Staphylococcus aureus Bacteraemia - an Interdisciplinary Challenge

To improve management of Staphylococcus aureus bacteremia (SAB), better understanding of host-pathogen interactions is needed. In vitro studies have shown that S. aureus bacteria induce dose-dependent immunosuppression that is evidenced by reduced expression of major histocompatibility complex (MHC) class II on antigen presenting cells. Thus, the aim of this study was to determine whether expression of the MHC class II-related genes HLA-DRA and CD74 is more greatly reduced in complicated SAB, with its probable higher loads of S. aureus, than in uncomplicated SAB. Adult patients with SAB were prospectively included and blood samples taken on the day of confirmation of SAB (Day 1) and on Days 2, 3, 5 and 7. HLA-DRA and CD74 mRNA expression was determined by quantitative reverse transcription PCR. Sepsis was defined according to the Sepsis-3 classification and SAB was categorized as complicated in patients with deep-seated infection and/or hematogenous seeding. Twenty patients with SAB were enrolled and samples obtained on all assessment days. HLA-DRA and CD74 expression did not differ significantly between patients with SAB and sepsis (n = 13) and those without sepsis (n = 7) on any assessment day. However, patients with complicated SAB (n = 14) had significantly weaker HLA-DRA expression on all five assessment days than patients with uncomplicated SAB (n = 6). Additionally, they tended to have weaker CD74 expressions. Neutrophil, monocyte and leukocyte counts did not differ significantly between complicated and uncomplicated SAB. In conclusion, patients with complicated SAB show weaker HLA-DRA expression than those with uncomplicated SAB during the first week of bacteremia.

BackgroundCurrent guidelines recommend at least 2 weeks duration of antibiotic therapy (DOT) for patients with uncomplicated Staphylococcus aureus bacteraemia (SAB) but the evidence for this recommendation is unclear. ObjectivesTo perform a systematic literature review assessing current evidence for recommended DOT for patients with SAB. MethodsThe following are the methods used for this study. Data sourcesWe searched MEDLINE, ISI Web of Science, the Cochrane Database and clinicaltrials.gov from inception to March 30, 2024. References of eligible studies were screened and experts in the field contacted for additional articles. Study eligibility criteriaAll clinical studies, regardless of design, publication status and language. ParticipantsAdult patients with uncomplicated SAB. InterventionsLong (>14 days; >18 days; 11–16 days) vs. short (≤14 days; 10–18 days; 6–10 days, respectively) DOT with the DOT being defined as the first until the last day of antibiotic therapy. Assessment of risk of biasRisk of bias was assessed using the ROBINS-I-tool. Methods of data synthesisThe primary outcome was 90-day all-cause mortality. Only studies presenting results of adjusted analyses for mortality were included. Data synthesis could not be performed. ResultsEleven nonrandomized studies were identified that fulfilled the pre-defined inclusion criteria, of which three studies reported adjusted effect ratios. Only these were included in the final analysis. We did not find any RCT. Two studies with 1230 patients reported the primary endpoint 90-day all-cause mortality. Neither found a statistically significant superiority for longer (>14 days; 11–16 days) or shorter DOT (≤14 days; 6–10 days, respectively) for patients with uncomplicated SAB. Two studies investigated the secondary endpoint 30-day all-cause mortality (>18 days; 11–16 days vs. 10–18 days; 6–10 days, respectively) and did not find a statistically significant difference. All included studies had a moderate risk of bias. ConclusionsSound evidence that supports any duration of antibiotic treatment for patients with uncomplicated SAB is lacking.

Staphylococcus aureus bacteraemia (SAB) is a common and severe disease. In 2012, a structured bedside consultation (SBC) was introduced at Rijnstate Hospital. We analysed the effect of this SBC on the overall survival of patients with SAB and the effect on the diagnostic workup. We performed a retrospective cohort study, including all patients over 18years with SAB from 2009 until 2017. The cases preceding versus those after implementation of SBC in 2012 were compared. In total, 613 episodes of SAB were analysed: 234 cases before and 379 cases since SBC. In 484 patients at risk for a complicated course, there was no significant difference in the 30-day survival (77 versus 82%, p = 0.18); however, an increase in 365-day survival was seen (56 versus 64%, p = 0.05). Overall, more patients received adequate therapy, both in the first 2weeks (67.8 versus 86.7%, p < 0.001), as in complicated SAB (70.5 versus 93.2%, p < 0.001). In 21% of patients with transoesophageal echocardiogram (TEE) following a negative or inconclusive TTE, endocarditis was diagnosed. In patients at risk for complicated SAB, the PET scan revealed a metastatic infection which was not clinically suspected in 65% of positive PET scans. Structured bedside consultation is associated with a better 365-day survival in patients at risk for complicated SAB. Moreover, the additional value of TEE and the PET scan was shown. We strongly advise compliance to SBC in all patients at risk for complicated SAB and the use of both TEE and PET scans in these patients. Even in uncomplicated SAB, TEE or PET scan can reveal metastatic infections.

