Treatment of experimental Salmonella typhimurium infection with mecillinam and ampicillin

Abstract

The activities of mecillinam and ampicillin, alone and in combination, were evaluated in mice infected with the LT-2 strain of Salmonella typhimurium. The minimal inhibitory concentrations of mecillinam and ampicillin for this strain were, respectively, 6.2 and 0.4 ,tg/ml of culture medium. In vitro synergy was demonstrated. CF-1 mice inoculated intraperitoneally with 104 colony-forming units of the LT-2 strain were used in the therapeutic assessments. Treatment of subgroups with graded doses of the respective penicillins or their combination was initiated 24 h after inoculation and repeated at 6-h intervals for 5 consecutive days. Animals were observed during 21 days for mortality or sacrificed for quantitative cultures of spleen homogenates at the end of the treatment. Ampicillin in doses of -0.03 mg and mecillinam in doses of -0.5 mg reduced mortality rates from 77% in the saline-treated controls to a range of 0 to 47% (P< 0.05). The same doses of antibiotics also extended the median times to death and lowered significantly the means of splenic bacterial counts. When both drugs were combined in doses that were partially effective or subinhibitory alone, no synergistic effects were observed. These results showed that mecillinam and ampicillin given alone were effective in treating S. typhimurium infection but that combinations of the two drugs were not synergistic in controlling the course of infections.

Oral ciprofloxacin treatment for Salmonella typhimurium infection of normal and immunocompromised mice

“…This experimental disease has therefore been well accepted for studies on the in vivo efficacy of chemotherapeutic drugs (1,5,6,38). S. typhimurium is considered to be a facultative intracellular bacterium in the mouse, because the organisms multiply within macrophages until T-cell-mediated immunity is established during the course of the infection (8,16,23).…”

“…Mice were infected subcuitaneously or orally with lethal doses of the virulent strain of S. typhimurium. The therapeutic regimens were selected to ensure that peak levels of drugs in sera exceeded the MICs, and if possible MBCs, for the challenge strains and to provide levels in serum consistent with those achieved in clinical practice (10 (1,5,6,9,26,39).…”

“…Therapeutic trials. The model of mouse typhoid has been described in detail previously (1,5,6,8,23,34,38,40). Mice were infected subcuitaneously or orally with lethal doses of the virulent strain of S. typhimurium.…”

Targeting plasmid-encoded proteins that contain immunoglobulin-like domains to combat antimicrobial resistance

“…For antibiotic treatment, we specifically selected ampicillin (Amp) due to its established efficacy in reducing the symptoms of Salmonella infection in mice (Butler et al, 1981;Rossi et al, 2017).…”

“…We first established that both Salmonella strains (WT and pHCM1) were capable of infecting mice, and that only the plasmid-bearing strain was antibiotic resistant. For antibiotic treatment, we specifically selected ampicillin (Amp) due to its established efficacy in reducing the symptoms of Salmonella infection in mice (Butler et al, 1981; Rossi et al, 2017).…”