Comparison of intermittent versus continuous-infusion vancomycin for treating severe patients in intensive care units

Yamada, Carolina Hikari; Telles, João Paulo; Oliveira, Dayana Dos Santos; Cieslinski, Juliette; Ribeiro, Victoria Stadler Tasca; Gasparetto, Juliano; Tuon, Felipe Francisco

doi:10.1016/j.bjid.2020.07.001

Cited by 8 publications

(8 citation statements)

References 22 publications

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“…Several studies have been published in the past with continuously administered vancomycin using different ranges for target serum levels. These were 15-20 mg/L, 29, 44, 52–55 15-25 mg/L, 42, 43, 45, 56–62 20-25 mg/L, 46, 47, 63–65 20-30 mg/L, 33, 39, 66–75 25-30 mg/L, 76 20-40 mg/L 75 and 30-40 mg/L, 77 respectively. As far as we are aware, there is a lack of a comprehensive comparative evaluation of the influence of vancomycin serum concentration during continuous infusion of vancomycin on therapeutic outcomes of efficacy (e.g.…”

Section: Introductionmentioning

confidence: 95%

“…CI appears to hold several advantages over II. These include a lower potential risk of AKI, [34][35][36][37][38] earlier or higher target attainment, [37][38][39][40][41][42][43][44][45][46][47][48] less variability in serum concentrations 39,45,47,49 and easier and less expensive monitoring of drug levels. 39,42,44,47 In 2020, it was recommended in the revised consensus guidelines on the administration of vancomycin in serious MRSA infections to target the area under the curve over 24 hours to minimum inhibitory concentration of the isolated strain ratio (AUC24/MIC) instead of the previously advised trough level monitoring.…”

Section: Introductionmentioning

confidence: 99%

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Serum Concentration of Continuously administered Vancomycin influences Efficacy and Safety in Critically Ill Adults: A Systematic Review

Viertel

Feles

Schulte

et al. 2022

Preprint

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BackgroundVancomycin is an antibiotic to empirically treat gram-positive infections in critically ill adults in the intensive care unit (ICU). For continuously administered vancomycin (CI), various target ranges have been used in the past, ranging from 15-20 mg/L to 30-40 mg/L.ObjectivesTo investigate the impact of steady-state serum concentration (Css) of CI on the safety and efficacy of therapy in adults in the intensive care unit: a systematic literature review.MethodsAccording to the PRISMA statement, relevant literature was identified by searching three electronic databases (MEDLINE through the PubMed interface, Cochrane Library and Google Scholar) from inception until March 2022, focussing on studies reporting measured steady-state serum concentration of vancomycin (Css) and treatment outcomes (mortality, nephrotoxicity) with CI. Due to the heterogeneity of the study designs and outcome measures, it was not possible to summarise the results in a meta-analysis. Therefore, a narrative synthesis of the evidence was performed.ResultsTwenty-one publications were included with a total of 2,949 patients (pts) with CI. In two studies (n=388 pts) mortality rates were reported and cohorts with different Css compared. Mortality was higher with a Css <15 mg/L measured approximately 24 hours after initiation of therapy with CI (C24). An adequate loading dose appeared most important for maintaining higher C24. Acute kidney injury (AKI) in cohorts with different Css was described in four studies (n=863 pts). In one study (n=129 pts), a mean Css throughout the duration of therapy (Cmean) of >30 mg/L was found to predict AKI. No clear cutoff value for Css has been identified in the other studies, but higher concentrations led to higher rates of AKI. We calculated that a Css <25 mg/L was preferable compared to a concentration ≥25 mg/L for reducing nephrotoxicity. Data on target attainment and Css was mentioned in eleven studies (n=1,391 pts). We noticed higher target attainment rates in the studies if the defined target ranges were lower and broader. No association between target attainment and effectiveness (e.g. mortality) of therapy with CI has been observed so far. In two studies (n=101 pts) data on clinical response was presented and compared in cohorts with different Css of which in one study (n=40 pts) higher clinical cure was detected with a C24 >15 mg/L while in the other study (n=61 pts), treatment success was reported at higher Cmean, with sparing out a clear cutoff calculation.ConclusionDespite sparse data availability, it seems that for continuous infusion of vancomycin the mortality was increased if C24 was <15 mg/L, AKI may be reduced if Cmean was <25 mg/L, clinical cure was more likely to occur at C24 >15 mg/L, while no relationship between target attainment and efficacy has yet been established. In future research, vancomycin serum concentration cohorts should be formed to allow evaluation of the impact of serum concentration of CI on treatment outcomes.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Serum Concentration of Continuously administered Vancomycin influences Efficacy and Safety in Critically Ill Adults: A Systematic Review

Viertel

Feles

Schulte

et al. 2022

Preprint

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“…These requirements, however, are often difficult to achieve due to the resistance of the patient to frequent blood sampling and in medical institutions where therapeutic drug monitoring devices are lacking. This results in a common phenomenon that clinicians prefer using the intermittent infusion (II) mode, although the CI mode has the advantages of safety, PK target, and steady-state attainment ( Flannery et al., 2020 ; Yamada et al., 2020 ). Besides the CI and II modes, a novel infusion mode, i.e., the OTSI mode [a combined infusion mode with an initial loading-rate rapid infusion (LRRI) in the first step and afterwards with immediate low-rate continuous infusion (LRCI) in the second step], for vancomycin, has been recently presented in our previous study, and it showed great attractiveness in terms of PK/PD exposure in non-critically ill patients ( Song et al., 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Target Attainment of Vancomycin, at Three Reported Infusion Modes, for Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections in Critically Ill Patients: Focus on Novel Infusion Mode

Song

Han

2022

Front. Cell. Infect. Microbiol.

