Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Fosfomycin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,027 records · Page 57Linked to original sources
PubMed2003

Prevalence and antimicrobial susceptibility of pathogens in uncomplicated cystitis in Europe. The ECO.SENS study.

The ECO.SENS study investigated the prevalence and antimicrobial susceptibility of pathogens causing community-acquired acute uncomplicated urinary tract infections (UTIs) in 4734 women aged 18-65 years presenting with symptoms of acute UTI, at 252 community healthcare centres in 16 countries in Europe plus Canada. Resistance in Escherichia coli occurred most frequently to ampicillin (30%) and sulphonamides (29%), followed by trimethoprim (15%), trimethoprim/sulphamethoxazole (14%) and nalidixic acid (5%) but was low to co-amoxiclav, mecillinam, cefadroxil, nitrofurantoin, fosfomycin, gentamicin and ciprofloxacin, all at<3%. Consumption of antibiotics in 1997 varied more than 4-fold within Europe and from 9 to 37 DDD/1000 inhabitants/day, the consumption being highest in Southern Europe. The consumption of broad-spectrum penicillins correlated with resistance to ampicillin and there was a clear correlation between quinolone consumption and resistance to ciprofloxacin and nalidixic acid. The 4-fold difference in antibiotic consumption within Europe and the correlation to resistance emphasises the importance of controlling antibiotic usage.

Adolescent↗
PubMed2003

Fluoroquinolones and resistance in the treatment of uncomplicated urinary tract infection.

Acute uncomplicated cystitis is one of the most common problems for which young women seek medical attention. Most of these infections are caused by Escherichia coli which are susceptible to many oral antimicrobials, although resistance is increasing to some of the commonly used agents, especially trimethoprim/sulphamethoxazole (TMP/SMX). In women with risk factors for infection with resistant bacteria, or in the setting of a high prevalence of TMP/SMX resistance, a fluoroquinolone or nitrofurantoin should be considered for empirical treatment. Use of nitrofurantoin does not share cross-resistance with more commonly prescribed antimicrobials and its more widespread use is justified from a public health perspective as a fluoroquinolone-sparing agent. beta-lactams and fosfomycin should be considered second-line agents for empirical treatment of cystitis. For acute uncomplicated pyelonephritis, fluoroquinolones are superior to TMP/SMX for empirical therapy due to the relatively high prevalence of TMP/SMX resistance among uropathogens causing pyelonephritis. TMP/SMX, effective for patients with mild to moderate disease, is an appropriate drug if the uropathogen is known to be susceptible. It is reasonable to use a 7-10 day oral fluoroquinolone regimen for outpatient management of mild to moderate pyelonephritis in the setting of a susceptible causative pathogen and rapid clinical response to therapy. Most women with acute uncomplicated pyelonephritis are now managed safely and effectively as outpatients.

Administration, Oral↗
PubMed2003

Listeriosis: therapeutic options.

Since overt listeriosis occurs mainly in immunocompromised persons it is quite consistent to try to restore the hampered defence system by supportive measurements. For direct antimicrobial treatment a series of different antibiotics is available, since Listeria strains isolated from patients are in general susceptible to a wide range of antibiotics, except fosfomycin, quinolones and cephalosporins of the third generation, although a few exceptional strains exist. Unfortunately, most antibiotics are not bactericidal for Listeria. Drug combinations may exert a synergistic effect. Furthermore, the efficacy of therapy is limited by the fact of intracellular habitat of pathogenic Listeria. Few agents, such as macrolides and quinolones, are accumulated within host cells and may attack the intracellular Listeriae. The clinical experience shows that the combination of amoxicillin and gentamicin is the best option.

Animals↗
PubMed2002

[Pneumococcal meningitis and resistant bacteria].

