Çoklu İlaca Dirençli Gram Negatif Bakteriyel Enfeksiyonlarda Fosfomisin İçeren Antibiyotik Kombinasyon Tedavilerinin Etkinliği

Abstract

Giriş: Gram-negatif bakterilerde, özellikle ÇİD, XDR ve PDR suşlarının etken olduğu enfeksiyonlara bağlı olarak artan antimikrobiyal direnç, mevcut tedavi seçeneklerini belirgin biçimde daraltmaktadır. Yeni antibiyotiklerin sınırlı olması, mevcut ajanların kombinasyon tedavilerinde yeniden değerlendirilmesini gündeme getirmiştir. Fosfomisin, özgün etki mekanizması ve geniş spektrumu nedeniyle bu alanda öne çıkmaktadır. Çalışmanın amacı ÇİD/XDR/PDR gram-negatif enfeksiyonların tedavisinde fosfomisin içeren kombinasyonların klinik etkisini değerlendirmektir. Yöntem: Şubat 2019–Haziran 2020 arasında üniversite hastanesinin yoğun bakımları ve servislerinde tedavi gören erişkin hastalar retrospektif olarak incelendi. Hastalar IV fosfomisin içeren kombinasyon (n=141) ya da fosfomisin içermeyen kombinasyon (n=137) tedavileri aldı. Klinik, laboratuvar ve tedavi verileri hastane bilgi yönetim sisteminden çekildi. Bulgular: Gruplar yaş, cinsiyet, APACHE II ve SOFA skoru açısından benzerdi; fosfomisin tedavisi alan grupta Charlson komorbidite indeksi daha yüksekti. 28 ve 60 günlük mortalite açısından gruplar arasında anlamlı fark saptanmadı (sırasıyla p=0.568 ve p=0.094); nokta tahminleri fosfomisin grubunun lehineydi (28 günlük mortalite %41,1 vs %44,5). Her iki grupta da mortalite yüksek hastalık şiddeti ve invaziv araç kullanımı ile ilişkiliydi. Fosfomisin alan 10 hastada hipernatremi izlendi. Sonuç: Komorbiditesi, ciddi hastalık yükü ve invaziv araç gereksinimi bulunan hastalarda, uygun ajanlarla birlikte ve güvenlik izlemiyle kullanıldığında fosfomisin içeren kombinasyonlar makul bir tedavi seçeneğidir. Klinik etkinlik ve güvenliği netleştirmek için PK/PD verileri ve iyi tasarlanmış klinik çalışmalar gereklidir.

Keywords

• Çok ilaca dirençli
• Aşırı ilaca dirençli
• Tüm ilaca dirençli
• Fosfomisin

The Efficacy of Antibiotic Combination Therapies with Fosfomycin For Multi-Drug Resistant Gram-Negative Bacterial Infections

Abstract

Background: Antimicrobial resistance in Gram-negative bacteria especially infections due to multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan drug-resistant (PDR) strains has narrowed therapeutic options. In the absence of many new agents, older antibiotics are being reconsidered in combination regimens. Fosfomycin, with a unique mechanism and broad spectrum, is a leading candidate in this context. Objective: To assess whether parenteral fosfomycin-based combinations influence mortality and morbidity in hospitalized adults with MDR/XDR/PDR Gramnegative infections. Methods: We conducted a retrospective study of adults treated between February 2019 and June 2020 in university hospital ICUs and wards. Patients received either combination therapy including IV fosfomycin (n=141) or combination therapy without fosfomycin (n=137). Demographic, clinical, laboratory and treatment data were extracted from the hospital information system. Results: Baseline age, sex, APACHE II and SOFA scores were similar between groups, whereas the fosfomycin group had a higher Charlson comorbidity index. No significant difference was observed in 28-day or 60-day mortality between fosfomycin and control groups (p=0.568 and p=0.094, respectively); point estimates favored the fosfomycin group (28-day mortality 41.1% vs 44.5%). Mortality correlated with higher illness severity and invasive device use in both groups. Ten patients receiving fosfomycin developed hypernatremia. Conclusion: In patients with high illness severity, comorbidity, and invasive device needs, fosfomycin-containing combinations, when used with suitable companion agents and accompanied by careful safety monitoring, constitute a rational treatment option against MDR/XDR/PDR Gram-negative infections. Pharmacokinetic (PK) and pharmacodynamic (PD) data and well-designed clinical studies are required to clarify clinical efficacy and safety.

Keywords

• Multidrug resistant
• extremely drug resistant
• pan drug resistant
• fosfomycin

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