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The New Microbiologica Sep 2023Carbapenemase-producing Enterobacteriaceae (CPE) are an increasing threat to global public health. Treatment of CPE isolates, like New Delhi metallo-β-lactamase (NDM),...
Carbapenemase-producing Enterobacteriaceae (CPE) are an increasing threat to global public health. Treatment of CPE isolates, like New Delhi metallo-β-lactamase (NDM), is limited and often necessitates combination therapies. The aim of this study was to evaluate the synergistic meropenem/fosfomycin combination against K.pneumoniae-producing NDM isolates. Fosfomycin/meropenem, fosfomycin/colistin and meropenem/colistin were tested alone and in combination, using e-test and time-kill assay against 20 clinical carbapenemase-producing K. pneumonia (CPKp NDM) isolates collected from September 2022 to December 2022. K. pneumoniae strains were resistant to meropenem, ceftazidime/avibactam and ceftolozano/tazobactam, 75% and 80% of isolates were susceptible for cefiderocol and for colistin respectively. Fosfomycin/meropenem combination was synergic in 95% (n=19) strains. Fosfomycin/colistin and colistin/meropenem combination showed only 10% synergistic combination strains. In 16 isolates (80%) indifference action for fosfomycin/colistin and colistin/meropenem was reported. For 0.8% of CpKP NDM isolates colistin/meropenem and fosfomycin/colistin combinations found to be antagonistic. In this study, time kill assay showed combination therapies action versus K.pneumoniae metallo-b-lactamase producing (NDM) strains and confirmed the synergistic action of fosfomycin/meropenem combination. In vitro synergy testing should be routinely performed in multidrug resistance infections and combo therapies can be used as a possible alternative in targeted patients with the goal of reducing overall antibiotic costs.
Topics: Humans; Meropenem; Fosfomycin; Colistin; Klebsiella pneumoniae; Carbapenem-Resistant Enterobacteriaceae
PubMed: 37747471
DOI: No ID Found -
Archivos Espanoles de Urologia Aug 2022Fosfomycin has been with us for more than 50 years; however the history of its discovery is largely unknown. The objective of this article is to recover and make known... (Review)
Review
INTRODUCTION AND OBJECTIVES
Fosfomycin has been with us for more than 50 years; however the history of its discovery is largely unknown. The objective of this article is to recover and make known its lost history.
MATERIAL AND METHODS
Retrospective review study on the history of the discovery of fosfomycin based on articles and documents located in Medline/PubMed and Google between 1945 and 2020. For the search of articles in PubMed the MeSH keywords fosfomycin OR fosfomycin history, fosfomycin discovery, , and in Google the free terms; fosfomycin, fosfomycin history, fosfomycin discovery, were used. All the papers found were reviewed and those containing any historical review of interest to this research were selected for study.
RESULTS
We found 3500 articles on fosfomycin, of which 32 (0.9%) dealt with some aspect related to its discovery, and 21 corresponded to its history (0.6%), divided between 13 publications and 7 press releases, 8 to the genus (0.2%) and 3 to fosfomycin (0.1%).
CONCLUSIONS
The story of the discovery of fosfomycin begins with the finding of the bacterium in a soil sample from mount Montgó between Dénia and Jávea (Alicante). There is little published literature and the existing one is mostly incomplete. Some medical publications and press releases have made it possible to recover its history.
Topics: Fosfomycin; Humans; Soil; Streptomyces
PubMed: 36138496
DOI: 10.56434/j.arch.esp.urol.20227506.72 -
The Journal of Antimicrobial... Jul 2023Fosfomycin is a potentially attractive option as step-down therapy for bacteraemic urinary tract infections (BUTI), but available data are scarce. Our objective was to... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness of fosfomycin trometamol as oral step-down therapy for bacteraemic urinary tract infections due to MDR Escherichia coli: a post hoc analysis of the FOREST randomized trial.
BACKGROUND
Fosfomycin is a potentially attractive option as step-down therapy for bacteraemic urinary tract infections (BUTI), but available data are scarce. Our objective was to compare the effectiveness and safety of fosfomycin trometamol and other oral drugs as step-down therapy in patients with BUTI due to MDR Escherichia coli (MDR-Ec).
