Risk Factors for Recurrent Staphylococcus aureus Bacteremia

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.

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189. Risk Factors and Outcomes of Hematogenous Vertebral Osteomyelitis in Patients with staphylococcus Aureus Bacteremia: Results from a 20-year Prospective Cohort

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.499 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S223-S223

Author(s):

Michael M Dagher ◽

Tori Kinamon ◽

Felicia Ruffin ◽

Larry Park ◽

Stacey Mascarinec ◽

...

Keyword(s):

Risk Factors ◽

Staphylococcus Aureus ◽

Surgical Intervention ◽

Vertebral Osteomyelitis ◽

Suppressive Therapy ◽

Research Support ◽

Staphylococcus Aureus Bacteremia ◽

All Cause Mortality ◽

Persistent Bacteremia ◽

Research Grant

Abstract Background Hematogenous vertebral osteomyelitis (HVOM) is a rare, but devastating complication of Staphylococcus aureus bacteremia (SAB). Risk factors and outcomes associated with HVOM among patients with SAB remain incompletely understood. Methods All adult, hospitalized, non-neutropenic patients with SAB were prospectively enrolled from 1995 to 2015. Additional data was subsequently collected on all patients with HVOM. Diagnosis of HVOM was made either radiographically or microbiologically by culture from the infection site. Patients who underwent lumbar puncture or spinal surgery within 30 days prior to the diagnosis of HVOM were excluded. Results Of 2,475 cases of prospectively enrolled patients with SAB, 90 (3.6%) developed HVOM. The most common site of involvement was the lumbar spine (65.6%). MRI was used in the diagnosis of 90% of patients and although only 28.9% underwent bone biopsy, 88.5% of these bone cultures grew S. aureus. Patients with HVOM were more likely to have community-acquired SAB (22.2% vs. 9.9%, P < 0.0001) and persistent bacteremia (47.8% vs. 20.5%, P < 0.0001). Patients with HVOM who required surgical intervention were more likely to have motor deficit (60.9% vs. 21.4%, P = 0.0013) and have associated epidural abscesses (69.6% vs. 44.8%, P = 0.0400). Prolonged antibiotic use for HVOM was common, with 13.3% remaining on therapeutic antibiotics and 16.6% on suppressive therapy at 6 months. This dropped to 2.2% on therapeutic and 15.5% on suppressive therapy at 12 months. All-cause mortality was high in the HVOM cohort at 14.4% at 90-days, increasing to a cumulative 18.9% and 20.0% at 6 and 12-months, respectively. Rates of readmission, recurrent bacteremia, paralysis, and mortality at 6 and 12-months were similar for those who required surgical intervention and those who did not. Demographics, comorbidities, and clinical characteristics of patients with and without hematogenous vertebral osteomyelitis (HVOM) Conclusion HVOM in patients with SAB was associated with high rates of all-cause mortality up to 12 months following date of diagnosis. Patients with community-acquired bacteremia and persistent bacteremia were more likely to develop HVOM. Disclosures Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Actavis (Grant/Research Support)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Research Grant or Support)Affinium (Consultant)Allergan (Grant/Research Support)Ampliphi Biosciences (Consultant)Basilea (Consultant, Research Grant or Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Research Grant or Support)Contrafect (Consultant, Research Grant or Support)Cubist (Grant/Research Support)Debiopharm (Consultant)Destiny (Consultant)Durata (Consultant)Forest (Grant/Research Support)Genentech (Consultant, Research Grant or Support)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Research Grant or Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)Medimmune (Consultant, Research Grant or Support)Merck (Consultant, Research Grant or Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Research Grant or Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Research Grant or Support)Tetraphase (Consultant)Theravance (Consultant, Research Grant or Support)Trius (Consultant)xBiotech (Consultant)

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1060. Risk Factors for Recurrent Staphylococcus aureus Bacteremia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.897 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S317-S317 ◽

Cited By ~ 1

Author(s):

Seong-Ho Choi ◽

Felicia Ruffin ◽

Lawrence Park ◽

Batu K Sharma-Kuinkel ◽

Maria Souli ◽

...

Keyword(s):

