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 577 records · Page 32Linked to original sources
PubMed1994

[Laboratory and clinical study on combined effects of fosfomycin plus sulbactam/cefoperazone for mixed infections of MRSA and Pseudomonas aeruginosa].

Pseudomonas aeruginosa has been a major bacterial partner when MRSA (Methicillin-resistant Staphylococcus aureus) is isolated clinically. Hence, we studied the in vitro combined effect of fosfomycin (FOM) plus sulbactam/cefoperazone (SBT/CPZ) against mixed infections of MRSA and P. aeruginosa. The combined effect of FOM plus SBT/CPZ was observed through an FIC index using the checkerboard method, log reduction of colony counts on the time killing curve, and morphological changes observed using scanning electron micrography. Under serum concentration at 3 hours after administration in consider of pharmacokinetics, the combination effect was also evaluated. Furthermore, we evaluated a time-lag combination therapy in which FOM is administered 60 minutes before SBT/CPZ administration for mixed infections. Synergistic effects of FOM plus SBT/CPZ were clearly observed against mixed infections of MRSA and P. aeruginosa. Log reduction of colony counts on the time killing curve seemed to be an appropriate indicator in the evaluation of synergistic effects.

Aged↗
PubMed1993

[In vitro effects of combinations of antibiotics against highly-fosfomycin-resistant, methicillin-resistant Staphylococcus aureus. With special reference to efficacies of combinations of imipenem/cilastatin and cephems].

The author evaluated in vitro effects of combinations of antibiotics against 27 clinical isolates of highly-fosfomycin (FOM)-resistant, methicillin-resistant Staphylococcus aureus (MRSA). In combinations of FOM and cephems (CEPs), MICs of CEPs were decreased by FOM significantly, and synergistic effects were observed when the MIC of FOM was below 50 micrograms/ml. Combinations of imipenem/cilastatin (IPM/CS) and CEPs, however, was superior to those of FOM and CEPs in terms of synergistic effects. In these combinations, good synergism was found when the MIC of IPM/CS was below 25 micrograms/ml and those of CEPs were relatively low. In combinations of aminoglycoside and CEPs, no apparent synergism was observed. Most significant synergistic effect was achieved in the combination between IPM/CS and cefamandole. We believe that both fractional inhibitory concentration indices and achievement rates of effective serum concentrations should be taken into account to determine an effective combination of antibiotics.

Cephalosporins↗
PubMed1993

[Clinical evaluation of imipenem/cilastatin sodium and fosfomycin as second-line combination chemotherapy in severe infections associated with hematologic disorders].

Imipenem/cilastatin sodium (IPM/CS) which is a broad-spectrum agent against both Gram-positive and -negative bacteria was used in combination with fosfomycin (FOM) as a second-line chemotherapy for severe infections associated with hematologic disorders. FOM was partnered with IPM because FOM may enhance the bacteriocidal effects of IPM when given as pretreatment to IPM/CS therapy. Fifty two patients were treated with IPM/CS plus FOM. Of them, 41 were evaluated for effectiveness. Eleven patients were not evaluated: 4 were treated with a combination of other regimens such as cefixime, gamma-globulin, G-CSF and a large dose of methyl prednisolone; 2 were given IPM/CS plus FOM as a first choice; 3 were observed to have gastrointestinal side effects such as nausea which led to the discontinuation of the combination therapy; and 2 were thought to be suffering from not infectious but tumor fever. An excellent response was observed in 15 (36.6%) patients and a good response in 10 (24.4%), for a overall efficacy rate of 61.0%. Efficacies was 71.4% (5/7) in patients with sepsis, and 60.0% (9/15) in patients whose peripheral granulocyte count was below 100/microliters before chemotherapy. The elimination rates of Gram-positive and -negative bacteria were 57.1% (4/7) and 75.0% (6/8), respectively. In particular, 75.0% (3/4) of Pseudomonas aeruginosa identified were eliminated. Two patients who suffered from tumor fever, 2 who did not receive chemotherapy before the combination chemotherapy and 3 who did not receive a full course of the combination chemotherapy because of side effects, were included in the final evaluation of safety. Side effects were observed in 18 of 48 patients (37.5%). In 1 patient, skin eruption occurred 3 days after the initiation of the combination chemotherapy. In 17 patients, gastrointestinal symptoms such as nausea and vomiting were identified after a few days of IPM/CS plus FOM administration. Degree's of the symptoms were mild, however. Therefore, the treatment was not withdrawn. No abnormal laboratory results such as eosinophilia, liver disfunction or renal disfunction were observed. These results show that IPM/CS plus FOM is effective as a second-line combination chemotherapy for the treatment of severe infections in patients with hematologic disorders.

Adolescent↗
PubMed1993

[Activities of antibiotics against methicillin-resistant Staphylococcus aureus with particular reference to synergetic effect between ticarcillin and fosfomycin on penicillinase non-producing methicillin-resistant S. aureus].

