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S Ohya

Publications and source records attributed to S Ohya.

At least 73 records · Page 4Linked to original sources
PubMed1994

[An experimental examination of the significance of the peak antimicrobial concentration value in urine and time above MIC on the effect of antimicrobial agents--an examination using a severely complicated in vitro bladder model with an autosimulation system for antimicrobial concentration in urine].

Using a severely complicated in vitro bladder model with a computer-controlled autosimulation system for antimicrobial concentration in urine, we examined the significance of the peak concentration value and time above MIC, and obtained the following results. 1. Regarding the initial bactericidal speed, the higher the peak concentration value was, the more quickly the bacterial concentration decreased. 2. Concerning the minimum value of bacterial concentration in the model bladder, the higher the peak concentration value was, the more the level tended to decrease. 3. Regarding inhibition of regrowth of bacteria (ERT) 1) When a particular antimicrobial agent had no PAE on bacteria, the viable bacterial count curve was similar in cases of peak antimicrobial concentration values of higher than 8 MIC. 2) On the other hand, when an antimicrobial agent had PAE on bacteria, regrowth of bacteria occurred quickly below a certain peak concentration (24 MIC or 64 MIC value), although there was some difference depending on the type of antimicrobial agents. Thus, it was suggested that the peak concentration above that level be attained and maintration above that level be attained and maintained for some time were in order to obtain PAE adequately. 4. It is concluded from the aforementioned facts that two factors, a certain high concentration and a certain continued time are necessary for both antimicrobial agent with metabolic disorder and antimicrobial agent with cell wall synthetic inhibition to obtain proper antimicrobial effect. The condition of their necessity differed slightly according to the two different agents.

Adult↗
PubMed1994

[Study on MIC breakpoint and method of antimicrobial chemotherapy for moderately complicated urinary tract infection--study using an automatic simulator of urinary antimicrobial agent concentrations].

We experimentally investigated an efficient administrating method of antimicribials prior to the clinical treatment of complicated urinary tract infection without catheter. An experimental model of moderately complicated urinary tract infection, which can simulate changes in the urinary concentration of antimicrobials by means of previously reported computer control method, was used for the experiment. The following results were obtained. 1. At first, for complicated UTI cases without an indwelling catheter, an investigation was made of the clinical therapy results to determine the upper MIC range of bacteria, including isolated strains, that can be nearly eliminated following treatment, by the administration method. We then estimated the clinical breakpoint. 2. By adjusting the size of the diverticulum in a urinary bladder model, we prepared a model which gave comparatively good agreement between the clinical and experimental breakpoints. 3. The clinical therapy results revealed that by the clinical breakpoint was higher in degree of coverage of the MIC distribution of causative bacteria associated with a higher actual clinical elimination rate and a higher efficacy rate. 4. It was surmised that an efficient administration method for complicated UTI without an indwelling catheter can be established if the urinary bladder model and the following approach are applied: prior to clinical treatment it should be determined what would be high enough to cover 70% of the MIC distribution of the estimated causative bacteria of UTI, and then an administration method which would yield that concentration as the experimental breakpoint should be devised.

Anti-Bacterial Agents↗
PubMed1994

[Therapeutic study on biofilm of the urinary tract using a severely complicated bladder model (biofilm model of the urinary tract)--experimental study using an automatic simulator of urinary antimicrobial agent concentration, and clinical study].

For the purpose of conducting a therapeutic study on biofilm of the urinary tract, we devised a computer-controlled severely complicated bladder model (biofilm model of the urinary tract) enabling us to simulate the time-course of the concentration of antimicrobial agents in the urine. Using this model, we investigated clarithromycin (CAM), which has been reported to have anti-biofilm action, at concentrations close to its urinary levels at the time of clinical use in order to predict its effect on biofilm of the urinary tract. On the basis of those experimental results, we also conducted a clinical examination. The following results were obtained. 1. The action of ciprofloxacin (CPFX, MIC: 8 micrograms/ml) alone, which shows anti-P. aeruginosa activity, caused apparent elimination of P. aeruginosa from the model. However, regrowth of the microbes occurred when CPFX was removed from the bladder model. Moreover, the biofilm was not eliminated by the antimicrobial action of CPFX, and this was surmised to be the cause of the regrowth. 2. CAM (MIC: above 128 micrograms/ml), which has no anti-P. aeruginosa activity, was similarly tested as anti-biofilm agent when added alone to the biofilm model. The P. aeruginosa recovered to its initial concentration within 48 hours, but the biofilm disappeared due to the action of CAM. 3. The combined action of CPFX and CAM caused microbial elimination from the bladder model without microbial regrowth, even after these antimicrobial agents were removed from the bladder model. After the action of CPFX and CAM, the biofilm disappeared, and no microbial adherence was noted. 4. Measurement of time-course of the alginate content, which is the main component of P. aeruginosa biofilm, in the presence of CAM found that the alginate content decreased below the limit of detection after day 5. 5. The clinical study of complicated urinary tract infection revealed the microbial elimination rate and the efficacy rate to be higher in the combined CPFX-CAM administration group than in the CPFX-only administration group. 6. Based on the above results, we surmise that the combined use of an antimicrobial agent which is active against the causative microbe and anti-biofilm agent such as CAM will show some degree of efficacy in eliminating biofilm of the urinary tract.

