In vitro antibacterial activity of norfloxacin (MK-0366, AM-715) and other agents against gastrointestinal tract pathogens

The major outer membrane protein was extracted from Campylobacter coli by Triton X-100/EDTA fractionation of cell envelopes. This heat-modifiable protein was shown to have pore-forming activity in black lipid bilayers. The C. coli porin formed a relatively small cation-selective pore with a mean single-channel conductance of 0.53 + 0.16 nS in 1.0 M KCI. There was no evidence of oligomer formation, which suggested that each protein monomer formed a pore. Pore-forming activity of the C. coli porin and similarly prepared Campylobacterjejuni porin was also measured in liposome-sweiling assays. These results confirmed the cation selectivity of both pores. The C. coli porin formed a small pore, which hindered the penetration of solutes with a molecular weight of 262, and a larger pore, which hindered the penetration of solutes with a molecular weight of 340, in a protein-concentration-dependent manner. C. jejuni formed one size of pore that was slightly larger than the C. coli pore and just permitted the passage of solutes, with a molecular weight of 340.

Section: Resultsmentioning

confidence: 99%

Characterization of the porins of Campylobacter jejuni and Campylobacter coli and implications for antibiotic susceptibility

Page

Huyer

et al. 1989

“…The new fluorinated piperazinyl quinolones have markedly enhanced in vitro activity against enterobacteria and against all other enteric pathogens with the exception of Clostridium difficile (5,6,11,25). Some of the newer analogs are 100-fold more active than nalidixic acid, and resistant clones are less likely to appear with these drugs, which remain active against nalidixic acid-resistant variants.…”

Section: Norfloxacin Versus Nalidixic Acid For Dysenterymentioning

confidence: 99%

Comparison of norfloxacin and nalidixic acid for treatment of dysentery caused by Shigella dysenteriae type 1 in adults

Rogerie¹,

Ott²,

Vandepitte³

et al. 1986

A severe epidemic of dysentery began late in 1979 in northeast Zaire and spread to Rwanda, Burundi, and Tanzania. The epidemic strain is a multiply resistant Shigella dysenteriae type 1, which acquired resistance against trimethoprim and more recently against nalidixic acid in the course of the epidemic. A comparative open trial in Rwandan adults with Shiga dysentery involved 18 patients treated with norfloxacin at 400 mg twice daily and 12 patients treated with nalidixic acid at 1 g three times daily for 5 days. All isolates showed in vitro susceptibility to both drugs. Though norfloxacin eliminated Shigella organisms from stools more rapidly than nalidixic acid, its clinical superiority did not reach the level of significance. Norfloxacin is a promising drug and is more effective than nalidixic acid in the treatment of multiresistant shigellosis.

“…Appearance of these strains has prompted a search for alternative antimicrobial agents with activity against vibrios. Norfloxacin is a new carboxyquinoline derivative that has in vitro activity against a number of enteric pathogens, including campylobacter, salmonella, shigella, toxigenic Escherichia coli, yersinia, and, in testing involving a limited number of strains, V. parahaemolyticus and V. cholerae (4,8,11,13). In vitro activity against V. cholerae 01 would make norfloxacin an attractive drug for further study in areas with tetracycline-resistant cholera.…”

mentioning

confidence: 99%

In vitro susceptibility of pathogenic Vibrio species to norfloxacin and six other antimicrobial agents

Morris¹,

Tenney²,

Drusano³

1985

The in vitro activity of norfloxacin and six other antimicrobial agents was tested against 93 vibrio strains representing the currently described pathogenic Vibrio species. Norfloxacin had excellent activity against all species, with the following MICs for 90% of the strains: 0.016 ,ug/ml for Vibrio cholerae (including tetracycline-resistant V. cholerae 01 strains), 0.25 ,ug/ml for V. parahaemolyticus, and 0.063 ,ig/ml for V.vulnificus.Tetracycline is currently the drug of choice for serious vibrio infections (10,14). Since 1978, however, an increasing number of Vibrio cholerae 01 strains have been identified that have plasmid-mediated resistance to multiple antibiotics, including tetracycline. These strains have been responsible for major epidemics in Tanzania (9) and Bangladesh (7) and are currently endemic in parts of Africa (J. G. Morris 503, 1984). Appearance of these strains has prompted a search for alternative antimicrobial agents with activity against vibrios. Norfloxacin is a new carboxyquinoline derivative that has in vitro activity against a number of enteric pathogens, including campylobacter, salmonella, shigella, toxigenic Escherichia coli, yersinia, and, in testing involving a limited number of strains, V. parahaemolyticus and V. cholerae (4,8,11,13). In vitro activity against V. cholerae 01 would make norfloxacin an attractive drug for further study in areas with tetracycline-resistant cholera. Demonstration of activity against the other known pathogenic Vibrio species would also enhance the potential usefulness of norfloxacin as a broad-spectrum agent for treatment of bacterial gastroenteritis. In this study we compared the in vitro activity of norfloxacin to that of nalidixic acid, tetracycline, chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, and gentamicin against 93 vibrio strains representing all known pathogenic Vibrio species (10).( Results of the microtiter MIC assays are given in Tables 1 and 2. All vibrio strains tested were susceptible to norfloxacin, with MICs of .0.5 pLg/ml. V. cholerae strains were very susceptible to the drug, with MICs of 0.016 ,ug/ml for 90% of the strains tested. The presence of an R factor did not influence the norfloxacin MICs. Only one V. cholerae strain had a norfloxacin MIC of >0.016 ,ug/ml: the MIC for this strain was 0.25 ,ug/ml, with a corresponding MIC of nalidixic acid of 32 jLg/ml. A significant inoculum effect was observed for one of the four V. cholerae 01 strains tested, with MICs of <0.008 ,ug/ml at 103 and 105 organisms per ml and 1.0 ,ug/ml at 107 organisms per ml. For one of the two V. parahaemolyticus strains tested, the MIC increased from 0.25 to 1.0 ,ug/ml with an increase in the inoculum from 105 to 107 organisms per ml. The MIC for the V. vulnificus strain increased from 0.031 ,ug/ml at 103 organisms per ml to 0.125 ,ug/ml at 105 organisms per ml and 1 ,ug/ml at 107 organisms per ml.Our data indicate that norfloxacin may be a useful agent for treatment of cholera. Peak stool concentrations of the drug after a single 400-mg o...