FACTORS AFFECTING MEROPENEM TROUGH LEVELS IN CRITICALLY ILL PATIENTS: A THERAPEUTIC DRUG MONITORING STUDY

Öz

Objective: This study primarily aimed to determine meropenem the trough level (C_min) in intensive care unit (ICU), with an exploratory secondary aim of evaluating factors influencing C_min and clinical cure.

Material and Method: This prospective study included adult ICU patients receiving meropenem for ≥48 hours, and C_min levels were measured using a ready-to-use ELISA kit.

Result and Discussion: The study included 38 patients, 26 of whom were male. Mean meropenem C_min value was found to be 0.40 ± 0.07 mg/l which is statistically different than the target value of 8 mg/l (p < 0.001). We found no statistically significant difference in mean C_min between the patient groups whose creatinine clearance was smaller than 50 ml/min and not. Erythrocyte and hemoglobin values decreased after meropenem treatment compared to baseline (p < 0.05). C-Reactive Protein (CRP) decreased, and Sequential Organ Failure Assessment (SOFA) values increased after meropenem treatment (p < 0.001). Logistic regression in patients with Systemic Inflammatory Response Syndrome (SIRS) showed that only SOFA reduced the clinical cure rate (OR 0.534, 95% CI 0.311–0.917). In this study, the target 100% fT > MIC < 4×MIC was not achieved with standard or extended meropenem infusion, potentially limiting clinical cure in ICUs with resistant pathogens, highlighting the need for alternative dosing strategies.

Anahtar Kelimeler

• Drug trough level
• intensive care unit
• meropenem
• therapeutic drug monitoring

Destekleyen Kurum

This work was supported by the Research Fund of the Inonu University [Grant number: TDK-2022-2993].

Proje Numarası

TDK-2022-2993

Etik Beyan

The ethics committee approval required for the research was obtained from Malatya Clinical Research Ethics Committee on 02.03.2022 with the decision number 2022/16.

Teşekkür

We express our deepest gratitude to Research Fund of the XXXXX Reanimation ICU medical team for their support. This work was supported by the Research Fund of the Inonu University [Grant number: TDK-2022-2993]. We presented this study as a poster at the 16th World Intensive and Critical Care Congress. This manuscript was prepared based on the findings of a thesis study conducted as part of a clinical pharmacy residency program in Türkiye (Council of Higher Education Thesis No. 825022).

KRİTİK HASTALARDA MEROPENEM SEVİYELERİNİ ETKİLEYEN FAKTÖRLER: TERAPÖTİK İLAÇ İZLEME ÇALIŞMASI

Öz

Amaç: Bu çalışmanın öncelikli amacı yoğun bakım ünitesinde (YBÜ) meropenem çukur seviyesini (C_min) belirlemek, ikincil amacı ise C_min ve klinik iyileşmeyi etkileyen faktörleri değerlendirmektir.

Gereç ve Yöntem: Bu prospektif çalışmaya, ≥48 saat meropenem alan yetişkin yoğun bakım hastaları dahil edildi ve Cmin düzeyleri hazır kullanıma uygun ELISA kiti ile ölçüldü.

Sonuç ve Tartışma: Çalışmaya 26’sı erkek toplam 38 hasta dahil edildi. Ortalama meropenem Cmin değerinin 0.40 ± 0.07 mg/l olduğu bulundu; bu değer, hedef değer olan 8 mg/l'den istatistiksel olarak farklıdır (p < 0.001). Kreatinin klirensi 50 ml/dk'dan az olan ve olmayan hasta grupları arasında ortalama C_min açısından istatistiksel olarak anlamlı bir fark bulunmadı. Meropenem tedavisi sonrası eritrosit ve hemoglobin değerleri başlangıç değerlerine göre azaldı (p < 0.05). Meropenem tedavisi sonrasında C-reaktif protein (CRP) azaldı ve Sekansiyel Organ Yetmezliği Değerlendirmesi (SOFA) değerleri arttı (p < 0.001). Sistemik İnflamatuvar Yanıt Sendromu (SIRS) olan hastalarda yapılan lojistik regresyon analizinde yalnızca SOFA’nın klinik iyileşme oranını düşürdüğü görüldü (OR 0.534, %95 CI 0.311–0.917). Çalışmamızda, standart veya uzatılmış meropenem infüzyonu ile hedeflenen 100% fT >MIC < 4×MIC sağlanamadı; bu durum, dirençli patojenlerin sık görüldüğü yoğun bakım ünitelerinde klinik iyileşmeyi sınırlayabilir ve alternatif dozlama stratejilerinin geliştirilmesi gerektiğini göstermektedir.

Anahtar Kelimeler

• İlaç çukur düzeyi
• meropenem
• terapötik ilaç izlemi
• yoğun bakım ünitesi

Destekleyen Kurum

Bu çalışma, İnönü Üniversitesi Bilimsel Araştırma Projeleri Birimi tarafından desteklenmiştir [Burs numarası: TDK-2022-2993].

Proje Numarası

TDK-2022-2993

Etik Beyan

Araştırma için gerekli etik kurul onayı, Malatya Klinik Araştırmalar Etik Kurulu'ndan 02.03.2022 tarihinde 2022/16 sayılı kararla alınmıştır.

Teşekkür

İnönü Üniversitesi Bilimsel Araştırma Projeleri Birimi ve İnönü Üniversitesi Anesteziyoloji ve Reanimasyon Yoğun Bakım ekibine destekleri için en derin şükranlarımızı sunarız. Bu çalışmayı 16. Dünya Yoğun ve Kritik Bakım Kongresi'nde poster olarak sunulmuştur. Bu makale, Türkiye'de bir klinik eczacılık uzmanlık programı kapsamında yürütülen bir tez çalışmasının (Yükseköğretim Kurulu Tez No. 825022) bulgularına dayanarak hazırlanmıştır.

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