Fosfomycin Research Articles

Bactericidal activity of cefotaxime and fosfomycin in cerebrospinal fluid during the treatment of rabbit meningitis experimentally induced by methicillin-resistant Staphylococcus aureus.

The purpose of this study was to evaluate the therapeutic effect of cefotaxime (CTX) and fosfomycin (FOS), alone or in combination, in an experimental meningitis, with cerebrospinal fluid (CSF) concentrations of the two antibiotics reproducing those obtained in human CSF during bacterial meningitis. With a dose of 50 mg/kg of CTX and 100 mg/kg of FOS injected i.v. (CTX over 0.5 h and FOS over 3 h), CSF concentrations were comparable to those observed in man. In a series of five rabbits per treatment group, the bacterial population was counted before and after treatment (two doses with a six-hour interval) with CTX, FOS or CTX + FOS (CTX over 0.5 h before the end of FOS infusion). By the 12th hour of treatment, the percentage of bacteria surviving in CSF compared to the initial population was 4.35% for CTX, 0.20% for FOS and 0.19% for CTX + FOS. Thus, it seemed that CTX + FOS was not more active than FOS alone. In another series of four rabbits per group, the bactericidal effect was followed at T0, T6, T12, T24 and T48 after treatment (two doses with a six-hour with a six-hour interval). With CTX, a variable drop in bacterial count from one rabbit to the other occurred during the first 12 h, and then a bacteriostasis followed. With FOS, a quick bactericidal effect was observed during the first 12 h, becoming slower during the following 36 h (0.03% of bacteria surviving at the 48th hour). With CTX and FOS in combination, a quick bactericidal effect was achieved, remaining steady over a 48-hour period (0.001% of bacteria surviving at the 48th hour).

Experimental and Pathological Study of the Safety of Fosfomycin (FOM) Otic Solution on the Cochlear Organ

Experimental and Pathological Study of the Safety of Fosfomycin (FOM) Otic Solution on the Cochlear Organ

Mechanism of Protective Effect of Fosfomycin Against Aminoglycoside Ototoxicity

The purpose of this study was to clarify the mechanism of the protective effect of fosfomycin (FOM) against inner ear damage induced by an aminoglycoside dibekacin (DKB), when administered concurrently DKB and FOM. Rats were treated with 50 mg/kg of DKB with or without 500 mg/kg of FOM for short-term administration. No significant difference was seen in the serum peak level and in the area under the curve between the group receiving DKB alone and the combined administration group of DKB and FOM. On the other hand, the DKB level in the kidney was significantly lower in the combined administration group than in the group receiving DKB alone. The mechanism of protective effect of FOM against DKB-induced ototoxicity may be considered as follows: FOM inhibits the accumulation of DKB in the kidney and reduces its concentration in the kidney and serum. Consequently, the transferability of DKB into the inner ear is decreased, and finally inner ear damage is reduced.

Protective Effect of Fosfomycin against Cisplatin-induced Ototoxicity in Rats

Protective Effect of Fosfomycin against Cisplatin-induced Ototoxicity in Rats

アミノ配糖抗生剤による聴器障害に対するＦｏｓｆｏｍｙｃｉｎの軽減作用とその機序に関する研究

The influence of Fosfomycin (FOM) on inner ear and renal damage due to Dibekacin(DKB) was investigated using Fischer 344 rats as the experimental animals. DKB (100mg/kg/dayor 50mg/kg/day) was administered in single daily either alone or in combination with 500mg/kg/day of FOM for 60 or 120 consecutive days. Four hours after the last injection the animalswere decapitated and the DKB levels of serum, kidney and perilymph were measured by the bioassay method. Using the surface preparation technique the hair cell damage of the inner ear was examined by means of a phase contrast microscope. The renal damage was examined with a light microscope. Renal function parameters, BUN, urinary NAG activity and urinary protein, were measured. DKB levels of the serum and kidneys were also observed after the first and fifth injection of DKB (50mg/kg) alone and in combination with FOM (500mg/kg). The results were as follows. 1. The hair cell damage and renal damage including both histological and functional damage due to DKB were reduced by combined administration with FOM. 2. When administered in combination with FOM, the DKB levels of the serum, kidneys and perilymph after 60 or 120 injections were lower than when DKB was administered alone. 3. After the first and fifth injection the serum DKB levels were not significantly different between the two groups but the kidney DKB levels after the fifth injection were lower in the animals receiving FOM, although the accumulation of DKB was observed in both groups.It is thought that the protective effect of FOM against DKB induced ototoxicity is related to the concentration of DKB in the kidneys, serum and perilymph. The decrease of the concentration of DKB was attributed to FOM's inhibition of the accumulation of DKB in the kidneys and not to the acceleration of DKB excretion from the kidneys by FOM.It is concluded that this combined administration first inhibits the accumulation of DKB in the kidneys and then decreases the serum and perilymph DKB levels, resulting in a subsequent reduction in inner ear damage.