We tested susceptibilities of 46 strains of clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) to arbekacin (ABK), tobramycin (TOB), ticarcillin (TIPC), clavulanic acid/ticarcillin (CVA/TIPC) and fosfomycin (FOM). Twelve strains had penicillinase activity. Most strains were resistant to TOB, TIPC, FOM and CVA/TIPC, but ABK inhibited 80% of the 46 MRSA strains at a concentration of 1.56 microgram/ml. The combination of ABK and FOM was indifferent. Synergism was observed, however, between FOM and TIPC against 79% of penicillinase non-producing MRSA. This synergism may mean that FOM inhibits the production of penicillin-binding protein 2' in some strains of penicillinase non-producing MRSA.

Bacterial Proteins↗
PubMed1993

Analysis of oral fosfomycin calcium (Fosmicin) side-effects after marketing.

For about 6 years after the marketing of oral formulations of fosfomycin calcium (FOM-Ca) in December, 1980, we collected the data on 35,481 cases and analyzed it regarding safety. Primary side-effects consisted mainly in gastrointestinal disturbances, damage to skin and adnexa, liver and bile duct disorders. Specifically, diarrhea, nausea, abdominal pain, anorexia, eruption and increased serum transaminase were frequent. Serious and newly detected side-effects after marketing were pseudomembranous colitis and melena, one case each. As for the oral administration of FOM-Ca to 83 patients hypertensive to beta-lactams, gastrointestinal side-effects were seen but none of them developed hypersensitivity, an allergic reaction.

Adolescent↗
PubMed1995

[Active transport of fosfomycin into cells of Escherichia coli, multidrug-resistant Pseudomonas aeruginosa and Staphylococcus aureus].

We examined effect of fosfomycin (FOM) on growth of Escherichia coli (E. coli) NIHJ JC-2, multidrug-resistant Pseudomonas aeruginosa (P. aeruginosa) PFS80 and Staphylococcus aureus (S. aureus) Smith. FOM inhibited the growth of these organisms at 0.1 approximately 0.5, 10 approximately 50 or 5 approximately 50 micrograms ml, respectively. In E. coli, FOM clearly lyzed the cells at 0.5 microgram/ml. These 3 bacteria incorporated radiolabeled FOM proportionately to incubation time. Intracellular concentration of FOM was estimated by considering the water content of E. coli cells. The ratio of intracellular to extracellular concentrations of FOM was larger than 1 after 5 approximately 10 min. incubation with FOM and reached about 7 after 40 min. FOM was incorporated actively into P. aeruginosa over extracellular concentration after 40-min. incubation on the basis of the above-mentioned water content. It was suggested that FOM was incorporated actively into various bacterial cells, and inhibited efficiently cell wall peptidoglycan synthesis, thus inhibited bacterial growth or lyzed the bacterial cells.

Anti-Bacterial Agents↗
PubMed1996

[Isolation and characterization of isogenic transductants related with the resistance from in vitro fosfomycin resistant strains].

The mutation sites in FR182 and FR190, which were selected as fosfomycin (FOM) resistant mutants in vitro from an Escherichia coli (E. coli) K-12 derivative, were found to be close to the 52 min. and the 85 min., respectively, on linkage map of E. coli K-12. Therefore, the site of mutation in FR182 appears to be ptsI and that in FR190 to be cyaA based on the physiological and biochemical characteristics. We isolated isogenic transductants from the FOM resistant strains (from FR182, resistant strain AMG3 and sensitive strain AMG4, and from FR190, resistant strain AMI5 and sensitive strain AMI6) by transducing the genes of the resistant strains into recipients that were deficient in alkaline phosphatase. Under anaerobic conditions, MICs in the isogenic transductants were all decreased and the resistant transductants showed similar FOM sensitivities to the respective sensitive transductants. The FOM resistant strains were clearly lysed by much lower concentrations of FOM in the presence of cyclic adenosine-3',5'-monophosphate (cAMP) or glucose 6-phosphate (G6P) than in their absence, but the extent of lysis was more pronounced when both cAMP and G6P were present together, resembling the lysis of sensitive strains in same condition.

Alkaline Phosphatase↗
PubMed1997

[Combination effect of fosfomycin to beta-lactam, aminoglycoside, and macrolide antibiotics against clinical isolates of Klebsiella pneumoniae].

It is well known that fosfomycin (FOM) shows the combination effects with some other antibiotics. Suck effects have not been known against Klebsiella pneumoniae, however. In this report, combination effects of FOM with beta-lactam, aminoglycoside, and macrolide antibiotics were investigated against clinical isolates of both FOM-susceptible and resistant Klebsiella pneumoniae. FOM had synergistic activities with beta-lactams such as ampicillin (ABPC) and cefminox (CMNX), and macrolide antibiotics as erythromycin (EM) and midecamycin (MDM) against all strains tested. Among beta-lactams, penicillin V showed synergistic actions against FOM-susceptible strain of Tf341A and additive actions against FOM-resistant 3 strains with FOM. Pheneticillin was synergistic with FOM against FOM-highly susceptible strain Tf341A and the additive or nearly synergistic effects against other strains. FOM with amoxicillin was synergistic against Tf341A, and FOM-resistant strain of Tf170B and additive against other strains. While the activities of combination of FOM with kanamycin or dibekacin against FOM-susceptible 2 strains were additive, those with amikacin were synergistic. Five different aminoglycosides tested showed antagonistic activities with FOM against 3 FOM-resistant strains. From these results, FOM appears to be clinically useful in treating FOM-susceptible and resistant strains of Klebsiella pneumoniae in combination of 4 antibiotics such as ABPC, CMNX, EM, and MDM.

