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Matthew E Falagas - One of the best experts on this subject based on the ideXlab platform.
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resistance to Fosfomycin mechanisms frequency and clinical consequences
International Journal of Antimicrobial Agents, 2019Co-Authors: Matthew E Falagas, Florentia Athanasaki, Georgios L Voulgaris, Nikolaos A Triarides, Konstantinos Z VardakasAbstract:ABSTRACT Fosfomycin has been used for the treatment of infections due to susceptible and multidrug-resistant (MDR) bacteria. It inhibits bacterial cell wall synthesis through a unique mechanism of action at a step prior to that inhibited by β-lactams. Fosfomycin enters the bacterium through membrane channels/transporters and inhibits MurA, which initiates peptidoglycan (PG) biosynthesis of the bacterial cell wall. Several bacteria display inherent resistance to Fosfomycin mainly through MurA mutations. Acquired resistance involves, in order of decreasing frequency, modifications of membrane transporters that prevent Fosfomycin from entering the bacterial cell, acquisition of plasmid-encoded genes that inactivate Fosfomycin, and MurA mutations. Fosfomycin resistance develops readily in vitro but less so in vivo. Mutation frequency is higher among Pseudomonas aeruginosa and Klebsiella spp. compared with Escherichia coli and is associated with Fosfomycin concentration. Mutations in cAMP regulators, Fosfomycin transporters and MurA seem to be associated with higher biological cost in Enterobacteriaceae but not in Pseudomonas spp. The contribution of Fosfomycin inactivating enzymes in emergence and spread of Fosfomycin resistance currently seems low-to-moderate, but their presence in transferable plasmids may potentially provide the best means for the spread of Fosfomycin resistance in the future. Their co-existence with genes conferring resistance to other antibiotic classes may increase the emergence of MDR strains. Although susceptibility rates vary, rates seem to increase in settings with higher Fosfomycin use and among multidrug-resistant pathogens.
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Evaluation of Fosfomycin activity against uropathogens in a Fosfomycin-naive population in South India: a prospective study.
Future Microbiology, 2013Co-Authors: Rani Diana Sahni, Veeraraghavan Balaji, Rosemol Varghese, James John, Giannoula S. Tansarli, Matthew E FalagasAbstract:Aim: The aim was to evaluate the in vitro activity of Fosfomycin against common uropathogens in a Fosfomycin-naive population in India. Methods: The authors prospectively collected and tested all consecutive isolates of Escherichia coli and Enterococcus spp. from urine samples between December 2009 and April 2010. Results: A total of 3141 isolates were included in the study, 2416 E. coli and 725 Enterococcus spp. Fosfomycin was the most active antibiotic against both pathogens with an overall susceptibility of 83 and 99% for E. coli and Enterococcus spp, respectively. Among E. coli, 47.6% of the isolates were extended-spectrum β-lactamase producing, of which 81% were susceptible to Fosfomycin, while 51.5% were multidrug resistant, with 75.7% of this portion being susceptible to Fosfomycin. Conclusion: Fosfomycin exhibits good in vitro activity against both the uropathogens tested. Therefore, it might be considered as a treatment option for urinary tract infections in India; however, clinical trials should...
