Characteristics of aztreonam as a substrate, inhibitor and inducer for beta-lactamases. (25/94)

Aztreonam was investigated as to its characteristics as a substrate, inhibitor and inducer for the well-defined beta-lactamases of Gram-negative bacteria, and its antibacterial efficacy as to bacterial cells producing eight types of beta-lactamases was also evaluated. Aztreonam was hydrolyzed at measurable rates by class A beta-lactamases, a TEM-2 type penicillinase and the Proteus vulgaris cephalosporinase with a broad substrate range. However, the affinity of aztreonam for the class A enzymes was low, this property being well reflected by its high antibacterial activity toward producers of class A beta-lactamases. Aztreonam was extremely stable as to the typical class C cephalosporinase of Citrobacter freundii, and acted as a competitive and progressive inhibitor for the beta-lactamase. While the MICs of aztreonam in the cases of the constitutive producers of class C beta-lactamases were evidently affected by enzyme production. An experiment involving aztreonam as a inhibitor in combination with a hydrolyzable beta-lactam gave ambiguous results, however, a strong synergistic effect was found in combination with mecillinam. Using Pseudomonas aeruginosa, aztreonam was confirmed to be a poor inducer of beta-lactamases.  (+info)

High and selective resistance to mecillinam in adenylate cyclase-deficient or cyclic adenosine 3',5'-monophosphate receptor protein-deficient mutants of Escherichia coli. (26/94)

Adenylate cyclase-deficient (cya) mutants of Escherichia coli K-12 were selectively and highly resistant to mecillinam (FL1060) among several beta-lactam antibiotics in the absence of cyclic adenosine 3',5'-monophosphate (cAMP). They became sensitive to the drug in the presence of cAMP. Also, cAMP receptor protein-negative (crp) mutants, with the exception of strain 5333, were highly resistant to mecillinam in the presence and in the absence of cAMP. Mecillinam exerted two distinct and sequential effects in both cya+ strains and cya strains supplemented with cAMP: (i) rounding of cells and (ii) cessation of cell division. The first effect was accompanied by a decrease in growth rate, whereas the second effect was accompanied by enlargement and lysis of the rounded cells. The second effect of mecillinam was dependent on inoculum size and cAMP. When the cell density was above about 10(6) cells per ml, the rounded cells stopped dividing but did not lyse. In the absence of cAMP, cya strains neither stopped dividing nor lysed; they were resistant to the second, lethal effect of mecillinam.  (+info)

Mecillinam in enteric fever. (27/94)

Twelve consecutive patients with enteric fever entered a trial of 14 days' treatment with mecillinam. Only three patients became afebrile within three days; four continued unimproved with fever and toxaemia for seven to nine days, when treatment was changed to chloramphenicol with good results. In one case the fever did not settle until the 13th day, and five days later the patient had a clinical relapse. Although all organisms recovered were fully sensitive to mecillinam, this drug is not an effective or consistent treatment for enteric fever.  (+info)

The bacterial actin MreB rotates, and rotation depends on cell-wall assembly. (28/94)

 (+info)

Factors influencing the absorption and disposition of mecillinam and pivmecillinam in man. (29/94)

In a pharmacokinetic study in six volunteers peak serum mecillinam concentrations were proportional to the oral dose of pivmecillinam at two dose levels of 200 and 400 mg. Effects of bed rest, probenecid and a 6 day course of treatment with pivmecillinam on serum mecillinam concentrations after an oral dose of pivmecillinam (two 200 mg capsules) have been investigated. Resting subjects had lower peak serum levels and a decreased rate of clearance than moderately active subjects, changes which are similar to those previously reported for benzylpenicillin. Pretreatment with probenecid produced significantly higher serum mecillinam levels, a longer serum antibiotic half-life and a decreased rate of drug clearance which suggests that mecillinam is actively excreted by kidney tubules. Plasma mecillinam level profiles obtained after the first dose of a 6 day treatment period were not significantly different from corresponding values after the first dose on the seventh day which indicates that each dose of mecillinam is eliminated in healthy young adults before succeeding doses are taken.  (+info)

Mecillinam/clavulanate combination: a possible option for the treatment of community-acquired uncomplicated urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. (30/94)

 (+info)

Mecillinam-ampicillin synergism in experimental Enterobacteriaceae meningitis. (31/94)

The in vitro activities of mecillinam, a new beta-amidinopenicillin, and ampicillin, alone and in combination, against an Escherichia coli strain and a Klebsiella pneumoniae strain were compared, and these results were correlated with their respective activities in vivo in experimental meningitis. The mecillinam-ampicillin combination was synergistic in vitro against both strains when tested by a modified checkerboard technique (bacteriostatic synergy). However when quantitative bactericidal synergy studies were made, the relative bactericidal rate of the combination was more rapid than that of either drug alone ("bactericidal synergy") against the Escherichia coli isolate only. In a rabbit model of Enterobacteriaceae meningitis, in vivo bactericidal activity correlated with results obtained in vitro. Both drugs were administered by continuous intravenous infusion for 8 h. Serum and cerebrospinal fluid antibiotic levels were similar to those achieved in humans. Cerebrospinal fluid bacterial concentrations (colony-forming units [CFU] per milliliter) were quantitatively titrated at 2-h intervals. Both drugs, alone or the combination, were ineffective against the K. pneumoniae strain in vivo (change in titer <1 log in 8 h). In contrast, the combination produced a markedly enhanced bactericidal effect against the E. coli strain (mean +/- standard deviation, decrease of log(10) CFU per milliliter of 3.65 +/- 1.02) compared with those of ampicillin alone (decrease of log(10) CFU per milliter of 0.07 +/- 0.8) and mecillinam alone (decrease of log(10) CFU per milliliter of 1.6 +/- 0.05) (P < 0.001). When bactericidal synergism can be demonstrated for mecillinam-ampicillin in vitro in a case of gram-negative-bacillary meningitis this combination may be useful in the therapy of the illness.  (+info)

Activity of semisynthetic penicillins and synergism with mecillinam against Bacteroides species. (32/94)

The minimal inhibitory concentrations (MIC) of six penicillins (ampicillin, carbenicillin, ticarcillin, piperacillin, mezlocillin, and Bay k 4999) against 29 clinical isolates of Bacteriodes spp. (including Bacteroides fragilis, Bacteroides thetaiotaomicron, and Bacteroides vulgatus) were determined by an agar dilution method. Bay k 4999 was most active, followed in descending order by ampicillin, piperacillin, mezlocillin, ticarcillin, and carbenicillin. Mecillinam, a 6 beta-amidino-penicillanic acid, inhibited no strains at 50 micrograms/ml, but when compared with ampicillin, a fourfold or greater increase in MIC for ampicillin (antagonism) was noted in 3 of 29 strains, with no effect on MIC for 26 strains, whereas when combined with carbenicillin, a fourfold or greater decrease in MIC for both antibiotics (synergism) was noted in 12 strains, 4 of which had an MIC of greater than or equal to 250 micrograms/ml for carbenicillin alone. These studies demonstrate the increased activity of some newer semisynthetic penicillins and the potential synergy obtained with mecillinam and carbenicillin against Bacteroides sp.  (+info)