Pharmacokinetics of linezolid for methicillin-resistant Staphylococcus aureus pneumonia in an adult receiving extracorporeal membrane oxygenation

2020 ◽  
Vol 77 (11) ◽  
pp. 877-881 ◽  
Author(s):  
Peter Nikolos ◽  
Justin Osorio ◽  
Kerry Mohrien ◽  
Christina Rose
Keyword(s):  
Staphylococcus Aureus ◽  
Respiratory Failure ◽  
Extracorporeal Membrane Oxygenation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Volume Of Distribution ◽  
Minimum Concentration ◽  
Methicillin Resistant ◽  
Membrane Oxygenation

Abstract Purpose We present a case of a 55-year-old man post right lung transplantation receiving ECMO for treatment of respiratory failure secondary to methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Summary Extracorporeal membrane oxygenation (ECMO) is a frequently utilized support therapy for patients with cardiac and/or respiratory failure. Dosing of medications during ECMO can be challenging due to several factors, including sequestration of medications within ECMO circuits, alterations in volume of distribution, and changes in drug clearance. The patient was initiated on empiric antibiotics, then switched to linezolid at a dose of 600 mg every 8 hours. Linezolid plasma concentrations were collected 30 minutes prior to the sixth administered dose and 30 minutes following the 1-hour infusion of the sixth dose, which resulted in values of 0.4 and 1.7 μg/mL, respectively. The ratio of 24-hour area under the curve (AUC0-24) to minimum inhibitory concentration (MIC), assuming a MIC of 2 μg/mL, was calculated using the extrapolated maximum concentration (1.9 μg/mL) and minimum concentration (0.35 μg/mL), resulting in an AUC0-24/MIC value of 10.8. Due to subtherapeutic linezolid plasma concentrations, ceftaroline was initiated and continued for a total of 18 days. To our knowledge, this is the second report to describe inadequate plasma concentrations of linezolid during ECMO. Conclusion In the case described here, linezolid at a dose of 600 mg every 8 hours did not achieve target plasma concentrations in a patient receiving concomitant venovenous ECMO support.

scholarly journals AUC/MIC Pharmacodynamic Target Is Not a Good Predictor of Vancomycin Efficacy in Methicillin-Resistant Staphylococcus aureus Experimental Endocarditis

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Ximena Castañeda ◽  
Cristina García-de-la-Mària ◽  
Oriol Gasch ◽  
Juan M. Pericas ◽  
Yolanda Armero ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Good Predictor ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Area Under The Curve ◽  
Methicillin Resistant ◽  
Bacterial Counts ◽  
Content Type ◽  
Treatment Groups ◽  
Mrsa Strains

ABSTRACT The aim of this in vivo study was to compare the efficacy of vancomycin at standard doses (VAN-SD) to that of VAN at adjusted doses (VAN-AD) in achieving a VAN area under the curve/MIC ratio (AUC/MIC) of ≥400 against three methicillin-resistant Staphylococcus aureus (MRSA) strains with different microdilution VAN MICs in an experimental endocarditis model. The valve vegetation bacterial counts after 48 h of VAN therapy were compared, and no differences were observed between the two treatment groups for any of the three strains tested. Overall, for VAN-SD and VAN-AD, the rates of sterile vegetations were 15/45 (33.3%) and 21/49 (42.8%) (P = 0.343), while the medians (interquartile ranges [IQRs]) for log10 CFU/g of vegetation were 2 (0 to 6.9) and 2 (0 to 4.5) (P = 0.384), respectively. In conclusion, this VAN AUC/MIC pharmacodynamic target was not a good predictor of vancomycin efficacy in MRSA experimental endocarditis.

