scholarly journals Interleukin (IL)-1β and IL-10 Host Responses in Patients With Staphylococcus aureus Bacteremia Determined by Antimicrobial Therapy

2019 ◽  
Vol 70 (12) ◽  
pp. 2634-2640 ◽  
Author(s):  
Cecilia F Volk ◽  
Sarah Burgdorf ◽  
Graham Edwardson ◽  
Victor Nizet ◽  
George Sakoulas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Therapy ◽  
Ex Vivo ◽  
Host Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Treatment Groups ◽  
Staphylococcus Aureus Bacteremia ◽  
Medical Centers ◽  
Persistent Bacteremia

Abstract Background Patient interleukin (IL)-1β and IL-10 responses early in Staphylococcus aureus bacteremia (SaB) are associated with bacteremia duration and mortality. We hypothesized that these responses vary depending on antimicrobial therapy, with particular interest in whether the superiority of β-lactams links to key cytokine pathways. Methods Three medical centers included 59 patients with SaB (47 methicillin-resistant S. aureus [MRSA], 12 methicillin-sensitive S. aureus [MSSA]) from 2015–2017. In the first 48 hours, patients were treated with either a β-lactam (n = 24), including oxacillin, cefazolin, or ceftaroline, or a glyco-/lipopeptide (n = 35), that is, vancomycin or daptomycin. Patient sera from days 1, 3, and 7 were assayed for IL-1β and IL-10 by enzyme-linked immunosorbent assay and compared using the Mann-Whitney U test. Results On presentation, IL-10 was elevated in mortality (P = .008) and persistent bacteremia (P = .034), while no difference occurred in IL-1β. Regarding treatment groups, IL-1β and IL-10 were similar prior to receiving antibiotic. Patients treated with β-lactam had higher IL-1β on days 3 (median +5.6 pg/mL; P = .007) and 7 (+10.9 pg/mL; P = .016). Ex vivo, addition of the IL-1 receptor antagonist anakinra to whole blood reduced staphylococcal killing, supporting an IL-1β functional significance in SaB clearance. β-lactam–treated patients had sharper declines in IL-10 than vancomycin or daptomycin –treated patients over 7 days. Conclusions These data underscore the importance of β-lactams for SaB, including consideration that the adjunctive role of β-lactams for MRSA in select patients helps elicit favorable host cytokine responses.

scholarly journals A Narrative Review of Early Oral Stepdown Therapy for the Treatment of Uncomplicated Staphylococcus aureus Bacteremia: Yay or Nay?

2020 ◽  
Vol 7 (6) ◽  
Author(s):  
Michael Dagher ◽  
Vance G Fowler ◽  
Patty W Wright ◽  
Milner B Staub
Keyword(s):  
Staphylococcus Aureus ◽  
Hospital Readmission ◽  
Potential Role ◽  
Review Article ◽  
Narrative Review ◽  
Oral Antibiotics ◽  
Staphylococcus Aureus Bacteremia ◽  
Complete Treatment

Abstract Historically, intravenous (IV) antibiotics have been the cornerstone of treatment for uncomplicated Staphylococcus aureus bacteremia (SAB). However, IV antibiotics are expensive, increase the rates of hospital readmission, and can be associated with catheter-related complications. As a result, the potential role of oral antibiotics in the treatment of uncomplicated SAB has become a subject of interest. This narrative review article aims to summarize key arguments for and against the use of oral antibiotics to complete treatment of uncomplicated SAB and evaluates the available evidence for specific oral regimens. We conclude that evidence suggests that oral step-down therapy can be an alternative for select patients who meet the criteria for uncomplicated SAB and will comply with medical treatment and outpatient follow-up. Of the currently studied regimens discussed in this article, linezolid has the most support, followed by fluoroquinolone plus rifampin.

scholarly journals Adjunctive ceftaroline in combination with daptomycin or vancomycin for complicated methicillin-resistant Staphylococcus aureus bacteremia after monotherapy failure

2019 ◽  
Vol 6 ◽  
pp. 204993611988650 ◽  
Author(s):  
Joseph Patrik Hornak ◽  
Seher Anjum ◽  
David Reynoso
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Treatment Options ◽  
Source Control ◽  
Optimal Timing ◽  
Methicillin Resistant ◽  
Staphylococcus Aureus Bacteremia ◽  
Persistent Bacteremia

