (n = 17) and non-treatment group (n = 5) were found to have recurrent SABU within 12 months (p = 1.00). Conclusion Patients without recent urinary tract instrumentation, overt urologic abnormalities, and SAB who were treated for SABU did not have significant differences in death, invasive diseases, or recurrent SABU at 12 months compared to those who did not receive treatment. Untreated patients did not appear to have frequent complications; however, our numbers were small and our analysis did not take confounding into account. Further analysis into SABU treatment may be warranted. Disclosures All Authors: No reported disclosures.

1829. Dalbavancin versus standard of care as directed therapy for Staphylococcus aureus bacteremia in patients unable to receive OPAT

Abstract Background The purpose of this study was to compare dalbavancin to standard of care (SOC) for patients with S. aureus bacteremia (SAB) who were unable to receive outpatient parenteral antimicrobial therapy (OPAT) and would otherwise remain hospitalized or require placement into post-acute care facilities. Methods This retrospective cohort compared readmission rates related to the index infection between patients treated with dalbavancin or SOC for SAB between January 1, 2016, and August 31, 2021. Patients at least 18 years old seen by the ID consult service who received at least one dose of dalbavancin or at least one week of SOC parenteral antibacterials as directed therapy for SAB at the time of discharge were included. The SOC group consisted of patients transferred from the main hospital to one of the post-acute care facilities in a surrounding county to complete parenteral antibacterials. Patients were excluded if they were treated for polymicrobial infections with organisms other than S. aureus, had a creatinine clearance less than 30 mL/min, or required renal replacement therapy. The primary outcome was readmission rates within 30 days after completion of therapy. Secondary outcomes included readmission rates within 90 days after completion of therapy as well as antibacterial regimen adherence defined as achieving goal duration of therapy deemed appropriate by the ID consult service. Results During the study period, 27 patients received dalbavancin, and 27 patients received SOC. Baseline demographics were comparable between groups, though more patients in the SOC group had indwelling prostheses or hardware (4% vs 22%). The majority of SAB was caused by MSSA in both groups (56% vs 59%). The most common source was osteoarticular (15% vs 30%) and source control was attempted in a higher percentage of the SOC group who had an identified source (53% vs 86%). Readmission rates in the dalbavancin group were similar to those in the SOC group within 30 days (15% vs 22%, p=0.484) and 90 days (19% vs 22%, p=0.735) after completion of therapy. However, adherence was significantly higher among patients treated with dalbavancin (85% vs 44%, p &amp;lt; 0.05). Conclusion Dalbavancin offers similar clinical outcomes to SOC for patients with SAB who are unable to receive OPAT. Disclosures All Authors: No reported disclosures.