Risk Factors ◽

Staphylococcus Aureus ◽

African American ◽

Abscess Formation ◽

First Episode ◽

Spa Typing ◽

Staphylococcus Aureus Bacteremia ◽

Persistent Bacteremia ◽

Independent Risk Factors ◽

African American Race

Abstract Background Recurrent Staphylococcus aureus bacteremia (Re-SAB) occurs in 2–17% of patients with SAB within 3–12 months after resolution of the first episode. The risk factors for Re-SAB are incompletely understood. Methods Re-SAB was defined as a second episode of SAB after the resolution of the first episode occurring at least 14 days from the date of the last positive blood culture of the first episode. Using the SAB Group Prospective Cohort Study (SABG-PCS) data between January 2008 and May 2015, patients with Re-SAB were selected and compared with those without it. Pulsed-field gel electrophoresis (PFGE) was done for the clinical isolates from the Re-SAB group, and spa typing was for those from both groups. Baseline sera from patients with Re-SAB and age/race/gender matched (1:1) control subjects with SAB but without Recurrence underwent Luminex multiplex cytokine array. Results Seventy patients experienced Re-SAB (9.3%) and 686 SAB patients did not. In the Re-SAB group, 156 episodes of SAB were observed. Median time to Re-SAB was 147.5d (IQR, 76–358). Among 65 PFGE-analyzed pairs of isolates from the first and the subsequent episodes, the time to Re-SAB of <300 days was more commonly found in the PFGE-identical pairs than in the PFGE-different pairs (75.6% vs. 33.8%, P = 0.001). In the comparison of clinical factors between 56 Re-SAB patients with available data and 686 without Re-SAB, African American race, dialysis dependence, the presence of foreign body, persistent bacteremia, metastatic abscess formation, and methicillin-resistant S. aureus (MRSA) were more frequently observed in patients with Re-SAB. In a multivariate analysis to identify risk factors for Re-SAB, African American race, dialysis dependence, metastatic abscess formation, and MRSA were independent risk factors. The distribution of spa types between the two group was presented in Figure 1. Conclusion Re-SAB involves a combination of multiple factors of host, microbe, and treatment. Further laboratory investigation for any determinants in host and microbe is required. Disclosures V. G. Fowler Jr., Merck, Cerexa/Actavis, Pfizer, Advanced Liquid Logis, NIH, MedImmune, Basilea, Karius, Contrafect, Regneron, Genentech, Affinergy, Locus, Medical Surface, Inc., Achaogen, Astellas, Arsanis, Bayer, Cubist, Debiopharm, Durata, Grifols, Medicines Co, Novartis: Collaborator, Consultant and Scientific Advisor, Consulting fee, Research grant and Research support.

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Risk Factors for Methicillin-Resistance among Patients with Staphylococcus aureus Bacteremia at the Time of Hospital Admission

The American Journal of the Medical Sciences ◽

10.1097/00000441-200203000-00001 ◽

2002 ◽

Vol 323 (3) ◽

pp. 117-123 ◽

Cited By ~ 56

Author(s):

Nilton A. Rezende ◽

Henry M. Blumberg ◽

Susan M. Ray ◽

Brian S. Metzger ◽

Nina M. Larsen ◽

...

Keyword(s):

Risk Factors ◽

Staphylococcus Aureus ◽

Hospital Admission ◽

Methicillin Resistance ◽

Staphylococcus Aureus Bacteremia

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

Clinical Infectious Diseases ◽

10.1093/cid/ciz686 ◽

2019 ◽

Vol 70 (12) ◽

pp. 2634-2640 ◽

Cited By ~ 7

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.

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172. Risk Factors for 30-Day Mortality in Patients with Staphylococcus aureus Bacteremia at a Community Hospital: A Prospective Case–Control Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.247 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S109-S110

Author(s):

Charles Hoffmann ◽

Gordon Watkins ◽

Patrick DeSimone ◽

Peter Hallisey ◽

David Hutchinson ◽

...

Keyword(s):

Risk Factors ◽

Staphylococcus Aureus ◽

Case Control Study ◽

Community Hospital ◽

Univariate Analysis ◽

Case Control ◽

Blood Cultures ◽

Staphylococcus Aureus Bacteremia ◽

Initial Blood ◽

Control Study

Abstract Background Staphylococcus aureus bacteremia (SAB) is associated with 30-day all-cause mortality rates approaching 20–30%. The purpose of this case–control study was to evaluate risk factors for 30-day mortality in patients with SAB at a community hospital. Methods As part of an antimicrobial stewardship program (ASP) initiative mandating Infectious Diseases consultation for episodes of SAB, our ASP prospectively monitored all cases of SAB at a 341-bed community hospital in Jefferson Hills, PA from April 2017–February 2019. Cases included patients with 30-day mortality from the initial positive blood culture. Only the first episode of SAB was included; patients were excluded if a treatment plan was not established (e.g., left against medical advice). Patient demographics, comorbidities, laboratory results, and clinical management of SAB were evaluated. Inferential statistics were used to analyze risk factors associated with 30-day mortality. Results 100 patients with SAB were included; 18 (18%) experienced 30-day mortality. Cases were older (median age 76.5 vs. 64 years, P < 0.001), more likely to be located in the intensive care unit (ICU) at time of ASP review (55.6% vs. 30.5%, P = 0.043), and less likely to have initial blood cultures obtained in the emergency department (ED) (38.9% vs. 80.5%, P < 0.001). Variables associated with significantly higher odds for 30-day mortality in univariate analysis: older age, location in ICU at time of ASP review, initial blood cultures obtained at a location other than the ED, and total Charlson Comorbidity Index (CCI). Variables with P < 0.2 on univariate analysis were analyzed via multivariate logistic regression (Table 1). Conclusion Results show that bacteremia due to MRSA and total CCI were not significantly associated with 30-day mortality in SAB, whereas older age was identified as a risk factor. Patients with initial blood cultures obtained at a location other than the ED were at increased odds for 30-day mortality on univariate analysis, which may raise concern for delayed diagnosis. Disclosures All authors: No reported disclosures.

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

Therapeutic Advances in Infectious Disease ◽

10.1177/2049936119886504 ◽

2019 ◽

Vol 6 ◽

pp. 204993611988650 ◽

Cited By ~ 1

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.

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