METHODS
Participants in the FOREST trial (comparing IV fosfomycin with ceftriaxone or meropenem for BUTI caused by MDR-Ec in 22 Spanish hospitals from June 2014 to December 2018) who were stepped-down to oral fosfomycin (3 g q48h) or other drugs were included. The primary endpoint was clinical and microbiological cure (CMC) 5-7 days after finalization of treatment. A multivariate analysis was performed using logistic regression to estimate the association of oral step-down with fosfomycin with CMC adjusted for confounders.
RESULTS
Overall, 61 patients switched to oral fosfomycin trometamol and 47 to other drugs (cefuroxime axetil, 28; amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole, 7 each; ciprofloxacin, 5) were included. CMC was reached by 48/61 patients (78.7%) treated with fosfomycin trometamol and 38/47 (80.9%) with other drugs (difference, -2.2; 95% CI: -17.5 to 13.1; P = 0.38). Subgroup analyses provided similar results. Relapses occurred in 9/61 (15.0%) and 2/47 (4.3%) of patients, respectively (P = 0.03). The adjusted OR for CMC was 1.11 (95% CI: 0.42-3.29, P = 0.75). No relevant differences in adverse events were seen.
CONCLUSIONS
Fosfomycin trometamol might be a reasonable option as step-down therapy in patients with BUTI due to MDR-Ec but the higher rate of relapses would need further assessment.
Topics: Humans; Fosfomycin; Tromethamine; Anti-Bacterial Agents; Escherichia coli; Urinary Tract Infections; Escherichia coli Infections; Recurrence
PubMed: 37260299
DOI: 10.1093/jac/dkad147 -
Revista Espanola de Quimioterapia :... May 2019Osteoarticular infections include septic arthritis and osteomyelitis, with Gram-positive microorganisms isolated most frequently. In recent years, there has been an... (Review)
Review
Osteoarticular infections include septic arthritis and osteomyelitis, with Gram-positive microorganisms isolated most frequently. In recent years, there has been an increase in the number of resistant strains in this type of infection, which complicates the treatment. Fosfomycin is active against a large percentage of Gram-positive and Gram-negative pathogens, including multidrug-resistant strains, and its properties include low protein binding, low molecular weight and good bone dissemination. In this article, we discuss fosfomycin's activity in vitro, its pharmacokinetic and pharmacodynamic parameters of interest in osteoarticular infections, the experimental models of osteomyelitis and foreign body infection and the clinical experience with these types of infections.
Topics: Animals; Anti-Bacterial Agents; Bone Diseases, Infectious; Cartilage Diseases; Fosfomycin; Humans
PubMed: 31131590
DOI: No ID Found -
Frontiers in Cellular and Infection... 2023Antimicrobial resistance is well-known to be a global health and development threat. Due to the decrease of effective antimicrobials, re-evaluation in clinical practice... (Review)
Review
Antimicrobial resistance is well-known to be a global health and development threat. Due to the decrease of effective antimicrobials, re-evaluation in clinical practice of old antibiotics, as fosfomycin (FOS), have been necessary. FOS is a phosphonic acid derivate that regained interest in clinical practice for the treatment of complicated infection by multi-drug resistant (MDR) bacteria. Globally, FOS resistant Gram-negative pathogens are raising, affecting the public health, and compromising the use of the antibiotic. In particular, the increased prevalence of FOS resistance (FOS) profiles among family is concerning. Decrease in FOS effectiveness can be caused by ) alteration of FOS influx inside bacterial cell or ) acquiring antimicrobial resistance genes. In this review, we investigate the main components implicated in FOS flow and report specific mutations that affect FOS influx inside bacterial cell and, thus, its effectiveness. FosA enzymes were identified in 1980 from but only in recent years the scientific community has started studying their spread. We summarize the global epidemiology of FosA/C2/L1-2 enzymes among family. To date, 11 different variants of FosA have been reported globally. Among acquired mechanisms, FosA3 is the most spread variant in , followed by FosA7 and FosA5. Based on recently published studies, we clarify and represent the molecular and genetic composition of genes enviroment, analyzing the mechanisms by which such genes are slowly transmitting in emerging and high-risk clones, such as ST69 and ST131, and ST11. FOS is indicated as first line option against uncomplicated urinary tract infections and shows remarkable qualities in combination with other antibiotics. A rapid and accurate identification of FOS type in is difficult to achieve due to the lack of commercial phenotypic susceptibility tests and of rapid systems for MIC detection.
