Staphylococcus Aureus Bacteremia Research Articles

269. Clinical Characteristics and Outcomes of Persistent Staphylococcus aureus Bacteremia

Background Staphylococcus aureus bacteremia (SAB) is a leading cause of bacteremia and persistent SAB is associated with poor outcomes. We evaluated key clinical characteristics and outcomes associated with persistent SAB.MethodsWe reviewed patients enrolled in a prospective cohort of adult patients with S. aureus bacteremia at a tertiary hospital from August 2008 to December 2018. Clinical characteristics, outcomes, and microbiologic characteristics of patients with persistent bacteremia (≥ 3 d) were evaluated.ResultsOf the total 969 patients, 617 (63.7%) patients had persistent bacteremia. The median duration of bacteremia with persistent bacteremia was 5 days. The most common sources of persistent bacteremia were central venous catheter-related infection (33.4%) and bone and joint infection (14.9%). Methicillin resistant S. aureus (MRSA) isolates were analyzed in 372 (60.3%) patients and metastatic infections were 217 (35.2%) with persistent bacteremia. In the multivariate analysis, APACHE Ⅱ score (adjusted odds ratio [aOR], 1.07; 95% confidence interval [CI], 1.03–1.10), Charlson comorbidity index score (aOR, 1.14; 95% CI, 1.04–1.25), liver cirrhosis (aOR, 2.47; 95% CI, 1.44–4.23), and S. aureus pneumonia (aOR, 3.04; 95% CI, 1.29–7.18) were independently associated with 30-d mortality. In persistent MRSA bacteremia, ST5-SCCmecⅡ was 59.7% (222/372) and agr dysfunction was 64.8% (241/372). After adjusting for confounding factors, APACHE Ⅱ score (aOR, 1.08; 95% confidence interval [CI], 1.04–1.12), liver cirrhosis (aOR, 3.09; 95% CI, 1.56–6.14), and S. aureus pneumonia (aOR, 4.37; 95% CI, 1.40–13.67) were independently associated with 30-d mortality.Table 1. Demographic and Clinical characteristics of Patients With Persistent Bacteremia Table 2. Microbiologic Characteristics and Genotypes in MRSA Isolates Responsible for Persistent Bacteremia Fig 1. Duration of Staphylococcus aureus bacteremia ConclusionIn persistent bacteremia, clinical factors, including APACHE Ⅱ score, Charlson comorbidity index score, liver cirrhosis, and S. aureus pneumonia contribute to 30-d mortality.Disclosures All Authors: No reported disclosures

255. Ticagrelor Aids Platelet-Mediated Clearance in a Refractory Staphylococcus aureus Endovascular Infection with Septic Emboli

BackgroundThe pore-forming alpha-toxin produced by Staphylococcus aureus (SA) decreases the viability and increases the clearance of platelets, a critical element of innate immune defense in endovascular infection. Our group recently identified that ticagrelor (TICA) blocks alpha-toxin-induced platelet clearance, protecting mice in a lethal systemic SA infection model. Here, we describe a case report in which TICA, added to antimicrobial therapy of a persistent methicillin-susceptible SA (MSSA) bacteremia associated with a septic aortic thrombus, resulted in immediate bacteremia clearance. We further explore TICA synergy with antibiotics and human platelets in vitro.MethodsAntibiotic susceptibility of an MSSA strain from a patient treated with TICA for refractory bacteremia was tested by MIC and checkerboard assays in MHB or RPMI at standard (105 CFU/mL) or high (107 CFU/mL) inocula using TICA, ertapenem (ETP), cefazolin (CZ), or nafcillin (NAF) alone vs. ETP+CZ ± TICA. Killing assays with human platelets ± TICA against SA were also performed.ResultsSA bacteremia secondary to a septic aortic thrombus (>4 mm) with multiple secondary pyogenic foci refractory to standard CZ and subsequent salvage CZ+ETP for 5 days rapidly cleared within 24 h after the addition of TICA. Thrombocytopenia resolved concurrently. Discontinuation of TICA on day 12 led to rebound thrombocytopenia, and TICA was restarted, once again resulting in resolution of thrombocytopenia. TICA alone lacked in vitro activity against SA, nor was TICA synergistic with ETP+CZ. In contrast, addition of a physiological achievable concentration of TICA dramatically sensitized SA to human platelet killing (p< 0.001) in vitro.Figure 1 Figure 2 Figure 3 ConclusionIn a complex case of aortic plaque rupture with septic thrombus, multiple septic emboli, and refractory MSSA bacteremia, addition of TICA to antimicrobial therapy yielded unanticipated immediate clinical and microbiological success. The profound therapeutic effect of TICA in vivo was corroborated by the enhanced staphylocidal activity of human platelets in vitro in the presence of physiological concentrations of the antiplatelet agent. TICA warrants further study as adjunctive treatment of refractory SA bacteremia due to a primary endovascular focus when thrombocytopenia is present.Disclosures Victor Nizet, MD, Centauri Therapeutics (Advisor or Review Panel member)Cidara Therapeutics (Advisor or Review Panel member)InhibRx (Advisor or Review Panel member)Roche Pharmaceutical (Advisor or Review Panel member)