203 cases of Campylobacter jejuni enteritis

Out of 1, 219 pediatric patients who were brought to our hospital with chief complaint of diarrhea and abdominal pain and in whom stool cultures were obtained for bacteriological studies in the 17 month period from May 1 in 1981 to September 30 in 1982, strains of Campylobacter jejuni were isolated from 203 patients (16.7%).In these patients clinical studies and statistical analysis were made. It was found that clinical symptoms of Campylobacter jejuni enteritis did not give any important clue for its differentiation from bacterial diarrhea. Antibiotic susceptibility tests revealed extremely high susceptibility of Campylobacter jejuni to fosfomycin (FOM) as well as erythromycin. Moreover, the effect of FOM on improvement of diarrheal symptoms and the period required for erradication of organisms were assessed with favourable results. However, since among strains of Campylobacter jejuni there were those resistant even to these drugs, although their incidence was very low, it was considered that isolation and susceptibility testing of Campylobacter jejuni were essential for treating enteritis caused by this species of organism.

Synergistic effects of a macrolide and a cell wall-affecting antibiotic on Pseudomonas aeruginosa in vitro and in vivo. 2. Combined effects of a macrolide with a fosfomycin and an aminoglycoside antibiotic.

Synergistic effects of the cell wall-affecting antibiotics, dibekacin (DKB) and fosfomycin (FOM) and a macrolide antibiotic, midecamycin (MDM) or its derivative 9,3"-di-O-acetylmidecamycin (MOM) against Pseudomonas aeruginosa were investigated in vitro and in vivo. Synergistic effects were evaluated by estimating the number of viable bacteria at varying intervals after the two kinds of antibiotics were added to the logarithmic phase of the bacterial solution. Six hours after addition of antibiotic, the viable bacterial count of the culture treated with FOM and MOM underwent 2 log reduction compared to that which treated with FOM alone. Thus synergistic effect was significant. The number of viable bacteria treated with DKB and MDM showed slight reduction at 3 hours after addition of the two antibiotics and a marked reduction was noted after 20 hours compared with the control. Synergistic action was also demonstrated in in vivo experiments using mice. Three experimental mouse infection models, intraperitoneal infection, subcutaneous infection with carrageenan solution and burn infection were used. FOM was administered subcutaneously. DKB was administered intramuscularly. MDM or MOM was administered by the oral route. In all three experiments the survival rate of infected mice treated with FOM and MOM increased significantly compared to control mice. Similar synergistic effect was also obtained with DKB and MDM.

Two kinds of mutants defective in multiple carbohydrate utilization isolated from in vitro fosfomycin-resistant strains of Escherichia coli K-12.

Two types of in vitro fosfomycin-resistant mutants defective in multiple carbohydrate utilization were selected from Escherichia coli strain K--12. One mutant, FR182, was defective in phosphoenolpyruvate: sugar phosphotransferase system and the ability to form adenosine 3',5'-cyclic monophosphate (cAMP) was lowered. Another mutant, FR190, was defective in cAMP formation. Restoration by cAMP of fosfomycin (FOM) sensitivity coupled with recovery of utilization of many carbohydrates including sn-glycerol-3-phosphate (G-3-P) was observed in both of the resistant mutants. FOM was not taken up by these resistant strains but, in the cells cultured in the presence of cAMP, accumulation of FOM was equivalent to that of the sensitive parent strain. Decreased uptake of G-3-P was also restored in both of the resistant strains cultured in the presence of cAMP. These results indicate that the resistance to FOM in these mutants is due to impairment of G-3-P transport system, one of the pathways for uptake of FOM. They were sensitized to FOM by D-glucose-6-phosphate because of the induction of hexose phosphate transport system, another uptake pathway.