Intraperitoneal vancomycin treatment of multifocal methicillin-resistant Staphylococcus aureus osteomyelitis in a patient on peritoneal dialysis

2020 ◽  
Vol 77 (21) ◽  
pp. 1746-1750
Author(s):  
Qassim Abid ◽  
Basim Asmar ◽  
Edward Kim ◽  
Leah Molloy ◽  
Melissa Gregory ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Peritoneal Dialysis ◽  
Central Venous Catheter ◽  
Shoulder Joint ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Area Under The Curve ◽  
Venous Catheter ◽  
Left Shoulder ◽  
Central Venous ◽  
Methicillin Resistant

Abstract Purpose We report the case of a 2-year-old girl with end-stage renal disease managed by peritoneal dialysis (PD) who developed methicillin-resistant staphylococcal osteomyelitis of the left shoulder and was successfully treated with intraperitoneal (IP) administration of vancomycin for 2 weeks followed by oral clindamycin therapy. Summary The patient was hospitalized with tactile fever and a 3-day history of worsening fussiness. Radiography of the left shoulder showed findings indicative of osteomyelitis. Vancomycin was administered via central venous line for 3 days, during which time the patient underwent PD 24 hours a day. After magnetic resonance imaging revealed proximal humeral osteomyelitis, septic arthritis of the shoulder joint, and osteomyelitis of the scapula, the patient underwent incision and drainage of the left shoulder joint. Both blood and joint drainage cultures grew methicillin-resistant Staphylococcus aureus that was sensitive to vancomycin. The patient’s central venous catheter was removed on hospital day 4; due to difficulties with peripheral i.v. access and a desire to avoid placing a peripherally inserted central venous catheter, vancomycin administration was changed to the IP route, with vancomycin added to the PD fluid. During IP treatment, serum vancomycin levels were maintained at 13.5 to 18.5 mg/L, and the calculated ratio of vancomycin area under the curve to minimum inhibitory concentration was maintained above 400. After completing a 14-day course of IP vancomycin therapy, the patient was switched to oral clindamycin, with subsequent complete resolution of osteomyelitis. Conclusion IP vancomycin was effective for treatment of invasive S. aureus infection in this case. This approach should be considered in patients undergoing PD for whom peripheral i.v. access options are limited and/or not preferred.

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.

Clindamycin clearance during Cytosorb® hemoadsorption: A case report and pharmacokinetic study

2019 ◽  
Vol 42 (5) ◽  
pp. 258-262 ◽  
Author(s):  
Elettra Camille Poli ◽  
Chiara Simoni ◽  
Pascal André ◽  
Thierry Buclin ◽  
David Longchamp ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pharmacokinetic Model ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Plasma Concentrations ◽  
Influenza B ◽  
Membrane Oxygenator ◽  
Refractory Shock ◽  
Methicillin Resistant ◽  
Aureus Infection ◽  
Very High

Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus infections are rare but associated with very high mortality rates. We report the case of a 14-year-old patient with Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus infection and Influenza B pneumonia requiring veno-arterial extra-corporeal membrane oxygenator for refractory shock. In the absence of response to conventional therapy, we have inserted a Cytosorb® cartridge within the extra-corporeal membrane oxygenator circuit. A spectacular decrease in vasopressor requirements followed. Since clindamycin, a key component of Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus treatment, might be removed by Cytosorb® hemoadsorption, we have performed serial plasma concentrations measurements of the drug. Based on these measurements, we were able to develop a pharmacokinetic model incorporating variable plasma clearance. Patient’s exposure was estimated before, during and after Cytosorb® hemoadsorption. According to this model, Cytosorb® hemoadsorption did not seem to result in significant clindamycin removal. Cytosorb® hemoadsorption during Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus infection appears safe and feasible and no adaptation of clindamycin dosage seems necessary

Sufentanil pharmacokinetics in a full-term neonate treated with extracorporeal membrane oxygenation: a case report

Perfusion ◽  
2019 ◽  
Vol 34 (5) ◽  
pp. 433-436 ◽  
Author(s):  
Pavla Pokorná ◽  
Martin Šíma ◽  
Václav Vobruba ◽  
Martina Bašková ◽  
Lenka Posch ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Case Report ◽  
Extracorporeal Membrane Oxygenation ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Analgesic Drug ◽  
Membrane Oxygenation ◽  
Ischemic Encephalopathy

