AT-4140, 5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(cis-3,5-dimethyl-1-piperazinyl)-4-oxoquinoline-3-carboxylic acid, showed broad and potent antibacterial activity. Its MICs for 90% of the strains tested were 0.1 to 0.78 ,ug/mi against gram-positive organisms, such as members of the genera Staphylococcus, Streptococcus, and Enterococcus, and 0.0125 to 1.56 ,ug/ml against gram-negative organisms, such as members of the family Enterobacteriaceae and the genera Pseudomonas, Branhamella, Campylobacter, Haemophilus, and Neisseria. Its MICs were 0.025 to 0.78 ,ig/ml against glucose nonfermenters, such as members of the genera Xanthomonas, Acinetobacter, Alcaligenes, Moraxella, Flavobacterium, and Brucella; 0.2 to 0.78 ,ug/mi against anaerobes, such as Clostridium perfringens and Bacteroides fragilis; 0.0125 to 0.05 p.g/ml against Legionella spp.; 0.0125 to 0.2 ,ug/ml against Mycoplasma spp.; 0.031 to 0.063 ,u.g/ml against Chlamydia spp.; and 0.1 to 0.3 ,ig/ml against Mycobacterium spp. The potencies of AT-4140 against gram-negative organisms were comparable to those of ciprofloxacin and higher than those of ofloxacin, enoxacin, and norfloxacin. The potencies of AT-4140 against gram-positive organisms, glucose nonfermenters, anaerobes, Mycoplasma spp., Chlamydia spp., and Mycobacterium spp. were generally higher than those of the quinolones with which AT-4140 was compared. AT-4140 showed good oral efficacy against systemic infections with Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Escherichia coli, and Pseudomonas aeruginosa in mice. Its efficacy was better when a daily dose was given once than when it was given in two doses. Good efficacies of the orally administered drug were also observed in pulmonary, dermal, and urinary tract infection models in mice. The in vivo efficacies of AT-4140 were equal to or better than those of ciprofloxacin, ofloxacin, enoxacin, and norfloxacin.New quinolones used clinically these days have a broad spectrum of activity against both gram-positive and gramnegative organisms. However, some important pathogens, such as streptococci, enterococci, Mycoplasma spp., Chlamydia spp., and Mycobacterium spp., are not sufficiently susceptible to the quinolones. To improve this point, we screened of this group of compounds and found a new compound called AT-4140 (Fig. 1) with a broader antibacterial spectrum. This paper describes the in vitro and in vivo antibacterial activities of AT-4140 compared with those of ciprofloxacin, ofloxacin, enoxacin, and norfloxacin.(
ABSTRACT. A variety of virulence factors (VFs) such as type 1 fimbriae, pilus associated with pyelonephritis, S fimbriae, afimbrial adhesin, α-hemolysin, aerobactin and cytotoxic necrotizing factor 1 are associated with uropathogenic Escherichia coli. In this study, 80 uropathogenic E. coli strains in 50 dogs and 30 cats suffering from UTI. In addition, 60 E. coli strains were isolated from fecal samples from 30 each of healthy dogs and cats. The distribution of VFs of uropathogenic E. coli strains isolated from dogs and cats suffering from urinary tract infections (UTI) were examined by the colony hybridization test with seven DNA probes specific for VFs, and the results were compared with those obtained in the studies on strains from humans with UTI. In uropathogenic E. coli strains isolated from dogs and cats suffering from UTI, VFs were detected as frequently as in the strains isolated from humans with UTI. Although less frequently, genes encoding these VFs especially pap, sfa, hly and cnf 1 genes were also associated with E. coli strains isolated from feces of healthy cats, in contrast to the distribution pattern of uropathogenic E. coli observed in humans. Furthermore, all VFs except pil were significantly more frequently detected in strains isolated from urine of animals with cystitis than in those isolated from feces of healthy humans. These results indicate that VFs of E. coli contribute to the pathogenesis of UTI in dogs and cats. -KEY WORDS: canine, Escherichia coli, feline, urinary tract infection, virulence factor.J. Vet. Med. Sci. 60(3): 287-290, 1998 there have been only few reports on urovirulence factors of E. coli derived from dogs and cats. Low et al. [10] analyzed E. coli strains isolated from dogs with UTI in an attempt to determine if any of these strains were similar to E. coli isolated from human UTI. All isolates shared similar DNA sequences for pap, hly and insertion sequence 5 on the basis of Southern blot analysis. These results suggest that similar uropathogenic E. coli organisms might be able to cause infection in dogs and humans. We used DNA probes specific for seven urovirulence factors including type 1 pilus (pil), pilus associated with pyelonephritis (pap), S fimbriae (sfa) and afimbrial adhesin of the X adhesin group (afa I), α-hemolysin (hly), cytotoxic necrotizing factor 1 (cnf 1) and aerobactin (aer) to examine the distribution of these factors in E. coli strains isolated from dogs and cats with UTI by the DNA colony hybridization test. We assessed also the utility of the multiplex polymerase chain reaction (PCR) for rapid detection of the virulence factors of uropathogenic E. coli by using a mixture of primers previously reported for the various factors [19]. MATERIALS AND METHODSIn the present study, 50 E. coli strains from dogs and 30 strains from cats were used. Diagnosis of UTI was based on clinical signs including rectal temperature, general condition and appetite, as well as urinary signs (micturition disorders, polyuria/polydipsia and microscopic urine appearance ...
Pipemidic acid, 8-ethyl-5,8-dihydro-5-oxo-2-(1-piperazinyl)-pyrido [2,3- d ]pyrimidine-6-carboxylic acid, is a new derivative of piromidic acid. It is active against gram-negative bacteria including Pseudomonas aeruginosa as well as some gram-positive bacteria. Its potency is generally greater than that of piromidic acid and nalidixic acid. Cross-resistance is not observed between pipemidic acid and various antibiotics, and most of bacteria resistant to piromidic acid and nalidixic acid are moderately susceptible to pipemidic acid. The activity of pipemidic acid is scarcely affected by the addition of serum, sodium cholate, or change of medium pH, but is subject to the influence of inoculum size. Its action is bactericidal above minimal inhibitory concentrations.
Our results indicate that usp may contribute to the causation of urinary tract infection and may be considered a major virulence determinant of uropathogenic E. coli.
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