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Fosfomycin evaluation of the published evidence on the emergence of antimicrobial resistance in gram negative pathogens
Journal of Antimicrobial Chemotherapy, 2012Co-Authors: Drosos E Karageorgopoulos, Matthew E Falagas, Rui Wang, Xuhong YuAbstract:Fosfomycin has attracted renewed interest for the treatment of lower urinary tract and even systemic infections caused by Gram-negative pathogens with resistance to traditionally used agents. The main concern regarding the clinical utility of Fosfomycin refers to the potential for the emergence of resistance during therapy. In this review, we evaluate the available published evidence regarding the mechanisms and the frequency of in vitro mutational resistance to Fosfomycin in Gram-negative pathogens. We also review data regarding the emergence of resistance in clinical studies of Fosfomycin therapy in various infectious syndromes and data from studies that evaluate the evolution of Fosfomycin resistance over time. There appears to be discordance between the high frequency of mutational resistance to Fosfomycin in vitro and the lower extent of this phenomenon in clinical studies. This discordance could at least partly be attributed to a biological cost associated with common mutations that confer resistance to Fosfomycin, including decreased growth rate and low adherence to epithelial cells for the resistant mutants. The development of resistance appears to be more frequent both in vitro and in clinical studies for Pseudomonas aeruginosa in comparison with Escherichia coli, whereas relevant data for other Enterobacteriaceae are relatively scarce. The urinary tract seems to provide a favourable environment for the use of Fosfomycin with a low associated likelihood for the emergence of resistance, owing to high drug concentrations and acidic pH. Additional data are needed to further clarify the optimal use of Fosfomycin for different infectious syndromes caused by contemporary multidrug-resistant pathogens.
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antimicrobial susceptibility of multidrug resistant mdr and extensively drug resistant xdr enterobacteriaceae isolates to Fosfomycin
International Journal of Antimicrobial Agents, 2010Co-Authors: Matthew E Falagas, Drosos E Karageorgopoulos, Antonia C Kastoris, Sofia Maraki, Emmanuel Mavromanolakis, G SamonisAbstract:The advancing antimicrobial drug resistance among Enterobacteriaceae renders the evaluation of potential novel therapeutic options necessary. We sought to evaluate the in vitro antimicrobial activity of Fosfomycin against multidrug-resistant (MDR) Enterobacteriaceae isolates. Antimicrobial susceptibility to Fosfomycin and 12 additional antibiotics of MDR Enterobacteriaceae isolates collected between November 2007 and April 2009 at the University Hospital of Heraklion, Crete, Greece, was examined using the Etest method. A total of 152 MDR Enterobacteriaceae isolates were studied, including Klebsiella pneumoniae (76.3%), Escherichia coli (17.1%), Proteus mirabilis (4.6%) and other species (2.0%). Antimicrobial susceptibility rates were highest for Fosfomycin (92.8%), tigecycline (92.1%) and colistin (73.0%) followed by imipenem (35.5%), tetracycline (20.4%), gentamicin (19.7%), trimethoprim/sulfamethoxazole (12.5%) and ciprofloxacin (10.5%). Of the 152 isolates, 85 (55.9%) were extensively drug-resistant (XDR), of which 78 (91.8%) remained susceptible to Fosfomycin. Susceptibility to Fosfomycin of the 79 carbapenemase-producing, 34 extended-spectrum β-lactamase-producing and 24 metallo-β-lactamase-producing isolates was 94.9%, 94.1% and 83.3%, respectively. In conclusion, in this study Fosfomycin exhibited good in vitro antimicrobial activity against MDR and XDR Enterobacteriaceae. We suggest further evaluation of the potential clinical utility of Fosfomycin against infections caused by these pathogens.
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intravenous Fosfomycin for the treatment of nosocomial infections caused by carbapenem resistant klebsiella pneumoniae in critically ill patients a prospective evaluation
Clinical Microbiology and Infection, 2010Co-Authors: Argyris Michalopoulos, Matthew E Falagas, Petros I Rafailidis, Simona Virtzili, G Chalevelakis, M DamalaAbstract:Abstract Intensive care unit (ICU)-acquired infections as a result of multidrug-resistant Gram-negative pathogens remain a serious problem in critically ill patients. Adult ICU patients who received intravenous Fosfomycin were prospectively examined to assess its safety and effectiveness as an adjunct to the antimicrobial therapy of life-threatening infections caused by carbapenem-resistant Klebsiella pneumoniae. Fosfomycin was administered intravenously in 11 patients for treatment of hospital-acquired infections caused by carbapenem-resistant K. pneumoniae. Fosfomycin (2–4 g every 6 h) was administered in combination with other antibiotics. The mean ± SD duration of treatment was 14 ± 5.6 days. All patients had good bacteriological and clinical outcome of infection. All-cause hospital mortality was two out of 11 (18.2%) patients. No patient experienced adverse events related to the administration of Fosfomycin. Intravenous Fosfomycin may be a beneficial and safe adjunctive treatment in the management of life-threatening ICU-acquired infections caused by carbapenem-resistant K. pneumoniae.