Impact of Infectious Diseases Consultation on Management and Outcome of Staphylococcus aureus Bacteremia in Children.

To examine the impact of infectious diseases consultation (IDC) on the management and outcome of Staphylococcus aureus bacteremia (SAB) in children. A retrospective cohort study of children with SAB at a teritary pediatric hospital (January 2009-June 2015) identified by medical record review as to whether they received an IDC for SAB at the discretion of the admitting physician or surgeon was conducted. Differences in management and outcomes for those with and without IDC were evaluated, and multivariate regression analysis was used to determine factors associated with cure. There were 100 patients included in the analysis. Fifty-five patients received IDC and 45 had no IDC (NIDC). Appropriate directed therapy within 24 hours (54/55 = 98.2% vs 34/45 = 75.6%, P < .01), choice (54/55 = 98.2% vs 37/45 = 82.2%, P < .01), dose (54/55 = 98.2% vs 36/45 = 80%, P < .01), and duration (52/55 = 94.5% vs 24/45 = 53.3%, P < .01) of directed antibiotic therapy were appropriate in more IDC group patients. Achievement of source control in indicated cases was also more common in the IDC group (28/32 = 87.5% vs 5/26 = 19.1%, P < .01). Appropriate investigation with repeat blood cultures and echocardiograms was not significantly different. All 55 patients in the IDC group had a complete response (cure) compared with 40 of the 45 (88.9%) patients in the NIDC group: 2 patients died and 3 patients had a relapse of infection with subsequent cure. In multivariate regression analysis, methicillin-susceptible SAB and IDC were factors independently associated with cure. Children who received IDC for SAB in a tertiary pediatric setting were more likely to have appropriate investigations and management and had improved outcomes.

The Effect of Insurance on Appropriate Hospital Discharge Antibiotics for Patients With Staphylococcus aureus Bacteremia.

BackgroundInappropriate antimicrobial therapy of Staphylococcus aureus bacteremia (SAB) is associated with worsened outcomes. The impact of insurance coverage on appropriate selection of antibiotics at discharge is poorly understood.MethodsWe used a retrospective cohort design to evaluate whether patients with SAB at a large academic medical center over 2 years were more likely to receive inappropriate discharge antibiotics, depending on their category of insurance. Insurance was classified as Medicare, Medicaid, commercial, and none. Logistic regression was used to determine the odds of being prescribed inappropriate discharge therapy.ResultsA total of 273 SAB patients met inclusion criteria, with 14.3% receiving inappropriate discharge therapy. In the unadjusted model, there was 2-fold increased odds of being prescribed inappropriate therapy for Medicare, Medicaid, and no insurance, compared with commercial insurance, respectively (odds ratio [OR], 2.08; 95% CI, 1.39–3.13). After controlling for discharge with nursing assistance and infectious diseases (ID) consult, there were 1.6-fold increased odds (OR, 1.57; 95% CI, 0.998–2.53; P = .064) of being prescribed inappropriate therapy for Medicare, Medicaid, and no insurance, compared with commercial insurance, respectively. We found that being discharged home without nursing assistance resulted in 4-fold increased odds of being prescribed inappropriate therapy (OR, 4.16; 95% CI, 1.77–9.77; P < .01), and failing to consult an ID team resulted in 59-fold increased odds of being prescribed inappropriate therapy (OR, 59.2; 95% CI, 11.4–306.9; P < .001).ConclusionsWe found strong evidence that noncommercial insurance, discharging without nursing assistance, and failure to consult ID are risk factors for being prescribed inappropriate antimicrobial therapy for SAB upon hospital discharge.

