Pharmacokinetic Evaluation of Meropenem and Imipenem in Critically Ill Patients with Sepsis

Novelli, Andréa; Adembri, Chiara; Livi, Paola; Fallani, Stefania; Mazzei, Teresita; Gaudio, Angelo Raffaele De

doi:10.2165/00003088-200544050-00007

Cited by 83 publications

(63 citation statements)

References 34 publications

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“…The NPAG (nonparametric adaptive grid with adaptive ␥) program of Leary et al was employed for the analysis (14a). Because of prior data relating to imipenem pharmacokinetic modeling (2,5,6,8,9,13,18,24), a two-compartment open model with a time-delimited zero-order input (intermittent administration) or a short (40-min; see above) intravenous infusion followed by a continuous drug infusion starting at 4 h was employed. In both instances, first-order elimination was employed in the model.…”

Section: Patientsmentioning

confidence: 99%

Population Pharmacokinetics and Pharmacodynamics of Continuous versus Short-Term Infusion of Imipenem-Cilastatin in Critically Ill Patients in a Randomized, Controlled Trial

Sakka

Glauner

Bulitta

et al. 2007

Antimicrob Agents Chemother

140

138

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Beta-lactams are regularly administered in intermittent short-term infusions. The percentage of the dosing interval during which free drug concentrations exceed the MIC (fT >MIC ) is the measure of drug exposure that best correlates with clinical outcome for beta-lactams. Therefore, administration by continuous infusion has gained increasing interest recently. We studied 20 critically ill patients with nosocomial pneumonia and investigated whether continuous infusion with a reduced total dose, compared to the standard regimen of intermittent short-term infusion, results in a superior probability of target attainment as assessed by the fT >MIC value of imipenem. In this prospective, randomized, controlled clinical study, patients received either a loading dose of 1 g/1 g imipenem and cilastatin (as a short-term infusion) at time zero, followed by 2 g/2 g imipenem-cilastatin per 24 h as a continuous infusion for 3 days (n ‫؍‬ 10), or 1 g/1 g imipenem-cilastatin three times per day as a short-term infusion for 3 days (total daily dose, 3 g/3 g; n ‫؍‬ 10). Imipenem concentrations in plasma were determined by using a validated liquid chromatography-tandem mass spectrometry assay. A two-compartment open model was employed for population pharmacokinetic modeling. We simulated 10,000 intensive-care-unit patients via Monte Carlo simulations for pharmacodynamic evaluation using the target 40% fT >MIC . The probability of target attainment by MIC for intermittent infusion was robust (>90%) up to MICs of 1 to 2 mg/liter. The corresponding value for continuous infusion was 2 to 4 mg/liter. Although all 20 patients had an fT >MIC of 100%, 3 patients died. Patient survival was best described by employing a sepsis-related organ failure assessment score as a covariate in a logistic regression analysis. Larger clinical trials are warranted for evaluation of continuous infusions at a reduced dose of imipenem for critically ill patients.In critically ill patients, intensive care unit (ICU)-acquired pneumonia has been shown to be associated with a significant increase in the length of stay and mortality (27). Besides other factors, early and adequate antibiotic treatment has a major prognostic impact and is therefore of particular clinical relevance (12,14). Furthermore, adequacy of antibiotic treatment is also determined by sufficient distribution to the site of action. Since antibiotic concentrations at the site of action are often difficult to determine, concentrations in plasma are most commonly used as a surrogate measure.Broad-spectrum ␤-lactam antibiotics are considered appropriate in the treatment of ICU-acquired pneumonia. However, the optimal method for administration of ␤-lactam antibiotics is currently under investigation. Although they are usually administered in clinical practice in regular intermittent shortterm infusions following the manufacturers' instructions, the administration of ␤-lactam antibiotics by continuous infusion has been proposed (4,15,21). Previous studies (3,7,17,28) repeatedly emphasized that the t...

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Section: Patientsmentioning

confidence: 99%

Population Pharmacokinetics and Pharmacodynamics of Continuous versus Short-Term Infusion of Imipenem-Cilastatin in Critically Ill Patients in a Randomized, Controlled Trial

Sakka

Glauner

Bulitta

et al. 2007

Antimicrob Agents Chemother

140

138

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“…Para Novelli et al (2005) a eficácia clínica do Meropenem depende principalmente da sua dosagem correta e que pacientes com sepse podem se beneficiar de doses diárias superiores, que poderia garantir um T> MIC, devido à baixa perfusão de tecidos periféricos.…”

Section: Discussionunclassified

“…A sua ação bactericida tem a característica de ser tempo-dependente (T>CIM), ou seja, o efeito depende do tempo em que o fármaco ficará em contato com a bactéria, sendo esse parâmetro um dos mais importantes da farmacocinética/farmacodinâmica na previsão da eficácia clínica. Demonstrando pouca atividade dependente da concentração e tem pouca relação com a magnitude da concentração do fármaco durante a exposição (NOVELLI et al, 2005).…”