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ObjectiveThe study aimed to evaluate and compare the pharmacokinetic/pharmacodynamic (PK/PD) exposure to vancomycin in the novel optimal two-step infusion (OTSI) vs. intermittent infusion (II) vs. continuous infusion (CI) mode, for MRSA bloodstream infections occurring in critical patients.MethodsWith PK/PD modeling and Monte Carlo simulations, the PK/PD exposure of 15 OTSI, 13 II, and 6 CI regimens for vancomycin, at 1, 2, 3, 4, 5, and 6 g daily dose, was evaluated. Using the Monte Carlo simulations, the vancomycin population PK parameters derived from critical patients, the PD parameter for MRSA isolates [i.e., minimum inhibitory concentration (MIC)], and the dosing parameters of these regimens were integrated into a robust mdel of vancomycin PK/PD index, defined as a ratio of the daily area under the curve (AUC0–24) to MIC (i.e., AUC0–24/MIC), to estimate the probability of target attainment (PTA) of these regimens against MRSA isolates with an MIC of 0.5, 1, 2, 4, and 8 mg/L in patients with varying renal function. The PTA at an AUC0–24/MIC ratio of >400, 400–600, and >600 was estimated. A regimen with a PTA of ≥90% at an AUC0–24/MIC ratio of 400–600, which is supposed to maximize both efficacy and safety, was considered optimal.ResultsAt the same daily dose, almost only the OTSI regimens showed a PTA of ≥90% at an AUC0–24/MIC ratio of 400–600, and this profile seems evident especially in patients with creatinine clearance (CLcr) of ≥60 ml/min and for isolates with an MIC of ≤2 mg/L. However, for patients with CLcr of <60 ml/min and for isolates with an MIC of ≥4 mg/L, the II regimens often displayed a higher or even ≥90% PTA at an AUC0–24/MIC ratio of >400 and of >600. The CI regimens frequently afforded a reduced PTA at an AUC0–24/MIC ratio of >400 and of >600, regardless of CLcr and MIC.ConclusionsThe data indicated that the OTSI regimens allowed preferred PK/PD exposure in terms of both efficacy and safety, and thus should be focused more on, especially in patients with CLcr of ≥60 ml/min and for isolates with an MIC of ≤2 mg/L.

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“…5 Vancomycin is a standard therapy for MRSA meningitis that can be administered through continuous infusion (CI) to attain constant serum bactericidal concentrations at a faster rate than intermittent infusion, with lower renal toxicity. 6,7 However, treating CNS infections is inherently challenging because of the presence of the blood-brain barrier (BBB), which greatly decreases the permeability of the CNS, resulting in inconsistent BBB penetration of vancomycin. 8,9 The Infectious Disease Society of America recommends antimicrobial concentration in the cerebrospinal fluid (CSF), which is 10-20 times higher than the minimal inhibitory concentration used in intraventricular therapy for the pathogen.…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Penetration of Vancomycin During Continuous Infusion Therapy in Patients With Nosocomial Ventriculitis

Tuon

Yamada

Cieslinski

et al. 2021

Therapeutic Drug Monitoring

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Background: This study aimed to evaluate the utility of a commercial kit used to measure serum vancomycin concentrations to determine vancomycin concentrations in cerebrospinal fluid (CSF) samples and evaluate CSF penetration when administered as a continuous high-dose infusion in patients with nosocomial ventriculitis.Methods: This study included patients with external ventricular drain infection who were admitted to the intensive care unit between January 2018 and September 2020. After validation, CSF samples from 33 patients were collected. All patients received 30 mg/kg of vancomycin as a loading dose followed by 60 mg/kg as a maintenance dose in continuous infusion; all CSF samples were collected at least 48 hours after the first dose.Results: Thirty-three patients were enrolled in this study. The median serum creatinine level was 0.66 mg/dL (0.5-0.92; n = 30), and median creatinine clearance was 119.2 mL/min (64.6-138.4; n = 13). The median serum vancomycin 24-hour area under the curve (AUC 24h ) was 838 mg*h/L (515-1010). The median CSF vancomycin concentration was 5.20 mg/L (1.95-12.4). Median serum vancomycin concentration was 34.9 mg/L (21.47-42.1), and median CSF/ serum ratio was 18.6% (8.4-41.5). Acute renal injury occurred in 21% (n = 7) of the patients by the end of the therapy. In addition, the vancomycin CSF/serum ratio was positively correlated with the median serum creatinine level (r = 0.670; P = 0.004).Conclusions: Commercial vancomycin kits used to measure serum samples may be used to evaluate vancomycin concentrations in the CSF. Vancomycin penetration into CSF was 18.6%.

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Comparison of intermittent versus continuous-infusion vancomycin for treating severe patients in intensive care units

Cited by 8 publications

References 22 publications

Serum Concentration of Continuously administered Vancomycin influences Efficacy and Safety in Critically Ill Adults: A Systematic Review

Serum Concentration of Continuously administered Vancomycin influences Efficacy and Safety in Critically Ill Adults: A Systematic Review

Pharmacokinetic/Pharmacodynamic Target Attainment of Vancomycin, at Three Reported Infusion Modes, for Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections in Critically Ill Patients: Focus on Novel Infusion Mode

Cerebrospinal Fluid Penetration of Vancomycin During Continuous Infusion Therapy in Patients With Nosocomial Ventriculitis

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