Background: Methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) may fail to improve with standard monotherapy, particularly in patients with multifocal infection, incomplete source control, or persistent bacteremia. Synergy observed in vitro between ceftaroline (CPT) and daptomycin (DAP) or vancomycin (VAN) may translate into clinical benefit. Here, we describe our experience with DAP/CPT and VAN/CPT for complicated MRSA-B after monotherapy failure. Methods: Single-center, retrospective review of consecutive patients treated with DAP/CPT or VAN/CPT for MRSA-B after monotherapy failure from 1 January 2016 to 30 November 2018. Results: We identified 11 instances of combination therapy in 10 patients (DAP/CPT = 6, VAN/CPT = 5) with 1 patient receiving VAN/CPT followed by DAP/CPT. Rates of multifocal infection, incomplete source control, persistent bacteremia, and infective endocarditis were high (100%, 80%, 60%, and 60%, respectively). Combination therapy was initiated most commonly for persistent bacteremia (60%). When patients were persistently bacteremic, median preceding duration was 13 days and median time to clearance was 3 days. Total microbiologic cure rate was 100%. There were zero instances of bacteremia relapse at 30 days (30D) or 60 days (60D). All-cause 30D and 60D mortality rates were 11.1% and 33.3%, respectively. Conclusions: Combination therapy demonstrated success in diverse cases of refractory MRSA-B, including instances of persistent bacteremia paired with incomplete source control. Optimal timing and therapeutic cadence for combination therapy remain unclear. Our findings suggest that DAP/CPT and VAN/CPT can be considered for complicated MRSA bacteremia when other treatment options fail or are unavailable. We propose persistent bacteremia with incomplete source control to be a clinical niche particularly worthy of further investigation.

scholarly journals Risk Factors for Recurrent Staphylococcus aureus Bacteremia

2020 ◽  
Author(s):  
Seong-Ho Choi ◽  
Michael Dagher ◽  
Felicia Ruffin ◽  
Lawrence P Park ◽  
Batu K Sharma-Kuinkel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Staphylococcus Aureus ◽  
Acute Phase ◽  
Hemodialysis Patients ◽  
Risk Modeling ◽  
Single Episode ◽  
Staphylococcus Aureus Bacteremia ◽  
Multivariate Risk ◽  
Persistent Bacteremia ◽  
Multiplex Bead

Abstract Background To understand the clinical, bacterial, and host characteristics associated with recurrent Staphylococcus aureus bacteremia (R-SAB), patients with R-SAB were compared to contemporaneous patients with a single episode of SAB (S-SAB). Methods All SAB isolates underwent spa genotyping. All isolates from R-SAB patients underwent pulsed-field gel electrophoresis (PFGE). PFGE-indistinguishable pairs from 40 patients underwent whole genome sequencing (WGS). Acute phase plasma from R-SAB and S-SAB patients was matched 1:1 for age, race, sex, and bacterial genotype, and underwent cytokine quantification using 25-analyte multiplex bead array. Results R-SAB occurred in 69 (9.1%) of the 756 study patients. Of the 69 patients, 30 experienced relapse (43.5%) and 39 reinfection (56.5%). Age, race, hemodialysis dependence, presence of foreign body, methicillin-resistant Staphyloccus aureus, and persistent bacteremia were individually associated with likelihood of recurrence. Multivariate risk modeling revealed that black hemodialysis patients were nearly 2 times more likely (odds ratio [OR] = 9.652 [95% confidence interval [CI], 5.402–17.418]) than white hemodialysis patients (OR = 4.53 [95% CI, 1.696–10.879]) to experience R-SAB. WGS confirmed PFGE interpretations in all cases. Median RANTES (regulated on activation, normal T cell expressed and secreted) levels in acute phase plasma from the initial episode of SAB were higher in R-SAB than in matched S-SAB controls (P = .0053, false discovery rate < 0.10). Conclusion This study identified several risk factors for R-SAB. The largest risk for R-SAB is among black hemodialysis patients. Higher RANTES levels in R-SAB compared to matched controls warrants further study.

scholarly journals Changing Characteristics of Staphylococcus aureus Bacteremia: Results From a 21-Year, Prospective, Longitudinal Study

2019 ◽  
Vol 69 (11) ◽  
pp. 1868-1877 ◽  
Author(s):  
Maria Souli ◽  
Felicia Ruffin ◽  
Seong-Ho Choi ◽  
Lawrence P Park ◽  
Shengli Gao ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Longitudinal Study ◽  
Medical Center ◽  
Spa Typing ◽  
Prospective Longitudinal Study ◽  
Staphylococcus Aureus Bacteremia ◽  
Persistent Bacteremia ◽  
Multivariable Regression Models ◽  
Changes Over Time ◽  
Prospective Longitudinal