Staphylococcus aureus (SA) is a major cause of bacteremia in children. Methicillin-resistant SA (MRSA) is considered a public health threat; however, the differences in the prognosis of children with methicillin-susceptible SA (MSSA) versus MRSA bacteremia are not well defined. Data from all SA bacteremia events in children (0-16 years) from 2002 to 2016 in a single Israeli tertiary center were collected. Positive cultures within 48 hours of hospitalization were considered community associated (CA). Those obtained afterward or from children hospitalized within the previous year were considered health-care associated (HA). We recorded 427 events, 284 (66%) were HA, 64 (15%) were MRSA and 9 (2%) were CA-MRSA. There was no increase in MRSA during the study period. In-hospital, 30-day and 1-year mortality were 3% (12 cases), 3.5% (16 cases), and 12% (50 cases), respectively. A multivariable analysis controlling for demographics, admitting department and prior morbidity showed an increased 1-year mortality in children with HA bacteremia (hazard ratio [HR] 4.1; 95% confidence interval [CI]: 1.3-12) and prior chronic disease (HR 3.4; 95% CI 1.2 to 9.0). MRSA was not independently associated with increased one-year mortality compared with MSSA: HR (95% CI: 1.4 [0.6-3.1]). Short-term pediatric mortality after SA bacteremia is low. HA-SA bacteremia has an increased long-term risk for mortality, particularly in children with chronic diseases. Our data suggest mortality was not increased for MRSA compared with MSSA bacteremia. The very low rate of CA-MRSA bacteremia justifies the current practice not to include glycopeptides in the empiric treatment of CA bacteremia in Israel.

BackgroundClinical outcomes and host immune response in solid-organ transplant recipients (Tx) with Staphylococcus aureus bacteremia (SAB) and Gram-negative bacteremia (GNB) are poorly understood. The aims of this study were to describe (1) clinical characteristics and outcomes and (2) acute-phase cytokine response in Tx recipients with SAB and GNB as compared with matched non-transplant subjects (Non-Tx).MethodsThirty-two Tx recipients who were prospectively enrolled in the Blood Stream Infection Biorepository (BSIB) were matched 1:1 with Non-Tx patients on age, race, gender and bacteria using a perfect matching algorithm (Tx-SAB n = 16, Non-Tx SAB n = 16; Tx GNB n = 16, Non-Tx GNB n = 16). GNB included Escherichia coli (n = 16) and Klebsiella pneumoniae (n = 16). Multiplex cytokine testing was performed (Luminex) to evaluate acute-phase serum cytokines levels. Baseline characteristics were summarized using mean with standard deviation (SD), median with interquartile range (IQR), and ranges (min and max), or frequency with %. Differences between the Tx and Non-Tx SAB and GNB were compared using either the equal or unequal variance version of the Student’s t-test or Wilcoxon rank-sum test for continuous variables. Fisher’s exact test was used for categorical variables.ResultsAn endovascular source was more common in Tx SAB vs. Non-Tx SAB (75.0% vs. 0.0%; P = 0.0003) and Tx-GNB (42.9% vs. 18.8%; P = 0.006). Fewer SAB cases were attributed to a skin/soft tissue/osteoarticular in Tx vs. Non-Tx (8.3% vs. 91.7%; P = 0.0001). APACHE II scores were higher in Tx SAB vs. Non-Tx SAB (14.0 [IQR: 11.0, 17.5] vs. 10.0 [IQR: 7.0, 12.5] P = 0.02), but not between Tx GNB vs. Non-Tx GNB (14 [IQR: 12.0, 15.5] vs. 13.5 [12.0, 15.0] P = 0.54). No significant difference length of stay, recurrent bacteremia or mortality were noted among or between groups. Patients with SAB had significantly higher levels of IL-10, CCL5, eotaxin vs. GNB in both Tx and Non-Tx. Conversely, IL-5, IL-13 and IL-17 levels were significantly lower in SAB compared with GNB in both Tx and Non-Tx. Within Tx alone, IL-8 and IL-15 were significantly higher in SAB as compared with GNB.ConclusionSignificant differences exist in etiology and host immune response in Tx and Non-Tx with SAB and GNB. Further research is needed to understand the host immune response to BSI in these patients.DisclosuresAll authors: No reported disclosures.

BackgroundThe 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 AnalysisThe 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.