Reduction of 30-day death rates from Staphylococcus aureus bacteremia by mandatory infectious diseases consultation: Comparative study interventions with and without an infectious disease specialist

ObjectivesMost 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). MethodsThis 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. ResultsA 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. ConclusionMandatory 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.

Correlation between time-to-positivity of blood culture and clinical outcomes in Staphylococcus aureus bacteremia

Background: Staphylococcus aureus bacteraemia (SAB) leads to significant morbidity and mortality, both in adults and children. There are few studies that establish the relation between early time to positivity (TTP) of blood cultures and clinical outcome of SAB in the patients, especially in developing countries like India. Methods and materials: All patients with blood culture confirmed Staphylococcus aureus infections admitted between January and September, 2019 were enrolled. BacT/Alert 3D system was used for automated continuous blood culture monitoring. Time to positivity (TTP) was defined as the time period between blood culture incubation and the positive signal. Demographic and clinical data including prior antibiotic exposure, site of infection, length of hospitalization and clinical outcome were noted. Species identification and antimicrobial susceptibility testing was performed by conventional methods as well as by Vitek 2 compact. Receiver operating characteristic (ROC) curves were plotted for the rate of sensitivity and 1-specificity. Youden's Index was used for optimal cut-off selection for TTP, and area under the curve (AUC) was calculated. The odds ratio (OR) and their 95% confidence interval (CI) were calculated for the statistically significant variables. Results: Sixty patients with ≥1 S. aureus blood culture positive were included. Most frequent infection source was pneumonia (33.9%), skin and soft tissue infections (16%) and CNS infections (16%). Nine cases (16%) of healthcare associated infection were detected. Methicillin-resistance was detected in 23 cases (41%). Among 30 patients with prior antibiotic exposure, appropriate antibiotic had been prescribed in only 21 cases (37.5%). ROC curves of TTP were plotted according to the primary outcome (in-hospital mortality). Following Youden's index methodology, we found 16.5 h to be the optimal cut-off point (62.5% sensitivity, 59.3% specificity). In the early detection group, 71.4% were children. Patients in early TTP group were more likely to need 39.3% invasive mechanical ventilation (39.3% vs 32.1%) and vasoactive agents (32.1% vs 25%). In-hospital mortality was also higher in early TTP group (53.6% vs 32.1%). Conclusion: Patients with a time-to-positivity of ≤16.5 h in cases of S. aureus bacteremia tend to have worse outcomes than patients with longer TTP in terms of mechanical ventilation, septic shock and mortality

Bacteremia in solid organ transplant recipients as compared to immunocompetent patients: Acute phase cytokines and outcomes in a prospective, matched cohort study.

