Continuous infusion versus intermittent administration of meropenem in critically ill patients (MERCY): A multicenter randomized double-blind trial. Rationale and design

Monti, Giacomo; Galbiati, Carola; Toffoletto, Fabio; Calabrò, Maria Grazia; Colombo, Sergio; Ferrara, Barbara; Giardina, Giuseppe; Lembo, Rosalba; Marzaroli, Matteo; Moizo, Elena; Mucci, María; Pasculli, Nicola; Plumari, Valentina Paola; Scandroglio, Anna Mara; Tozzi, Margherita; Momesso, Elena; Boffa, Nicoletta; Lobreglio, Rosetta; Montrucchio, Giorgia; Guarracino, Fabio; Benedetto, Umberto; Biondi‐Zoccai, Giuseppe; D’Ascenzo, Fabrizio; D’Andrea, Natascia; Paternoster, Gianluca; Ananiadou, Sofia; Ballestra, Mariano; Sio, A De; Pota, Vincenzo; Cotoia, Antonella; Selva, Andrea Della; Bruni, Andrea; Iapichino, G.; Bradić, Nikola; Corradi, Francesco; Gemma, Marco; Nogtev, Pavel; Petrova, Marina V.; Cabrini, Luca; Forfori, Francesco; Лихванцев, В. В.; Bove, Tiziana; Finco, Gabriele; Landoni, Giovanni; Zangrillo, Alberto; Ajello, Silvia; Cappelletti, Alberto; Fominskiy, Evgeny; Nisi, Fulvio; Pazzanese, Vittorio; Pieri, Marina; Canavosio, Federico; Palmesino, Filippo; Bernasconi, Mara; Gallioli, G; Marino, Giovanni; Vetrugno, Luigi; Millin, Chiara; Missio, Daniela; Gallicchio, Francesca; Azzali, Barbara; Bozzetti, Mattia; Cristadoro, Daniele; Perone, Romina; Cantatore, Leonarda Pia; Curci, G; Pabon, Ingrid Marcela; Garofalo, Eugenio; Mainetti, Manuela; Calamai, Italo; Maraggia, D; Mattei, Alessia; Yavorovskiy, Andrey

doi:10.1016/j.cct.2021.106346

Cited by 12 publications

(9 citation statements)

References 28 publications

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“…A dosage adjustment was made considering creatinine clearance. The stability of the prepared antibiotic solution was ensured by preparing a completely new solution of the drug every 4 h. Such a methodic infusion was recommended and described in the MERCY study protocol [ 5 ].…”

Section: Methodsmentioning

confidence: 99%

Usage of Meropenem Continuous Infusion for Treatment of Infectious Complications in Orthopedic Elderly Patients with Anemia: A Case Series

Konkayev,

Kadralinova,

Azimova

et al. 2024

Medicina

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Background and Objectives: The prolonged infusion of meropenem is recommended by guidelines for the treatment of sepsis. However, studies provide controversial data on the advantages of prolonged infusions over intermittent ones. In our opinion, this can be related to age, which possibly distorts the final data, as older people have age-related characteristics. In our study, we analyzed the ventilatory status, laboratory tests and vital signs of the patient and carried out microbiological cultures. Materials and Methods: This was a prospective single-center case series investigation conducted from June 2022 to June 2023. The objective of this study was to evaluate the effectiveness of continuous infusion in elderly patients with severe infectious complications after orthopedic interventions. The primary endpoints were 28-day survival and the emergence of new multidrug-resistant strains. Secondary endpoints were long-term mortality and length of stay in the ICU. Results: Three patients (median age 65, 100% female) received a continuous infusion of meropenem. Two patients were alive at hospital discharge, and one patient died on the 105th day of hospitalization. Multi-resistant bacteria were observed in one patient. Conclusions: The use of a continuous meropenem infusion in the complex treatment of purulent-septic complications in elderly patients with periprosthetic infection and anemia probably led to clinical improvement in these case reports. However, the emergence of new pan-resistant strains and overall mortality using this infusion technique remains unclear. Further, high-quality RCTs for the elderly are needed.

