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Clinical Microbiology Reviews Apr 2016The treatment of bacterial infections suffers from two major problems: spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) pathogens and lack of... (Review)
Review
The treatment of bacterial infections suffers from two major problems: spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) pathogens and lack of development of new antibiotics active against such MDR and XDR bacteria. As a result, physicians have turned to older antibiotics, such as polymyxins, tetracyclines, and aminoglycosides. Lately, due to development of resistance to these agents, fosfomycin has gained attention, as it has remained active against both Gram-positive and Gram-negative MDR and XDR bacteria. New data of higher quality have become available, and several issues were clarified further. In this review, we summarize the available fosfomycin data regarding pharmacokinetic and pharmacodynamic properties, the in vitro activity against susceptible and antibiotic-resistant bacteria, mechanisms of resistance and development of resistance during treatment, synergy and antagonism with other antibiotics, clinical effectiveness, and adverse events. Issues that need to be studied further are also discussed.
Topics: Anti-Bacterial Agents; Drug Antagonism; Drug Resistance, Multiple, Bacterial; Drug Synergism; Fosfomycin; Gram-Negative Bacteria; Gram-Positive Bacteria; Microbial Sensitivity Tests
PubMed: 26960938
DOI: 10.1128/CMR.00068-15 -
Drug and Therapeutics Bulletin Oct 2016Fosfomycin trometamol is a broad spectrum antibiotic recently marketed in the UK for the treatment of acute uncomplicated lower urinary tract infections (UTIs) in adults... (Review)
Review
Fosfomycin trometamol is a broad spectrum antibiotic recently marketed in the UK for the treatment of acute uncomplicated lower urinary tract infections (UTIs) in adults and in adult and adolescent females. It is also indicated for prophylaxis in diagnostic and surgical transurethral procedures. Fosfomycin was discovered in 1969 and the reference drug was first marketed as Monuril in France in 1986. Although Monuril had UK marketing authorisation, it was never distributed in the UK. However, national guidance included the option of using unlicensed imported fosfomycin. Branded and generic versions of fosfomycin are now available in the UK, and here we review the evidence for their use in the treatment of UTIs.
Topics: Anti-Bacterial Agents; Contraindications; Drug Resistance, Multiple, Bacterial; Fosfomycin; Humans; Urinary Tract Infections
PubMed: 27737907
DOI: 10.1136/dtb.2016.10.0429 -
Revista Espanola de Quimioterapia :... May 2019To date, there has been little experience in using fosfomycin in children. However, its broad spectrum of action and excellent safety profile have renewed interest in... (Review)
Review
To date, there has been little experience in using fosfomycin in children. However, its broad spectrum of action and excellent safety profile have renewed interest in this antibiotic, especially for treating infections by multidrug-resistant bacteria. The main indication for fosfomycin in pediatrics is currently community-acquired lower urinary tract infection. Given its good activity against bacteria, fosfomycin can also be useful in urinary infections caused by extended-spectrum beta-lactamase-producing enterobacteria. Fosfomycin presents very good dissemination to tissues including bone and is therefore an option in the combined therapy of osteomyelitis, especially in cases produced by methicillin-resistant Staphylococcus aureus (MRSA) or in cases with beta-lactam allergies. Fosfomycin can also be employed in combination for multidrug-resistant Gram-negative bacteremia (especially carbapenemase-producing enterobacteria), S. aureus (if there is a high suspicion of MRSA or complicated infections) and vancomycin-resistant Enterococcus spp. Other infections in which fosfomycin could be part of a combined therapy include staphylococcal endocarditis (in case of beta-lactam allergy or MRSA), central nervous system infections (mainly by MRSA, S. epidermidis, Listeria and resistant pneumococcus), nosocomial pneumonia and infections associated with mechanical ventilation.
Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Fosfomycin; Humans; Infant; Infant, Newborn; Pediatrics
PubMed: 31131593
DOI: No ID Found -
Revista Espanola de Quimioterapia :... May 2019The discovery of fosfomycin more than 40 years ago was an important milestone in antibiotic therapy. The antibiotic's usefulness, alone or in combination, for treating... (Review)
Review
The discovery of fosfomycin more than 40 years ago was an important milestone in antibiotic therapy. The antibiotic's usefulness, alone or in combination, for treating infections caused by multidrug-resistant microorganisms is clearer than ever. Both the European Medicines Agency and the US Food and Drug Administration have open processes for reviewing the accumulated information on the use of fosfomycin and the information from new clinical trials on this compound. The agencies' objectives are to establish common usage criteria for Europe and authorize the sale of fosfomycin in the US, respectively. Fosfomycin's single mechanism of action results in no cross-resistance with other antibiotics. However, various fosfomycin-resistance mechanisms have been described, the most important of which, from the epidemiological standpoint, is enzymatic inactivation, which is essentially associated with a gene carrying a fosA3-harboring plasmid. Fosfomycin has been found more frequently in Asia in extended-spectrum beta-lactamase-producing and carbapenemase-producing Enterobacterales. Although fosfomycin presents lower intrinsic activity against Pseudomonas aeruginosa compared with that presented against Escherichia coli, fosfomycin's activity has been demonstrated in biofilms, especially in combination with aminoglycosides. The current positioning of fosfomycin in the therapeutic arsenal for the treatment of infections caused by multidrug-resistant microorganisms requires new efforts to deepen our understanding of this compound, including those related to the laboratory methods employed in the antimicrobial susceptibility testing study.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Fosfomycin; Humans; Microbial Sensitivity Tests
PubMed: 31131587
DOI: No ID Found -
Current Opinion in Infectious Diseases Dec 2019In the last decade, an increasing interest in using fosfomycin for the treatment of multidrug-resistant gram-negative (MDR-GNB) infections have been registered,... (Review)
Review
PURPOSE OF REVIEW
In the last decade, an increasing interest in using fosfomycin for the treatment of multidrug-resistant gram-negative (MDR-GNB) infections have been registered, especially when none or only a few other active alternatives remained available.