Ciprofloxacin↗
PubMed1994

[Adaptation study for biofilm of the urinary tract via highly complicated bladder model (biofilm model of the urinary tract)--experimental study using automatic simulator of the urinary antimicrobial agent concentration].

With the view of making an adaptation study for biofilm of the urinary tract, we devised a computer-controlled highly complicated bladder model (biofilm model of the urinary tract) that allowed the simulation of time-course changes in the urinary concentration of antimicrobial agents. Clarithromycin (CAM), which is reported to have an anti-biofilm action, was examined at urinary levels approximating clinical concentrations and its effect on biofilm was determined. The following results were obtained. 1) Ofloxacin (OFLX, 200 mg x 2/day, MIC; 8 micrograms/ml), which is active against Pseudomonas aruginosa, caused apparent microbial elimination from the model at 42 hours, but bacterial regrowth occurred 4 hours after withdrawal of this agent. No disappearance of the biofilm was noted with OFLX suggesting that this was the cause of bacterial regrowth. 2) The combination of OFLX (200 mg x 2/day) and CAM (MIC; > 128 micrograms/ml, 200 mg x 2/day) on anti-biofilm agent, with no effect on P. aeruginosa, eliminated bacteria from the bladder model more rapidly and prolonged the regrowth time to 10 hours after withdrawal of the antimicrobial agents. Disappearance of most of the biofilm and only slight microbial adhesion was noted. 3) The combination of OFLX (200 mg x 2/day) and CAM (400 mg x 3/day) caused microbial elimination from the bladder model with no regrowth at 30 hours after withdrawal of the antimicrobial agents. The biofilm disappeared completely and no microbial adhesion was noted. 4) CAM alone (400 mg x 3/day) allowed microbial recovery to the initial level within 48 hours after withdrawal, but led to disappearance of the biofilm and the adhesion of microbes without a glycocalyx. 5) These results suggest that the anti-biofilm action of CAM is dose-dependent, and that combined use of an appropriate antimicrobial agent and anti-biofilm agent like CAM may be effective for biofilm infections of the urinary tract.

Anti-Bacterial Agents↗
PubMed1993

Activity of the carbapenem panipenem and role of the OprD (D2) protein in its diffusion through the Pseudomonas aeruginosa outer membrane.

Evidence of permeation of panipenem through the OprD (D2) channel of Pseudomonas aeruginosa outer membrane was shown by using OprD protein-producing and -nonproducing strains which contained plasmid pHN4, which codes for L-1 beta-lactamase of Xanthomonas maltophilia. Permeation by panipenem was determined by measuring hydrolysis of the carbapenem by beta-lactamase in the periplasmic space. Permeation by panipenem was also determined by counting uptake of [14C]panipenem into P. aeruginosa PAO1 and its OprD protein-deficient mutant, and this permeation of PAO1 was inhibited by L-lysine. These results indicate that panipenem, as well as imipenem, uses the OprD channel, which functions as a specific channel for diffusion of basic amino acids. Panipenem and imipenem showed stronger activities against PAO1 and clinical isolates in human serum than in Mueller-Hinton broth, which contains more amino acids than human serum does. The activities of the carbapenems were reduced by addition of L-lysine to human serum. Similar results were obtained with mouse serum and ascitic fluid. In contrast, such a change in the activities of carbapenems was not observed with an OprD protein-deficient mutant, suggesting that the main reason for the strong activities of carbapenems in biological fluids is a decrease in competition between the antibiotics and basic amino acids for permeation through the OprD channel. Panipenem and imipenem showed much stronger therapeutic efficacies against experimental infections with P. aeruginosa in mice than did the reference antibiotics. Their in vivo activities were more consistent with their MICs in biological fluids than with those in Mueller-Hinton broth.

Animals↗
PubMed1992

[A clinical study on postantibiotic effect (PAE) and its application to chemotherapy for complicated cystitis with an automatic simulator of urinary drug concentration].