Abstract Background We conducted a longitudinal study to evaluate changes in the clinical presentation and epidemiology of Staphylococcus aureus bacteremia (SAB) in an academic, US medical center. Methods Consecutive patients with monomicrobial SAB were enrolled from January 1995 to December 2015. Each person’s initial bloodstream S. aureus isolate was genotyped using spa typing. Clonal complexes (CCs) were assigned using Ridom StaphType software. Changes over time in both the patient and bacterial characteristics were estimated with linear regression. Associations between genotypes or clinical characteristics and complications were estimated using multivariable regression models. Results Among the 2348 eligible participants, 54.2% had an implantable, foreign body of some type. This proportion increased significantly during the 21-year study period, by 0.96% annually (P = .002), as did comorbid conditions and acquisition outside of the hospital. Rates of any metastatic complication also significantly increased, by 0.94% annually (P = .019). Among the corresponding bloodstream S. aureus isolates, spa-CC012 (multi-locus sequence type [MLST] CC30), -CC004 (MLST CC45), -CC189 (MLST CC1), and -CC084 (MLST CC15) all significantly declined during the study period, while spa-CC008 (MLST CC8) significantly increased. Patients with SAB due to spa-CC008 were significantly more likely to develop metastatic complications in general, and abscesses, septic emboli, and persistent bacteremia in particular. After adjusting for demographic, racial, and clinical variables, the USA300 variant of spa-CC008 was independently associated with metastatic complications (odds ratio 1.42; 95% confidence interval 1.02–1.99). Conclusions Systematic approaches for monitoring complications of SAB and genotyping the corresponding bloodstream isolates will help identify the emergence of hypervirulent clones and likely improve clinical management of this syndrome.

scholarly journals Phase II, Randomized, Double-Blind, Multicenter Study Comparing the Safety and Pharmacokinetics of Tefibazumab to Placebo for Treatment of Staphylococcus aureus Bacteremia

2006 ◽  
Vol 50 (8) ◽  
pp. 2751-2755 ◽  
Author(s):  
J. John Weems ◽  
James P. Steinberg ◽  
Scott Filler ◽  
John W. Baddley ◽  
G. Ralph Corey ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Primary Objective ◽  
Related Complication ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Adhesion Protein ◽  
Treatment Groups ◽  
Staphylococcus Aureus Bacteremia ◽  
Humanized Monoclonal Antibody ◽  
Healthcare Associated

ABSTRACT Tefibazumab (Aurexis), a humanized monoclonal antibody that binds to the surface-expressed adhesion protein clumping factor A, is under development as adjunctive therapy for serious Staphylococcus aureus infections. Sixty patients with documented S. aureus bacteremia (SAB) were randomized and received either tefibazumab at 20 mg/kg of body weight as a single infusion or a placebo in addition to an antibiotic(s). The primary objective of the study was determining safety and pharmacokinetics. An additional objective was to assess activity by a composite clinical end point (CCE). Baseline characteristics were evenly matched between groups. Seventy percent of infections were healthcare associated, and 57% had an SAB-related complication at baseline. There were no differences between the treatment groups in overall adverse clinical events or alterations in laboratory values. Two patients developed serious adverse events that were at least possibly related to tefibazumab; one hypersensitivity reaction was considered definitely related. The tefibazumab plasma half-life was 18 days. Mean plasma levels were <100 μg/ml by day 14. A CCE occurred in six patients (four placebo and two tefibazumab patients) and included five deaths (four placebo and one tefibazumab patient). Progression in the severity of sepsis occurred in four placebo and no tefibazumab patients. Tefibazumab was well tolerated, with a safety profile similar to those of other monoclonal antibodies. Additional trials are warranted to address the dosing range and efficacy of tefibazumab.

scholarly journals Early Oral Antibiotic Switch for Staphylococcus aureus Bacteremia: Many Are Called, but Few Are Chosen

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
Thomas L. Holland
Keyword(s):  
Staphylococcus Aureus ◽  
Low Risk ◽  
Oral Antibiotic ◽  
Beta Lactams ◽  
Content Type ◽  
Staphylococcus Aureus Bacteremia ◽  
Intravenous Antibiotics ◽  
High Risk Disease ◽  
Prospective Trials

ABSTRACT Staphylococcus aureus bacteremia (SAB) is a complicated, high-risk disease. For selected low-risk SAB, the role of oral antibiotic stepdown therapy is unknown. Bupha-Intr et al. report a retrospective cohort of low-risk SAB patients who did well with a short duration of intravenous antibiotics, followed by an additional ∼10 days of oral antibiotics, primarily using beta-lactams. Prospective trials will help further define the efficacy of this approach.

