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 >400. Whether or not attaining AUC/ MIC >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 >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 >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 < 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 >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>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 Vancomycin Treatment Failure in Children With Methicillin-Resistant Staphylococcus aureus Bacteremia

2019 ◽  
Vol 24 (4) ◽  
pp. 312-319 ◽  
Author(s):  
Rebecca B. Regen ◽  
Sarah S. Schuman ◽  
Rebecca F. Chhim ◽  
Sandra R. Arnold ◽  
Kelley R. Lee
Keyword(s):  
Staphylococcus Aureus ◽  
Treatment Failure ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Treatment Success ◽  
Area Under The Curve ◽  
Failure Criteria ◽  
Methicillin Resistant ◽  
Staphylococcus Aureus Bacteremia ◽  
Persistent Bacteremia ◽  
Vancomycin Treatment

OBJECTIVES Limited data exist regarding clinical outcomes of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in children treated with vancomycin. Treatment success in adults correlates best with an area under the curve/minimum inhibitory concentration (AUC24/MIC) ratio ≥400. It is unknown if this relationship is useful in children. METHODS Charts of children who received vancomycin ≥5 days for MRSA bacteremia with a steady state trough were reviewed. AUC24/MIC ratios were estimated using 2 different vancomycin clearance equations. Vancomycin treatment failure was defined as persistent bacteremia ≥7 days, recurrent bacteremia within 30 days, or 30-day mortality. RESULTS There were 67 bacteremia episodes in 65 patients. Nine (13.4%) met failure criteria: persistent bacteremia (n = 6), recurrent bacteremia (n = 2), 30-day mortality (n = 1). There were no differences between patients receiving <60 mg/kg/day and ≥60 mg/kg/day of vancomycin in median trough (11.9 versus 12.3 mg/L, p = 0.1). Troughs did not correlate well with AUC24/MIC ratios (R2 = 0.32 and 0.22). Patients receiving ≥60 mg/kg/day had greater probability of achieving ratios ≥400. There were no significant differences in median dose (p = 0.8), trough (p = 0.24), or AUC24/MIC ratios (p = 0.07 and p = 0.6) between patients with treatment success and failure. CONCLUSIONS Treatment failure was lower than previously reported in children. AUC24/MIC ratios ≥400 were frequently achieved but were not associated with treatment success, dose, or troughs. Prospective studies using standard definitions of vancomycin treatment failure are needed to understand treatment failure in children with MRSA bacteremia.

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 The Emperor’s New Clothes: PRospective Observational Evaluation of the Association Between Initial VancomycIn Exposure and Failure Rates Among ADult HospitalizEd Patients With Methicillin-resistant Staphylococcus aureus Bloodstream Infections (PROVIDE)

2019 ◽  
Vol 70 (8) ◽  
pp. 1536-1545 ◽  
Author(s):  
Thomas P Lodise ◽  
Susan L Rosenkranz ◽  
Matthew Finnemeyer ◽  
Scott Evans ◽  
Matthew Sims ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Treatment Failure ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Bloodstream Infections ◽  
Hospitalized Patients ◽  
Methicillin Resistant ◽  
Primary Endpoints ◽  
Persistent Bacteremia

Abstract Background Vancomycin is the most commonly administered antibiotic in hospitalized patients, but optimal exposure targets remain controversial. To clarify the therapeutic exposure range, this study evaluated the association between vancomycin exposure and outcomes in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Methods This was a prospective, multicenter (n = 14), observational study of 265 hospitalized adults with MRSA bacteremia treated with vancomycin. The primary outcome was treatment failure (TF), defined as 30-day mortality or persistent bacteremia ≥7 days. Secondary outcomes included acute kidney injury (AKI). The study was powered to compare TF between patients who achieved or did not achieve day 2 area under the curve to minimum inhibitory concentration (AUC/MIC) thresholds previously found to be associated with lower incidences of TF. The thresholds, analyzed separately as co-primary endpoints, were AUC/MIC by broth microdilution ≥650 and AUC/MIC by Etest ≥320. Results Treatment failure and AKI occurred in 18% and 26% of patients, respectively. Achievement of the prespecified day 2 AUC/MIC thresholds was not associated with less TF. Alternative day 2 AUC/MIC thresholds associated with lower TF risks were not identified. A relationship between the day 2 AUC and AKI was observed. Patients with day 2 AUC ≤515 experienced the best global outcomes (no TF and no AKI). Conclusions Higher vancomycin exposures did not confer a lower TF risk but were associated with more AKI. The findings suggest that vancomycin dosing should be guided by the AUC and day 2 AUCs should be ≤515. As few patients had day 2 AUCs <400, further study is needed to define the lower bound of the therapeutic range.