We undertook a prospective, matched cohort study of patients with Staphylococcus aureus bacteremia (SAB) and gram-negative bacteremia (GNB) to compare the characteristics, outcomes, and chemokine and cytokine response in transplant recipients to immunocompetent, nontransplant recipients. Fifty-five transplant recipients (GNB n=29; SAB n=26) and 225 nontransplant recipients (GNB n=114; SAB n=111) were included for clinical analysis. Transplant GNB had a significantly lower incidence of septic shock than nontransplant GNB (10.3% vs 30.7%, p=.03). Thirty-day mortality did not differ significantly between transplant and nontransplant recipients with GNB (10.3% vs 15.8%, p=.57) or SAB (0.0% vs 11.7%, p=.13). Next, transplant patients were matched 1:1 with nontransplant patients for the chemokine and cytokine analysis. Five cytokines and chemokines were significantly lower in transplant GNB vs nontransplant GNB: IL-2 (median [IQR]: 7.1pg/ml [7.1, 7.1] vs 32.6pg/ml [7.1, 88.0]; p=.001), MIP-1β (30.7pg/ml [30.7, 30.7] vs 243.3pg/ml [30.7, 344.4]; p=.001), IL-8 (32.0pg/ml [5.6, 53.1] vs 59.1pg/ml [39.2, 119.4]; p=.003), IL-15 (12.0pg/ml [12.0, 12.0] vs 12.0pg/ml [12.0, 126.7]; p=.03), and IFN-α (5.1pg/mL [5.1, 5.1] vs 5.1pg/ml [5.1, 26.3]; p=.04). Regulated upon Activation, Normal T Cell Expressed and Secreted (RANTES) was higher in transplant SAB vs nontransplant SAB (mean [SD]: 750.2pg/ml [194.6] vs 656.5pg/ml [147.6]; p=.046).

Time to blood culture positivity in Staphylococcus aureus bacteraemia to determine risk of infective endocarditis

ObjectivesPatients with Staphylococcus aureus bacteraemia (SAB) at risk for infective endocarditis (IE) need to be identified because they should undergo echocardiography. We validated previous scoring systems for IE risk determination and evaluated whether time to blood culture positivity (TTP) could improve scoring systems. MethodsThis retrospective population-based study included adults with SAB in 2016 in a derivation cohort and those from 2017 in a validation cohort. TTP was compared between patients with and without IE. A new score including TTP was constructed using a least absolute shrinkage selection operator. The new POSITIVE score was compared to the previously described PREDICT and VIRSTA scores. ResultsA total of 465 episodes with SAB were included in the derivation cohort, of which 38 (8.2%) represented IE. Median (interquartile range) TTP was significantly shorter in episodes with IE, at 8.7 (7.7–10.6) hours compared to those without, at 13.3 (10.5–16.5) hours. When using a cutoff at 13 hours, TTP had a sensitivity of 100% (95% confidence interval (CI), 91–100) and specificity of 52% (95% CI, 47–57) for IE. The POSITIVE score included TTP, intravenous drug use, embolizations and presence of preexisting heart conditions. It had a sensitivity of 93% (95% CI, 76–99) and a specificity of 70% (95% CI, 66–74) in the validation cohort. The performance of POSITIVE was superior to PREDICT, and the specificity was higher than that of VIRSTA. ConclusionsTTP, either by itself or as part of the POSITIVE score, can be used to identify patients with SAB at low risk for IE. Further validation is needed because TTP is sensitive to several external factors.

The smart activatable P2&3TT probe allows accurate, fast, and highly sensitive detection of Staphylococcus aureus in clinical blood culture samples

Staphylococcus aureus bacteraemia (SAB) is associated with high mortality and morbidity rates. Yet, there is currently no adequate diagnostic test for early and rapid diagnosis of SAB. Therefore, this study was aimed at exploring the potential for clinical implementation of a nuclease-activatable fluorescent probe for early diagnosis of SAB. To this end, clinical blood culture samples from patients with bloodstream infections were incubated for 1 h with the “smart” activatable P2&3TT probe, the total assay time being less than 2 h. Cleavage of this probe by the secreted S. aureus enzyme micrococcal nuclease results in emission of a readily detectable fluorescence signal. Incubation of S. aureus-positive blood culture samples with the P2&3TT probe resulted in 50-fold higher fluorescence intensity levels than incubation with culture-negative samples. Moreover, incubation of the probe with non-S. aureus-positive blood cultures yielded essentially background fluorescence intensity levels for cultures with Gram-negative bacteria, and only ~ 3.5-fold increased fluorescence intensity levels over background for cultures with non-S. aureus Gram-positive bacteria. Importantly, the measured fluorescence intensities were dose-dependent, and a positive signal was clearly detectable for S. aureus-positive blood cultures with bacterial loads as low as ~ 7,000 colony-forming units/mL. Thus, the nuclease-activatable P2&3TT probe distinguishes clinical S. aureus-positive blood cultures from non-S. aureus-positive blood cultures and culture-negative blood, accurately, rapidly and with high sensitivity. We conclude that this probe may enhance the diagnosis of SAB.