Introduction: Sufentanil is a potent analgesic drug used for pain management. A few studies describe the pharmacokinetics of sufentanil in neonates; however, no pharmacokinetic data about sufentanil during extracorporeal membrane oxygenation have been published yet. Case report: A 1-day-old neonate with moderate hypoxic–ischemic encephalopathy received veno-arterial extracorporeal membrane oxygenation support for refractory respiratory and circulatory failure. Sufentanil plasma concentrations were determined during both extracorporeal membrane oxygenation (n = 14) and non–extracorporeal membrane oxygenation (n = 17) period. Based on these measurements, individual sufentanil pharmacokinetic parameters were calculated. Discussion: We observed increased sufentanil volume of distribution (11.6 vs 5.6 L/kg) and decreased sufentanil clearance (0.535 vs 0.746 L/h/kg) in extracorporeal membrane oxygenation period. The increment of volume of distribution was attributed to ECMO influence, while difference in clearance was probably due to drug interaction. Conclusions: This is the first description of sufentanil pharmacokinetics in neonate treated with extracorporeal membrane oxygenation. We observed considerably larger volume of distribution during extracorporeal membrane oxygenation period in comparison with non–extracorporeal membrane oxygenation period.

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 Evaluation of Ceftaroline, Vancomycin, Daptomycin, or Ceftaroline plus Daptomycin against Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus in anIn VitroPharmacokinetic/Pharmacodynamic Model of Simulated Endocardial Vegetations

2014 ◽  
Vol 58 (6) ◽  
pp. 3177-3181 ◽  
Author(s):  
Brian J. Werth ◽  
Katie E. Barber ◽  
Cortney E. Ireland ◽  
Michael J. Rybak
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Activity ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Active Agent ◽  
Minimum Concentration ◽  
Ceftaroline Fosamil ◽  
Methicillin Resistant ◽  
Content Type ◽  
Sustained Activity

ABSTRACTInfective endocarditis (IE) caused by methicillin-resistantStaphylococcus aureus(MRSA) with reduced susceptibility to vancomycin and daptomycin has few adequate therapeutic options. Ceftaroline (CPT) is bactericidal against daptomycin (DAP)-nonsusceptible (DNS) and vancomycin-intermediate MRSA, but supporting data are limited for IE. This study evaluated the activities of ceftaroline, vancomycin, daptomycin, and the combination of ceftaroline plus daptomycin against DNS MRSA in a pharmacokinetic/pharmacodynamic (PK/PD) model of simulated endocardial vegetations (SEVs). Simulations of ceftaroline-fosamil (600 mg) every 8 h (q8h) (maximum concentration of drug in serum [Cmax], 21.3 mg/liter; half-life [t1/2], 2.66 h), daptomycin (10 mg/kg of body weight/day) (Cmax, 129.7 mg/liter;t1/2, 8 h), vancomycin (1 g) q8h (minimum concentration of drug in serum [Cmin], 20 mg/liter;t1/2, 5 h), and ceftaroline plus daptomycin were evaluated against 3 clinical DNS, vancomycin-intermediate MRSA in a two-compartment,in vitro, PK/PD SEV model over 96 h with a starting inoculum of ∼8 log10CFU/g. Bactericidal activity was defined as a ≥3-log10CFU/g reduction from the starting inoculum. Therapeutic enhancement of combinations was defined as ≥2-log10CFU/g reduction over the most active agent alone. MIC values for daptomycin, vancomycin, and ceftaroline were 4 mg/liter, 4 to 8 mg/liter, and 0.5 to 1 mg/liter, respectively, for all strains. At simulated exposures, vancomycin was bacteriostatic, but daptomycin and ceftaroline were bactericidal. By 96 h, ceftaroline monotherapy offered significantly improved killing compared to other agents against one strain. The combination of DAP plus CPT demonstrated therapeutic enhancement, resulting in significantly improved killing versus either agent alone against 2/3 (67%) strains. CPT demonstrated bactericidal activity against DNS, vancomycin-intermediate MRSA at high bacterial densities. Ceftaroline plus daptomycin may offer more rapid and sustained activity against some MRSA in the setting of high-inoculum infections like IE and should also be considered.

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