Intravenous fosfomycin therapy in critically ill patients infected with colistin-resistant enterobacteriacae

Abstract

Introduction: Carbapenem resistant enterobacteriacae (CRE) emerged in recent years as one of the most challenging group of antibiotic resistant pathogens. Polymyxins are considered as the last resort for the treatment of infections with CR (Carbapenem resistant) gram negative bacilli (GNB). Inadequate or extensive use of colistin leads to emergence of colistin resistance in GNB (gram negative bacilli), jeopardizing treatment options in Intensive Care Units (ICUs), potentially increasing mortality and morbidity and necessitating prudent use of alternative antibiotics. Fosfomycin, a phosponic acid derivative which acts primarily by disrupting bacterial cell wall synthesis, is a broad spectrum antibiotic. Fosfomycin tromethamine is an oral formulation approved for the treatment of uncomplicated Urinary Tract Infection (UTI) caused by Multi Drug Resistant (MDR) bacteria. Recently fosfomycin is also available as sodium/disodium formulation for intravenous use, which is showing promising result against MDR (Multi Drug Resistant)/PDR (Potentially Drug Resistant) pathogens. Method: A total of four colistin resistant (MIC>=4) GNB were isolated from ICU patients with nosocomial MDR infections. All four isolates were Klebsiella pneumonia. Among these isolates three were from blood and one from endotracheal aspirate and all four isolates were sensitive to fosfomycin in vitro. All of these patients had multiple co-morbidities with recent history of colistin exposure. Intravenous fosfomycin sodium (inj Fosmicin-Meiji/Japan) was started as a combination therapy with carbapenem. Result: Among the three bacterimic patients, two recovered completely from sepsis as well as the patient with ventilator associated pneumonia. There was clinical as well as microbiological cure with normalization of sepsis markers. The only one bacterimic patient who died during the course of therapy was later on diagnosed to have azole resistant fungemia as super infection. Discussion: Based on the evidence of clinical experience and available studies, intravenous fosfomycin therapy may be considered as the last option for the treatment of MDR (Multi Drug Resistant) GNB (gram negative bacilli) infection where there is documented colistin resistance and where there is literally no other choice of antibiotic therapy. The success of the therapy is encouraging in selected group of patients. Further research on intravenous fosfomycin use specially against MDR pathogens and on the effectiveness and safety of the drug in the treatment of patients with such infections may be warranted.