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PubMed1997

Comparison of five agents in protecting the cochlea against the ototoxic effects of cisplatin in the hamster.

The purpose of this investigation was to study the ameliorating effects of four agents on cisplatin-induced ototoxicity. Hamsters were given a series of five cisplatin injections either alone or in combination with sodium thiosulfate (STS), diethyldihydrothiocarbamate (DDTC), and S-2(3-aminopropylamino) ethylphosphorothioic acid (WR-2721), or fosfomycin. Ototoxicity was assessed anatomically by quantifying the extent of cochlear damage with the scanning electron microscope and physiologically with measures of the auditory brain stem response. When administered alone, cisplatin induced widespread loss of outer hair cells (OHCs) along much of the cochlea in the hamster, especially in the basal and middle turns, with an average survival of only 56% of the OHC population. In contrast, inner hair cells resisted cisplatin ototoxicity in the hamster. Thus the ameliorative effects of the different test agents were assessed by counting the number of surviving OHCs in each treatment group and comparing with cisplatin-treated controls. STS provided the most effective protection against the ototoxic effects of cisplatin, yielding 91% survival of OHCs. DDTC also reduced the ototoxic effects of cisplatin, yielding 68% survival of OHCs. Cotreatment with WR-2721 and fosfomycin yielded 45% and 52% OHC survival, respectively, and thus did not provide any chemoprotection. The results closely paralleled those based on auditory brain stem response recordings in that the magnitude of threshold shift was proportional to the amount of OHC loss; also, the amount of threshold shift at each frequency was in good agreement with the pattern of hair cell loss along the cochlear spiral. Thus both histologic and physiologic results suggest that STS and DDTC hold promise for ameliorating the ototoxic effects of cisplatin chemotherapy.

Amifostine↗

PubMed2001

Natural antibiotic susceptibility of strains of the Enterobacter cloacae complex.

The natural susceptibility to 70 antibiotics of 104 strains of the Enterobacter cloacae complex was examined using a microdilution procedure in Isosensitest broth. One hundred and one clinical strains designated as 'E. cloacae' were identified as E. hormaechei (n=65), E. asburiae (n=20) and E. cloacae genospecies 1 or 2 (n=16). Apart from fosfomycin susceptibility, there were only minor differences in natural antibiotic susceptibility patterns. All species were naturally sensitive or naturally sensitive and intermediate to numerous beta-lactams (e.g. carbapenems, aztreonam, acylaminopenicillins, ticarcillin, and some 'modern' cephalosporins), quinolones, aminoglycosides, tetracyclines, antifolates, chloramphenicol, and nitrofurantoin. Uniform natural resistance was found in benzylpenicillin, oxacillin, amoxycillin, amoxycillin/clavulanate, cefoxitin, rifampicin, lincosamides, glycopeptides, streptogramins and fusidic acid. Enterobacter hormaechei was the species most susceptible to fosfomycin. beta-Lactam susceptibility patterns pointed to the presence of chromosomally-encoded AmpC enzymes in all taxa of the E. cloacae complex.

Anti-Bacterial Agents↗

PubMed2003

Short term therapy for uncomplicated urinary tract infection today. Clinical outcome upholds the theories.

The clinical and bacteriological activity of fosfomycin trometamol (FT) has been compared with several other antibiotics in the treatment of uncomplicated urinary tract infections. A single dose of FT had activity comparable with a 5-day course of trimethoprim in a trial where the causative organism and its sensitivity were unknown. In another trial FT showed better long term eradication compared with a 5-day course of cephalexin and other studies suggested a single dose of FT was comparable with a 7-day course of nitrofurantoin or norfloxacin. There were few important side effects with fosfomycin therapy and it was considered a safe and effective first line treatment in uncomplicated urinary tract infection.

Anti-Bacterial Agents↗

PubMed1991

Effect of non-beta-lactam antibiotics on penicillin-binding protein synthesis of Enterococcus hirae ATCC 9790.

Fosfomycin, bacitracin and vancomycin in combination with penicillin exhibit a synergic effect against Enterococcus hirae ATCC 9790. This strain, when incubated in presence of the MIC of non-beta-lactam antibiotics, showed an alternated pattern of PBPs. Bacitracin and vancomycin caused a decrease in the density of all PBPs while fosfomycin only reduced that of PBP 6. It is suggested that the observed synergy is a consequence of the inhibition of PBP synthesis by antibiotics which act on the early stages of peptidoglycan synthesis prior to the formation of cross-links.