Drosos E Karageorgopoulos - One of the best experts on this subject based on the ideXlab platform.
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Fosfomycin evaluation of the published evidence on the emergence of antimicrobial resistance in gram negative pathogens
Journal of Antimicrobial Chemotherapy, 2012Co-Authors: Drosos E Karageorgopoulos, Matthew E Falagas, Rui Wang, Xuhong YuAbstract:Fosfomycin has attracted renewed interest for the treatment of lower urinary tract and even systemic infections caused by Gram-negative pathogens with resistance to traditionally used agents. The main concern regarding the clinical utility of Fosfomycin refers to the potential for the emergence of resistance during therapy. In this review, we evaluate the available published evidence regarding the mechanisms and the frequency of in vitro mutational resistance to Fosfomycin in Gram-negative pathogens. We also review data regarding the emergence of resistance in clinical studies of Fosfomycin therapy in various infectious syndromes and data from studies that evaluate the evolution of Fosfomycin resistance over time. There appears to be discordance between the high frequency of mutational resistance to Fosfomycin in vitro and the lower extent of this phenomenon in clinical studies. This discordance could at least partly be attributed to a biological cost associated with common mutations that confer resistance to Fosfomycin, including decreased growth rate and low adherence to epithelial cells for the resistant mutants. The development of resistance appears to be more frequent both in vitro and in clinical studies for Pseudomonas aeruginosa in comparison with Escherichia coli, whereas relevant data for other Enterobacteriaceae are relatively scarce. The urinary tract seems to provide a favourable environment for the use of Fosfomycin with a low associated likelihood for the emergence of resistance, owing to high drug concentrations and acidic pH. Additional data are needed to further clarify the optimal use of Fosfomycin for different infectious syndromes caused by contemporary multidrug-resistant pathogens.
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antimicrobial susceptibility of multidrug resistant mdr and extensively drug resistant xdr enterobacteriaceae isolates to Fosfomycin
International Journal of Antimicrobial Agents, 2010Co-Authors: Matthew E Falagas, Drosos E Karageorgopoulos, Antonia C Kastoris, Sofia Maraki, Emmanuel Mavromanolakis, G SamonisAbstract:The advancing antimicrobial drug resistance among Enterobacteriaceae renders the evaluation of potential novel therapeutic options necessary. We sought to evaluate the in vitro antimicrobial activity of Fosfomycin against multidrug-resistant (MDR) Enterobacteriaceae isolates. Antimicrobial susceptibility to Fosfomycin and 12 additional antibiotics of MDR Enterobacteriaceae isolates collected between November 2007 and April 2009 at the University Hospital of Heraklion, Crete, Greece, was examined using the Etest method. A total of 152 MDR Enterobacteriaceae isolates were studied, including Klebsiella pneumoniae (76.3%), Escherichia coli (17.1%), Proteus mirabilis (4.6%) and other species (2.0%). Antimicrobial susceptibility rates were highest for Fosfomycin (92.8%), tigecycline (92.1%) and colistin (73.0%) followed by imipenem (35.5%), tetracycline (20.4%), gentamicin (19.7%), trimethoprim/sulfamethoxazole (12.5%) and ciprofloxacin (10.5%). Of the 152 isolates, 85 (55.9%) were extensively drug-resistant (XDR), of which 78 (91.8%) remained susceptible to Fosfomycin. Susceptibility to Fosfomycin of the 79 carbapenemase-producing, 34 extended-spectrum β-lactamase-producing and 24 metallo-β-lactamase-producing isolates was 94.9%, 94.1% and 83.3%, respectively. In conclusion, in this study Fosfomycin exhibited good in vitro antimicrobial activity against MDR and XDR Enterobacteriaceae. We suggest further evaluation of the potential clinical utility of Fosfomycin against infections caused by these pathogens.
