Comparison of ciprofloxacin versus fosfomycin versus fosfomycin plus trimethoprim/sulfamethoxazole for preventing infections after transrectal prostate biopsy. To evaluate antibiotic prophylaxis in transrectal prostate biopsies due to the recommendation of the European Medicines Agency (EMA): We describe our single center experience switching from ciprofloxacin to fosfomycin trometamol (FMT ) alone and to an augmented prophylaxis combining fosfomycin and trimethoprim/sulfamethoxazole (TMP/SMX). Between 01/2019 and 12/2020 we compared three different regimes. The primary endpoint was the clinical diagnosis of an infection within 4 weeks after biopsy. We enrolled 822 men, 398 (48%) of whom received ciprofloxacin (group-C), 136 (16.5%) received FMT (group-F) and 288 (35%) received
Burning Evidence for Fosfomycin in Cystitis July 27, 2020 Burning Evidence for Fosfomycin in Cystitis Clinical Question: What is the efficacy of fosfomycin for uncomplicated cystitis in non-pregnant women? Bottom Line: At best, single dose fosfomycin has similar efficacy to other antibiotics for uncomplicated cystitis. However, the best quality, publicly funded trial showed it was not as efficacious as nitrofurantoin, with 58% of cases clinically resolving at 28 days compared to 70% for nitrofurantoin. Evidence: • Most recent systematic review1, 11 randomized controlled trials (RCTs), 1976 women, fosfomycin versus other antibiotics (examples norfloxacin, trimethoprim/sulfamethoxazole, nitrofurantoin) showed: o Clinical cure or improvement (non
Activity of fosfomycin and amikacin against fosfomycin-heteroresistant Escherichia coli strains in a hollow-fiber infection model. To evaluate human-like intravenous doses of fosfomycin (8g/Q8h) and amikacin (15mg/kg/Q24h) efficacy in monotherapy and in combination against six fosfomycin-heteroresistant isolates using a hollow-fiber infection model (HFIM).Six fosfomycin-heteroresistant isolates (4 with strong mutator phenotype) and the control strain ATCC 25922 were used. Mutant frequencies for rifampin (100mg/L), fosfomycin (50 and 200mg/L) and amikacin (32mg/L) were determined. Fosfomycin and amikacin MICs were assessed by agar dilution (AD), gradient strip (GSA) and broth microdilution (BMD) assays. Fosfomycin and amikacin synergies were studied by checkerboard and time-kill assays
Evaluation of the safety profile and intrapulmonary pharmacokinetics of intravenous fosfomycin in healthy adults. This Phase 1 trial described the intrapulmonary pharmacokinetics and safety profile of IV fosfomycin in healthy participants Fosfomycin, a broad-spectrum antibiotic mainly used to treat urinary tract infections, is being considered for treatment of more complex conditions, including lung infections, due to the emergence of multidrug-resistant (MDR) organisms. Despite its potential, the pharmacokinetics and safety profile of intravenous (IV) fosfomycin, particularly its penetration into the lower respiratory tract, are unknown. To address this gap, we conducted a Phase 1, open-label trial to assess the safety and pulmonary pharmacokinetics of IV fosfomycin in healthy participants
Chromosomal genes modulating fosfomycin susceptibility in uropathogenic Escherichia coli: a genome-wide analysis. acquires fosfomycin resistance through chromosomal mutations that reduce drug uptake and by drug-inactivating enzymes. However, the complete resistance mechanisms remain to be elucidated. The aim of this study was to elucidate the genetic mechanisms regulating fosfomycin susceptibility in uropathogenic (UPEC). We constructed a highly saturated transposon mutant library containing >340,000 unique Tn5 insertions in a clinical UPEC strain. We conducted transposon-directed insertion site sequencing (TraDIS) to screen for chromosomal genes whose mutations are beneficial for bacterial growth and survival in the presence of fosfomycin at 4 and 32 µg/mL. TraDIS analysis identified 67
"Effectiveness and tolerability of intravenous fosfomycin in treating complicated urinary tract infections caused by Escherichia coli: A prospective cohort study from the FOSFO-MIC Project". The FOSFO-MIC study assessed the clinical and microbiological effectiveness, and safety of intravenous fosfomycin in treating complicated urinary tract infections (cUTIs) caused by Escherichia coli , in comparison with other intravenous antimicrobials. A prospective, multinational matched-cohorts study involving adults with community-acquired cUTIs and receiving targeted therapy with intravenous fosfomycin or other first-line drugs (beta-lactams or fluoroquinolones) was conducted from November 2019 to May 2023 in 10 centres from Spain, Italy, and Türkiye. Matching criteria included healthcare-relation
