Diastereomeric 7-ureidoacetyl cephalosporins. I. Superiority of 7alpha-H-L-isomers over D-isomers.

The synthesis and in vitro structure-activity relationship of 7-ureidoacetyl cephalosporins carrying various substituents in the 3-position, compounds that showed an enhanced broad spectrum of antibacterial activity, has been outlined. Contrary to most of the previous observations with diastereomeric isomers of cephalosporins, it has been found that the L-side chain isomers also are very potent antibiotics and are even more active inhibitors of certain beta-lactamase-producing Gram-negative bacteria than the corresponding D-side chain isomers. SQ 69,613, 7beta-[[L-[(aminocarbonyl)amino]-2-furanylacetyl]amino]-3-[[(1-methyl-1H-tetrazol-5-yl) thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, sodium salt, the most active compound tested, except for activity against staphylococci, was as active in vitro as cefamandole.

Diastereomeric 7-ureidoacetyl cephalosporins. III. Contribution of D- and L-isomers to the growth inhibiting activities of 7alpha-H and 7alpha-OCH3 derivatives for gram-positive and gram-negative bacteria.

A series of 7beta-ureidoacetyl, 7alpha-H and 7alpha-OCH3 cephalosporin antibiotics have shown broad-spectrum antibacterial activity in vitro. In the 7alpha-H but not in the 7alpha-OCH3 series, contrary to experience in the antibiotic field, the L-isomers were substantially more active than the D-isomers both in vitro and in vivo particularly, but not exclusively, against Enterobacteriaceae that produce potent chromosomal cephalosporinases. Enhanced resistance to and inhibition of beta-lactamase (s) appeared to be responsible for this effect. Studies in vitro specifically with 7beta-thienylureidoacetyl derivatives showed that D-isomers interacted with L-isomers in the 7alpha-OCH3 series in a synergistic manner against "cephalosporinase-type" enzyme producers while isomers in the 7alpha-H series did not. Examples were presented in which this favorable event resulted in improved efficacy of the racemic mixture over the pure D- or L-isomer alone in appropriate experimental infections.

New antimicrobial nitrofuran, trans-5-amino-3-[2-(5-nitro-2-furyl)vinyl]-delta2-1,2,4-oxadiazole: antibacterial, antifungal, and antiprotozoal activities in vitro.

trans-5-amino-3-[2-(5-nitro-2-furyl)vinyl]-Delta(2) -1,2,4-oxadiazole, a new antimicrobial nitrofuran, has shown microbial activity in vitro against a wide range of bacteria and fungi, and against several protozoa. The antimicrobial activity of the nitrofuran is not significantly diminished in vitro in the presence of 50% human serum. The compound is not cross-resistant with a number of common antibiotics or synthetic antimicrobial agents; some cross-resistance with furazolidone is encountered. The development of resistance to the compound in vitro, when it occurs, is mixed, but is unrelated to increase in pathogenicity of the test organism.

Biological characterization of prasinomycin, a phosphorus-containing antibiotic.

Prasinomycin, a new antibiotic from the green spore streptomycete, Streptomyces prasinus, primarily inhibits the growth of gram-positive microorganisms. Like penicillin, it is effective only against growing cells. Though primarily bacteriostatic at levels about the minimal inhibitory concentration, it is bactericidal at higher levels. Neither synergism nor antagonism could be demonstrated for prasinomycin with a variety of other antibiotics. It is highly active upon subcutaneous administration to mice infected with Staphylococcus aureus, Streptococcus pyogenes C203, or Diplococcus pneumoniae. Prasinomycin has a unique prophylactic action whereby one dose protects mice against experimental infections for as long as 2 months. It is more effective against S. aureus infections in mice when administered subcutaneously 20 hr prior to infection than when given in divided doses 1 hr before and 4 hr after infection.

Activity of selected penicillins in vitro and in experimental bacterial infections in mice.

The minimal inhibitory concentration and the 50% mouse protective dose for five key penicillins are presented. Such data provide a useful guide in evaluating the activity of new penicillins, in comparison with those already commercially available, and establishes the amounts of antibiotic necessary to obtain a PD(50) for several experimental model infections in mice.