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Fosfomycin for the treatment of multidrug resistant including extended spectrum β lactamase producing enterobacteriaceae infections a systematic review
Lancet Infectious Diseases, 2010Co-Authors: Matthew E Falagas, Antonia C Kastoris, Anastasios Kapaskelis, Drosos E KarageorgopoulosAbstract:Summary Rising rates of resistance to antimicrobial drugs among Enterobacteriaceae limit the choice of reliably active forms of these drugs. We evaluated the evidence on Fosfomycin as a treatment option for infections caused by members of the family Enterobacteriaceae with advanced resistance to antimicrobial drugs, including producers of extended-spectrum β-lactamase (ESBL). We systematically reviewed studies evaluating the antimicrobial activity, or the clinical effectiveness of Fosfomycin. 17 antimicrobial-susceptibility studies were found and included in our Review, accounting for 5057 clinical isolates of Enterobacteriaceae with advanced resistance to antimicrobial drugs (4448 were producers of ESBL); 11 of the 17 studies reported that at least 90% of the isolates were susceptible to Fosfomycin. Using a provisional minimum inhibitory concentration susceptibility breakpoint of 64 mg/L or less, 1604 (96·8%) of 1657 Escherichia coli isolates producing ESBL were susceptible to Fosfomycin. Similarly, 608 (81·3%) of 748 Klebsiella pneumoniae isolates producing ESBL were susceptible to Fosfomycin. In two clinical studies, oral treatment with Fosfomycin–trometamol was clinically effective against complicated or uncomplicated lower urinary tract infections caused by ESBL-producing E coli in, cumulatively, 75 (93·8%) of the 80 patients evaluated. Initial clinical data support the use of Fosfomycin for the treatment of urinary tract infections caused by these pathogens, although further research is needed.
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clinical significance of the pharmacokinetic and pharmacodynamic characteristics of Fosfomycin for the treatment of patients with systemic infections
International Journal of Antimicrobial Agents, 2009Co-Authors: Nikos Roussos, Matthew E Falagas, Drosos E Karageorgopoulos, G SamonisAbstract:The advancing antimicrobial drug resistance in common bacterial pathogens, along with the relative shortage of new antibacterial agents, call for the re-evaluation of available therapeutic options. Fosfomycin is an established treatment option for uncomplicated urinary tract infections. Here we review and evaluate the main pharmacokinetic and pharmacodynamic parameters of intravenously administered Fosfomycin with regard to its use for systemic infections. Fosfomycin is a relatively small, hydrophilic agent with almost negligible serum protein binding. It is excreted unchanged in urine, achieving high concentrations for a prolonged period. Fosfomycin has good distribution into tissues, achieving clinically relevant concentrations in sites such as serum, soft tissue, lungs, bone, cerebrospinal fluid and heart valves. Fosfomycin has shown antimicrobial activity against biofilms, particularly in combination with fluoroquinolones. It also exerts immunomodulatory effects, mainly on lymphocyte and neutrophil function. Potentially useful properties of Fosfomycin regarding its use in combination regimens include reduction in the expression of certain penicillin-binding proteins and attenuation of nephrotoxicity caused by several antimicrobial agents. In conclusion, the pharmacokinetic and pharmacodynamic properties of Fosfomycin do not preclude its use for various types of systemic infections and suggest further research on relevant clinical applications of this agent.