The pharmacodynamics of fosfomycin in combination with meropenem against Klebsiella pneumoniae studied in an in vitro model of infection. Intravenous fosfomycin is used in combination with other antimicrobials for the management of severe and/or multidrug resistant Gram-negative infection. We used an in vitro pharmacokinetic model to study the combination of fosfomycin plus meropenem. Six Klebsiella pneumoniae fosfomycin MICs 8-1024 mg/L, meropenem MICs 0.06->1024 mg/L were employed. A dilutional pharmacokinetic model was used to generate fosfomycin exposure ranges up to a fAUC/MIC 500. Exposure-ranging experiments were repeated in the presence of meropenem at exposures associated with 2 g 8-hourly human dosing for strains with meropenem MICs ≥32 mg/L and at half the bacteriostatic fT > MIC
Identification of the novel Fosfomycin Resistance Gene fosSC in Staphylococcus capitis. Fosfomycin has regained attention for treating infections caused by methicillin-resistant Staphylococcus aureus and multidrug-resistant coagulase-negative staphylococci. In this research, our objective was to investigate the mechanisms underlying fosfomycin resistance in Staphylococcus capitis. The minimum inhibitory concentrations (MICs) of fosfomycin were assessed in 109 clinical S. capitis isolates by the agar dilution method. By cloning the fos-like genes into the shuttle vector, pTSSCm-Pcap, and observing the change in fosfomycin MICs, the gene function was verified. Core genome multilocus sequence typing and comparative genomics analysis were conducted to determine the population characteristics of S
Population pharmacokinetic/pharmacodynamic target attainment analysis of IV fosfomycin for the treatment of MDR Gram-negative bacterial infections. IV fosfomycin is used against MDR Gram-negative bacilli (GNB) but has dose-limiting side effects, especially in patients with impaired kidney function. To determine the optimal dosage of IV fosfomycin for patients with varying degrees of kidney function. Adult patients receiving IV fosfomycin for treatment of GNB were eligible. Five serial blood samples were collected after at least three doses of fosfomycin; plasma was assayed by LC-MS/MS and modelled by population pharmacokinetic analysis. The PTA for AUC24/MIC of 98.9 for Escherichia coli and Klebsiella pneumoniae, and 40.8 for Pseudomonas aeruginosa were computed by Monte Carlo simulations
Back to the Future: Intravenous Fosfomycin Is Safe and Effective for the Treatment of Complicated Infections in Children. Despite its broad spectrum and excellent safety profile, fosfomycin is still rarely used in pediatrics, with very limited experience from clinicians. We retrospectively reviewed the medical records of all children admitted to Bambino Gesù Children's Hospital, IRCCS, Rome , Italy, and treated with fosfomycin for any serious infection. Children with immunodeficiency and oncological diseases were excluded. Of each, we reported and analyzed demographic and clinical data. The clinical charts of 20 patients were reviewed and analyzed. The mean age was 10.2 years. Most children were males (85%). Most patients treated had an osteo-articular infection (65%). In our sample, 7
INTRAVENOUS FOSFOMYCIN IN COMBINATION REGIMENS AS A TREATMENT OPTION FOR DIFFICULT-TO-TREAT INFECTIONS DUE TO MULTIDRUG-RESISTANT GRAM-NEGATIVE ORGANISMS: A REAL-LIFE EXPERIENCE. We aim to investigate the efficacy of intravenous (IV) Fosfomycin as combination therapy for treatment of difficult-to-treat (DTT) multidrug-resistant (MDR) gram negative bacteria (GNB) acute and subacute infections and risk factors associated with 90-day mortality. A retrospective, observational, monocentric study enrolled patients treated with IV Fosfomycin in combination regimens (>/= 72 h) for proven DTT-MDR-GNB based infection . Multivariate regression analysis identified independent risk factors for 90-day mortality. A propensity score for receiving Fosfomycin was performed to control for confounding factors
[Antibacterial prophylaxis with fosfomycin at the time of the urethral catheter removal after radical prostatectomy (prospective randomized trial)]. To evaluate the effect of antibacterial prophylaxis using oral fosfomycin during the removal of a urethral catheter after radical prostatectomy on the development of urinary tract infection, severity of leukocyturia and bacteriuria, as well as the severity of lower urinary tract symptoms. A single-center, non-blind, prospective, randomized controlled trial was carried out. The main group included 40 patients, and the control group included 37 patients. In the group 1, patients received two doses of oral fosfomycin, 3 g, namely in the evening on the day of catheter removal (the first dose) and 48 hours after catheter removal (the second dose
The use of fosfomycin in infections caused by multidrug-resistant pathogens, especially pneumonia in children: a five-year retrospective single-centre experience. Fosfomycin is gaining increasing attention for its activity against MDR or XDR pathogens. Currently, IV fosfomycin is a potential option for treating various infections, including urinary tract infections, pneumonia and skin infections when first-line treatments fail. To evaluate the demographic, clinical, microbiological and treatment modality of children received IV fosfomycin to treat infections caused by MDR pathogens since there are few data on the use of fosfomycin in children. This study was conducted retrospectively with patients under 18 years of age who were treated with IV fosfomycin for at least 72 h due to infections