1858. Sequential Time to Positivity as a Prognostic Indicator in Staphylococcus aureus bacteremia

Abstract Background The role of sequential blood culture time to positivity (TTP) as a surrogate marker for bacterial load and as a prognostic indicator in S. aureus bacteremia (SAB) is not well established in the literature. Methods We performed a single healthcare system, multi-site, retrospective review of adult patients with positive blood culture for S. aureus between January 2019 and December 2019. Sequential TTP was defined as the TTP of the first subsequent blood cultures obtained from patients with SAB for at least 24 hours. We adapted the previously described TTP ratio of &amp;lt; 1.5 as the cut-off for study groups. Infective endocarditis (IE) was defined according to modified Duke’s criteria. High-grade bacteremia was defined as the growth of the organism in two or more sets of blood cultures or growth in &amp;gt;50% of all bottles collected. Descriptive, comparative statistics and survival analysis were performed using Python 3 and IBM SPSS Statistics for Windows, Version 27.0. Armonk, NY: IBM Corp. Results A total of 602 patients with SAB were identified, and 186 patients who met the study criteria were included. Sixty-nine patients (37%) were female, and the mean age was 63.6 years. Patients with initial TTP &amp;lt; 12 hours had higher 30-day and 90-day mortality than those with initial TTP ≥ 12 hours. Patients with TTP ratio of &amp;gt; 1.5 had higher rates of cardiac prosthetic device (30 [26.1%] vs. 9 [12.7%], p = .03) and high-grade bacteremia (106 [92.2%] vs. 56 [78.9%], p = .01). In univariate analysis, history of myocardial infarction, cardiac prosthetic device, and findings of high-grade bacteremia and native valve vegetation in echocardiogram were significant predictors for a TTP ratio of &amp;lt; 1.5. In multivariate analysis, native valve vegetation (OR 2.4; 95% CI 1.2-4.84), and high-grade bacteremia (OR, 0.3; 95% CI, 0.13- 0.77) were independent predictors (Table 1 and 2). No differences in 30- day or 90-day survival based on the TTP ratio were seen (Figure 1). Figure 1.Kaplan-Meier (KM) curves and log rank test results based on time to positivity (TTP) of initial blood cultures and TTP ratio of sequential to initial blood culture The X-axis represents the days elapsed from the initial blood culture collection. Number of patients at risk and events are given below the x-axis for each group. 30-day and 90-day survival rates were significantly lower in patients with initial TTP of &amp;lt; 12 hours compared with those with ≥ 12 hours. There were no statistically significant differences in survival based on TTP ratio. Conclusion In patients with SAB, a second TTP to first TPP ratio of &amp;gt; 1.5 was associated with higher rates of presence of the cardiac prosthetic device and high-grade bacteremia. Initial TTP &amp;lt; 12 hours was associated with lower survival; however sequential TTP ratio didn’t predict mortality. Disclosures All Authors: No reported disclosures.

425: RISK FACTORS FOR PERSISTENT S AUREUS BACTEREMIA IN PEDIATRIC PATIENTS: A SINGLE-CENTER COHORT STUDY

Introduction: Staphylococcus aureus is a leading cause of infection-related hospitalization in children and accounts for approximately 23% of pediatric bacteremia. Persistent S. aureus bacteremia (SAB) is associated with worse outcomes, but there is limited understanding of the risk factors for sustained infection in children. Our objective was to identify risk factors associated with persistent SAB in our pediatric population. Methods: This was a single-center study using an established biorepository of children with S. aureus infection. Patients with at least one S. aureus positive blood culture were included. Persistent SAB was defined as positive blood cultures on 2 or more consecutive hospital days and at least 24 hours apart. Characteristics of patients with and without persistent SAB were compared using Fisher’s exact test, Wilcoxon rank sum test, and Wilcoxon rank sum exact test. Results: Of 65 patients included in the study, 38 (58%) had persistent SAB. The median age was 8.7 years, 65% were male (n=42) and 85% were white (n=54). 95% (n=62) had community-onset bacteremia, 64% (n=42) had infection caused by a methicillin-susceptible S. aureus (MSSA) isolate, and 57% (n=57) had another site of infection (e.g., abscess or bone/joint). Only 14% (n=9) of patients required ICU care. Of those, 67% (n=6) were caused by an MRSA isolate. Patients with persistent SAB had shorter duration to culture positivity than those without persistent SAB: 16 hours (IQR, 4-20h) vs. 20 hours (IQR, 16-25h) (p=0.017); and longer time to source control: 43 hours (IQR, 21-66h) vs. 17 hours (IQR,13-22h) (p=0.011). Conclusions: Our findings reveal that persistent SAB is associated with shorter time to culture positivity and longer time to source control, suggesting that a higher and sustained bacterial burden contributes to persistent infection. Interestingly, we found higher rates of persistent SAB (58%) and SAB due to MSSA (64%) than previously reported. This may be due to a combination of factors including an inconsistent definition of persistent bacteremia across studies, regional variability in S. aureus virulence, differences in the racial and ethnic diversity, and potential sampling bias. Further analysis of laboratory values, antibiotic use, chronic and co-occurring conditions of our cohort are warranted and pending.