Aminoglycosides↗
PubMed1999

Activities of beta-lactams, fluoroquinolones, amikacin and fosfomycin alone and in combination against Pseudomonas aeruginosa isolated from complicated urinary tract infections.

Using the checkerboard titration method as well as the time-kill curve technique, we investigated the activities of beta-lactams, fluoroquinolones, amikacin, and fosfomycin alone and in combination against Pseudomonas aeruginosa isolated from patients with complicated urinary tract infections. In the checkerboard titration studies, none of 21 combinations demonstrated antagonism against 26 strains tested, and the mean fractional inhibitory concentration (FIC) indices for these combinations ranged between 0.4694 and 0.9828. Corresponding to the respective FIC indices, the bactericidal activity determined in combinations of meropenem with ciprofloxacin or amikacin and ceftazidime with ciprofloxacin at sub-minimum inhibitory concentrations (MICs) produced a great reduction in bacterial counts (>/=2 log10 CFU/ml) within 6 h of administration against most of the strains, including strains resistant to one or both drugs, and these synergistic effects were confirmed morphologically by scanning electron microscopy. In time-lag combinations, the first administration of ciprofloxacin or amikacin supplemented by meropenem with 1-h lag diminished bactericidal activity, in comparison with the simultaneous administration of the drugs. These results suggest that simultaneous combinations of beta-lactams with fluoroquinolones or amikacin may be useful alternatives for the treatment of serious infections due to P. aeruginosa.

Journal Article↗
PubMed1990

Fosfomycin trometamol versus pipemidic acid in the treatment of bacteriuria in pregnancy.

The Italian multihospital study of bacteriuria in pregnancy randomized 153 pregnant bacteriuric patients to receive fosfomycin trometamol (FT) as a single dose of 3 g and 138 such patients to receive conventional therapy with pipemidic acid (PA), 400 mg b.i.d. for seven days. The two groups were well matched for age, parity, pregnancy course, symptoms and past history of cystitis. Infecting organisms were eradicated in 147 (96%) of FT and 129 (94%) of PA patients. Similar recurrence rates occurred. Minimal side effects (mostly nausea and dyspepsia) occurred (9%) FT; 15% PA). Single-dose FT appeared equivalent to conventional treatment with PA.

Adult↗
PubMed1990

The significance of timing of metronidazole prophylaxis and addition of fosfomycin in colorectal surgery. An experimental study in rats.

A novel approach to antibiotic prophylaxis in colonic surgery, suggested by our previous clinical experience, was experimentally tested. Intravenous administration of metronidazole or fosfomycin at greater than or equal to 4 hours before surgery effectively prevented lethal infectious complications, whereas metronidazole prophylaxis begun at induction of anaesthesia proved to be much less efficacious (4% and 43% deaths vs. 50% among controls, p less than 0.001 and p greater than 0.7, respectively). The in vivo efficacy of antibiotic prophylaxis correlated better with mucosal counts of Clostridium and Bacteroides than with luminal counts of aerobic or anaerobic bacteria. Earlier initiation of intravenous metronidazole prophylaxis thus markedly increased its in vivo efficacy, apparently due to preoperative mucosal suppression of endogenous potential pathogens. This 'early timing' approach to systemic prophylaxis against infection in abdominal surgery warrants further evaluation both for other antibiotics and clinically.

Animals↗
PubMed2000

Comparative X-ray analysis of the un-liganded fosfomycin-target murA.

MurA, an essential enzyme for the synthesis of the bacterial cell wall, follows an induced-fit mechanism. Upon substrate binding, the active site forms in the interdomain cleft, involving movements of the two domains of the protein and a reorientation of the loop Pro112-Pro121. We compare two structures of un-liganded MurA from Enterobacter cloacae: a new orthorhombic form, solved to 1.80 A resolution, and a monoclinic form, redetermined to 1.55 A resolution. In the monoclinic form, the loop Pro112-Pro121 stretches into solvent, while in the new form it adopts a winded conformation, thereby reducing solvent accessibility of the critical residue Cys115. In the interdomain cleft a network of 27 common water molecules has been identified, which partially shields negative charges in the cleft and stabilizes the orientation of catalytically crucial residues. This could support substrate binding and ease domain movements. Near the hinge region an isoaspartyl residue has been recognized, which is the product of post-translational modification of the genetically encoded Asn67-Gly68. The homogeneous population with L-isoaspartate in both structures suggests that the modification in Enterobacter cloacae MurA is not a mere aging defect but rather the result of a specific in vivo process.

Alkyl and Aryl Transferases↗