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Section: Methodsmentioning

confidence: 99%

Usage of Meropenem Continuous Infusion for Treatment of Infectious Complications in Orthopedic Elderly Patients with Anemia: A Case Series

Konkayev,

Kadralinova,

Azimova

et al. 2024

Medicina

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“…The trial protocol appears in Supplement 1 and was approved by the ethics committees of all participating centers. Details of the trial methods were published together with the statistical analysis plan (appears in Supplement 2). Additional information appears in the eMethods in Supplement 3.…”

Section: Methodsmentioning

confidence: 99%

“…Based on published literature, we hypothesized the primary outcome (composite outcome of all-cause mortality and emergence of new pandrug-resistant or extensively drug-resistant bacteria at day 28) would occur in 52% of patients in the intermittent administration group and that the continuous administration of meropenem would lead to an absolute risk reduction of 12% (40% of patients would have composite outcome in continuous administration group) …”

Section: Methodsmentioning

confidence: 99%

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Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis

Monti

Bradić

Marzaroli

et al. 2023

JAMA

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ImportanceMeropenem is a widely prescribed β-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes.ObjectiveTo determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis.Design, Setting, and ParticipantsA double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022.InterventionsPatients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304).Main Outcomes and MeasuresThe primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events.ResultsAll 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients).Conclusions and RelevanceIn critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28.Trial RegistrationClinicalTrials.gov Identifier: NCT03452839

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“…Furthermore, high inter-individual variability of the pharmacokinetic [PK) profile of beta-lactams and ciprofloxacin has been reported in critically ill patients [ 13 , 14 ]. These arguments have led to an increasing number of studies aiming at improving the efficacy of beta-lactams and ciprofloxacin for ICU patients [ 15 – 17 ].…”

Section: Introductionmentioning

confidence: 99%

Barriers and facilitators for therapeutic drug monitoring of beta-lactams and ciprofloxacin in the ICU: a nationwide cross-sectional study

et al. 2022

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Background Recent studies demonstrated that failure of achieving pharmacodynamic targets of commonly used antibiotics is common in critically ill patients. Therapeutic drug monitoring (TDM) can contribute to optimize the exposure of beta-lactams and ciprofloxacin. While evidence for TDM of these antibiotics is growing, translation into clinical implementation remains limited. Therefore, perceived barriers and facilitators are important for implementing TDM in this population. The primary aim of this study was to identify healthcare professionals’ barriers and facilitators for the implementation of TDM of beta-lactams and ciprofloxacin in Dutch intensive care units (ICU). Methods We conducted a nationwide cross-sectional online survey among healthcare professionals (HCPs) involved in antibiotic treatment of ICU patients. An adapted version of the Measurement Instrument for Determinants of Innovations was sent out. Items were considered barriers when ≥ 20% of participants responded with a negative answer. If ≥ 80% of the participants responded with a positive answer, the item was considered a facilitator. Results Sixty-four HCPs completed the survey, of which 14 were from academic hospitals, 25 from general hospitals, and 25 from teaching hospitals. Most participants were hospital pharmacists (59%) or medical specialists (23%). Eleven barriers and four facilitators for implementation of TDM of beta-lactams were identified; 17 barriers for TDM of ciprofloxacin and no facilitators. The most important barriers were a lack of conclusive evidence, organizational support, and low availability of assays. Additional barriers were a lack of consensus on which specific patients to apply TDM and which pharmacodynamic targets to use. Identified facilitators for beta-lactam TDM implementation are low complexity and high task perception, combined with the perception that TDM is important to prevent side effects and to adequately treat infections. Twenty-eight percent of participants reported that flucloxacillin could be analyzed in their hospital. Assay availability of other beta-lactams and ciprofloxacin was lower (3–17%). Conclusion Several barriers were identified that could obstruct the implementation of TDM of beta-lactams and ciprofloxacin in the ICU. In particular, education, clear guidelines, and organizational support should be considered when creating tailored implementation strategies. Finally, evidence of beneficial clinical outcomes on TDM of beta-lactams and ciprofloxacin can enhance further implementation.

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Continuous infusion versus intermittent administration of meropenem in critically ill patients (MERCY): A multicenter randomized double-blind trial. Rationale and design

Cited by 12 publications

References 28 publications

Usage of Meropenem Continuous Infusion for Treatment of Infectious Complications in Orthopedic Elderly Patients with Anemia: A Case Series

Usage of Meropenem Continuous Infusion for Treatment of Infectious Complications in Orthopedic Elderly Patients with Anemia: A Case Series

Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis

Barriers and facilitators for therapeutic drug monitoring of beta-lactams and ciprofloxacin in the ICU: a nationwide cross-sectional study

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