EPIDEMIOLOGY, PREDISPOSING FACTORS AND OUTCOME OF STAPHYLOCOCCUS AUREUS BACTEREMIA IN NEUTROPENIC PATIENTS

Staphylococcus aureus is a common cause of bloodstream infection in neutropenic patients. We analyzed trends in incidence, epidemiology, predisposing factors and outcome of S. aureus bacteremia (SAB) in febrile neutropenic patients. We reviewed a database of febrile neutropenia at a single institution in Brazil in a 30-year period (January 1991 to December 2020). We divided in 3 periods: 1991-1994 (period 1), 2001-2010 (period 2) and 2011-2020 (period 3), and looked at incidence rates, risk factors and mortality. Risk factors and prognostic factors were evaluated by univariate (Fisher or Chi-square for categorical variables and Wilcoxon test for continuous variables) and multivariate (logistic regression) analysis. We diagnosed 62 (3%) episodes of SAB in 2,243 episodes of febrile neutropenia, 23 (38%) of which were caused by methicillin-resistant S. aureus (MRSA). The incidence of SAB per 1,000 days of neutropenia was 1.57, 2.53 and 1.50 in periods 1, 2 and 3, respectively (p > 0.05), and of MRSA was 0.49, 0.84 and 1.07, respectively (p > 0.05). Most infections (70%) were diagnosed in the first day of fever and the clinical presentation were skin infection (19%), catheter-related infection (14%) and pneumonia (3%). Complications like endocarditis or osteomyelitis were not observed. The only factor associated with S. aureus bacteremia by multivariate analysis was cellulitis at site of catheter exit site or tunnel on day 1 of fever (odds ratio [OR] 4.34, 95% confidence interval [CI] 2.05 – 9.16), whereas quinolone prophylaxis was protective (OR 0.37, 95% CI 0.18 - 0.74). The crude mortality of SAB was 30.6%, compared 13.8% in patients without this infection (p < 0.001). However, early mortality (within 3 days of start of empiric antibiotic therapy) was not significantly different (4.8% vs. 1.9%, p = 0.08). The mortality with MRSA was higher than with methicillin-susceptible S. aureus (47.8% vs. 13.9%, p < 0.001), but no difference was found regarding early mortality (5.0 vs 1.7%, p = 0.27). Among various predictors of death during febrile neutropenia MRSA bacteremia (but not methicillin-sensitive) was associated with an increased risk of death by multivariate analysis. The median time from febrile neutropenia to death in MRSA episodes was 19 days. The incidence of SAB over the period remained stable. Complication of SAB were not common. Although the crude mortality was higher with SAB (including MRSA), it was not associated with early deaths, thus not demanding anti-staphylococcal coverage in the first day of febrile neutropenia. MRSA bacteremia was associated with increased risk of death, with most deaths occurring after 2 weeks of febrile neutropenia.