The emergence of resistance has imposed a modification of the protocols for the treatment of Streptococcus pneumoniae (S pneumoniae) bacterial meningitis. Amoxicillin is no longer adapted. As resistance to C3G appeared, a synergistic effect of an association C3G + vancomycine was demonstrated. Thus currently this association should be recommended in any case of meningitis supposedly due to S pneumoniae. The treatment is then modified according to the evolution and the minimal inhibition concentration (MIC) of the bacteria. The strains carrying a high level of resistance to cephalosporin (MIC > or = 4 micrograms ml-1) or tolerant to vancomycine may cause a therapeutic failure despite an increase of the dosage of cephalosporin. Rifampicin, fosfomycine, or imipenem (despite its risk of convulsions), may represent alternative options, as long as we do not have safe quinolones active on resistant strains of S. pneumoniae. Dexamethasone has been formerly implicated in the relapse of pneumococcal meningitis. Furthermore, its use is questionable since no evidence of a therapeutic benefit has been clearly demonstrated. As a consequence of the resistance phenomenon the management of S. pneumoniae meningitis must include particular measures: at least resistance to penicillin must be checked by the oxacilline disk and the MIC to C3G must be measured by E test; aCSF sample should be obtained between 36 and 48 hours following the beginning of the treatment to check its sterilization. All recent studies have shown a similar prognosis of meningitis due to resistant S. pneumoniae as compared to those due to sensitive strains. However, these data should be interpreted with caution since in these studies, pneumococcus resistant to cephalosporin (the real problem) are not separated from those only resistant to penicillin. Furthermore, presently, the incidence of strains highly resistant to cephalosporin is still low. The new conjugated vaccine against pneumococcus should change the situation if its ability to prevent the circulation of resistant strains is confirmed.

Adrenal Cortex Hormones↗
PubMed1993

In vitro susceptibility of Pasteurella multocida subspecies multocida strains isolated from swine to 42 antimicrobial agents.

The minimal inhibitory concentrations (MICs) of 42 antimicrobial agents were determined against 59 strains of Pasteurella multocida subspecies multocida, all isolated from swine lungs with lesions indicative of pneumonia. Penicillins (except cloxacillin), aminoglycosides, tetracyclines, erythromycin, josamycin, thiamphenicol, colistin, rifampin and mupirocin showed good activities, with ranging resistance between 0 and 6.8%. Higher resistance was observed for spiramycin and fosfomycin. Tylosin, vancomycin, metronidazole, dapsone and tiamulin, to which strains showed high rates of resistance, were ineffective. Cephalosporins (especially the third-generation cephalosporins) and quinolones (especially the fluorinated quinolones) were the most effective antimicrobial agents against P. multocida subsp. multocida strains and they might be of value for in vivo use.

Animals↗
PubMed1989

Hospital dispersion of Staphylococcus epidermidis isolates resistant to a fluoroquinolone, pefloxacin.

Since 1985, nosocomial infections have been frequently treated with a new fluoroquinolone, pefloxacin, at the Cardiological and Neurological Hospital in Lyon. From 1986 to 1988, the incidence of resistance of clinical Staphylococcus epidermidis strains to pefloxacin increased from 31 to 57%. Dispersion of these resistant strains in the hospital environment was recognized when they were detected on 22% of staff members' fingers (139 samples were investigated) and in 28% of the environmental samples (180 were investigated). There was an association between carriage rate and work place. Most of the pefloxacin-resistant S. epidermidis were resistant to oxacillin, gentamicin, erythromycin, cotrimoxazole and fosfomycin. Intensive use of pefloxacin selected multiresistant S. epidermidis which became ubiquitous in the hospital environment.

Carrier State↗
PubMed2000

Determination of the pKa value of C115 in MurA (UDP-N-acetylglucosamine enolpyruvyltransferase) from Enterobacter cloacae.