The benefits and safety of oral sequential antibiotic therapy in non-complicated and complicated Staphylococcus aureus bacteremia

BackgroundTreatment 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). ObjectivesThe objective of the study was to analyze the usefulness and safety of oral sequential therapy (OST) in SAB. Patients and methodsWe 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. ResultsOf 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). ConclusionsOST for properly selected patients with SAB could be a safe therapeutic option and can reduce their use of CIT and their hospital stay.

Clinical Characteristics and Outcomes of S. Aureus Bacteremia in Patients Receiving Total Parenteral Nutrition.

Background: Patients on total parenteral nutrition (TPN) are at risk of developing central line-associated infections. Specifically, Staphylococcus aureus bacteremia (SAB) is feared for its high complication rates. This prospective cohort study compares characteristics, clinical course and outcome of SAB in patients with and without TPN support. Methods: Clinical and microbiological data from all patients with positive blood cultures for S. aureus from two facilities, including our referral center for TPN support, were retrieved (period 2013–2020). Primary outcome was overall mortality, and included survival analysis using a multivariate Cox regression model. Secondary outcomes comprised a comparison of clinical characteristics and outcomes between both patient groups and analysis of factors associated with complicated outcome (e.g., endocarditis, deep-seated foci, relapse and death) in patients on TPN specifically. Results: A total of 620 SAB cases were analyzed, of which 53 cases received TPN at the moment the blood culture was taken. Patients in the TPN group were more frequently female, younger and had less comorbidity (p < 0.001). In-hospital death and overall mortality were significantly lower in TPN patients (4% vs. 18%, p = 0.004 and 10% vs. 34%, p < 0.001, respectively). Positive follow-up blood cultures, delayed onset of therapy and previous catheter problems were associated with a higher incidence of complicated SAB outcome in patients on TPN. Conclusion: Our data show that patients on TPN have a milder course of SAB with lower mortality rates compared to non-TPN SAB patients.

LPS induced PCT production via TLR-4/NF-кB passway:it is the difference of G−/G+ bacteremia rats

Sepsis by Gram-negative bacteria infection leads to further increase in procalcitonin (PCT). Herein, we examined the expression of PCT after 24 h in rats by injecting Escherichia coli (E. coli) or Staphylococcus aureus (SA). Healthy male SD rats were divided into six groups (n = 8): (1) Control group: no treatment; (2) SA group: injected with 106CFU/ml SA suspension 0.1 ml in the tail vein; (3) SA and antibiotics group: injected with 106/ml SA bacterial suspension 0.1 ml and 4 mg/kg Cefotaxime sodium, q8h in the tail vein; (4) E. coli group: injected with 106CFU/ml E. coli suspension 0.1 ml in the tail vein; (5) E. coli and antibiotics group: injected with 106/ml E. coli bacterial suspension 0.1 ml and 4 mg/kg Cefotaxime sodium, q8h in the tail vein; and (6) Endotoxin group: injected with 5 mg/kg endotoxin in the tail vein. Expression of PCT was significantly increased in the E. coli, SA or endotoxin-induced bacteremia rats than in the control rats. Compared with SA, PCT was more significantly increased in E. coli rats. NF-κB changes were in line with PCT. Next, we investigated whether the expression of PCT decreased when TLR4 or NF-κB were inhibited after injecting E. coli in rats. A total of 40 healthy male SD rats were divided into five groups (n = 8): (1) Control group: no treatment; (2) E. coli group: injected with 106CFU/ml E. coli suspension 0.1 ml in the tail vein. (3) E. coli and PBS group: injected with 106CFU/ml E. coli suspension 0.1 ml and PBS 0.1 ml in the tail vein. (4) E. coli and TAK242: injected with 106CFU/ml E. coli suspension 0.1 ml and 3 mg/kg TAK242 in the tail vein. (5) E. coli and BAY-11–7082: injected with 106/ml E. coli suspension 0.1 ml and 25 mg/kg BAY-11–7082 in the tail vein. A marked increase of TLR4, NF-κB, LPS and PCT expression was observed in the lungs after E. coli induced bacteremia. Expressions of TLR4, NF-κB, and PCT proteins were decreased in the lungs at 24 h after injection of TAK-242 or BAY-11–7082. In summary, this study suggested that LPS is the key factor for differential expression of PCT between E. coli and SA bacteremia. E. coli induces PCT elevation via the TLR4/NF-κB pathway.

Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP) Annual Report 2019.

From 1 January to 31 December 2019, 39 institutions around Australia participated in the Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP). The aim of ASSOP 2019 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to methicillin and on characterising the molecular epidemiology of the methicillin-resistant isolates. A total of 3,157 S. aureus bacteraemia episodes were reported, of which 79.8% were community-onset. 18.5% of S. aureus were methicillin resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 14.0%, which was not significantly different from the 14.3% mortality associated with methicillin-susceptible SAB (p = 0.9). 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 36% of methicillin-resistant S. aureus (MRSA) were resistant to ciprofloxacin, 34% to erythromycin, 13% to tetracycline, 9% to gentamicin and 4% to co-trimoxazole. When applying the EUCAST breakpoints, teicoplanin resistance was detected in two S. aureus isolates. Resistance was not detected for vancomycin and linezolid. Resistance to non-beta-lactam antimicrobials was largely attributable to two healthcare-associated MRSA clones: ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). ST22-IV [2B] (EMRSA-15) is the predominant healthcare-associated clone in Australia. Eighty percent of methicillin-resistant SAB, however, were due to community-associated clones. Although polyclonal, approximately 71.4% of community-associated clones were variously characterised as ST93-IV [2B] (Queensland CA-MRSA), ST5-IV [2B], ST45-VT [5C2&5], ST1-IV [2B], ST30-IV [2B], ST78-IV [2B] and ST8-IV [2B]. Community-associated MRSA (CA-MRSA), in particular the ST45-VT [5C2&5] clone, have acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and tetracycline. The multiresistant ST45-VT [5C2&5] clone accounted for 12.7% of CA-MRSA. As CA-MRSA is well established in the Australian community, it is important that antimicrobial resistance patterns in community- and healthcare-associated SAB are monitored, as this information will guide therapeutic practices in treating S. aureus sepsis.

Mortality Risk Profiling of Staphylococcus aureus Bacteremia by Multi-omic Serum Analysis Reveals Early Predictive and Pathogenic Signatures

Staphylococcus aureus bacteremia (SaB) causes significant disease in humans, carrying mortality rates of ∼25%. The ability to rapidly predict SaB patient responses and guide personalized treatment regimens could reduce mortality. Here, we present a resource of SaB prognostic biomarkers. Integrating proteomic and metabolomic techniques enabled the identification of >10,000 features from >200 serum samples collected upon clinical presentation. We interrogated the complexity of serum using multiple computational strategies, which provided a comprehensive view of the early host response to infection. Our biomarkers exceed the predictive capabilities of those previously reported, particularly when used in combination. Last, we validated the biological contribution of mortality-associated pathways using a murine model of SaB. Our findings represent a starting point for the development of a prognostic test for identifying high-risk patients at a time early enough to trigger intensive monitoring and interventions.

Do written diagnosis-treatment recommendations on microbiological test reports improve the management of Staphylococcus aureus bacteremia? A single-center, retrospective, observational study

The objective of this study was to assess the impact of microbiological test reports that provide specific written recommendations on the appropriate management of Staphylococcus aureus bacteremia (SAB). We performed a retrospective analysis of laboratory and clinical data of all SAB patients treated at one German University hospital, 2012–2015. Among 467 included patients, methicillin-resistant S. aureus (MRSA) accounted for 15.2% of all SAB cases. All-cause in-hospital mortality was 25.2%, and was significantly elevated in individuals aged >55 years, in MRSA bacteremia and if the source of infection remained unidentified. Focus identification was achieved in 71.1%, with the most prevalent foci being catheter-associated bloodstream infection (23.1%), soft tissue infection (15.4%), osteomyelitis (5.1%) and endocarditis (4.9%). Standardized written recommendations on microbiological test reports led to a significant increase of transesophageal echocardiography, additional imaging studies for focus identification and more frequent follow-up blood cultures, but no significant effect on mortality was observed.