IFI44 is an immune evasion biomarker for SARS-CoV-2 and Staphylococcus aureus infection in patients with RA.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic of severe coronavirus disease 2019 (COVID-19). Staphylococcus aureus is one of the most common pathogenic bacteria in humans, rheumatoid arthritis (RA) is among the most prevalent autoimmune conditions. RA is a significant risk factor for SARS-CoV-2 and S. aureus infections, although the mechanism of RA and SARS-CoV-2 infection in conjunction with S. aureus infection has not been elucidated. The purpose of this study is to investigate the biomarkers and disease targets between RA and SARS-CoV-2 and S. aureus infections using bioinformatics analysis, to search for the molecular mechanisms of SARS-CoV-2 and S. aureus immune escape and potential drug targets in the RA population, and to provide new directions for further analysis and targeted development of clinical treatments.MethodsThe RA dataset (GSE93272) and the S. aureus bacteremia (SAB) dataset (GSE33341) were used to obtain differentially expressed gene sets, respectively, and the common differentially expressed genes (DEGs) were determined through the intersection. Functional enrichment analysis utilizing GO, KEGG, and ClueGO methods. The PPI network was created utilizing the STRING database, and the top 10 hub genes were identified and further examined for functional enrichment using Metascape and GeneMANIA. The top 10 hub genes were intersected with the SARS-CoV-2 gene pool to identify five hub genes shared by RA, COVID-19, and SAB, and functional enrichment analysis was conducted using Metascape and GeneMANIA. Using the NetworkAnalyst platform, TF-hub gene and miRNA-hub gene networks were built for these five hub genes. The hub gene was verified utilizing GSE17755, GSE55235, and GSE13670, and its effectiveness was assessed utilizing ROC curves. CIBERSORT was applied to examine immune cell infiltration and the link between the hub gene and immune cells.ResultsA total of 199 DEGs were extracted from the GSE93272 and GSE33341 datasets. KEGG analysis of enrichment pathways were NLR signaling pathway, cell membrane DNA sensing pathway, oxidative phosphorylation, and viral infection. Positive/negative regulation of the immune system, regulation of the interferon-I (IFN-I; IFN-α/β) pathway, and associated pathways of the immunological response to viruses were enriched in GO and ClueGO analyses. PPI network and Cytoscape platform identified the top 10 hub genes: RSAD2, IFIT3, GBP1, RTP4, IFI44, OAS1, IFI44L, ISG15, HERC5, and IFIT5. The pathways are mainly enriched in response to viral and bacterial infection, IFN signaling, and 1,25-dihydroxy vitamin D3. IFI44, OAS1, IFI44L, ISG15, and HERC5 are the five hub genes shared by RA, COVID-19, and SAB. The pathways are primarily enriched for response to viral and bacterial infections. The TF-hub gene network and miRNA-hub gene network identified YY1 as a key TF and hsa-mir-1-3p and hsa-mir-146a-5p as two important miRNAs related to IFI44. IFI44 was identified as a hub gene by validating GSE17755, GSE55235, and GSE13670. Immune cell infiltration analysis showed a strong positive correlation between activated dendritic cells and IFI44 expression.ConclusionsIFI144 was discovered as a shared biomarker and disease target for RA, COVID-19, and SAB by this study. IFI44 negatively regulates the IFN signaling pathway to promote viral replication and bacterial proliferation and is an important molecular target for SARS-CoV-2 and S. aureus immune escape in RA. Dendritic cells play an important role in this process. 1,25-Dihydroxy vitamin D3 may be an important therapeutic agent in treating RA with SARS-CoV-2 and S. aureus infections.

Outer membrane vesicles of the oral pathogen Porphyromonas gingivalis promote aggregation and phagocytosis of Staphylococcus aureus

Staphylococcus aureus is an opportunistic Gram-positive bacterial pathogen that causes a wide variety of infectious diseases, including S. aureus bacteremia (SAB). Recent studies showed that rheumatoid arthritis (RA) is a risk factor for SAB, as RA patients appear to be more susceptible to SAB and display higher degrees of disease severity or complications, such as osteoarticular infections. On the other hand, Porphyromonas gingivalis is a Gram-negative bacterial oral pathogen, which is notable for its implication in the etiopathogenesis of RA due to its unique citrullinating enzyme PPAD and its highly effective proteases, known as gingipains. Both PPAD and gingipains are abundant in P. gingivalis outer membrane vesicles (OMVs), which are secreted nanostructures that originate from the outer membrane. Here we show that P. gingivalis OMVs cause the aggregation of S. aureus bacteria in a gingipain- and PPAD-dependent fashion, and that this aggregation phenotype is reversible. Importantly, we also show that the exposure of S. aureus to OMVs of P. gingivalis promotes the staphylococcal internalization by human neutrophils with no detectable neutrophil killing. Altogether, our observations suggest that P. gingivalis can eliminate its potential competitor S. aureus by promoting staphylococcal aggregation and the subsequent internalization by neutrophils. We hypothesize that this phenomenon may have repercussions for the host, since immune cells with internalized bacteria may facilitate bacterial translocation to the blood stream, which could potentially contribute to the association between RA and SAB.