The enzyme UDP-N-acetylglucosamine (UDP-NAG) enolpyruvyltransferase (MurA) catalyzes the formation of enolpyruvyl-UDP-NAG, a precursor in peptidoglycan biosynthesis. The residue at position 115 in MurA has been proposed to act as a general acid in the enzymatic reaction. This is also the primary site of action of the antibiotic fosfomycin. In this paper, the pK(a) of Cys-115 has been determined to be 8.3, by titration of Enterobacter cloacae MurA with the alkylating agent iodoacetamide as a function of pH. Use of site-directed mutagenesis has established that only C115 is essential for catalysis, and the three other cysteine residues (C251, C354, and C381) are nonessential. Mass spectrometric analysis demonstrated that C115 is not alkylated at pH <7, but is alkylated significantly at pH >7. Measurement of the enzymatic inhibition by iodoacetamide as a function of pH showed maximum inhibition at pH >9, with a second-order rate constant of inhibition of 44 M(-)(1) s(-)(1) at pH 10. The presence of either one of the substrates did not influence the inactivation behavior, while the presence of both substrates resulted in a 5-fold reduction in the extent of alkylation. The covalent species that results from PEP bound to C115 of MurA exhibited 50-100-fold increased resistance against alkylation by iodoacetamide. These results imply that C115 is appreciably protonated at physiological pH and, therefore, is capable of acting as a proton donor in the enzyme-catalyzed reaction. However, it also implies that C115 is appreciably deprotonated at physiological pH also, whereupon the resultant thiolate nucleophile may play an important role in the formation of the covalent O-phosphothioketal species, whose role in catalysis is yet to be established.

Alkyl and Aryl Transferases↗
PubMed1999

Substrate and inhibitor-induced conformational changes in the structurally related enzymes UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) and 5-enolpyruvylshikimate 3-phosphate synthase (EPSPS).

UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) and 5-enolpyruvylshikimate 3-phosphate synthase (EPSPS) have both a unique three-dimensional topology and overall reaction mechanism in common. In the case of MurA, the substrate-free, unliganded protein exhibits an "open" conformation. Upon binding of substrates, the protein forms a much more tightly packed so-called "closed" form following an induced fit mechanism. In this closed form, the substrates are properly positioned for catalysis. On the basis of the structural and mechanistic similarities of MurA and EPSPS, a similar conformational change is likely to occur in EPSPS to generate a catalytically competent active site. However, there is currently little experimental evidence available to support the occurrence of such a conformational change in EPSPS. Using limited tryptic digestion of MurA,(1) it could be shown that formation of the "closed" conformation of MurA is accompanied by a marked increase of stability toward proteolytic degradation. Formation of the closed conformation was achieved by addition of either an excess of both substrates or the sugar nucleotide substrate in conjunction with the antibiotic fosfomycin. Analysis of the MurA tryptic fragments by MALDI-TOF mass spectrometry demonstrates that the protection of the protein in either case is caused by (1) a specific shielding of regions thereby becoming less accessible as a result of the conformational change, and (2) an unspecific overall protection of the whole protein due to an apparently reduced flexibility of the peptide backbone in the binary and ternary complexes. The establishment of methods to describe the effects of tryptic digestion on MurA under various conditions was then extended to EPSPS. Although EPSPS was found to be much more stable toward proteolysis than MurA, the presence of shikimate 3-phosphate (S3P) and the inhibitor glyphosate led to a pronounced suppression of proteolytic degradation. When unliganded EPSPS was treated with trypsin, three of the peptide fragments obtained could be identified by mass spectrometry. Two of these are located in a region corresponding to the "catalytic" loop in MurA which participates in the conformational change. This indicates a conformational change in EPSPS, similar to the one observed in MurA, leading to the protection mentioned above. Corroborating evidence was obtained using a conformational sensitive monoclonal antibody against EPSPS which showed a 20-fold reduced affinity toward the protein complexed with S3P and glyphosate as compared to the unliganded enzyme.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMed1998

In vitro toxic effects of certain antibiotics on the fibroblasts of two children with I-cell disease.