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Fosfomycin for the treatment of infections caused by multidrug resistant non fermenting gram negative bacilli a systematic review of microbiological animal and clinical studies
International Journal of Antimicrobial Agents, 2009Co-Authors: Matthew E Falagas, Drosos E Karageorgopoulos, Antonia C Kastoris, Petros I RafailidisAbstract:Abstract The treatment of multidrug-resistant (MDR), extensively drug-resistant or pandrug-resistant non-fermenting Gram-negative bacterial infections constitutes a challenge in an era of few new antibiotic choices. This mandates the re-evaluation of already existing antibiotics such as Fosfomycin. We systematically reviewed the literature to assess the clinical and microbiological effectiveness of Fosfomycin in the treatment of these infections by searching PubMed, Scopus and the Cochrane Library databases. In 23 microbiological studies identified, 1859 MDR non-fermenting Gram-negative bacterial isolates were examined. The susceptibility rate to Fosfomycin of MDR Pseudomonas aeruginosa isolates was ≥90% and 50–90% in 7/19 and 4/19 relevant studies, respectively. Cumulatively, 511/1693 (30.2%) MDR P. aeruginosa isolates were susceptible to Fosfomycin. Serotype O12 isolates exhibited greater susceptibility. Only 3/85 (3.5%) MDR Acinetobacter baumannii and 0/31 MDR Burkholderia spp. isolates were susceptible to Fosfomycin. Variable criteria of susceptibility were used in the included studies. Fosfomycin was synergistic in combination with a β-lactam, aminoglycoside or ciprofloxacin in 46/86 (53.5%) MDR P. aeruginosa isolates. One animal study found a good therapeutic effect of the combination Fosfomycin/gentamicin against MDR P. aeruginosa endocarditis. In six clinical studies, 33 patients with MDR P . aeruginosa infections (mainly pulmonary exacerbations of cystic fibrosis) received Fosfomycin (25/33 in combination with other antibiotics); 91% of the patients clinically improved. In conclusion, Fosfomycin could have a role as a therapeutic option against MDR P. aeruginosa infections. Further research is needed to clarify the potential utility of this agent.
U Thyrofffriesinger - One of the best experts on this subject based on the ideXlab platform.
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Fosfomycin trometamol versus ofloxacin co trimoxazole as single dose therapy of acute uncomplicated urinary tract infection in females a multicentre study
Infection, 1990Co-Authors: K G Naber, U ThyrofffriesingerAbstract:20 urologists took part in a single blind, randomized study. Female patients with acute uncomplicated UTI were recruited. The patients received either a single dose of 3 g Fosfomycin trometamol versus 200 mg ofloxacin or 1.92 g cotrimoxazole. Follow-up examinations were carried out after one and four weeks. Of 562 patients 446 could be evaluated for efficacy and 496 for tolerance. Patients were analysed according to the amount of bacteriuria: “significant” (≥ 105/ml), “low count” (102–104 ml) and “no bacteriuria” (≤ 101/ml), as well as according to the sensitivity of the infecting organisms: sensitive (resistant): Fosfomycin trometamol ≤ 16 mg/l (≥ 128 mg/l), ofloxacin ≤ 1 mg/l (≥ 8 mg/l), co-trimoxazole ≤ 2/38 mg/l (≥ 16/304 mg/l). Up to one week the following results could be achieved: clinical improvement was attained in patients with “significant” bacteriuria (Fosfomycin trometamol-150, ofloxacin-89, co-trimoxazole -69) in 94.7% for Fosfomycin trometamol, in 95.4% for ofloxacin, and in 94% for co-trimoxazole; in patients with “low count” bacteriuria (Fosfomycin trometamol-44, ofloxacin-18, co-trimoxazole-30) in 95.2% for Fosfomycin trometamol, in 93.7% for ofloxacin, and in 96.4% for co-trimoxazole; and in patients with no bacteriuria (Fosfomycin trometamol-11, ofloxacin-6, co-trimoxazole-4) in 81.8% for Fosfomycin trometamol, in 100% for ofloxacin and in 100% for co-trimoxazole. Sterile urine or non-significant bacteriuria was achieved in the group with “significant” bacteriuria in 87.4% for Fosfomycin trometamol, in 91% for ofloxacin and in 88.4% for co-trimoxazole; and in the group with “low count” bacteriuria in 86.4% for Fosfomycin trometamol, in 94.4% for ofloxacin, and in 96.7% for cotrimoxazole. In patients infected by resistant (intermediary sensitive) strains sterile urine or non-significant bacteriuria could be achieved in 7/11 (5/6) patients for Fosfomycin trometamol and 2/5 (0/1) for co-trimoxazole. Concerning side effects a total of 6.8% for Fosfomycin trometamol, 5.9% for ofloxacin and 7.9% for co-trimoxazole was experienced mostly at the gastrointestinal site (Fosfomycin trometamol-6.4%, ofloxacin-5.9%, co-trimoxazole-6.3%). This study demonstrates that Fosfomycin trometamol was equally effective and tolerable in single-dose therapy of acute uncomplicated UTI in females when compared to other established drugs such as ofloxacin and co-trimoxazole.
