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
The present report highlights a case of successful treatment of a 59-year-old patient who experienced pain, swelling, hyperemia, the presence of a wound of the right knee joint, impaired function of the right lower limb, weakness, fatigue, and labored breathing. Sepsis was detected in the patient as a result of periprosthetic infection with concomitant severe COVID-19. The patient was admitted to the hospital for 59 days, with 57 days of treatment of the patient at the intensive care unit. A therapy of multiple organ failure involved complex treatment using antiviral and combined antibiotic therapy, taking into account the sensitivity of the pathogen to antibiotics; glucocorticoid therapy; anticoagulant therapy; the concept of non-invasive ventilation; and vibroacoustic pulmonary therapy as a method of physiotherapy as well. An integrated approach using a vibroacoustic device in the therapy of the patient with sepsis due to periprosthetic infection with concomitant coronavirus infection had a positive effect despite the lack of etiological treatment against the COVID-19.
This article highlights a clinical case of successful treatment of a 79-year-old multimorbid patient with a hip fracture resulting from a household injury. On the first day, the patient’s injury was complicated by infection and pneumonia. As a result, arterial hypotension, tachysystole, and respiratory failure progressed. With manifestations of sepsis, the patient was transferred to the intensive care unit. Surgical treatment in such a situation was contraindicated due to the high operational and anesthesiological risks, the unstable severe condition of the patient, as well as the presence of concomitant pathology in the form of coronary heart disease, obesity, and schizophrenia. According to the new sepsis management guideline, it was decided to use a continuous 24-h infusion of meropenem in addition to the complex treatment of sepsis. The use of continuous infusion of meropenem in this clinical situation may have caused the patient’s clinical improvement, which increased her quality of life and decreased the length of ICU stay and total hospital stay, despite an unfavorable cumulative prognosis and a high risk of in-hospital mortality.
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