Topics: Fosfomycin; Escherichia coli; Drug Resistance, Bacterial; Anti-Bacterial Agents; Escherichia coli Proteins; Klebsiella pneumoniae
PubMed: 37469601
DOI: 10.3389/fcimb.2023.1178547 -
Revista Espanola de Quimioterapia :... Mar 2003Fosfomycin is an natural antibiotic with an epoxide structure and low molecular weight which acts in the first stage of peptidoglycan synthesis of the bacterial wall. It... (Review)
Review
Fosfomycin is an natural antibiotic with an epoxide structure and low molecular weight which acts in the first stage of peptidoglycan synthesis of the bacterial wall. It has a rapid bactericide effect, and a wide spectrum, including methicillin-resistant Staphylococcus aureus and intermediate glycopeptide-susceptible or -resistant enterococci. Over the years it has maintained its activity and has shown stable rates of resistance. It has synergistic action, which is additive or indifferent with glycopeptides, linezolid, quinupristin-dalfopristin, betalactams, aminoglycosides, ansamycines, nitroimidazoles and quinolones, without antagonism. It can be administered orally or parenterally in a wide range of doses, it does not bind to plasma proteins, and has a good distribution volume, reaching high concentrations in the interstitial fluid and tissues. It is eliminated in the kidneys in its active form without metabolites and is dialyzable. It has been used in a number of indications, including urinary, respiratory, intraabdominal, obstetric-gynecologic, central nervous system and osteoarticular infections, with satisfactory overall results in 80% of cases and minimal side effects. It does not cause important changes in the normal human flora. As additional effects it has the capacity to favor phagocytosis, act as an immunomodulator and protect human cells from cisplatin, cyclosporin, aminoglycoside, vancomycin, amphotericin B and polymixin toxicity. Oral fosfomycin is currently clearly indicated in urinary infections and gastroenteritis, and parenteral fosfomycin in high doses and in combination with other drugs in severe inhospital infections caused by problematic pathogens, including multiresistant staphylococci and enterococci, and in immunodepressed patients treated with nephrotoxic drugs.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Fosfomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans
PubMed: 12750755
DOI: No ID Found -
Medicina (Kaunas, Lithuania) May 2023To assess the effects of fosfomycin compared with other antibiotics as a prophylaxis for urinary tract infections (UTIs) in men undergoing transrectal prostate... (Meta-Analysis)
Meta-Analysis Review
To assess the effects of fosfomycin compared with other antibiotics as a prophylaxis for urinary tract infections (UTIs) in men undergoing transrectal prostate biopsies. We searched multiple databases and trial registries without publication language or status restrictions until 4 January 2022. Parallel-group randomized controlled trials (RCTs) and non-randomized studies (NRS) were included. The primary outcomes were febrile UTI, afebrile UTI, and overall UTI. We used GRADE guidance to rate the certainty of evidence of RCTs and NRSs. The protocol was registered with PROSPERO (CRD42022302743). We found data on five comparisons; however, this abstract focuses on the primary outcomes of the two most clinically relevant comparisons. Regarding fosfomycin versus fluoroquinolone, five RCTs and four NRSs with a one-month follow-up were included. Based on the RCT evidence, fosfomycin likely resulted in little to no difference in febrile UTIs compared with fluoroquinolone. This difference corresponded to four fewer febrile UTIs per 1000 patients. Fosfomycin likely resulted in little to no difference in afebrile UTIs compared with fluoroquinolone. This difference corresponded to 29 fewer afebrile UTIs per 1000 patients. Fosfomycin likely resulted in little to no difference in overall UTIs compared with fluoroquinolone. This difference corresponded to 35 fewer overall UTIs per 1000 patients. Regarding fosfomycin and fluoroquinolone combined versus fluoroquinolone, two NRSs with a one- to three-month follow-up were included. Based on the NRS evidence, fosfomycin and fluoroquinolone combined may result in little to no difference in febrile UTIs compared with fluoroquinolone. This difference corresponded to 16 fewer febrile UTIs per 1000 patients. Compared with fluoroquinolone, fosfomycin or fosfomycin and fluoroquinolone combined may have a similar prophylactic effect on UTIs after a transrectal prostate biopsy. Given the increasing fluoroquinolone resistance and its ease to use, fosfomycin may be a good option for antibiotic prophylaxis.