Bacitracin↗

PubMed1994

In-vitro antibacterial activity of fusidic acid alone and in combination with other antibiotics against methicillin-sensitive and -resistant Staphylococcus aureus.

The activity of fusidic acid alone and in combination with gentamicin, oxacillin, rifampicin, fosfomycin and ciprofloxacin was investigated against 36 strains of Staphylococcus aureus. The fusidic acid MIC50 of 0.06 mg/L and MIC90 of 0.125 mg/L were determined for 36 strains. Bactericidal activity of fusidic acid was confirmed. Several types of interaction were observed with other antibiotics: dominant effect of fusidic acid over gentamicin; synergy with rifampicin for three or four strains; indifference or dominance with oxacillin, indifference with vancomycin, indifference or dominance with fosfomycin, and indifference with ciprofloxacin. Antagonism was seen with only one strain, following exposure to fusidic acid and rifampicin.

Ciprofloxacin↗

PubMed2004

In vitro bactericidal activity of antimicrobial agents against enterohaemorrhagic Escherichia coli.

OBJECTIVES: In vitro bactericidal activity of four antimicrobial agents was determined against nine strains of enterohaemorrhagic Escherichia coli. METHODS: Pulsed-field gel electrophoresis was carried out with the Bio-Rad Gene Path system. Each antimicrobial agent was added to logarithmic phase of enterohaemorrhagic E. coli (four strains of E. coli O157:H7, two of E. coli O26, two of E. coli O111, and one of E. coli O165) in broth to obtain a concentration of 10 or 50 mg/L, and viable cells were counted after 1, 2, 6 and 24 h. RESULTS: All nine strains were confirmed to differ in their DNA pattern by pulsed-field gel electrophoresis. Norfloxacin at concentrations of 10 and 50 mg/L had bactericidal effects on all nine strains of enterohaemorrhagic E. coli. However, cefoperazone, kanamycin and fosfomycin had no bactericidal effects on some strains. In particular, after addition of 10 mg/L fosfomycin or kanamycin, four of the nine strains showed proliferation. CONCLUSIONS: Norfloxacin had marked bactericidal effects on enterohaemorrhagic E. coli. This information could be of value in planning randomized clinical trials of antimicrobial agents as treatment for enterohaemorrhagic E. coli infection.

Anti-Bacterial Agents↗

PubMed2006

Regulation of the homologous two-component systems KvgAS and KvhAS in Klebsiella pneumoniae CG43.

In Klebsiella pneumoniae CG43, deletion of the sensor gene kvgS reduced the kvgAS expression in M9 medium with 0.2 mM paraquat, 0.2 mM 2,2-dihydropyridyl, or 300 mM NaCl. This result shows an autoregulatory role of KvgS and a stress-responsive expression of the two-component system (2CS). The kvgS deletion also appeared to decrease the expression of kvhAS, paralogous genes of kvgAS. Additionally, measurements of the promoter activity in kvgA(-) mutant revealed that KvgA is probably an activator for the expression of kvgAS and kvhAS. The subsequent electrophoretic mobility shift assay, indicating a specific binding of the recombinant KvgA to the putative promoters P(kvgAS) and P(kvhAS), also supported an interacting regulation between the 2CSs. In P(kvgAS) and P(kvhAS), the presence of RpoS binding elements suggested an RpoS-dependent regulation. Nevertheless, the rpoS deletion reduced the expression of kvgAS but increased that of kvhAS. Moreover, the kvgA deletion reduced the expression of katG and sodC. The overexpression of KvhA altered the susceptibility to fosfomycin and an increasing activity of UDP-N-acetylglucosamine enolpyruvyl transferase, the target protein of fosfomycin, which suggesting a regulation by KvhA. Taken together, these indicated that the two 2CSs probably belong to different regulatory circuits of the RpoS regulon.

Amino Acid Sequence↗

PubMed2001

Effect of phosphate transporter and methylation inhibitor drugs on the disposition of arsenate and arsenite in rats.