K G Naber - One of the best experts on this subject based on the ideXlab platform.
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Fosfomycin trometamol versus ofloxacin/co-trimoxazole as single dose therapy of acute uncomplicated urinary tract infection in females: a multicentre study.
Infection, 1990Co-Authors: K G Naber, Ursula Thyroff-friesingerAbstract:20 urologists took part in a single blind, randomized study. Female patients with acute uncomplicated UTI were recruited. The patients received either a single dose of 3 g Fosfomycin trometamol versus 200 mg ofloxacin or 1.92 g co-trimoxazole. Follow-up examinations were carried out after one and four weeks. Of 562 patients 446 could be evaluated for efficacy and 496 for tolerance. Patients were analysed according to the amount of bacteriuria: "significant" (greater than or equal to 10(5)/ml), "low count" (10(2) - 10(4) ml) and "no bacteriuria" (less than or equal to 10(1)/ml), as well as according to the sensitivity of the infecting organisms: sensitive (resistant): Fosfomycin trometamol less than or equal to 16 mg/l (greater than or equal to 128 mg/l), ofloxacin less than or equal to 1 mg/l (greater than or equal to 8 mg/l), co-trimoxazole less than or equal to 2/38 mg/l (greater than or equal to 16/304 mg/l). Up to one week the following results could be achieved: clinical improvement was attained in patients with "significant" bacteriuria (Fosfomycin trometamol-150, ofloxacin-89, co-trimoxazole-69) in 94.7% for Fosfomycin trometamol, in 95.4% for ofloxacin, and in 94% for co-trimoxazole; in patients with "low count" bacteriuria (Fosfomycin trometamol-44, ofloxacin-18, co-trimoxazole-30) in 95.2% for Fosfomycin trometamol, in 93.7% for ofloxacin, and in 96.4% for co-trimoxazole; and in patients with no bacteriuria (Fosfomycin trometamol-11, ofloxacin-6, co-trimoxazole-4) in 81.8% for Fosfomycin trometamol, in 100% for ofloxacin and in 100% for co-trimoxazole.(ABSTRACT TRUNCATED AT 250 WORDS)
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Fosfomycin trometamol versus ofloxacin/co-trimoxazole as single dose therapy of acute uncomplicated urinary tract infection in females: a multicentre study.