Using fosfomycin to prevent infection following ureterorenoscopy in response to shortage of cephalosporins: a retrospective preliminary study. In 2019, the shortage of cefazolin led to the demand for cefotiam and cefmetazole exceeding the supply. The Department of Nephro-urology at Nagoya City University Hospital used fosfomycin as a substitute for perioperative prophylaxis. This retrospective preliminary study evaluated the efficacy of fosfomycin and cefotiam for preventing infections following ureterorenoscopy. The study included 182 patients who underwent ureterorenoscopy between January 2018 and March 2021). Perioperative antibacterial treatment with fosfomycin (n = 108) or cefotiam (n = 74) was administered. We performed propensity score matching in both groups for age, sex, preoperative
Evaluation of several routine methods for fosfomycin and mecillinam susceptibility testing of Enterobacterales urine isolates. Performance evaluation of routine laboratory methods to determine the susceptibility of Enterobacterales urinary isolates to fosfomycin (oral administration) and mecillinam. We collected 347 Enterobacterales isolates from monomicrobial midstream urine samples from women with significant bacteriuria and leukocyturia. Mostly non-Escherichia coli isolates (i.e. Klebsiella spp., Citrobacter koseri, Enterobacter cloacae complex and Proteus mirabilis) were included (n = 298). Performance of VITEK®2, ETEST®, and disc diffusion to determine fosfomycin and mecillinam susceptibility was evaluated following International Organization for Standardization (ISO) 20776-2:2021 (or 20776-2:2007
Probing fosfomycin's potential: a study on susceptibility testing and resistance in Staphylococcus epidermidis from prosthetic joint infections. There are limited treatment options for prosthetic joint infections (PJI) due to multidrug-resistant Staphylococcus epidermidis (MDRSE). Fosfomycin (FOF) has gained attention as a potential therapy, but there is a paucity of information
Combination therapy with IV fosfomycin for adult patients with serious Gram-negative infections: a review of the literature. Treatment of patients with serious infections due to resistant Gram-negative bacteria remains highly problematic and has prompted clinicians to use existing antimicrobial agents in innovative ways. One approach gaining increased therapeutic use is combination therapy with IV fosfomycin. This article reviews the preclinical pharmacokinetic/pharmacodynamic (PK/PD) infection model and clinical data surrounding the use of combination therapy with IV fosfomycin for the treatment of serious infections caused by resistant Gram-negative bacteria. Data from dynamic in vitro and animal infection model studies of highly resistant Enterobacterales and non-lactose fermenters
Intravenous fosfomycin for treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii: a multicenter clinical experience. severe infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have been increasingly reported over the past few years. Many in vivo and in vitro studies suggest a possible role of intravenous fosfomycin for the treatment of CRAB infections. this multicenter, retrospective study included patients treated with intravenous fosfomycin for severe infections caused by CRAB admitted consecutively from December 2017 to December 2022 in four Hospitals in Italy. The primary goal of the study was to evaluate the risk factors associated with 30-day mortality in the study population. A propensity score matched analysis was added to the model
Intravenous Fosfomycin as Adjunctive Therapy for Gram-Negative Bacteria Bloodstream Infections: a Propensity Score Adjusted Retrospective Cohort Study. The role of intravenous fosfomycin (iv-FOS), as a part of combination therapy for Gram-negative bacteria bloodstream infections (GNB-BSI), needs to be evaluated in clinical practice as in vitro data show a potential efficacy. All consecutive =0.52, 95%CI=0.31-0.91). Subgroup analysis suggested a benefit in severe infections (SOFA>6, PITT≥4) and when iv-FOS was initiated within 24 hours from GNB-BSI onset. Fosfomycin in combination therapy for GNB-BSI may have a role to improve survival. These results justify the development of further clinical trials.
Adverse events during intravenous fosfomycin therapy in a real-life scenario. Risk factors and the potential role of therapeutic drug monitoring. Intravenous fosfomycin (IVFOF) is gaining interest in severe infections. Its use may be limited by adverse events (AEs). Little experience exists on IVFOF therapeutic drug monitoring (TDM) in real-life setting. Retrospective study of patients receiving deserves further research as it may represent a valid tool to predict AEs. Real world data on intravenous fosfomycin for severe bacterial infections. AEs occurred in over 40% (therapy discontinuation in 17%) and were related to baseline clinical severity but not to fosfomycin dose. TDM showed promising results in predicting AEs.