In vitro activity of mecillinam against anaerobic bacteria. (57/94)

A microtiter broth dilution method was employed to determine the in vitro activity of mecillinam against 201 recent clinical isolates of anaerobic bacteria. Both the anaerobic gram-positive and anaerobic gram-negative bacilli displayed a wide range of minimal inhibitory concentrations of mecillinam; most strains were resistant to the antibiotic. The anaerobic cocci exhibited a narrower range of minimal inhibitory concentrations than were observed with other anaerobes, but also exhibited mecillinam resistance. As a single drug, mecillinam does not appear to be an effective antimicrobial agent against anaerobic bacteria.  (+info)

Carbenicillin plus cefazolin with or without mecillinam as an early treatment of bacteremia caused by gram-negative organisms: randomized double-blind study. (58/94)

Mecillinam or a placebo was added to a combination of cefazolin and carbenicillin as an early therapy of septicemia caused by gram-negative organisms in patients with serious underlying diseases, none of whom was neutropenic, however. Patients in whom infection was caused by pathogens against which mecillinam and cefazolin or mecillinam and carbenicillin were synergistic might have responded more often than patients treated with nonsynergistic combinations. However, overall results did not show any benefit from combining mecillinam with cefazolin and carbenicillin. This study suggests that in nonneutropenic patients with septicemia caused by gram-negative organisms, there is no need to intensify antimicrobial therapy beyond a certain point of efficacy. The measurement of the bactericidal activity in the serum of treated patients might serve as guide for adequate therapy.  (+info)

Effect of beta-lactamase and salt on mecillinam susceptibility of enterobacterial strains. (59/94)

Out of 15 selected enterobacterial strains resistant to ampicillin, 12 were able to transfer resistance to mecillinam to Escherichia coli K-12. This resistance to mecillinam was found to be coupled to the presence of beta-lactamase. One strain contained a beta-lactamase characterized as a class IV beta-lactamase, whereas the other 14 strains possessed a class III (TEM-like) beta-lactamase. The specific activity of the class IV beta-lactamase against mecillinam was 55%, and those of the class III beta-lactamase sensitivity of mecillinam, the minimal inhibitory concentrations were lower than might be expected. However, after enzymatic hydrolysis of mecillinam, no antibacterial activity was found. At increasing salt or buffer concentrations the minimal inhibitory concentrations of mecillinam increase to a varying extent for all strains, independently of beta-lactamase production. This study indicates that the increase in minimal inhibitory concentration is dependent on the salt concentration. The study also shows that this increase is not due to salt-mediated hydrolysis or to stimulation either of beta-lactamase activity or of beta-lactamase production. To explain the difference between ampicillin and mecillnam resistance in the beta-lactamase-positive strains, a hypothetical model is presented and discussed.  (+info)

Activity of mecillinam alone and in combination with other beta-lactam antibiotics. (60/94)

The in vitro activities of mecillinam, ticarcillin, cefamandole, and cefoxitin, singly and in all possible combinations, against 53 clinical isolates were studied by a checkerboard method of determining minimal inhibitory concentrations. For selected representative strains, bactericidal activity was determined by minimal bactericidal concentrations and killing curves. Mecillinam was the least active antibiotic against gram-positive cocci, Pseudomonas aeruginosa, and Bacteroides fragilis and the most active against Enterobacteriaceae. Reproducibility of mecillinam minimal inhibitory concentrations for susceptible Enterobacteriaceae was often poor, however, due to minor variations in inoculum size. When mecillinam resistance was observed with Enterobacteriaceae, partial inhibition could be demonstrated at concentrations below minimal inhibitory concentrations, and bacterial cells were consistently ovoid or round; under those conditions the addition of a second study antibiotic resulted in marked synergistic inhibition and killing which was independent of inoculum size and susceptibility to the second antibiotic. In contrast, synergy with mecillinam against mecillinam-susceptible strains or with other antibiotic combinations against any species was not consistently observed.  (+info)

Pharmacokinetics of mecillinam in health subjects. (61/94)

Mecillinam is an amidino penicillinate derivative with a broad spectrum of activity against many gram-negative bacilli. Moreover, marked in vitro synergy against these organisms occurs when mecillinam is combined with other beta-lactam antibiotics. The purpose of this study was to determine the pharmacokinetic disposition of this antibiotic. A single dose of 10 mg/kg was administered to 12 healthy volunteers as a 15-min intravenous infusion. Multiple plasma and urine samples were collected at frequent intervals for 8 and 24 h, respectively. Plasma samples were assayed for mecillinam by using a specific high-pressure liquid chromatographic assay developed in our laboratory. Peak plasma levels ranged from 34 to 80 micrograms/ml, and after 4 h, plasma levels were 0.7 to 1.9 microgram/ml. The mean terminal plasma half-life was 51.1 +/- 8.6 min. The mean steady-state volume of distribution was calculated to be 0.23 +/- 0.04 liter/kg. The mean plasma and renal clearances were 3.5 +/- 0.4 and 2.5 +/- 0.4 ml/min per kg, respectively. The mean percentage of the dose excreted unchanged in the urine at 4 h was 67 +/- 5%; 71 +/- 6% was recovered in 24 h. Urine concentrations at 4 h were far above the minimum inhibitory concentration for susceptible gram-negative organisms.  (+info)

Filament formation of Fusobacterium nucleatum cells induced by mecillinam. (62/94)

Subinhibitory concentrations of mecillinam transformed Fusobacterium nucleatum cells into a marked filament form, quite different from a spherical form demonstrated in Escherichia coli.  (+info)

Mecillinam susceptibility of Escherichia coli K-12 mutants deficient in the adenosine 3',5'-monophosphate system. (63/94)

The mecillinam resistance of Escherichia coli K-12 mutants deficient in the enzyme responsible for the synthesis of adenosine 3',5'-monophosphate, adenylate cyclase, has been investigated. The results suggest that resistance to this antibiotic may be a consequence of the slow growth rate of these mutants rather than an intrinsic property of their genetic lesion.  (+info)

The X-ray structural investigation of 6-(n,n-1,6-hexyleneformamidine)-penicillanic acid (mecillinam). (64/94)

A new type of 6-formamidinepenicillanic acid in which the omega-nitrogen atom is involved in the azaheptane ring (mecillinam) having a strong selective activity against Gram-negative bacteria strains has been investigated by the X-ray single-crystal diffraction methods using crystals in the solvated state. The conformation of penam part as well as of the amidine group is discussed. Two independent molecules of mecillinam found in the asymmetric unit of the crystal cell differ from each other in their detailed conformations. The problem of the stability of the compound has been discussed also.  (+info)