Infection, 1990Co-Authors: K G Naber, Ursula Thyroff-friesingerAbstract:20 urologists took part in a single blind, randomized study. Female patients with acute uncomplicated UTI were recruited. The patients received either a single dose of 3 g Fosfomycin trometamol versus 200 mg ofloxacin or 1.92 g cotrimoxazole. Follow-up examinations were carried out after one and four weeks. Of 562 patients 446 could be evaluated for efficacy and 496 for tolerance. Patients were analysed according to the amount of bacteriuria: “significant” (≥ 105/ml), “low count” (102–104 ml) and “no bacteriuria” (≤ 101/ml), as well as according to the sensitivity of the infecting organisms: sensitive (resistant): Fosfomycin trometamol ≤ 16 mg/l (≥ 128 mg/l), ofloxacin ≤ 1 mg/l (≥ 8 mg/l), co-trimoxazole ≤ 2/38 mg/l (≥ 16/304 mg/l). Up to one week the following results could be achieved: clinical improvement was attained in patients with “significant” bacteriuria (Fosfomycin trometamol-150, ofloxacin-89, co-trimoxazole -69) in 94.7% for Fosfomycin trometamol, in 95.4% for ofloxacin, and in 94% for co-trimoxazole; in patients with “low count” bacteriuria (Fosfomycin trometamol-44, ofloxacin-18, co-trimoxazole-30) in 95.2% for Fosfomycin trometamol, in 93.7% for ofloxacin, and in 96.4% for co-trimoxazole; and in patients with no bacteriuria (Fosfomycin trometamol-11, ofloxacin-6, co-trimoxazole-4) in 81.8% for Fosfomycin trometamol, in 100% for ofloxacin and in 100% for co-trimoxazole. Sterile urine or non-significant bacteriuria was achieved in the group with “significant” bacteriuria in 87.4% for Fosfomycin trometamol, in 91% for ofloxacin and in 88.4% for co-trimoxazole; and in the group with “low count” bacteriuria in 86.4% for Fosfomycin trometamol, in 94.4% for ofloxacin, and in 96.7% for cotrimoxazole. In patients infected by resistant (intermediary sensitive) strains sterile urine or non-significant bacteriuria could be achieved in 7/11 (5/6) patients for Fosfomycin trometamol and 2/5 (0/1) for co-trimoxazole. Concerning side effects a total of 6.8% for Fosfomycin trometamol, 5.9% for ofloxacin and 7.9% for co-trimoxazole was experienced mostly at the gastrointestinal site (Fosfomycin trometamol-6.4%, ofloxacin-5.9%, co-trimoxazole-6.3%). This study demonstrates that Fosfomycin trometamol was equally effective and tolerable in single-dose therapy of acute uncomplicated UTI in females when compared to other established drugs such as ofloxacin and co-trimoxazole.
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Fosfomycin trometamol versus ofloxacin co trimoxazole as single dose therapy of acute uncomplicated urinary tract infection in females a multicentre study
Infection, 1990Co-Authors: K G Naber, U ThyrofffriesingerAbstract:20 urologists took part in a single blind, randomized study. Female patients with acute uncomplicated UTI were recruited. The patients received either a single dose of 3 g Fosfomycin trometamol versus 200 mg ofloxacin or 1.92 g cotrimoxazole. Follow-up examinations were carried out after one and four weeks. Of 562 patients 446 could be evaluated for efficacy and 496 for tolerance. Patients were analysed according to the amount of bacteriuria: “significant” (≥ 105/ml), “low count” (102–104 ml) and “no bacteriuria” (≤ 101/ml), as well as according to the sensitivity of the infecting organisms: sensitive (resistant): Fosfomycin trometamol ≤ 16 mg/l (≥ 128 mg/l), ofloxacin ≤ 1 mg/l (≥ 8 mg/l), co-trimoxazole ≤ 2/38 mg/l (≥ 16/304 mg/l). Up to one week the following results could be achieved: clinical improvement was attained in patients with “significant” bacteriuria (Fosfomycin trometamol-150, ofloxacin-89, co-trimoxazole -69) in 94.7% for Fosfomycin trometamol, in 95.4% for ofloxacin, and in 94% for co-trimoxazole; in patients with “low count” bacteriuria (Fosfomycin trometamol-44, ofloxacin-18, co-trimoxazole-30) in 95.2% for Fosfomycin trometamol, in 93.7% for ofloxacin, and in 96.4% for co-trimoxazole; and in patients with no bacteriuria (Fosfomycin