Impact of antimicrobial stewardship and rapid diagnostics in children with Staphylococcus aureus bacteremia

AbstractIntroductionRapid diagnostic testing (RDT) in combination with antimicrobial stewardship programs (ASPs) has been associated with improved outcomes in adults with Staphylococcus aureus bacteremia (SAB); however, pediatric data are limited.ObjectivesThe primary objective of this study was to assess the clinical impact of concomitant implementation of an ASP and RDT in children with SAB.MethodsThis pre‐post quasi‐experimental study compared time to optimal antibiotic in children with SAB in 2015/2016 (pre‐intervention [PRE]) and 2017/2018 (post‐intervention [POST]). During the PRE period there was no RDT or ASP available. However, in the POST period, RDT was performed on all positive blood cultures, followed by feedback from an ASP. Secondary outcomes included time to effective antibiotic, antibiotic exposure, duration of bacteremia, hospital length of stay (LOS), transfer to the intensive care unit (ICU), SAB recurrence, and inpatient mortality.ResultsSixty‐eight patients were included in the study (PRE: n = 32, POST: n = 36). Median time to optimal antibiotic therapy decreased by 23 hours (PRE: 44.3 hours vs POST: 21.3 hours; P = .008). Duration of bacteremia (PRE: 65 hours vs POST: 40.9 hours; P = .03) and inpatient mortality (PRE: 12.5% vs POST: 0%; P = .04) were also reduced. However, further review revealed that only one death was related to SAB. Differences in time to effective therapy, antibiotic exposure, and hospital LOS were not significantly different between the groups. There were similar rates of infectious disease (ID) consultation (PRE: 78% vs POST: 89%, P = .23), but a shorter time to central line removal in the POST group (PRE: 68.2 hours vs POST: 19.8 hours; P = .04). Throughout the study period, recurrence of SAB only occurred in one patient (PRE).ConclusionASP interventions, facilitated by RDT, resulted in a shorter time to optimal antibiotic therapy in children with SAB. Although these interventions may have led to improved overall SAB management, further studies are needed to confirm clinical benefits.

Ticagrelor and the risk of Staphylococcus aureus bacteraemia and other infections.

To investigate the 1-year risks of Staphylococcus aureus bacteraemia (SAB), sepsis, and pneumonia in patients who underwent percutaneous coronary intervention and were treated with ticagrelor vs. clopidogrel. In this nationwide observational cohort study, 26606 patients who underwent urgent or emergent percutaneous coronary intervention (January 2011-December 2017) and initiated treatment with ticagrelor [N = 20073 (75.5%); median age 64 years (25th-75th percentile 55-72 years); 74.8% men] or clopidogrel [N = 6533 (24.5%); median age 68 years (25th-75th percentile 58-77 years); 70.2% men] were identified using Danish nationwide registries. The 1-year standardized absolute risks of outcomes was calculated based on cause-specific Cox regression models, and average treatment effects between treatment groups were obtained as standardized differences in absolute 1-year risks. The absolute 1-year risk of SAB was 0.10% [95% confidence interval (CI), 0.05-0.15%] in the ticagrelor group and 0.29% (95% CI, 0.17-0.42%) in the clopidogrel group. Compared with clopidogrel, treatment with ticagrelor was associated with a significantly lower absolute 1-year risk of SAB [absolute risk difference -0.19% (95% CI, -0.32% to -0.05%), P value 0.006]. Likewise, treatment with ticagrelor was associated with a significantly lower absolute 1-year risk of sepsis [0.99% (95% CI, 0.83-1.14%) vs. 1.49% (95% CI, 1.17-1.80%); absolute risk difference -0.50% (95% CI, -0.86% to -0.14%), P value 0.007] and pneumonia [3.13% (95% CI, 2.86-3.39%) vs. 4.56% (95% CI, 4.03-5.08%); absolute risk difference -1.43% (95% CI, -2.03% to -0.82%), P value < 0.001] compared with clopidogrel. Treatment with ticagrelor was associated with a significantly lower 1-year risk of SAB, sepsis, and pneumonia compared with clopidogrel.