In an in vitro complicated cystitis model, the concentrations of the urinary antimicrobial agents were determined using a computer-controlled automatic urine concentration simulator. The effects on the bacterial count curves showing the presence or absence of PAE in antimicrobial agents were studied by comparing the times required for regrowth to the concentration at the initial inoculation, i.e., effective regrowth time (ERT). The following results were obtained. 1. When beta-lactam antimicrobial agents (such as AMPC and CFIX) with no PAE against the gram-negative rods were tested, the ERT of the gram-negative rods were about two hours shorter than that of the gram-positive coccus. 2. When new quinolone antimicrobial agents (such as OFLX) and aminoglycosides (such as ISP) that possess PAE against both the gram-positive and negative organisms were used there was no difference between ERT of the gram-negative rods and gram-positive coccus. Therefore, it was demonstrated that the presence or absence of PAE is also reflected in the cell number curve in the case of this in vitro model, more closely related to clinical cases, when the antibiotics is simulated in urinary concentration shifting.

Amoxicillin↗
PubMed1992

[Significance of the combined treatment with isepamicin and piperacillin in an in vitro model for complicated cystitis operated by automatic simulator apparatus for urinary concentration].

Isepamicin (ISP) and piperacillin (PIPC) were shifted to the urinary concentration by employing an in vitro complicated cystitis model operated by a computer-controlled automatic simulator for urinary concentration, and administrated to bacteria in the urinary bladder model (Pseudomonas aeruginosa: P. aeruginosa, initial cell concentration: 10(7) cfu/ml). In this case, effects by single treatment with ISP or PIPC on cell number curves were examined. Further, significance of the combined treatment with ISP and PIPC were investigated by changing the order of each treatment. And following the results were obtained. 1. In a single treatment with PIPC the cell concentration was minimum (10(4) cfu/ml) at 9th hour after its treatment and thereafter, regrowth to the same level as the initial concentration was observed at 16th hour. 2. In the case of single treatment with ISP, the cell concentration became minimum (10(2) cfu/ml) at 13th hour after the treatment and raised to the same concentration as the initial one at 25th hour. 3. In the combined treatment, the cell concentration was minimum (less than 10(1) cfu/ml) at 26th hour in the case of prior treatment with ISP. Thereafter, regrowth was observed and the cell concentration at 42nd hour reached to the initial cell concentration. 4. In simultaneous treatment with ISP and PIPC, the cell concentration at 24th hour was minimum (10(1) cfu/ml) and reached to the same level as the initial one after regrowth. From these results, it was found that the combined treatment with ISP and PIPC caused more reduction of the cell concentration than either single treatment. Further, regrowth of the cells was suppressed for longer duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Simulation↗
PubMed1992

Cross-resistance to meropenem, cephems, and quinolones in Pseudomonas aeruginosa.

Multiple-drug-resistant mutants were isolated from Pseudomonas aeruginosa PAO1 on agar plates containing ofloxacin and cefsulodin. These mutants were four to eight times more resistant to meropenem, cephems, carbenicillin, quinolones, tetracycline, and chloramphenicol than the parent strain was. In contrast, these mutants showed no significant changes in their susceptibilities to all carbapenems except meropenem. In these mutants, the amounts of an outer membrane protein with an apparent molecular weight of 49,000 (designated OprM) were increased compared with the amount in PAO1. Multiple-drug-resistant mutants of this type were also isolated from PAO1 on agar plates containing meropenem. Approximately 5% of clinical isolates showed cross-resistance to meropenem, cephems, and quinolones, concomitant with overproduction of OprM. Moreover, these two phenotypes, i.e., multiple-drug resistance and overproduction of OprM, were cotransferable by transduction. These data suggest that overproduction of OprM is associated with cross-resistance to meropenem, cephems, and quinolones in P. aeruginosa. The ofloxacin-cefsulodin-resistant mutant required higher concentrations of meropenem to induce beta-lactamase than PAO1 did, indicating the possibility that this mutation involves decreased outer membrane permeability to meropenem.

Anti-Bacterial Agents↗
PubMed1991

beta-Lactamase produced by a highly beta-lactam-resistant strain of Bacteroides fragilis: an obstacle to the chemotherapy of experimental mixed infections.