RECENT FINDINGS
Fosfomycin may remain active against a considerable proportion of MDR-GNB. In observational studies, a possible curative effect of oral fosfomycin monotherapy has been described for uncomplicated urinary tract infections (UTI) and bacterial prostatitis caused by MDR-GNB, whereas intravenous fosfomycin has been mostly used in combination with other agents for various type of severe MDR-GNB infections. The ZEUS randomized controlled trial (RCT) has started to provide high-level evidence about the possible use of fosfomycin for complicated UTI caused by extended-spectrum β-lactamase-producing GNB, but no results of large RCT are currently available to firmly guide the use of fosfomycin for carbapenem-resistant GNB.
SUMMARY
Fosfomycin is an important therapeutic option for MDR-GNB infections. Further pharmacokinetic/pharmacodynamic and clinical research is needed to optimize its use.
Topics: Anti-Bacterial Agents; Clinical Studies as Topic; Drug Resistance, Multiple, Bacterial; Fosfomycin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31567411
DOI: 10.1097/QCO.0000000000000597 -
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 -
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 -
Revista Espanola de Quimioterapia :... May 2019Fosfomycin, a low molecular weight and hydrophilic drug with negligible protein binding, is eliminated almost exclusively by glomerular filtration, whose clearance is... (Review)
Review
Fosfomycin, a low molecular weight and hydrophilic drug with negligible protein binding, is eliminated almost exclusively by glomerular filtration, whose clearance is subject to patient renal function. The volume of distribution approximates to the extracellular body water (about 0.3 L/Kg) in healthy volunteers, but it is increased in critically ill patients with bacterial infections. Fosfomycin presents a high ability to distribute into many tissues, including inflamed tissues and abscess fluids. Based on PK/PD analysis and Monte Carlo simulations, we have evaluated different fosfomycin dosing regimen to optimize the treatment of septic patients due to Enterobacterales and Pseudomonas aeruginosa. As PK/PD targets, we selected %T>MIC > 70% for all pathogens, and AUC24/MIC > 24 and AUC24/MIC > 15 for net stasis of Enterobacterales and P. aeruginosa, respectively. Pharmacokinetic parameters in critically ill patients were obtained from the literature. Several dosing regimens were studied in patients with normal renal function: fosfomycin 2-8 g given every 6-12 hours, infused over 30 minutes- 24 hours. At the susceptibility EUCAST breakpoint for Enterobacterales and Staphylococcus spp. (MIC ≤ 32 mg/L), fosfomycin 4 g/8h or higher infused over 30 minutes achieved a probability of target attainment (PTA) > 90%, based in both %T>MIC and AUC24/MIC. For MIC of 64 mg/L, fosfomycin 6 g/6h in 30-minute infusion and 8 g/ 8h in 30-minute and 6 hours infusions also achieved PTA values higher than 90%. No fosfomycin monotherapy regimen was able to achieve PK/PD targets related to antimicrobial efficacy for P. aeruginosa with MICs of 256-512 mg/L.
Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Fosfomycin; Humans
PubMed: 31131588
DOI: No ID Found -
Clinical Microbiology and Infection :... Jan 2012Fosfomycin is a broad-spectrum antibiotic discovered in Spain in 1969. It has bactericidal activity against a wide range of bacteria, including gram-negative... (Review)
Review
Fosfomycin is a broad-spectrum antibiotic discovered in Spain in 1969. It has bactericidal activity against a wide range of bacteria, including gram-negative micro-organisms and some gram-positive bacteria, such as staphylococci. Initially fosfomycin was administered parenterally and only to patients with severe infections. Today it is often dispensed as fosfomycin-trometamol, an oral formula recommended in the treatment of urinary tract infections. Fosfomycin-trometamol in a single dose is indicated for the treatment of women with uncomplicated urinary tract infections.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Female; Fosfomycin; Humans; Urinary Tract Infections
PubMed: 21914036
DOI: 10.1111/j.1469-0691.2011.03636.x -
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