1242. Efficacy and Safety of Intravenous Fosfomycin for the Treatment of Multi-resistant Gram Negative Infections

Abstract Background To describe the clinical use, efficacy and safety of intravenous (IV) fosfomycin in the treatment of infections caused by Gram-negative bacteria (GNB). Methods Hospitalized patients who received ≥48 hours of IV fosfomycin therapy during September 27, 2017 thru January 31, 2020 were included. The primary outcome was the proportion of subjects with clinical improvement at the end of IV fosfomycin therapy; defined as resolution of baseline signs and symptoms of infection. Results Thirty patients were included, of which 19 (63.3%) were males, and the median age was 63.5 years (interquartile range 46─73). Frequent risk factors for GNB infection included hospitalization (23, 76%), receipt of broad-spectrum antibiotics (15, 50%), and surgery (10, 33.3%), all within the preceding 90 days. Urinary tract infection (17, 56.7%) was the most common indication for use of IV fosfomycin, followed by bacteremia (4, 13.3), and skin and soft tissue infections (4, 13.3%). Kelbsiella pneumoniae (17, 56.7%), Escherichia coli (7, 23.3%) and Pseudomonas species (4, 13.3%) were the most common target pathogens. Almost all target pathogens (29, 96.7%) were resistant in vitro to ≥1 agent from ≥3 different antimicrobial classes. The primary outcome was achieved in 22 (73.3%) patients. The most frequently observed adverse events were hypokalemia (13, 43.3%) and hypernatremia (7, 23.3%). However, the majority of adverse events were classified as Grade 1 or Grade 2 severity. Microbiological characteristics The table describes microbiological characteristics of the isolated organism species, resistance pattern, development of fosfomycin resistance Management outcomes and safety profile The table describes percentage of primary outcome (clinical success ) along with safety profile and mortality rate Conclusion IV fosfomycin is a potentially effective and safe option for the treatment of patient with GNB infections. Disclosures All Authors: No reported disclosures

Background. Prior investigations evaluating the predictive value of zinc-depleted media for MBL-susceptibility testing have focused on Enterobacterales. Therein, bacterial killing observed with meropenem (MEM) in vivo was concordant with its pharmacodynamic profile using MIC values determined in zinc-depleted media compared with conventional cation-adjusted Mueller-Hinton broth (CAMHB). This study aims to evaluate the exposure-response relationship of MEM against VIM-and NDMharboring P. aeruginosa (PSA) using the murine thigh infection model and zinc-depleted MICs.
Methods. MBL-harboring PSA isolates (VIM n=11; NDM n=10) were tested both in vivo (neutropenic murine thigh infection model) and in vitro (broth microdilution). The 24h murine thigh study was conducted with treatment groups receiving a humanized MEM 2g q8h (3h infusion) dose. Six different zinc-limited media were prepared by the addition of EDTA at concentrations ranging from 3 to 300 mg/L to CAMHB. MEM MICs were determined in triplicate in conventional CAMHB and zinc-limited media. Time > MIC values (generated in each zinc-depleted media) were then plotted against the change in 24h bacterial density count in an Emax model.
Results. Average 0 h bacterial densities were 5.21 ± 0.40 and 5.13 ± 0.81 log 10 CFU/thigh for NDM and VIM isolates, respectively. MEM resulted in -0.09 CFU reduction to +3.69 CFU growth against NDM isolates. MEM resulted in -2.59 CFU reduction to +4.81 CFU growth against VIM isolates. All MEM MICs in conventional CAMHB were >64 µg/mL for NDM and ranged from 8 to >64 µg/mL for VIM isolates. Increasing EDTA concentrations resulted in several-fold MIC reductions and on average, a larger magnitude of reduction was observed among VIM-(6-fold) compared with NDM-harboring PSA (4-fold) in CAMHB-EDTA 300 mg/L relative to CAMHB. For both NDM-and VIM-harboring PSA, an Emax model with MICs generated in CAMHB+EDTA 30 mg/L (r 2 = 0.88) provided the highest correlation with MEM in vivo activity compared with CAMHB (r 2 = 0.55).
Conclusion. Results indicate that MIC values generated in conventional CAMHB do not appropriately characterize the in vivo efficacy of meropenem against MBLharboring PSA, and addition of EDTA (30 mg/L) to CAMHB appears to be a viable option for in vitro testing of these organisms.
Disclosures. David P. Nicolau, PharmD, Abbvie, Cepheid, Merck, Paratek, Pfizer, Wockhardt, Shionogi, Tetraphase (Other Financial or Material Support, I have been a consultant, speakers bureau member, or have received research funding from the above listed companies.) Methods. Hospitalized patients who received ≥48 hours of IV fosfomycin therapy during September 27, 2017 thru January 31, 2020 were included. The primary outcome was the proportion of subjects with clinical improvement at the end of IV fosfomycin therapy; defined as resolution of baseline signs and symptoms of infection.
Microbiological characteristics The table describes microbiological characteristics of the isolated organism species, resistance pattern, development of fosfomycin resistance Management outcomes and safety profile The table describes percentage of primary outcome (clinical success ) along with safety profile and mortality rate Conclusion. IV fosfomycin is a potentially effective and safe option for the treatment of patient with GNB infections.
Disclosures. All Authors: No reported disclosures