Six antibiotics, pefloxacin (Peflacine), fosfomycin (Fosfocine), teicoplanin (Targocid), vancomycin (Vancocine), ceftazidime (Fortum), piperacillin (Piperilline), that may be used as a systematic coverage during bone marrow transplantation have been tested on dermal fibroblasts of one control subject and two I-cell disease patients, along with five subcultures, corresponding to 5 weeks of culture. The possible toxicity of these molecules was assessed. The evaluation of lysosomal enzyme sphingomyelinase activity, detection of free intracellular cholesterol and the light- and electron-microscopic examination of treated cells were used as measures of metabolic interference and cytotoxicity. Our study shows that despite a lack of any metabolic sign of interference (no modification in enzyme activity, no increase in free intracellular cholesterol), all the antibiotics tested induced a cytotoxic effect which was notably amplified in the I-cell populations. This may be due to the lysosomal lipid storage of these cells which modifies the relationship between the antibiotic and the cell by inducing a different kind of lipid-antibiotic interference.

Anti-Bacterial Agents↗
PubMed1998

Veno-occlusive disease of the liver after allogeneic bone marrow transplantation in children with hematologic malignancies: incidence, onset time and risk factors.

One hundred and forty children with hematologic malignancies undergoing allogeneic BMT were reviewed in order to clarify the incidence, onset time, and risk factors for veno-occlusive disease (VOD) of the liver. Thirty-eight patients (27.1%) developed VOD diagnosed according to the Seattle clinical criteria. Seventeen patients developed VOD within 20 days of transplantation (early-onset) and in 21 patients developed after day 20 (late-onset) including eight patients with histological confirmation. Late-onset VOD occurred from day 21 to day 508 (median day 39). Moderate or severe VOD developed in 11 early-onset and 13 late-onset patients. Death occurred in eight early-onset and 10 late-onset patients. Serum albumin and cholinesterase levels prior to the start of pretransplant conditioning were significantly lower in early-onset VOD than in late-onset VOD. Multivariate analysis showed that low serum albumin levels (< or =3.7 g/dl) prior to the start of pretransplant conditioning was most strongly associated with the development of VOD. Donor mismatch (other than HLA-matched relatives), use of minocycline, and a long interval (> or =13 months) between diagnosis and BMT were also significantly associated with the development of VOD. In contrast, use of fosfomycin was associated with a decreased risk. Our data suggest that hepatic function reserve is important in the development and onset time of VOD. Veno-occlusive disease of the liver is a complication which may occur a long time after transplantation.

Adolescent↗
PubMed2003

Proteus mirabilis glutathione S-transferase B1-1 is involved in protective mechanisms against oxidative and chemical stresses.

We investigated the effects of several xenobiotics, including antimicrobial agents and general stress factors such as starvation, heat and osmotic shock, on the modulation of expression of Proteus mirabilis glutathione S-transferase B1-1 (PmGST B1-1). The level of expression of PmGST B1-1 was established by both Western- and Northern-blot experiments. Our results show that several compounds can modulate expression of PmGST B1-1. The level of PmGST B1-1 increased when bacterial cells were exposed to a variety of stresses such as 1-chloro-2,4-dinitrobenzene, H(2)O(2), fosfomycin or tetracycline. A knock-out gst B gene was also constructed using the suicide vector pKNOCKlox-Ap. Successful inactivation of the wild-type gene was confirmed by PCR, DNA sequence analysis and Western blotting. Under normal culture conditions, this mutant was viable and displayed no significant phenotypic differences compared with the wild-type. However, viability tests revealed that the null mutant was more sensitive to oxidative stress in the form of H(2)O(2) and to several antimicrobial drugs when compared with the wild-type. These results suggest that PmGST B1-1 has an active role in the protection against oxidative stress generated by H(2)O(2) and it appears to be involved in the detoxification of antimicrobial agents.

Base Sequence↗
PubMed1997

Minimum inhibitory concentrations for selected antimicrobial agents against Fusobacterium necrophorum isolated from hepatic abscesses in cattle and sheep.

Minimum inhibitory concentrations for 35 antimicrobial agents against 100 Fusobacterium necrophorum isolates from hepatic abscesses in sheep and cattle were determined. Twelve of the thirteen beta-lactam antibiotics tested inhibited growth of 100% of strains tested. Of the remaining antimicrobial agents, extensive susceptibility was found for: spiramycin, josamycin, lincomycin, tylosin, oxytetracycline, chlortetracycline, rufloxacin, metronidazole, cotrimoxazole, sulfadimethoxine, virginiamycin and fosfomycin.

