Activities of newer fluoroquinolones against Shigella sonnei

Abstract

Antibiotic treatment is usually indicated for individuals with moderate or severe symptoms of shigellosis (7). The traditionally used therapeutic agents, such as ampicillin and trimethoprim-sulfamethoxazole, have lost much of their effectiveness over the last decade because of increasing multiple antibiotic resistance of shigellae because of their conjugative resistance plasmids (2, 5,15). The fluoroquinolones are attractive agents for therapy of bacterial enteric diseases for a variety of reasons. They are highly active against many members of the family Enterobacteriaceae (11,17) and achieve high fecal levels (16); they also have good intracellular and bowel wall penetration (14). Fluoroquinolones act at sites different from those at which other antimicrobial agents act, and resistance to them has not been associated with resistance plasmids (6). Among members of the family Enterobacteriaceae, Shigella spp. are one of the leading causes of diarrhea. The most prominent species, Shigella sonnei, now constitutes up to 90% of Shigella isolates in industrialized countries (8,12,19) and may also serve as a barometer of acquisition and expression of the antimicrobial resistance (5). In the study described here we assessed the in vitro activities of six fluoroquinolones against 117 strains of S. sonnei from several countries in North America, Europe, Africa, and Asia. The activities of three new investigational quinolones (CI-960, PD-131628-2, and sparfloxacin) were compared with those of three marketed fluoroquinolones (ciprofloxacin, enoxacin, and temafloxacin).One were provided by the indicated suppliers: CI-960, enoxacin, PD-131628-2, and sparfloxacin (Parke-Davis, Ann Arbor, Mich.); ciprofloxacin (Miles Inc., West Haven, Conn.); and temafloxacin (Abbott Laboratories, North Chicago, Ill.). All of the isolates were first studied for susceptibility by the disk diffusion method with a batteiy of antimicrobial agents (3). The strains were next tested in duplicate for their susceptibilities to the quinolones listed above by an agar dilution technique. Serial two-fold dilutions of the agents were incorporated into Mueller-Hinton agar kept at 50°C, and agar was immediately poured into the plates. The isolates were subcultured from MacConkey agar plates into 5.0-ml volumes of Mueller-Hinton broth and were then incubated at 37c overnight. These broth samples were inoculated onto the antibiotic-containing plates by using a Steers replicator device (18). An inoculum of approximately 104 organisms per spot was used, and the MIC of an agent was the lowest concentration at which visible growth of an isolate was not present. When there were discrepancies between the duplicate results, the higher MIC was chosen. For all antimicrobial agents used, time-kill curves were determined with three selected strains. The strains were grown for 24 h at 37c in 5.0 ml of Mueller-Hinton broth, and 0.5-ml samples were used to inoculate Erlenmeyer flasks (500 ml) containing 4x the MICs of the test antimicrobial agents in 100 ml of Mueller-Hinton...

A Quantitative Survey of Bacterial Persistence in the Presence of Antibiotics: Towards Antipersister Antimicrobial Discovery

“…A selection of 847 primary publications deemed relevant to the theme of antibiotic bacterial persisters were manually surveyed for quantitative data from work carried out in planktonic cultures. Numerical data were finally extracted from 187 articles [ 3 , 4 , 7 , 8 , 11 , 12 , 36 , 39 , 40 , 49 , 51 , 52 , 55 , 56 , 57 , 58 , 61 , 66 , 67 , 68 , 89 , 115 , 116 , 117 , 119 , 121 , 122 , 126 , 133 , 141 , 142 , 143 , 150 , 163 , 173 , 177 , 184 , 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 ,…”