[Antibacterial activity of fosfomycin against the causative bacteria isolated from bacterial enteritis].

The in vitro antibacterial activities of fosfomycin (FOM) and 3 fluoroquinolones against Salmonella spp., pathogenic Escherichia coli, Campylobacter spp. and Shigella spp. were investigated. The activity upon the environmental condition in the inflammation was compared with standard condition in vitro. On standard condition, the MIC90 of tosfloxacin (TFLX), norfloxacin (NFLX) and levofloxacin (LVFX) against E. coli (77 strains), Shigella spp. (50) and Salmonella spp. (41) were < or = 0.025-0.10, 0.10, and 0.05 microgram/ml, respectively. The MIC90 of FOM against those organisms was 0.39-1.56 micrograms/ml. The MIC90 of TFLX, NFLX, LVFX against Campylobacter spp. were 6.25, 100 and 3.13 micrograms/ml, respectively. The MIC90 of FOM was 50 micrograms/ml. The activity of FOM was unaffected by pH and in anaerobic condition. On the other hand, the activity of NFLX was decreased in low pH and in anaerobic condition. In the presence of horse blood and addition of Na+, the activities of both agents were unaffected. These results suggested that FOM is equally active with or superior to fluoroquinolone in the intestinal infection treatment.

[Study on the verotoxin-producing Escherichia coli--isolation of the bacteria from deer dung].

To identify the source and route of verotoxin-producing Escherichia coli (VTEC) infection in humans, we tried to isolate VTEC from fresh deer dung collected from free-range animals in two parks during the period from August 1997 to January 1998. The results are presented below. 1) VTEC were isolated from 21 of 200 deer dung samples (10.5%), consisting of 15 of 100 samples (15.0%) collected in park A and 6 of 100 samples (6.0%) collected in park B, suggesting that the incidence of VTEC isolation differs depending on location. 2) With respect to typing of verotoxin, the 21 isolated VTEC strains consisted of 10 strains (47.6%) as VT1 producer, 5 strains (23.8%) as VT2 producer, and 6 strains (28.6%) as double producer of both types. 3) With respect to serogroup of the isolated VTEC strains, 2 strains belonged to O128:H2.1 strain each belonged to the O8:H10, O128:H12, and O169:HUT groups. The remaining 16 strains failed to be identified as particular serotypes. Regarding local distribution of the serotype, in park A, 1 strain each belonged to the O128:H2, O8:H10, and O169:HUT groups. The remaining 12 strains did not clearly show particular serotypes. In park B, 2 strains belonged to O128:H2, and 4 strains failed to show particular serotypes. The remaining 1 strains showed autoagglutination. In conclusion, we isolated VTEC strains from deer that showed types of toxin and serogroups identical to those of human VTEC. Therefore, VTEC found in deer dung could well be a source of VTEC-infectious diseases in humans.

[A case of bacillary dysentery caused by new quinolone-resistant Shigella flexneri 2a].

A 73-year-old male was admitted to our hospital because of detection of Shigella flexneri 2a from his stool. Antimicrobial treatment with levofloxacin (LVFX) was started, but could not eliminate the organism in the stool. In the examination of drug susceptibility, this strain was highly resistant to all new quinolones. The minimal inhibitory concentration of norfloxacin, ofloxacin and ciprofloxacin to this strain was 12.5 micrograms/ml, 6.25 micrograms/ml and 6.25 micrograms/ml, respectively. The dual mutations were detected in the codon 83 and 87 of the gyrA gene by sequencing the quinolone-resistance determining region (QRDR). There was, however, no significant difference between the intracellular uptake of ciprofloxacin in this strain and in the ciprofloxacin-sensitive strain. The amount of ciprofloxacin in this strain unchanged when carbonyl cyanide m-chlorophenyl hydrazone (CCCP) was added. These results suggest that the advanced resistance in Shigella flexneri against new quinolones could be acquired by only this dual mutations without the change of the active efflux mechanism.

[Mechanism of resistance of Shigella flexneri 2a resistant to new quinolone antibiotics].