Topics: Male; Humans; Fosfomycin; Antibiotic Prophylaxis; Prostate; Anti-Bacterial Agents; Urinary Tract Infections; Biopsy; Fluoroquinolones
PubMed: 37241143
DOI: 10.3390/medicina59050911 -
Deutsches Arzteblatt International Feb 2020
Topics: Fosfomycin
PubMed: 32164828
DOI: 10.3238/arztebl.2020.0118b -
Revista Espanola de Quimioterapia :... May 2019Urinary tract infections are one of the most common health problems and entail a high consumption of health system resources. Due to the increase in global antibiotic... (Review)
Review
Urinary tract infections are one of the most common health problems and entail a high consumption of health system resources. Due to the increase in global antibiotic resistances in recent years, it is increasingly common to find uropathogens with multiple resistance mechanisms, including quinolone-resistant bacteria, broad-spectrum β-lactamase producers and carbapenemase producers. In this scenario, the role of fosfomycin has gained considerable importance, given its spectrum of activity against multidrug resistant microorganisms (Gram-positive and Gram-negative), becoming an attractive alternative therapy. Regarding the use of fosfomycin in complicated urinary tract infections, there is increasing clinical experience with patients with infections caused by multidrug resistant bacteria, those with recurrent urinary tract infection and special populations such as those with kidney transplants. Randomized comparative studies and series are underway, which will provide greater evidence. Nevertheless, more studies are needed to confirm the enormous potential of fosfomycin in complicated urinary tract infection in the era of multiresistance.
Topics: Administration, Intravenous; Administration, Oral; Animals; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Fosfomycin; Humans; Urinary Tract; Urinary Tract Infections
PubMed: 31131591
DOI: No ID Found -
Journal of Infection and Chemotherapy :... May 2016Fosfomycin was discovered over four decades ago, yet has drawn renewed interest as an agent active against a range of multidrug-resistant (MDR) and extensively... (Review)
Review
Fosfomycin was discovered over four decades ago, yet has drawn renewed interest as an agent active against a range of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens. Its unique mechanism of action and broad spectrum of activity makes it a promising candidate in the treatment of various MDR/XDR infections. There has been a surge of in vitro data on its activity against MDR/XDR organisms, both when used as a single agent and in combination with other agents. In the United States, fosfomycin is only approved in an oral formulation for the treatment of acute uncomplicated urinary tract infections (UTIs), whereas in some countries both oral and intravenous formulations are available for various indications. Fosfomycin has minimal interactions with other medications and has a relatively favorable safety profile, with diarrhea being the most common adverse reaction. Fosfomycin has low protein binding and is excreted primarily unchanged in the urine. The clinical outcomes of patients treated with fosfomycin are favorable for uncomplicated UTIs, but data are limited for use in other conditions. Fosfomycin maintains activity against most Enterobacteriaceae including Escherichia coli, but plasmid-mediated resistance due to inactivation have appeared in recent years, which has the potential to compromise its use in the future. In this review, we summarize the current knowledge of this resurgent agent and its role in our antimicrobial armamentarium.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Fosfomycin; Humans; Microbial Sensitivity Tests
PubMed: 26923259
DOI: 10.1016/j.jiac.2016.01.010