Background Staphylococcus aureus bacteremia (SAB) and methicillin-resistant Staphylococcus aureus (MRSA) infection are associated with unfavorable outcomes. Aim To reveal the risk factors, sensitivity to antibiotics, and outcome of MRSA bacteremia in infants and children with sepsis. Settings and design A prospective observational cross-sectional study was performed in Mansoura University Children’s Hospital from March 2023 to January 2024. Patients and methods The study involved infants and children diagnosed with sepsis and confirmed SAB on blood culture. Demographic data and blood culture with antibiotics sensitivity were recorded. Risk factors for MRSA bacteremia, antibiotic susceptibility, and mortality are the study outcomes. Statistical analysis used Multivariate analysis was done to assess the predictors of MRSA infection. Results A total of 319 patients were admitted with sepsis. SAB was isolated from 133 patients, 99 (74.4%) with methicillin-sensitive Staphylococcus aureus and 34 (25.6%) with MRSA. Risk factors for the development of MRSA infection are the presence of hospital-acquired infection (adjusted odds ratio=6.95), prolonged mechanical ventilation, presence of shock, and decreased body weight. Mortality was higher in the MRSA group (20.6 vs. 6.1%, P=0.014) with prolonged median duration of pediatric intensive care unit admission (19.5 vs. 14 days; P=0.040). Linezolid and teicoplanin were the most efficient antibiotics used in MRSA with 100% sensitivity in-vitro cultures, whereas resistance to erythromycin (90.9%) was documented. Conclusion MRSA poses a significant threat in pediatric sepsis. The presence of hospital-acquired infection and prolonged mechanical ventilation are the chief predictors of MRSA infection. Linezolid and teicoplanin are the most sensitive antibiotics used in MRSA management.

From 1 January to 31 December 2022, fifty-five institutions across Australia participated in the Australian Staphylococcus aureus Surveillance Outcome Program (ASSOP). The aim of ASSOP 2022 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that were antimicrobial resistant, with particular emphasis on susceptibility to methicillin and on characterisation of the molecular epidemiology of the methicillin-resistant isolates. A total of 3,214 SAB episodes were reported, of which 77.5% were community-onset. Overall, 15.0% of S. aureus were methicillin resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 21.4%, which was significantly different to the 16.8% all-cause mortality associated with methicillin-susceptible SAB (p = 0.02). With the exception of the β-lactams and erythromycin, antimicrobial resistance in methicillin-susceptible S. aureus was rare. However, in addition to the β-lactams, approximately 31% of methicillin-resistant S. aureus (MRSA) were resistant to ciprofloxacin; 30% to erythromycin; 13% to tetracycline; 11% to gentamicin; and 2% to co-trimoxazole. One MRSA isolate, with a daptomycin MIC of 1.5 mg/L, harboured the A302V mprF and A23V cls2 mutations. When applying the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, teicoplanin resistance was detected in one MRSA isolate. Resistance to vancomycin or linezolid was not detected. Resistance to non-β-lactam antimicrobials was largely attributable to the healthcare-associated MRSA (HA-MRSA) clone ST22-IV [2B] (EMRSA-15), and to the community-associated MRSA (CA-MRSA) clone ST45-V [5C2&5] which has acquired resistance to multiple antimicrobials including ciprofloxacin, clindamycin, erythromycin, gentamicin, and tetracycline. The ST22-IV [2B] (EMRSA-15) clone is the predominant HA-MRSA clone in Australia. Nonetheless, 86% of methicillin-resistant SAB episodes were due to CA-MRSA clones. Although polyclonal, approximately 72% of CA-MRSA clones were characterised as ST93-IV [2B] (Queensland clone); ST5-IV [2B]; ST45-V [5C2&5]; ST1-IV [2B]; ST30-IV [2B]; ST97-IV [2B]; ST953-IV [2B]; and ST8-IV [2B]. As CA-MRSA is well established in the Australian community, it is important to monitor antimicrobial resistance patterns in community- and healthcare-associated SAB as this information will guide therapeutic practices in treating S. aureus bacteraemia.

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. 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. 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). 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.

Persistent Staphylococcus aureus bacteremia (SAB) has been associated with increased mortality. Enhanced microbial detection with new blood culture technology may improve detection of S. aureus in patients with SAB. We performed a 24-month retrospective study of hospitalized adults with SAB and an infectious diseases consult comparing two time periods pre- (January to December 2018) and postimplementation (January to December 2019) in which the VersaTREK and BacT/Alert Virtuo blood culture systems were used, respectively. Measurements included SAB duration, time to positivity, source of bacteremia, antimicrobial therapy, and mortality. A total of 416 episodes of SAB occurred during the study period: 176 (42%) pre- and 240 (58%) postimplementation. Patients in both periods had similar clinical characteristics; however, patients in the postimplementation period were more likely to have intermediate (3 to 6 days; 23% versus 40%; P < 0.001) and prolonged SAB duration (>7 days; 4% versus 14%; P < 0.001). Combination antistaphylococcal therapy was more frequent postimplementation (6.3% pre- versus 15.8% postimplementation; P = 0.003), and the median time to source control was shorter (4 versus 2 days; P = 0.02). Median time to positivity for the index blood culture was shorter postimplementation (17.8 h pre- versus 13.3 h postimplementation; P < 0.001). There was no difference in 90-day all-cause readmissions (51% versus 44%; P = 0.11) or mortality (32% versus 32%; P = 0.95). An increased frequency of prolonged SAB with increased use of combination antistaphylococcal therapy was noted with implementation of a new blood culture system, likely secondary to the blood culture media; however, no differences on adverse outcomes were noted.

