Although earlier pleuromutilin analogues showed potent in vitro antibacterial activity against some Gram-positive pathogens, their in vivo efficacy was low because of insufficient pharmacokinetic properties. We designed novel thioether pleuromutilin derivatives having a purine ring as a polar and water solubilizing group and identified a promising pleuromutilin analogue 6 with good solubility in water ( approximately 50 mg/mL). Compound 6 exhibited excellent in vitro and in vivo antibacterial activity against some Gram-positive strains, including drug-resistant pathogens.

ABSTRACT. Susceptibility to 13 antimicrobial agents was examined for 138 Escherichia coli isolates obtained from 192 fecal samples of wild cranes that migrated for wintering to the Izumi plain, Kagoshima prefecture in Japan. The numbers of isolates that were resistant to the antimicrobials used in this study are as follows: oxytetracycline (OTC), 22 isolates; minocycline, 7 isolates; ampicillin (ABPC), 4 isolates; nalidixic acid, 4 isolates; enrofloxacin, 2 isolates; kanamycin, one isolate. Multidrug resistant isolates exhibiting 2-4 drug resistances were obtained. All of the OTC-resistant isolates carried either the tet (A) or tet(B) gene. The bla TEM gene was found in all of the ABPC-resistant isolates.

ABSTRACT. From November 2002 to February 2008, 2,251 crane feces were collected at the Izumi Plain in Kagoshima Prefecture. Salmonella enterica was isolated from 359 feces (15.9%), of which 332 (92.5%) were Salmonella Typhimurium (ST), 9 were S. Hvittingfoss/II, 4 were S. Abaetetuba, 3 were S. Enteritidis, 2 were S. Konstanz, 1 was S. Pakistan and 8 were untyped isolates, respectively. Against 12 antimicrobial agents, no resistant strains were found in 154 isolates examined, but one was found to be resistant to ampicillin. By pulsed-field gel electrophoresis (PFGE), all but one of the 68 ST isolates tested showed indistinguishable banding patterns; one had a different pattern. The results suggest that ST strains from the same origin would spread in crane flocks during their stay at Izumi Plain every winter.

ABSTRACT. Urine samples of cats and dogs collected for 24 hr after a subcutaneous injection of orbifloxacin (OBFX) were analyzed. The metabolites were examined using HPLC. In the dog urine, 87% of total was the parent compound and 13% glucuronide compound of OBFX and 96% was parent and 4% metabolite in the cat urine. The metabolite of cat urine was identified as N-hydroxy OBFX, determined by comparison of the extraction of urine with chloroform with the standard compound of N-hydroxy OBFX, using LC/ APCIMS. N-hydroxy OBFX had a weaker antibacterial activity against fluoroquinolone sensitive bacteria than the parent compound. -KEY WORDS: canine, feline, orbifloxacin metabolite.J. Vet. Med. Sci. 60(11): 1259-1261, 1998 pressure, and the residue was dissolved in methanol. A portion (10 µl) of the resulting solution was subjected to LC/APCIMS. A Hitachi Model M-1000 LC/APCIMS spectrometer (Hitachi Co., Ltd., Tokyo, Japan) attached to a Model L-6200 HPLC system (Hitachi Co., Ltd., Tokyo, Japan) was used, with the following measurement conditions: drift voltage 40 V, focus voltage 113 V, vaporization temperature 270°C and desolvation temperature 399°C. The HPLC conditions were almost the same as those described above, except for the composition of mobile phase (methanol: 0.01% trifluoroacetic acid (42: 58 v/v)). The antibacterial activities of metabolites of OBFX were determined by the method of the Japanese Society of Chemotherapy for assay of minimum inhibitory concentration (MIC) [1].The elution patterns of HPLC chromatograms of urine samples were almost the same in the 4 cats. A typical pattern (cat no. 601) is shown in Fig. 1. (a, b). Two peaks (M-2, M-3) were detected at retention times (t R ) of about 10 min and 23 min. When the chloroform extract of the urine sample which including M-2 was analyzed by LC/APCIMS, a protonated molecule (MH + ) appeared at m/z 412 in the mass spectrum of M-2 (Fig. 2), suggesting that the molecular weight of M-2 was 411. The mass spectrum of N-hydroxy OBFX corresponded to that of M-2 (Fig. 2). The mass spectrum of M-3 corresponded to that of standard OBFX. On HPLC analysis, standard OBFX and standard N-hydroxy OBFX were eluted at t R s of 23 min and 10 min, respectively. These findings suggested that M-3 and M-2 were OBFX and N-hydroxy OBFX, respectively. Two peaks (M-1, M-3) were detected in dog urine at t R s of 5 min and 23 min. A typical pattern (dog no. 111 ) is shown in Fig. 1. (A-C). After the treatment of the urine sample of each dog with β-glucuronidase, the peak of M-1 disappeared and the peak of M-3 on the chromatograph increased.The ratio of each metabolite was calculated on the basis of the peak area on HPLC and the molecular absorption coefficient of each metabolite. In the urine of cats, the ratios of OBFX and N-hydroxy OBFX were 0.96 ± 0.004 Orbifloxacin (OBFX: 1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(cis-3,5-dimethyl-1-piperazinyl)-4-oxoquinoline-3-carboxylic acid), a fluoroquinolone antibacterial agent, has been developed especially for use in veterinary medi...