Arsenate (AsV) is biotransformed into the more toxic arsenite (AsIII) and monomethylarsonous acid (MMAsIII), but it is unknown how to decrease production of these harmful metabolites. We investigated the effects of foscarnet and fosfomycin, drugs interacting with the phosphate transporter, on biotransformation of AsV, an analog of inorganic phosphate. The effects of entacapone, an inhibitor of catechol-O-methyl transferase (COMT), and nitrous oxide, an inactivator of methylcobalamin, were also tested on the formation of MMAsIII from AsIII in order to clarify the role of COMT and methylcobalamin in biomethylation of AsIII. Arsenic in bile and urine of control and treated rats receiving AsV or AsIII was speciated by HPLC-HG-AFS. In AsV-injected rats, foscarnet, but not fosfomycin, increased the urinary excretion of AsV and decreased the biliary and urinary excretion of AsIII as well as biliary excretion of MMAsIII. In AsIII-injected rats, however, foscarnet failed to influence the excretion of AsIII and its metabolites, suggesting that this drug inhibits the hepatic uptake and renal reabsorption of AsV, thereby decreasing formation of AsIII and MMAsIII from AsV. Entacapone or nitrous oxide pretreatment slightly or not at all influenced the biliary excretion of MMAsIII and urinary excretion of dimethylarsinic acid (DMAsV) in AsIII-injected rats. In contrast, periodate-oxidized adenosine, an inhibitor of S-adenosylmethionine-dependent methyltransferases, nearly abolished appearance of methylated arsenic metabolites in bile and urine. Thus, foscarnet facilitates urinary clearance of AsV and decreases formation of toxic AsIII and MMAsIII, indicating that this drug may be used to promote elimination and counter toxification of AsV. Because entacapone and nitrous oxide influenced the excretion of MMAsIII and DMAsV negligibly, neither COMT nor methylcobalamin appears to be involved in arsenic methylation in rats.

Arsenates↗

PubMed1998

[Result of antibiotic therapy for children with Escherichia coli O26:H11 infection].

Between the end of November 1996 and the beginning of March 1997, there was an outbreak of Escherichia coli O26:H11 infection in Asahikawa. The strain produced only verotoxin type 1. The minimal inhibitory concentrations (microgram/ml) of the strain under aerobic condition and those of anaerobic were as follows: chloramphenicol (1.56, 0.78), minocycline (12.5, 3.13), kanamycin (3.13, 25), ampicillin (> 100, > 100), fosfomycin (12.5, 1.56), norfloxacin (0.1, 0.1), and cefaclor (6.25, 3.13). Forty-one episodes of antibiotic therapy to 32 children, who were treated in Asahikawa Kosei Hospital, Asahikawa Municipal Hospital, and Asahikawa Red Cross Hospital, were evaluated bacteriologically. In 26 episodes treated with fosfomycin, the pathogen from stools of 19 were eradicated, 4 were not eradicated, and 3 were isolated again within 2 weeks after the cessation of therapy. Eight episodes treated with norfloxacin and 5 episodes in kanamycin were all eradicated.

Anti-Bacterial Agents↗

PubMed1991

Protective effect of elastase on cis-platinum-induced renal toxicity.

The protective effects of elastase (Ela) and fosfomycin against renal toxicity of cis-diamminedichloroplatinum (II) (CDDP) were evaluated in an experimental study using rats. When Ela was used concomitantly with CDDP, the elevation of urinary N-acetyl-beta-D-glucosaminidase levels in the early phase and the sharp fall in these levels in the latter phase were prevented. It was also found that the blood urea nitrogen levels and serum creatinine levels were significantly lowered. Histologically, atrophic and necrotic changes in the tubular epithelium were prevented. The total serum platinum levels showed no change with the addition of Ela; however, the platinum levels in the renal tissues were significantly reduced. These results suggested that Ela is effective against platinum deposits in the renal tissues, particularly in the tubular epithelium, thus protecting the kidneys. On the other hand, fosfomycin demonstrated no such positive results suggestive of a protective effect on the renal function parameters or during histological observation.

Acetylglucosaminidase↗

PubMed1987

The microbiological and pharmacokinetic profile of an antibacterial agent useful for the single-dose therapy of urinary tract infection.

Single-dose therapy of uncomplicated urinary tract infection (UTI) has been shown to be effective in many trials in adult women. The question which will be explored in this presentation is what properties constitute the ideal agent for the therapy of UTI. Important microbiological properties include spectrum of activity to include all common urinary pathogens, bactericidal action in urine and low prevalence of resistant bacteria. The vital feature of an antibacterial drug useful in the therapy of UTI is prolonged urinary concentrations. The agent must therefore be well absorbed and have slow renal excretion. Most beta-lactam drugs do not have these combined properties. Aminoglycosides are effective drugs but cannot be administered orally. Quinolones and the calcium salt of fosfomycin are useful but do not have an ideal pharmacokinetic profile. Cotrimoxazole, trimethoprim alone and the trometamol salt of fosfomycin all have good antibacterial activity combined with slow urinary excretion.