scholarly journals Association of Infectious Disease Consultation With Clinical Outcomes in Patients With Staphylococcus aureus Bacteremia at Low Risk for Endocarditis

2018 ◽  
Vol 5 (7) ◽  
Author(s):  
Anna Yousaf ◽  
Grayson L Baird ◽  
Leonard Mermel
Keyword(s):  
Infectious Disease ◽  
Staphylococcus Aureus ◽  
Survival Analysis ◽  
Hospital Mortality ◽  
Antimicrobial Therapy ◽  
Readmission Rate ◽  
Low Risk ◽  
Secondary Site ◽  
Staphylococcus Aureus Bacteremia ◽  
Kaplan Meier

Abstract Infectious disease (ID) consultation in patients with Staphylococcus aureus bacteremia who were at low risk for endocarditis and who had no secondary site of infection was associated with a longer course of antibiotics (median duration of intravenous antimicrobial therapy of 31 days and 15 days in those with and without ID consultation, respectively; P ≤ .01), and based on Kaplan-Meier survival analysis, reduced in-hospital mortality (P = .2), and reduced 30-day mortality after discharge (P = .4). ID consultation was also associated with a higher readmission rate within 90 days of discharge: 46% and 34% with and without ID consultation, respectively (P = .2).

scholarly journals Evaluation of early achievement of an AUC/MIC of >400 for Vancomycin in children with methicillin-resistant Staphylococcus aureus bacteremia

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S293-S294
Author(s):  
Takemi Murai ◽  
Hiroshi Higuchi ◽  
Junichi Suwa ◽  
Hanako Funakoshi ◽  
Ryuu Yoneda ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Outcomes ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Medical Center ◽  
Area Under The Curve ◽  
Interquartile Range ◽  
Methicillin Resistant ◽  
Staphylococcus Aureus Bacteremia ◽  
Microdilution Method ◽  
Persistent Bacteremia

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia causes morbidity and mortality in children. The standard treatment for MRSA bacteremia is vancomycin, which should achieve a 24 hour area under the curve over the minimum inhibitory concentration ratio (AUC/ MIC) of &gt;400. Whether or not attaining AUC/ MIC &gt;400 early in the disease course improves outcomes in children is controversial. The aim of our study was to determine whether early achievement of AUC/ MIC &gt;400 improved outcomes in children with MRSA bacteremia. Methods Children whose blood culture grew MRSA between March 2010 and April 2017 at Tokyo Metropolitan Children’s Medical Center were enrolled. The exclusion criteria were no vancomycin administration, use of extracorporeal membrane oxygenation, no data on dosage and vancomycin MIC, and cases of contamination. Susceptibility testing was performed by a microdilution method. The outcomes of patients who achieved an AUC/MIC &gt;400 at the first assessment prior to the Fourth or Fifth vancomycin dose were compared with those of patients who did not. The clinical outcomes were persistent bacteremia on Days 3 and 7, mortality at 30 days, and the recurrence of MRSA bacteremia. Results In total 175 MRSA isolates from 50 children were identified. Of these 56 episodes were eligible for enrollment. Forty-one subjects (73.2%) were boys. The median age was 9 months (interquartile range: 1.8–120.5 months). The median initial dose of vancomycin was 40 mg/kg (interquartile range: 30–44.3 mg/kg). Among MRSA isolates, vancomycin MIC of &lt; 0.5 mcg/mL, 1 mcg/mL and 2 mcg/mL were 1 (1.8%), 53 (94.6%) and 2 (3.6%), respectively. Fifteen patients (26.8%) achieved AUC/MIC &gt;400 early. The two groups did not differ significantly in terms of persistent bacteremia on Days 3 (P = 0.96) or 7 (P = 0.82), mortality at 30 days (P = 0.47), or the recurrence of MRSA bacteremia (P = 1.0). Conclusion Children with bacteremia who achieved AUC/ MIC&gt;400 early did not differ significantly from children who did not in terms of their clinical outcomes. Disclosures All authors: No reported disclosures.

scholarly journals Role of SCCmec Type in Outcome of Staphylococcus aureus Bacteremia in a Single Medical Center

2009 ◽  
Vol 47 (3) ◽  
pp. 590-595 ◽  
Author(s):  
R. Ganga ◽  
K. Riederer ◽  
M. Sharma ◽  
M. G. Fakih ◽  
L. B. Johnson ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Medical Center ◽  
Sccmec Type ◽  
Staphylococcus Aureus Bacteremia
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