scholarly journals Impact of initial vancomycin pharmacokinetic/pharmacodynamic parameters on the clinical and microbiological outcomes of methicillin-resistant Staphylococcus aureus bacteremia in children

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0247714
Author(s):  
Reenar Yoo ◽  
Hyejin So ◽  
Euri Seo ◽  
Mina Kim ◽  
Jina Lee
Keyword(s):  
Staphylococcus Aureus ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Methicillin Resistant ◽  
Demographic Profiles ◽  
Staphylococcus Aureus Bacteremia ◽  
Median Dosage ◽  
Persistent Bacteremia ◽  
Underlying Diseases ◽  
The Impact

Optimal vancomycin exposure is important to minimize treatment failure of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. We aimed to analyze the impact of initial vancomycin pharmacokinetic/pharmacodynamic (PK/PD) parameters, including the initial vancomycin C trough and the area under the curve (AUC)/minimal inhibitory concentration (MIC) on the outcomes of pediatric MRSA bacteremia. The study population consisted of hospitalized children aged between 2 months and 18 years with MRSA bacteremia, in whom C trough was measured at least one time within the time period of January 2010 to March 2018. Demographic profiles, underlying diseases, and clinical/microbiological outcomes were abstracted retrospectively. During the study period, 73 cases of MRSA bacteremia occurred in children with a median age of 12.4 months. Severe clinical outcomes leading to intensive care unit stay and/or use of mechanical ventilation occurred in 47.5% (35/73); all-cause 30-day mortality was 9.7% (7/72). The median dosage of vancomycin was 40.0 mg/kg/day. There was a weak linear relationship between C trough and the corresponding AUC/MIC (r = 0.235). ROC curves for achieving an AUC/MIC of 300 suggested that the initial C trough at 10 μg/mL could be used as a cut-off value with a sensitivity of 90.5% and a specificity of 44%. Although persistent bacteremia at 48–72 hours after vancomycin administration was observed more frequently when the initial C trough was < 10 μg/mL and initial AUC/MIC was < 300, initial AUC/MIC < 300 was the only risk factor associated with persistent bacteremia at 48–72 hours (adjusted OR 3.05; 95% CI, 1.07–8.68). Initial C trough and AUC/MIC were not associated with 30-day mortality. Although there was a weak relationship between C trough and AUC/MIC, initial AUC/MIC < 300 could be used as a predictor of persistent MRSA bacteremia at 48–72 hours. Further prospective data on optimal vancomycin dosing are necessary to improve clinical and microbiological outcomes in pediatric MRSA bacteremia.

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 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 &lt;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.

The Impact of AUC-Based Monitoring on Pharmacist-Directed Vancomycin Dose Adjustments in Complicated Methicillin-Resistant Staphylococcus aureus Infection

2018 ◽  
Vol 32 (4) ◽  
pp. 442-446 ◽  
Author(s):  
Andrew M. Stoessel ◽  
Cory M. Hale ◽  
Robert W. Seabury ◽  
Christopher D. Miller ◽  
Jeffrey M. Steele
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Area Under The Curve ◽  
Monitoring Method ◽  
Methicillin Resistant ◽  
Vancomycin Dose ◽  
Monitoring Group ◽  
Mrsa Infection ◽  
Auc Estimation ◽  
The Impact

Objective: This study aimed to assess the impact of area under the curve (AUC)-based vancomycin monitoring on pharmacist-initiated dose adjustments after transitioning from a trough-only to an AUC-based monitoring method at our institution. Methods: A retrospective cohort study of patients treated with vancomycin for complicated methicillin-resistant Staphylococcus aureus (MRSA) infection between November 2013 and December 2016 was conducted. The frequency of pharmacist-initiated dose adjustments was assessed for patients monitored via trough-only and AUC-based approaches for trough ranges: 10 to 14.9 mg/L and 15 to 20 mg/L. Results: Fifty patients were included: 36 in the trough-based monitoring and 14 in the AUC-based-monitoring group. The vancomycin dose was increased in 71.4% of patients when troughs were 10 to 14.9 mg/L when a trough-only approach was used and in only 25% of patients when using AUC estimation ( P = .048). In the AUC group, the dose was increased only when AUC/minimum inhibitory concentration (MIC) <400; unchanged regimens had an estimated AUC/MIC ≥400. The AUC-based monitoring did not significantly increase the frequency of dose reductions when trough concentrations were 15 to 20 mg/L (AUC: 33.3% vs trough: 4.6%; P = .107). Conclusions: The AUC-based monitoring resulted in fewer patients with dose adjustments when trough levels were 10 to 14.9 mg/L. The AUC-based monitoring has the potential to reduce unnecessary vancomycin exposure and warrants further investigation.