Aminoglycosides↗

PubMed2006

Biocompatability of hydroxyapatite composite as a local drug delivery system.

PURPOSE: To investigate the biocompatibility of hydroxyapatite composite (hydroxyapatite, plaster of Paris, and chitosan) impregnated with gentamicin, fosfomycin, imipenem, or amphotericin B. METHODS: The interactions of the extract from each drug against osteoblast were tested using the methylthiotetrazole test. RESULTS: Extracts from all drugs showed good biocompatibility at concentrations varying from 10 microgram/ml to 1000 microgram/ml. Imipenem and amphotericin B at a concentration of 1000 microgram/ml had a significantly higher percentage of cell viability than the control group. No morphological change of osteoblast was observed in all drug tests at any concentrations. CONCLUSION: The hydroxyapatite composite had a good biocompatibility for carrying gentamicin, fosfomycin, imipenem, or amphotericin B.

Amphotericin B↗

PubMed2003

Fosmidomycin resistance in adenylate cyclase deficient (cya) mutants of Escherichia coli.

Adenylate cyclase deficient (cya) mutants of E. coli K-12 were found to be resistant to fosmidomycin, a specific inhibitor of the non-mevalonate pathway, just like to fosfomycin. E. coli glpT mutants were resistant to fosfomycin and also to fosmidomycin. This fact shows that fosmidomycin was transported inside via the glycerol-3-phosphate transporter, GlpT. DNA micro-array analysis showed that the transcription of glpT and other genes concerning glycerol utilization were highly dependent on the presence of cAMP.

Adenylyl Cyclases↗

PubMed1990

Fosfadecin and fosfocytocin, new nucleotide antibiotics produced by bacteria.

Two new nucleotide antibiotics, fosfadecin and fosfocytocin, have been isolated from the culture filtrates of Pseudomonas viridiflava PK-5 and Pseudomonas fluorescens PK-52, respectively. These antibiotics were purified by column chromatographies using adsorption, gel filtration and ion exchange resins. On the basis of the spectroscopic and degradation studies, the chemical structures of fosfadecin and fosfocytocin were determined. These antibiotics were either enzymatically or chemically hydrolyzed to generate fosfomycin and a new antibiotic, fosfoxacin, which are also produced in the culture filtrates. They showed antibacterial activity against Gram-positive and Gram-negative bacteria. The antibacterial activity of these nucleotide antibiotics was weaker than that of fosfomycin and fosfoxacin.

Adenosine Diphosphate↗

PubMed2006

[Antimicrobial susceptibility and mechanism of resistance to antibiotics for Escherichia coli O157 and verotoxin-producing E. coli isolated in northern Kyushu and Yamaguchi area].

The purpose of this study was to investigate the biochemical characteristics and antimicrobial susceptibility of Escherichia (E.) coli O157 and verotoxin-producing E. coli isolates from the Northern Kyushu Island and Yamaguchi area of Japan. A total of 54 isolates- 50 E. coli O157, 3 verotoxin-producing E. coli O26 and 1 verotoxin-producing E. coli O111 - were used in this study. Regarding H antigen, H7 type in E. coli O157 accounted for 98% (49/50), and residual 1 strain of E. coli O157 was untypable H type. Two of 3 E. coli O26 isolates were H11 type, residual 1 strain of E. coli O26 was untypable H type, and E. coli O111 isolate was non-motile strain. All 54 isolates were susceptible to cephems, fosfomycin, kanamycin, amikacin and co-trimoxazole. Tetracycline-resistant isolates existed in 13 of all 54 isolates, 5 of those 13 isolates had tetA, and the other 7 isolates had tetB. Eight amoxicillin-resistant isolates had TEM-1 beta-lactamase. Four of the 5 isolates that had tetA also had TEM-1 beta-lactamase. Nalidixic acid and 6 fluoroquinolone used had no insensitive or resistant isolates. Kanamycin-resistant isolates, fosfomycin- and nalidixic acid-insensitive isolates have been reported, so we must notice the antibiogram of such strains. It is important that the surveillance of antimicrobial susceptibility of enterohemorragic E. coli should be continued after this.

Amoxicillin↗

PubMedDate not supplied

[Evaluation of antimicrobial drugs and atmospheres for the isolation of Campylobacter fetus subspp. from the bovine genital tract].