trometamol-11, ofloxacin-6, co-trimoxazole-4) in 81.8% for Fosfomycin trometamol, in 100% for ofloxacin and in 100% for co-trimoxazole. Sterile urine or non-significant bacteriuria was achieved in the group with “significant” bacteriuria in 87.4% for Fosfomycin trometamol, in 91% for ofloxacin and in 88.4% for co-trimoxazole; and in the group with “low count” bacteriuria in 86.4% for Fosfomycin trometamol, in 94.4% for ofloxacin, and in 96.7% for cotrimoxazole. In patients infected by resistant (intermediary sensitive) strains sterile urine or non-significant bacteriuria could be achieved in 7/11 (5/6) patients for Fosfomycin trometamol and 2/5 (0/1) for co-trimoxazole. Concerning side effects a total of 6.8% for Fosfomycin trometamol, 5.9% for ofloxacin and 7.9% for co-trimoxazole was experienced mostly at the gastrointestinal site (Fosfomycin trometamol-6.4%, ofloxacin-5.9%, co-trimoxazole-6.3%). This study demonstrates that Fosfomycin trometamol was equally effective and tolerable in single-dose therapy of acute uncomplicated UTI in females when compared to other established drugs such as ofloxacin and co-trimoxazole.
Nicola Jones - One of the best experts on this subject based on the ideXlab platform.
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Oral Fosfomycin for treatment of urinary tract infection: a retrospective cohort study
BMC Infectious Diseases, 2016Co-Authors: Philippa C. Matthews, Lucinda K. Barrett, Stephanie Warren, Nicole Stoesser, Mel Snelling, Matthew Scarborough, Nicola JonesAbstract:Background Fosfomycin is increasingly called upon for the treatment of multi drug-resistant (MDR) organisms causing urinary tract infection (UTI). We reviewed oral Fosfomycin use for UTI treatment in a large UK hospital. The primary goal was to audit our clinical practice against current national guidelines. Secondary aims were to identify factors associated with treatment failure, and to investigate the potential for using Fosfomycin in patients with co-morbidities. Methods We retrospectively studied 75 adult patients with UTI who received 151 episodes of treatment with Fosfomycin from March 2013 to June 2015. We collected clinical data from our electronic patient record, and microbiology data pre- and post- Fosfomycin treatment. We recorded additional data for patients receiving prolonged courses in order to make a preliminary assessment of safety and efficacy. We also reviewed >18,000 urinary tract isolates of Escherichia coli and Klebsiella spp . processed by our laboratory over the final year of our study period to determine the prevalence of Fosfomycin resistance. Results There was a significant increase in Fosfomycin treatment episodes over the course of the study period. Co-morbidities were present in 71 % of patients. The majority had E. coli infection (69 %), of which 59 % were extended spectrum beta-lactamase (ESBL)-producers. Klebsiella infections were more likely than E. coli to fail treatment, and more likely to be reported as Fosfomycin resistant in cases of relapse following treatment. There were no adverse events in five patients treated with prolonged Fosfomycin. Among all urinary isolates collected over a year, Fosfomycin resistance was documented in 1 % of E. coli vs. 19 % of Klebsiella spp. ( p
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oral Fosfomycin for treatment of urinary tract infection a retrospective cohort study
BMC Infectious Diseases, 2016Co-Authors: Philippa C. Matthews, Lucinda K. Barrett, Stephanie Warren, Nicole Stoesser, Mel Snelling, Matthew Scarborough, Nicola JonesAbstract:Background Fosfomycin is increasingly called upon for the treatment of multi drug-resistant (MDR) organisms causing urinary tract infection (UTI). We reviewed oral Fosfomycin use for UTI treatment in a large UK hospital. The primary goal was to audit our clinical practice against current national guidelines. Secondary aims were to identify factors associated with treatment failure, and to investigate the potential for using Fosfomycin in patients with co-morbidities.