scholarly journals β-Lactams Enhance Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus Bacteremia Compared to Vancomycin Alone

2013 ◽  
Vol 58 (1) ◽  
pp. 102-109 ◽  
Author(s):  
Thomas J. Dilworth ◽  
Omar Ibrahim ◽  
Pamela Hall ◽  
Jora Sliwinski ◽  
Carla Walraven ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Synergistic Activity ◽  
Methicillin Resistant ◽  
Content Type ◽  
Staphylococcus Aureus Bacteremia ◽  
High Incidence ◽  
The Difference ◽  
Initiation Of Therapy ◽  
The Impact

ABSTRACTVancomycin (VAN) is often used to treat methicillin-resistantStaphylococcus aureus(MRSA) bacteremia despite a high incidence of microbiological failure. Recentin vitroanalyses of β-lactams in combination with VAN demonstrated synergistic activity against MRSA. The goal of this study was to examine the impact of combination therapy with VAN and a β-lactam (Combo) on the microbiological eradication of MRSA bacteremia compared to VAN alone. This was a retrospective cohort study of patients with MRSA bacteremia who received Combo therapy or VAN alone. Microbiological eradication of MRSA, defined as a negative blood culture obtained after initiation of therapy, was used to evaluate the efficacy of each regimen. A total of 80 patients were included: 50 patients in the Combo group and 30 patients in the VAN-alone group. Microbiological eradication was achieved in 48 patients (96%) in the Combo group compared to 24 patients (80%) in the VAN-alone group (P= 0.021). In a multivariable model, the Combo treatment had a higher likelihood of achieving microbiological eradication (adjusted odds ratio, 11.24; 95% confidence interval, 1.7 to 144.3;P= 0.01). In patients with infective endocarditis (n= 22), 11/11 (100%) who received Combo therapy achieved microbiological eradication compared to 9/11 (81.8%) treated with VAN alone, but the difference was not statistically significant (P= 0.20). Patients with MRSA bacteremia who received Combo therapy were more likely to experience microbiological eradication of MRSA than patients who received VAN alone.

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 &lt;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

Pediatric and Neonatal Staphylococcus aureus Bacteremia Epidemiology, Risk Factors, and Outcome

2009 ◽  
Vol 30 (7) ◽  
pp. 636-644 ◽  
Author(s):  
Robert E. Burke ◽  
Meira S. Halpern ◽  
Ellen Jo Baron ◽  
Kathleen Gutierrez
Keyword(s):  
Risk Factors ◽  
Staphylococcus Aureus ◽  
Demographic Data ◽  
Hispanic Children ◽  
Methicillin Resistant ◽  
Staphylococcus Aureus Bacteremia ◽  
Outcomes For Children ◽  
Associated Risk Factors ◽  
Healthcare Associated ◽  
The Impact

Objective.To evaluate the impact of methicillin-resistant Staphylococcus aureus on the prevalence of S. aureus bloodstream infection among children.Methods.Retrospective analysis of demographic data, risk factors for infection, and clinical outcomes for children (age, less than 18 years) with S. aureus bacteremia hospitalized at a children's hospital during 2001–2006.Results.We identified 164 episodes of S. aureus bacteremia among 151 children. The prevalence of bacteremia due to methicillin-susceptible S. aureus during 2001–2003 was approximately the same as that during 2004–2006 (29 and 30 cases, respectively, per 10,000 hospitalized children [hereafter, “per 10,000 hospitalizations”]), but the prevalence of bacteremia due to methicillin-resistant S. aureus increased from 4 to 11 cases, respectively, per 10,000 hospitalizations (P = .015). A total of 48% of infections involved children who had S. aureus-positive blood cultures less than 3 days after hospital admission. Seventy-four percent of these children had a preexisting comorbidity. When the prevalence of S. aureus bacteremia was stratified by race, sex, or age, neonates hospitalized at birth and Hispanic children had significantly reduced risks of infection. Children younger than 1 year of age (excluding neonates hospitalized at birth) had an increased prevalence of hospital-onset S. aureus bacteremia. There was a disproportionate increase in the risk of S. aureus bacteremia for each additional week of hospitalization among children with hospital-onset S. aureus bacteremia. Children with methicillin-resistant S. aureus bacteremia had a longer hospital stay, were transferred to another facility at a greater rate than they were discharged home, and had a greater mortality rate, compared with children with methicillin-susceptible S. aureus bacteremia.Conclusion.This study documents the prevalence of S. aureus bacteremia among children with a high risk for acquiring this infection, and it describes populations of children who are at higher risk for bacteremia due to either methicillin-susceptible or methicillin-resistant S. aureus. Methods to improve prevention of S. aureus bacteremia are needed for children with healthcare-associated risk factors for S. aureus bacteremia.

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