Impact of Staphylococcus aureus bacteremia in COVID-19 patients

IntroducciónLa enfermedad causada por SARS-CoV-2 (COVID-19) ha supuesto un desafío para los profesionales sanitarios desde su aparición. Staphylococcus aureus es uno de los principales patógenos causantes de infecciones bacterianas en pandemias virales. Sin embargo, se debe estudiar bien la co-infección por S. aureus causante de bacteriemia en pacientes con COVID-19.MétodosSe analizaron los casos de bacteriemia por S. aureus (BSA) atendidos en el Hospital Miguel Servet (Zaragoza) desde marzo de 2020 hasta febrero de 2021. Se compararon las características clínicas, los factores de riesgo y mortalidad de los pacientes con BSA asociada a COVID-19 respecto los pacientes no-COVID-19.ResultadosSe identificaron 95 pacientes con BSA. El 27,3% fueron COVID-19 positivos. La BSA representó el 9,9% de las bacteriemias, siendo el segundo microorganismo en frecuencia tras E. coli. La bacteriemia nosocomial fue más frecuente en el grupo de pacientes con COVID-19. La fuente de BSA fue desconocida en el 46,2% de los pacientes con COVID-19. La fuente de BSA más frecuente en estos pacientes fue la respiratoria (26,9% vs 0%; P<0,001) seguida de la cutánea (15,5% vs 15,9%; P=1). El desarrollo de sepsis fue más frecuente en los pacientes con COVID-19 (61,5% vs 7,8%; P=0,336) y de ellos, los que recibieron dosis de dexametasona >6 mg/día (62,5% vs 37,5%; P< 0,05).ConclusionesNuestros datos sugieren que la BSA influye negativamente en la evolución de los pacientes con COVID-19. Sin embargo, se requieren más estudios y preferiblemente prospectivos para obtener datos sólidos sobre el impacto de la BSA en los pacientes con coronavirus.

Prevalence, mortality, and resource utilization of Staphylococcus aureus bacteremia in liver transplant recipients: A 2012–2016 nationwide analysis

BackgroundBacteremia due to Staphylococcus aureus is a known, serious complication of liver transplantation (LT). ObjectivesThe purpose of our study was to evaluate the national impact of S. aureus bacteremia (SAB) in LT recipients in terms of mortality rates and the economic impact on an institution. MethodsThis retrospective cohort study used 2012–2016 National Inpatient Sample data, the largest public inpatient database in the United States, to separate LT recipients with SAB during index LT admission from those unaffected by SAB. The SAB cohorts are further defined by speciation, methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). The primary outcome was the odds of inpatient mortality. Secondary outcomes included inpatient morbidity, resource utilization, hospital length of stay, and inflation-adjusted total hospital costs and charges. ResultsDuring the study period, 26,415 patients underwent LT. SAB was found in 340 patients (MSSA n = 180 [52.9%], MRSA n = 160 [47.1%]), while 26,075 LT patients had no SAB episode during the index admission. Patients with MSSA and MRSA bacteremias displayed higher inpatient mortality rates (11.1% and 9.4%, respectively) compared to the non-SAB cohort (3.4%, p < 0.01). ConclusionsDuring the index LT hospitalization, SAB was directly correlated with increased mortality rates, sepsis occurrence, and shock. More extended hospital stays, higher healthcare costs and charges were found in the SAB cohort. SAB occurring during the index hospitalization of LT-recipients have higher mortality rates than LT-recipients without SAB. More healthcare resources as determined by inflation-adjusted total hospital costs and charges were spent on LT-recipients with SAB compared to those without SAB.