A strain of Bacteroides fragilis, which produces a metallo-beta-lactamase, was inoculated into pouches on the backs of rats together with a beta-lactamase-negative Escherichia coli highly sensitive to beta-lactam antibiotics. The mixed infection rat pouch model was treated with either flomoxef (susceptible to hydrolysis by the beta-lactamase produced by B. fragilis), or cefmetazole (relatively resistant to hydrolysis). In this model of mixed infection flomoxef showed weak in-vivo activity against E. coli, although showing the same strong activity in a model of single infection with E. coli. On the other hand, cefmetazole showed strong activity against E. coli, even in the model of mixed infection. The concentrations of both drugs in the pouches were decreased in infections with the strain of B. fragilis. There was a greater decrease in the concentration of flomoxef than of cefmetazole. Flomoxef was unstable whereas cefmetazole was relatively stable in the pouch exudates that had been infected with B. fragilis. These experimental data suggest that bacteria that produce a metallo-beta-lactamase decrease the in-vivo efficacy of beta-lactam antibiotics against other co-infecting bacteria. Thus, it is suggested that it is important in the chemotherapy of mixed bacterial infections that include these highly resistant beta-lactamase-producing bacteria to use antibiotics that are stable to hydrolysis by these enzymes.

Animals↗
PubMed1991

Increase in susceptibility of Pseudomonas aeruginosa to carbapenem antibiotics in low-amino-acid media.

The in vitro susceptibility of Pseudomonas aeruginosa PAO1 to carbapenem antibiotics, such as CS-533, was influenced by various concentrations of basic amino acids, i.e., L-lysine, L-histidine, and L-arginine, in agar media. P. aeruginosa PAO1 showed higher susceptibility to carbapenems in minimal medium than it did in rich media such as Mueller-Hinton II agar. The susceptibility was decreased by the addition of a basic amino acid to the minimal medium, whereas it was influenced less by other amino acids. The susceptibility of PAO1 to cephalosporins, piperacillin, quinolones, and gentamicin was not influenced by the addition of a basic amino acid to the minimal medium. A significant change in susceptibility to carbapenems by the addition of a basic amino acid was not observed with D2 protein-deficient mutants of PAO1. Clinical isolates of P. aeruginosa also showed an increase in susceptibility in minimal medium. L-Lysine in minimal medium did not have any influence on the production of D2 protein, beta-lactamases, or penicillin-binding proteins of PAO1 or on the chemical degradation of CS-533. These results strongly indicate that the increase in susceptibility of P. aeruginosa to carbapenems relates to less competition with basic amino acids for permeation through the D2 protein channel of P. aeruginosa.

Agar↗
PubMed1990

[An in vitro study on the treatment of complicated cystitis using an automatic simulator].

A computer simulation of a Kidney-bladder model was prepared for automatic control of the urine concentration of antibacterial drug administrated. The following results were obtained in an investigation of the problems of complicated cystitis in vitro using ofloxacin. 1) It was suggested that the time required for elimination of the bacteria was prolonged as the level of complication of the disease state in the urinary tract increased. 2) In the model of highly complicated cystitis caused by urinary flow stagnation, recurrences were observed in vitro even with administration of a large dose of ofloxacin. 3) The time required for a elimination of bacteria tended to become shorter as the dose of the antibacterial agent increased. 4) The time until the start of regrowth of the bacteria tended to be prolonged as the dose of the antibacterial agent increased. 5) It was suggested by our in vitro experiment that if the background disease became more complicated, it would be more difficult to treat, as in the case of complicated cystitis.

Computer Simulation↗
PubMed1986

Antibacterial activity of cefmetazole alone and in combination with fosfomycin against methicillin- and cephem-resistant Staphylococcus aureus.

In vitro and in vivo antibacterial activities of cefmetazole alone and in combination with fosfomycin against methicillin- and cephem-resistant (MR) strains of Staphylococcus aureus were investigated, and the mechanism of synergistic effect between cefmetazole and fosfomycin was also studied. Cefmetazole inhibited the growth of 71 strains of MR S. aureus at concentrations ranging from 1.56 to 50 micrograms/ml; the antibacterial activity of cefmetazole against these strains was enhanced approximately 4 times with the addition of fosfomycin at a concentration of 1.56 micrograms/ml. The binding affinity of cefmetazole for the penicillin-binding protein 2' fraction specific for MR S. aureus was higher than that of methicillin, cloxacillin, cefazolin, and cefotaxime. A synergy experiment in vitro was performed by checkerboard titration with Mueller-Hinton agar plates containing various concentrations and ratios of cefmetazole and fosfomycin. The fractional inhibitory concentration index ranged from 0.09 to 0.75. Exposure of cefmetazole plus fosfomycin to exponentially growing cultures at a concentration at which both antibiotics had no bactericidal effect when given alone exerted bactericidal action. Combined administration of cefmetazole with fosfomycin at a ratio of 1:1 against systemic MR S. aureus infections with mice showed an excellent therapeutic efficacy as compared with administration of either antibiotic alone. Penicillin-binding protein 2', 2, and 4 fractions were scarcely detectable in MR S. aureus strains grown in the presence of fosfomycin at concentrations of 0.25 MIC and 0.5 MIC, respectively.

Animals↗