Section: Introductionunclassified

Infusão Contínua Versus Intermitente De Meropenem Na Prática Clínica

Simonato

Teixeira

Rebecca

et al. 2017

Arq. Ciênc. Saúde Unipar

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Ligiane de Lourdes da Silva 5 SIMONATO, B. S.; TEIXEIRA, G. C.; REBECCA, E. S. W.; ROSS, C.; SILVA, L. de L. da. Infusão contínua versus intermitente de meropenem na prática clínica. Arq. Cienc. Saúde UNIPAR, Umuarama, v. 21, n. 1, p, 59-64, jan./abr. 2017. RESUMO:Analisar as evidências científicas relacionadas ao tempo de administração endovenosa do Meropenem na prática clínica. Trata-se de uma revisão integrativa de literatura, retrospectiva, de natureza descritiva, com abordagem quantitativa com destaque para a produção científica de estudos clínicos randomizados, revisão sistemática e meta-análise. As bases de dados utilizadas foram Cochrane e Pubmed. A seleção da amostra foi realizada por dois pesquisadores independentes, utilizou-se instrumento adaptado para verificar o nível de evidência, grau de recomendação e classificação pela escala de Jadad. Foram selecionados 12 artigos referentes à administração endovenosa de forma contínua e intermitente do Meropenem. Dos quais nove eram ensaio clínico randomizado, dois eram ensaio clínico randomizado controlado e um meta-análise, destes 11 apresentavam nível II de evidência científica. A maioria dos estudos comparou a infusão rápida, em 30 minutos e/ou 3 horas, seguidos de estudos com administração rápida e/ou 30 minutos em infusão contínua. Os resultados dos estudos apontam que na infusão intermitente, com tempo de administração rápida, o pico da concentração plasmática não é suficiente para garantir eficácia do Meropenem. Já, para os estudos que abordaram a infusão intermitente clássica com tempo ≥ 3 horas demonstram que a técnica mantém melhor concentração inibitória mínima, devido à infusão ser prolongada. PALAVRAS-CHAVE: Antibacterianos. Ações Farmacológicas. Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos. CONTINUOUS VERSUS INTERMITTENT INFUSION OF MEROPENEM IN CLINICAL PRACTICE ABSTRACT:This study aims to analyze the scientific evidence regarding the intravenous administration time of Meropenem in clinical practice. This is an integrative, retrospective, descriptive literature review, with a quantitative approach and emphasis on the scientific work of randomized clinical trials, with systematic review and meta-analysis. The databases used were Cochrane and PubMed. The samples were selected by two independent researchers, and an adapted instrument was used to verify the evidence level, recommendation grade and classification against the Jadad scale. A total of 12 articles related to the intravenous administration of continuous and intermittent Meropenem were selected. Nine of which were randomized studies, two were randomized controlled trials and one was a meta-analysis. From the total studies, 11 presented level II scientific evidence. Most studies compared rapid infusion, 30 minutes and/or 3 hour infusions, followed by rapid administration and/or 30 minute studies in continuous infusion. The results of the studies show that intermittent infusion with rapid time management presented peak plasma concentration that is not sufficient to gua...

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“…Although direct comparison between agents is difficult, imipenem/cilastatin and meropenem 1000 mg intravenously every 8 hours infused over 30 minutes achieve adequate T > MIC in most patients and for organisms with low MICs. 28,29 However, these regimens may have lower T > MIC in critically ill patients with high MIC organisms. Results of a study 30 in critically ill patients with ventilatorassociated pneumonia (VAP) indicate that meropenem 1000 mg or 2000 mg intravenously every 8 hours with a 3-hour infusion was necessary to achieve T > MIC, especially for infections caused by bacteria with higher MICs.…”

Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

Application of Antibiotic Pharmacodynamics and Dosing Principles in Patients With Sepsis

Fleet

Mueller

2016

Critical Care Nurse

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Sepsis is associated with marked mortality, which may be reduced by prompt initiation of adequate, appropriate doses of antibiotic. Critically ill patients often have physiological changes that reduce blood and tissue concentrations of antibiotic and high rates of multidrug-resistant pathogens, which may affect patients' outcomes. All critical care professionals, including critical care nurses, should understand antibiotic pharmacokinetics and pharmacodynamics to ensure sound antibiotic dosing and administration strategies for optimal microbial killing and patients' outcomes. Effective pathogen eradication occurs when the dose of antibiotic reaches or maintains optimal concentrations relative to the minimum inhibitory concentration for the pathogen. Time-dependent antibiotics, such as β-lactams, can be given as extended or continuous infusions. Concentration-dependent antibiotics such as aminoglycosides are optimized by using high, once-daily dosing strategies with serum concentration monitoring. Vancomycin and fl uoroquinolones are dependent on both time and concentration above the minimum inhibitory concentration. (Critical Care Nurse. 2016;36[2]:22-32) S epsis is a major cause of morbidity and mortality in the United States, affecting more than 650 000 patients per year. The spectrum of sepsis to septic shock is associated with crude mortality rates of 20% to 70%. [1][2][3][4] From the onset of hypotension, the probability of survival is reduced by 12% for each hour of delay before administration of adequate empiric antibiotics. 5Hence, current guidelines advocate early administration of adequate, broad-spectrum, local antibiogram-based antibiotic therapy in appropriate doses to penetrate the suspected site of infection (eg, lungs, cerebral spinal fl uid, intra-abdominal fl uid).1 Physiological changes associated with sepsis can complicate antibiotic dosing, effectiveness, and safety.

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Pharmacokinetic Evaluation of Meropenem and Imipenem in Critically Ill Patients with Sepsis

Cited by 83 publications

References 34 publications

Population Pharmacokinetics and Pharmacodynamics of Continuous versus Short-Term Infusion of Imipenem-Cilastatin in Critically Ill Patients in a Randomized, Controlled Trial

Population Pharmacokinetics and Pharmacodynamics of Continuous versus Short-Term Infusion of Imipenem-Cilastatin in Critically Ill Patients in a Randomized, Controlled Trial

Infusão Contínua Versus Intermitente De Meropenem Na Prática Clínica

Application of Antibiotic Pharmacodynamics and Dosing Principles in Patients With Sepsis

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