Growth of 3 reference bovine C. fetus strains in media with and without antibiotics and bacteriostats active against the most common contaminant bacteria in the bovine genital tract was evaluated. In addition, 2 regional bovine C. fetus strains and 1 reference C. sputorum biovar bubulus strain were used in some experiments. Reference strain C. fetus subsp. venerealis was completely inhibited by polymyxin (> or = 0.25 IU/ml) whereas the other C. fetus strains were not inhibited. In Shepler's medium supplemented with rifampicin (10 micrograms/ml) subsp. fetus, was the only one to grow. When rifampicin was used at 5 micrograms/ml together with a reduced dose of the other Shepler's antibiotics, especially polymyxin B (0.85 IU/ml), subsp. venerealis was able to grow; nevertheless even at such a reduced dose, rifampicin was inhibitory for the biotype intermedius. It was demonstrated that triclosan (Irgasan) could be very useful at < or = 10 micrograms/ml in media with added blood, < or = 6 micrograms/ml in brucella broth and < or = 3 micrograms/ml in Mueller-Hinton broth for isolation of all subspecies of C. fetus. The sensitivity of C. fetus to 5-fluorouracil was variable: subsp. fetus was resistant (up to 800 micrograms/ml) whereas subspp. venerealis and biotype intermedius grew slowly or sometimes did not grow at all in concentrations of 6.25 micrograms/ml onwards. Fosfomycin was inhibitory to all C. fetus strains at > or = 50 micrograms/ml. C. sputorum biovar. bubulus was less inhibited than C. fetus with triclosan grew up to more than 100 micrograms/ml, with 5-fluorouracil up to 100 micrograms/ml and with fosfomycin up to 50 micrograms/ml. Growth of C. fetus subspp. was compared in different microaerophilic atmospheres contained in anaerobic jars (Oxoid HP 11) without palladium catalyzer. Growth with nitrogen or hydrogen was similar. When jars were replaced by 15 x 13 cm cylindrical cans without valves or gas measurement devices only pure hydrogen supported satisfactory growth of all C. fetus subspp. and C. sputorum biovar. bubulus strains. The candle system, a commercial nitrogen rich gas mixture and pure carbonic anhydride prepared in these cans failed to enable these strains to grow. C. fetus subsp. fetus was more aero-tolerant than subsp. venerealis and its biotype intermedius and was able to grow, although very weakly, with only carbonic anhydride added to an aerobic atmosphere. The growth obtained using a commercial gas generating microaerophilic kit (Oxoid BR-56) was comparable to the one achieved with the hydrogen rich atmosphere prepared in our laboratory.

Agar↗

PubMed1991

[Importance of the antimicrobial mode of action of antibiotics for their combined effect with glycine in subinhibitory concentrations on microbial growth].

Following previous observations of an increase in microbial sensitivity to the bactericidal beta-lactams ampicillin and imipenem in the presence of glycine, the aim of the presented study was to examine if such an effect is due to the antimicrobial mode of action of an antibiotic and/or to its bactericidal or bacteriostatic capacity. Using growth curves as an experimental parameter the same synergistic glycine effect could be shown if tested concomitantly with a number of other antibiotics acting equally on bacterial cell wall formation as cefaclor, cefadroxil, or fosfomycin. This glycine effect is, therefore, associated with the antibiotic mode of action, but is independent of wether the antibiotics are beta-lactams or not (fosfomycin). In contrast, glycine had no particular effect in combination with antibiotics inhibiting protein synthesis (sisomicin, kanamycin, chloramphenicol, oxy-tetracycline) or nucleic acid polymerase activity (ciprofloxacin, cinoxacin; rifampicin being a certain exception) as well as with those acting on cytoplasmic and external membrane as polymyxin B. The synergistic effect of glycine and cell wall active antibiotics was interpreted predominantly by an action on carboxypeptidases.

Anti-Bacterial Agents↗

PubMed1990

Assessment of antimicrobial penetration into the pancreatic juice in dogs.

The pancreatic ductal penetration of piperacillin, cefuzonam, fosfomycin and netilmicin, injected intravenously, was studied in four dogs with chronic pancreatic fistula. Serum and pancreatic juice were collected simultaneously, frozen, and later assayed for antibiotic concentration. Each antibiotic achieved its therapeutic serum level. The pancreatic ductal levels of piperacillin and cefuzonam were therapeutic, in contrast, the fosfomycin and netilmicin levels were subtherapeutic. These results are considered to be of interest in prevention and treatment of pancreatic infections.

Animals↗