Animals↗
PubMed2000

'Intergenic' blr gene in Escherichia coli encodes a 41-residue membrane protein affecting intrinsic susceptibility to certain inhibitors of peptidoglycan synthesis.

In the annotation of genomic sequences, small open reading frames (ORFs) are often neglected, particularly if they have no homology to other ORFs or proteins. A mini-TnphoA insertion in a 602 bp 'intergenic' region of the Escherichia coli chromosome at genomic nucleotide 1702674 gave rise to a membrane-bound PhoA fusion protein and a two- to fourfold increase in the intrinsic susceptibility to a wide spectrum of beta-lactam antibiotics without affecting beta-lactamase activity or susceptibility to tetracycline, chloramphenicol, gentamicin or quinolones. Susceptibility was also increased to cycloserine and bacitracin, but not to fosfomycin or valinomycin; these drugs, like beta-lactams, inhibit peptidoglycan synthesis, although by different mechanisms. A clone bearing only 358 bp of this 'blr' region restored resistance to the parental level. Two amber mutations in the clone prevented such restoration and were counteracted by an amber suppressor, proving that the active species is a protein. The Blr protein has 41 amino acids, with a single predicted transmembrane helix, but no clear homology to any other protein. A transcriptional start exists 39 bp upstream from the translational start. The membrane location of Blr suggests that it may be part of an efflux pump or involved in murein metabolism. The results indicate that genes for other very small functional proteins may lie within 'intergenic' regions.

Alkaline Phosphatase↗
PubMed2003

Structure and function of the Mur enzymes: development of novel inhibitors.

One of the biggest challenges for recent medical research is the continuous development of new antibiotics interacting with bacterial essential mechanisms. The machinery for peptidoglycan biosynthesis is a rich source of crucial targets for antibacterial chemotherapy. The cytoplasmic steps of the biosynthesis of peptidoglycan precursor, catalysed by a series of Mur enzymes, are excellent candidates for drug development. There has been growing interest in these bacterial enzymes over the last decade. Many studies attempted to understand the detailed mechanisms and structural features of the key enzymes MurA to MurF. Only MurA is inhibited by a known antibiotic, fosfomycin. Several attempts made to develop novel inhibitors of this pathway are discussed in this review. Three novel inhibitors of MurA were identified recently. 4-Thiazolidinone compounds were designed as MurB inhibitors. Many phosphinic acid derivatives and substrate analogues were identified as inhibitors of the MurC to MurF amino acid ligases.

Alkyl and Aryl Transferases↗
PubMed1998

Osteomyelitis and septic arthritis due to Citrobacter freundii and Haemophilus influenzae type b.

This report describes dual infection with Citrobacter freundii and Haemophilus influenzae type b causing septic arthritis and osteomyelitis of the elbow in a previously healthy 5-year-old boy. The patient was treated successfully with intravenous fosfomycin for 4 weeks. Infections with Citrobacter beyond the neonatal period are rare in paediatric patients. When Citrobacter spp. is isolated, coinfection with other bacterial pathogens should be considered.

Arthritis, Infectious↗
PubMed1998

Anti-MRSA activity of sophoraflavanone G and synergism with other antibacterial agents.

Anti-MRSA activity of sophoraflavanone G (SFG) and synergism between SFG and antibacterial agents against MRSA (methicillin-resistant Staphylococcus aureus) were evaluated by means of Minimal Inhibitory Concentrations (MIC). The MICs of SFG against 27 strains of MRSA ranged from 3.13 to 6.25 micrograms ml-1. Synergism between SFG and vancomycin hydrochloride (VCM) or fosfomycin (FOM) was observed (the fraction inhibitory concentration (FIC) indices were 0.16 and 0.48), while partial synergism was admitted between SFG and other antibacterial agents such as methicillin (DMPPC), cefzonam (CZON), gentamicin (GM), minocycline (MINO) and levofloxacin (LVFX) (the FIC indices were 0.71, 0.73, 0.69, 0.65 and 0.58, respectively). These findings suggest that SFG in combination with VCM or FOM may be useful in controlling MRSA infections.