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.

BackgroundMultiple studies have shown that Infectious Diseases (ID) consultation significantly improves adherence to guidelines for patients with SAB and decreases mortality. Data from a prior retrospective study done at Hahnemann University Hospital showed that ID consultation improved the use of guideline-based core measures for SAB management. Based on these data, a mandatory ID consultation was established at our institution in November 2016.MethodsA retrospective, observational study was conducted to evaluate patient characteristics, adherence to core measures for SAB, and in-hospital mortality. All patients with at least one documented blood culture positive for S. aureus were stratified into two groups: pre-mandatory consult (January 1, 2014–November 1, 2016) and post mandatory consult (November 2, 2016–February 1, 2018).ResultsThree hundred seventy-three discrete episodes of SAB were included in the final analysis, 238 episodes before mandatory consult, and 135 episodes after the mandatory consult policy was enacted. Mandatory consultation significantly improved the use of the following core measures for SAB: surveillance blood cultures (87.7% pre vs. 99.2% post, P < 0.001), echocardiography (81.9% vs. 96.9%, P < 0.001), early targeted antimicrobial therapy with nafcillin or cefazolin in MSSA (71.7% vs. 88.6%, P < 0.001), and appropriateness of final antibiotic choice (80.2% vs. 95.2%, P < 0.001). In addition, in-hospital mortality (15.4% vs. 6.2%, P = 0.011), and infection-related mortality (14.3% vs. 5.6%, P = 0.011) were found to be statistically significantly lower in the post mandatory consultation patients.ConclusionImplementation of a mandatory ID consultation for patients with SAB at our institution was associated with increased adherence to guideline-based core measures for management of SAB, and decreased in-hospital and infection-related mortality. Our results suggest that mandatory ID consultation for SAB should be considered at all institutions.DisclosuresAll authors: No reported disclosures.

Incidences of Staphylococcus aureus bacteraemia (SAB) in Israeli children are unknown. The characteristics of SAB in children have not been evaluated. SAB from children aged ≤18years old, admitted to a tertiary hospital in Israel during 2002-2015, were included. The proportional rate of SAB was calculated per 1000 admissions. SAB were classified as community acquired (CA), hospital acquired (HA) and healthcare related (HCR). Patients' characteristics, antibiotic susceptibility and outcomes were assessed in each group. The rate of SAB was stable, 1.48 per 1000 admissions. HA, CA and HCR-SAB comprised 53%, 25% and 22%, respectively. Only 27/185 (14.6%) were caused by methicillin-resistant Saureus (MRSA): 22%, 6% and 5% of HA, CA and HCR-SAB, respectively. Central venous catheter, recent surgery, immunodeficiency and age <6years were the main risk factors for HA and HCR-SAB (adjusted OR: 68.9, 7.5, 5.8 and 5.5, respectively). Treatment duration for CA was >21days: and for HA and HCR, 14-20days. All-cause in-hospital mortality and 30-day mortality were documented in 10 (5%) and 3 (2%) episodes, respectively. The rate of SAB; the proportions of CA, HA and HCR-SAB; and the proportion of MRSA was stable over the years. MRSA was mainly in HA-SAB. Thirty-day mortality was rare.

Multiple studies have shown that Staphylococcus aureus bacteremia (SAB) has been a major cause of death in hemodialysis patients. We examined whether SAB is a risk for mortality among chronic hemodialysis patients in Japan where the standard vascular access is arteriovenous fistula (AVF). This was a multicenter, retrospective study of maintenance hemodialysis patients with bloodstream infection (BSI) from 2011 to 2013 at tertiary care centers in Japan. The endpoint was hospital mortality. Our cohort contained 32 SAB cases (14 MRSA and 18 MSSA) and 42 non-SAB cases. Hospital mortality was higher among SAB cases than non-SAB cases (46.9% vs. 23.8%, P=0.038). In patients with BSI, SAB was significantly associated with hospital mortality after adjustment for potential confounders, including type of vascular access (OR 3.26). S. aureus was the leading cause of BSI and hospital mortality among this cohort. Therefore, initial empiric treatment should cover for S. aureus.

BackgroundWe 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.MethodsWe 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.ResultsOf 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.ConclusionsOur 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.Supplementary InformationThe online version contains supplementary material available at 10.1007/s15010-024-02284-z.