A Shigella flexneri 2a strain, which did not respond clinically or in laboratory tests to treatment with new quinolone derivatives, was isolated for the first time in Japan from a patient admitted for diarrhea to a Tokyo hospital. The mechanism of resistance was examined by sequencing the quinolone resistance determining region (QRDR) of the gyrA (a quinolone target enzyme) gene and by comparing the active efflux mechanisms of two strains isolated from this patient (before hospitalization and after tosufloxacin treatment) and one strain isolated from a patient with secondary infection with that of the standard strain ATCC 29903. DNA sequencing revealed that two amino acid substitutions, namely, Ser (TCG)-83-->Leu (TTG) and Asp (GAC)-87-->Gly (GGC), had occurred in the gyrA of all 3 strains isolated from the patients. Examination of the accumulation of antibiotics in these 3 strains revealed that the strain isolated after tosufloxacin treatment had the highest resistance to tosufloxacin, and exhibited decreased accumulation of tosufloxacin in the bacterial cells discharged after 5 days of treatment with this antibiotic. However, accumulation was restored by addition of a proton-pump inhibitor. These results suggest that the strains isolated from the inpatient and the patient with secondary infection acquired resistance due to dual gyrA mutation induced by treatment with new quinolone antibiotics. Furthermore, in addition to this dual mutation, the active efflux mechanism also appears to be associated with resistance in bacteria that have been exposed to tosufloxacin.

[In vitro antibacterial activity of pazufloxacin (PZFX) against clinical isolates from infectious enteritis].

Antibacterial activity of pazufloxacin (PZFX) against 65 strains of Shigella spp., 13 strains of Salmonella spp., 7 strains of Escherichia coli, 4 strains of Vibrio parahaemolyticus, 4 strains of V. cholerae O1, 2 strains of Aeromonas spp., 4 strains of Plesionomas shigelloides and 3 strains of V. cholerae non-O1 isolated from patients of infectious enteritis and carriers was compared with that of ofloxacin (OFLX), ciprofloxacin (CPFX), tosufloxacin (TFLX) and nalidixic acid (NA). The MIC90 of PZFX against Shigella spp., Salmonella spp. and E. coli were 0.025, 0.025 and 0.025 micrograms/ml, respectively. The MIC90 of PZFX against Shigella spp. was comparable to that of CPFX, 2-fold higher than that of TFLX and 4-fold lower than that of OFLX. Against Salmonella spp., MIC90 of PZFX was comparable to TFLX and 2- to 8-fold lower than those of CPFX and OFLX. PZFX showed the highest antibacterial activity between the drugs tested. Against other species, the MIC90 values of PZFX were < or = 0.006-0.1 micrograms/ml. No NA-resistant isolates were observed. The antibacterial activity of PZFX against stocked strains (clinical isolates from Aug 1989 to Feb 1991), containing 51 strains of Shigella spp., 50 strains of Salmonella spp., 19 strains of E. coli, 12 strains of V. cholerae O1 and 13 strains of V. parahaemolyticus, was also investigated. The MIC90 of PZFX of each strains were 0.05 micrograms/ml for Shigella spp., 0.05 micrograms/ml for Salmonella spp., 0.1 micrograms/ml for E. coli, 0.0125 micrograms/ml for V. cholerae O1, 0.2 micrograms/ml for V. parahaemolyticus, respectively. As shown above, PZFX has strong antibacterial activity against isolates from infectious enteritis and this suggests the usefulness of PZFX for the treatment of these patients and carriers.

Visual influence on center of contact pressure in advanced Parkinson's disease.

The visual influence on upright posture was studied in seven patients with Parkinson's disease (PD), Yahr stage III to IV, and seven age-matched controls. The position of the center of contact pressure (CCP) between the feet and floor was analyzed by a photoelastic method. When the patients' eyes were closed, the CCP position shifted significantly backward in PD (open, 48.6 +/- 7.6%; closed, 45.0 +/- 4.8%; p < 0.01), whereas in controls, it shifted significantly forward (open, 45.5 +/- 5.8%; closed, 48.9 +/- 2.8%; p < 0.05). PD patients put their body weight less on the more affected foot (open, 49.6 +/- 4.5%; closed, 47.0 +/- 4.8%; p < 0.01) and more on the less affected foot (open, 50.4 +/- 4.5%; closed, 53.0 +/- 4.8%; p < 0.005), when the eyes were closed. Visual information is important in maintaining the upright posture in PD patients.