Anti-Bacterial Agents↗
PubMed2001

Deep wound infection after vagus nerve stimulator implantation: treatment without removal of the device.

Effective treatment of deep wound infection without removal of a previously implanted foreign body is difficult. The Neurocybernetic Prosthesis (NCP) System (Cyberonics Inc., Webster, TX, U.S.A.), implanted for vagus nerve stimulation in patients with medically refractory epilepsy, uses coil-like electrodes placed around the left vagus nerve after exposure of the nerve in the carotid sheath. Infection within this compartment endangers the contained structures and makes removal of the system hazardous. We report the case of one patient implanted with the NCP who underwent successful open wound treatment without removal of the system. A 35-year-old man had local signs of wound infection 5 weeks after implantation of a vagus nerve stimulator. Systemic signs of infection were absent. C-reactive protein was slightly elevated, but all other laboratory values were normal. After open wound debridement and thorough rinsing with bacitracin-containing solution, the wound was packed with 3% iodoformized gauze. The NCP was left in place. Systemic antibiotic therapy with fosfomycin and cefmenoxim was started. Cultures confirmed an infection with Staphylococcus aureus. The wound was rinsed daily with 3% hydrogen peroxide solution and 5% saline until cultures were sterile and granulation tissue started to fill the wound. Delayed primary closure was performed 2 weeks later. Wound healing was accomplished without removal of the device. No signs of recurrent infection were observed during a follow-up of 1 year. Open wound treatment without removal of the implanted vagus nerve stimulator is feasible in cases of deep cervical wound infection and can be an alternative if removal of the device appears hazardous.

Adult↗
PubMed2002

Comparative pulsed-field gel electrophoresis typing of gentamicin-resistant and -susceptible methicillin-resistant Staphylococcus aureus strains isolated in France between 1991 and 1998. Changes in antibiotic susceptibility.

Using macrorestriction of genomic DNA and pulsed-field gel electrophoresis, we examined 504 non-redundant, infection-causing human isolates of methicillin-resistant Staphylococcus aureus susceptible (G(S): 238 isolates) or resistant to gentamicin (G(R): 266 isolates). The strains were isolated at Albert Chenevier Hospital (Créteil, France) between 1 January 1991 and 31 December 1998. Their susceptibility to erythromycin, lincomycin, tetracycline, rifampicin, fusidic acid and fosfomycin was also studied. Seventy-six genotypes were identified (percentage similarity<80). Ten types, each containing at least eight strains, predominated. G(R) strains showed higher genetic polymorphism than G(S) strains: the 266 G(R) isolates belonged to 67 genotypes, five of which predominated (44, 42, 38, 30 and 15 isolates); the 238 G(S) isolates belonged to only 18 types, four of which predominated (112, 83, 11 and 10 isolates). Fifty-six percent of G(R) strains (34 Gt) were resistant to erythromycin, lincomycin, tetracycline and rifampicin, and were isolated at relatively stable frequencies. Resistance to five antibiotics studied (susceptible to fusidic acid) was observed among 16.5% of G(R) strains. The frequency of strains with this profile diminished from 30% in the early 1990s to 10% in 1998. One hundred and twenty-six G(S) isolates were susceptible to all six antibiotics; this profile was only found from 1993 onwards, and was increasingly frequent (60% of G(S) strains in 1996). Resistance to erythromycin and lincomycin only was found in 70 G(S) isolates; this profile accounted for approximately half the isolates in 1992/1993 and only one-third in 1998. These results, obtained over an eight-year period, show an overall increase in antibiotic susceptibility. They confirm the spread of two major clones of MRSA-G(S) and support the hypotheses that G(S) strains derive from G(R) strains that have lost the aac6'-aph2" gene; and that G(S) strains are genetically related to those that were present before the use of gentamicin and persisted at a low frequency until 1992-1993.

Anti-Bacterial Agents↗