scholarly journals 1624. Real World Experience with Daptomycin (DAP) and Ceftaroline (CPT) Combination Therapy for Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S804-S805
Author(s):  
Andrei Zidaru ◽  
Hannah Ryan Russo ◽  
Kady Phe
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Median Time ◽  
Real World ◽  
Salvage Therapy ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Real World Data ◽  
Methicillin Resistant ◽  
Staphylococcus Aureus Bacteremia ◽  
Persistent Bacteremia

Abstract Background Methicillin-resistant Staphylococcus aureus bacteremia is associated with significant mortality rates up to 30%. Guideline-recommended first-line therapy includes monotherapy with either vancomycin or DAP. Alternative regimens are recommended for persistent MRSA bacteremia of ≥ 7 days or earlier if evident clinical deterioration. The combination of DAP plus CPT has been investigated as salvage therapy due to its synergistic mechanism potential, but real-world data with the combination therapy is limited. The aim of this study was to evaluate the efficacy of DAP plus CPT combination therapy for the treatment of MRSA bacteremia and identify independent predictors of 30-day mortality. Methods This was a single center retrospective study of patients receiving DAP-CPT at any point in therapy for the treatment of MRSA bacteremia. Univariable and multivariable analyses were performed to identify independent predictors of 30-day mortality. Results Sixty-five unique patients received DAP-CPT with a median time to combination therapy of 7 days. There were no significant independent predictors of 30-day mortality. The most common reason for combination therapy was persistent bacteremia (80%, 52/65). Bacteremia was cleared in 90.8% (59/65) of patients and the 30-day mortality rate was 15.4% (10/65). Median time to bacteremia clearance after combination switch was 3 days. Eleven patients received DAP-CPT within 72 hours of index culture. Median time to bacteremia clearance for patients switched to DAP-CPT within 72 hours versus after 72 hours did not differ (2 vs 3 days; P = 0.526), however the overall median duration of bacteremia was 4 and 11 days (P = 0.018). In a sub analysis, the median time of bacteremia clearance following combination therapy was significantly longer for patients receiving renal replacement therapy (5 vs 2 days; P = 0.04). Conclusion There were no independent predictors of 30-day mortality identified. DAP-CPT combination therapy resulted in clearance of persistent bacteremia and may serve as an effective salvage therapy. Disclosures All Authors: No reported disclosures

scholarly journals A Retrospective Analysis of Treatment and Clinical Outcomes among Patients with Methicillin-Susceptible Staphylococcus aureus Bloodstream Isolates Possessing Detectable mecA by a Commercial PCR Assay Compared to Patients with Methicillin-Resistant Staphylococcus aureus Bloodstream Isolates

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Dylan Jones ◽  
Ramy H. Elshaboury ◽  
Erik Munson ◽  
Thomas J. Dilworth
Keyword(s):  
Staphylococcus Aureus ◽  
Retrospective Analysis ◽  
Clinical Outcomes ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Bloodstream Infections ◽  
Clinical Failure ◽  
Pcr Assay ◽  
Methicillin Resistant ◽  
Content Type ◽  
Persistent Bacteremia

ABSTRACT mecA-positive Staphylococcus aureus isolates phenotypically susceptible to cefoxitin (mecA-methicillin-sensitive S. aureus [MSSA]) have been identified. We describe the treatment and outcomes among patients with mecA-MSSA bloodstream infections (BSI) and MRSA BSI matched 1:1 for age, BSI origin, and BSI type (n = 17 per group). Compared to MRSA BSI patients, mecA-MSSA BSI patients more often experienced clinical failure (58.8% and 11.8%, P = 0.010), driven largely by persistent bacteremia (35.3% and 11.8%). mecA-MSSA BSI patients may be at higher risk for poor clinical outcomes.

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