Does extraction of cardiac implantable electronic devices improve outcome in patients with Staphylococcus aureus bacteraemia?

Background Staphylococcus aureus bacteraemia (SAB) is recognized as an infection that is difficult to treat and with high risk of device related infection. Extraction/explantation of cardiac implantable electronic devices (CIED) is recommended in SAB patients but studies evaluating long-term prognosis are scarce. Materials and methods In this retrospective cohort study, 626 consecutive SAB patients were identified in routine diagnostics (November 2014–October 2016). Patient characteristic, infective endocarditis (IE) incidence and mortality were compared for patients with and without CIED. Results SAB patients with CIED (n = 33) compared to non-CIED patients (n = 593) were older (83 versus 70 years, p = .0001), had a higher 30-day mortality (12/33, 36% versus 119/593, 20%, p = .044) and higher incidence of IE (9/33, 27% versus 41/593, 7%, p = .0006). One-year mortality was 19/33 (58%) among the SAB CIED patients. Echocardiography was performed in all nine patients with CIED-IE but only in 14/24 (58%) of the 24 SAB CIED patients that were considered not having IE. However, if patients with very early mortality were excluded, echocardiography was performed in 14/17 (82%) of SAB CIED-non-IE patients. CIED extraction/explantation during intravenous antibiotic treatment was only performed in three patients with SAB CIED-IE and in one non-IE patient. One year post treatment initiation, 14 out of 33 SAB CIED patients were alive of whom only one had CIED extraction/explantation performed as part of treatment. Conclusion Staphylococcus aureus bacteraemia in CIED patients is associated with poor prognosis but in a subgroup of patients survival beyond one year was seen despite retainment of the electronic device.

Scoring the Risk for Endocarditis During Staphylococcal Bacteremia

Predicting which patients with Staphylococcus aureus bacteremia (SAB) will develop infective endocarditis (IE) can be difficult. Transesophageal

Early differentiation between uncomplicated and complicated Staphylococcus aureus bacteraemia: Potential value and limitations of a clinical risk score.

ObjectiveA cornerstone in the management of Staphylococcus aureus bacteraemia (SAB) is the differentiation between a complicated and an uncomplicated SAB course. The ability to early and accurately identify patients with ‐ and without ‐ complicated bacteraemia may optimise the utility of diagnostics and prevent unnecessary prolonged antibiotic therapy.MethodsDevelopment and validation of a prediction score in SAB using demographic, clinical, and laboratory data from two independent Dutch cohorts; estimating the risk of complicated disease at the time of the first positive blood culture. Models were developed using logistic regression and evaluated by c‐statistics, ie area under the ROC‐curve, and negative predictive values (NPV).ResultsThe development‐ and validation cohorts included 150 and 183 patients, respectively. The most optimal prediction model included: mean arterial pressure, signs of metastatic infection on physical examination, leucocyte count, urea level and time to positivity of blood cultures (c‐statistic 0.82, 95% CI 0.74‐0.89). In the validation cohort, the c‐statistic of the prediction score was 0,77 (95% CI 0.69‐0.84). The NPV for complicated disease for patients with a score of ≤2 was 0.83 (95% CI 0.68‐0.92), with a negative likelihood ratio of 0.14 (95% CI 0.06‐0.31).ConclusionThe early SAB risk score helps to identify patients with high probability of uncomplicated SAB. However, the risk score's lacked absolute discriminative power to guide decisions on the management of all patients with SAB on its own. The heterogenicity of the disease and inconsistency in definitions of complicated SAB are important challenges in the development of clinical rules to guide the management of SAB.