Comparative in-vitro activity of selected new beta-lactam antimicrobials against Neisseria gonorrhoeae. (73/94)

Four new beta-lactam antimicrobials, ceftriaxone, cefotiam, cefonicid, and mecillinam, were evaluated in vitro against 72 beta-lactamase-negative and 26 beta-lactamase-positive isolates of Neisseria gonorrhoeae. Ceftriaxone was the most active of the antimicrobials tested. It inhibited all isolates, regardless of beta-lactamase activity, at a concentration of less than or equal to 0.015 microgram/ml. Cefotiam and cefonicid were also active against both groups but not as active as ceftriaxone. Both groups of N gonorrhoeae showed a high degree of resistance against mecillinam.  (+info)

Susceptibility of shigellae to mecillinam, nalidixic acid, trimethoprim, and five other antimicrobial agents. (74/94)

A total of 199 strains of shigella (1 Shigella dysenteriae, 15 S. boydii, 47 S. flexneri, and 136 S. sonnei) isolated in Malmo, Sweden, within a 3-year period (1977 through January 1980) were tested with the agar plate dilution method for susceptibility to commonly used and newer antimicrobial agents. Mecillinam, nalidixic acid, and trimethoprim had the best in vitro activity. S. flexneri dominated among strains resistant to three or more antimicrobial agents and were less susceptible to ampicillin, chloramphenicol, and doxycycline than other types studied. Sixty-four percent of the strains were resistant to sulfamethoxazole. In vitro, a synergistic effect with trimethoprim was shown only in strains susceptible to sulfamethoxazole. The amidinopenicillin mecillinam was highly active against shigellae. When resistance occurred, it was linked to ampicillin in 17 of 18 strains. The quinolines, here represented by nalidixic acid, might be the drugs of choice.  (+info)

Treatment of experimental Salmonella typhimurium infection with mecillinam and ampicillin. (75/94)

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 microgram/ml of culture medium. In vitro synergy was demonstrated. CF-1 mice inoculated intraperitoneally with 10(4) 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 greater than or equal to 0.03 mg and mecillinam in doses of greater than or equal to mg reduced mortality rates from 77% in the saline-treated controls to a range of 0 to 4% (P less than 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.  (+info)

Synergistic activity of mecillinam in combination with the beta-lactamase inhibitors clavulanic acid and sulbactam. (76/94)

The beta-lactamase inhibitors clavulanic acid and sulbactam were combined with mecillinam. beta-Lactamase-containing Escherichia coli resistant to mecillinam was synergistically inhibited by both clavulanic acid and sulbactam. beta-Lactamase-containing Enterobacter was synergistically inhibited, but strains lacking beta-lactamases were not synergistically inhibited. Synergistic inhibition was noted for beta-lactamase-containing, mecillinam-resistant Klebsiella, Citrobacter, Serratia, and Salmonella isolates, but only 18% of beta-lactamase-containing Proteus mirabilis, Providencia rettgeri, Providencia stuartii, and Morganella morganii were synergistically inhibited by the combinations.  (+info)

Effect of protein synthesis inhibition on the induction of cell lysis in Escherichia coli by mecillinam plus nocardicin A. (77/94)

Cell lysis can be induced in Escherichia coli by the combined use of the beta-lactam antibiotics nocardicin A and mecillinam. Apparently, the induction of cell lysis occurs by a sequential mechanism in which mecillinam acts first, and nocardicin A has a triggering action insensitive to the inhibition of protein synthesis.  (+info)

Pharmacokinetics of amdinocillin in healthy adults. (78/94)

The pharmacokinetics of amdinocillin (mecillinam) were determined in 10 healthy volunteers. Single doses of 10 and 15 mg/kg of body weight were administered intravenously and intramuscularly in a crossover study. Plasma concentrations of amdinocillin were determined by microbiological assay. Mean peak plasma concentrations were 49 and 87 micrograms/ml after intravenous doses of 10 and 15 mg/kg, respectively. The terminal half-life value of 0.89 h was similar for both doses. After intramuscular injections, the mean concentration of drug in plasma was 26.2 micrograms/ml for the 10-mg/kg dose and 29.6 micrograms/ml for the 15-mg/kg dose, with terminal half-lives of 0.96 and 0.86 h, respectively. The mean apparent volumes of distribution at steady state were 18 and 16 liters/100 kg for the intravenous doses of 10 and 15 mg/kg, respectively. Drug concentrations in plasma at 4 h were above the minimal inhibitory concentrations for gram-negative organisms categorized as susceptible to this drug.  (+info)

Inhibition of lateral wall elongation by mecillinam stimulates cell division in certain cell division conditional mutants of Escherichia coli. (79/94)

The effect of mecillinam, a beta-lactam antibiotic that specifically binds penicillin-binding protein 2 of Escherichia coli, causes transition from rod to coccal shape, and inhibits cell division in sensitive cells, has been tested on three different E. coli temperature-sensitive cell division mutants. At the nonpermissive temperature, the antibiotic allows an increase in cell number for strains BUG6 and AX655 but not for AX621. In strain AX655, the cell division stimulation was observed only if the antibiotic was added immediately after shifting to the nonpermissive temperature, whereas in BUG6, the rise in cell number was observed also when mecillinam was added after 90 min of incubation at the nonpermissive temperature. In all cases, cell division began occurring 30 min after addition of the antibiotic. Mecillinam had no effect on division of dnaA, dnaB temperature-sensitive mutants or on division of BUG6 derivatives made resistant to this antibiotic. Other beta-lactam antibiotics such as penicillin, ampicillin, cephalexin, and piperacillin and non beta-lactam antibiotics such as fosfomycin, teichomycin, and vancomycin that inhibit cell wall synthesis did not show any effect on cell division for any of the mutants. The response of the three cell division mutants to mecillinam is interpreted in terms of a recently proposed model for shape regulation in bacteria.  (+info)

Quaternary heterocyclylamino beta-lactams. III. The mode of action of L-640,876 and the effect of NaCl on membrane permeability and binding. (80/94)

L-640,876, 7-beta(1-benzylpyridinium-4-yl)amino-3-[( (1-methyl-1 H-tetrazol-5-yl)thio]methyl)-ceph-3-em-4-carboxylate, is a potent representative of a new family of beta-lactam antibiotics which are similar in some respects to mecillinam. When L-640,876 and mecillinam were compared for effects on growth and morphology of Escherichia coli, it was observed that both drugs caused the formation of lemon-shaped cells during the first 30 minutes of exposure and during this period the culture turbidity increased without an appreciable change in culture viability. Unlike mecillinam, after 60 minutes of exposure to L-640,876 the majority of the lemon-shaped cells transformed into spindle-shaped cells and in the continuing presence of the drug formed osmotically fragile spheroplasts. Membrane binding studies indicated that, like mecillinam, L-640,876 was bound to the PBP-2 of E. coli and Proteus morganii; however, some binding of L-640,876 to the PBP-3 of E. coli was detected. In Staphylococcus aureus binding differences were more evident as L-640,876 was more rapidly bound to PBP-1 and 2 whereas mecillinam was rapidly bound to PBP-3. The reversal of inhibition of certain strains of Gram-negative bacteria by high ionic strength media could not be directly attributed to a reversal of antibiotic binding to the PBPs. Permeability studies indicated that the superior potency of L-640,876 in E. coli was partly due to its higher concentration in the periplasm which was unaffected by the simultaneous addition of drug and NaCl, however, in cells cultured in high ionic strength medium there was a marked reduction in penetration rate of all beta-lactams tested.  (+info)