Teichomycin, a new glycopeptide antibiotic with a spectrum of activity similar to that of vancomycin, was highly active against staphylococci, streptococci and Gram-positive anaerobes (Propionibacterium acnes, Clostridium perfringens and Cl. difficile). Ninety per cent of the Staphylococcus aureus and streptococcal strains, including enterococci, were inhibited by 0.4 mg/l; 90% of Staph. epidermidis strains were susceptible to 1.6 mg/l. Vancomycin was less active than teichomycin against all clinical isolates tested. Multiply resistant strains, including methicillin-resistant Staph. aureus, were all susceptible to teichomycin and vancomycin. Teichomycin was highly bactericidal for growing cells of staphylococci and Streptococcus pyogenes and moderately bactericidal for Str. faecalis. In mice, teichomycin was well absorbed upon subcutaneous administration and had a half-life of 2.5 h. It was very effective in curing experimental mouse septicemias caused by Gram-positive bacteria (ED50 values less than 1 mg/kg).

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Basic carboxamides of teicoplanin A2 (CTA) and its aglycon (TD) are prepared by condensation of the 63-carboxyl function of these antibiotics with linear or branched polyamines. The antimicrobial activities of some of the resulting compounds were better than those of the unmodified antibiotics. The presence of more than one basic group in the amidic chain enhanced the in vitro activity of some TD-amides against Gram-negative bacteria; two of these derivatives were also effective in vivo against Escherichia coli septicemia in the mouse. Among the CTA derivatives, the amide with spermine showed some unexpected in vitro activity against Gram-negatives. Both CTA- and TD-amides with polyamines are very soluble in water over a wide range of pH and are very hydrophilic.

The condensation of the carboxyl function of teicoplanin A2 (CTA) and its acidic hydrolysis pseudoaglycons (TB, TC) and aglycon (TD) with amines carrying various functional groups and chains produced amide derivatives with different isoelectric points and lipophilicities. Amide formation did not affect the ability of these compounds to bind to Ac2-L-Lys-D-Ala-D-Ala, a model for the natural peptide binding site in bacterial cell walls. The antimicrobial activities of teicoplanin amides were found to depend mostly on their ionic and lipophilic character and on the type and number of sugars present. Positively charged amides were generally more in vitro active than the respective unmodified antibiotics against Gram-positive organisms. In particular, most basic amides of CTA were markedly more active than teicoplanin against coagulase-negative staphylococci. A few amides of TC and most of those of TD also showed a certain activity against Gram-negative bacteria. In experimental Streptococcus pyogenes septicemia in the mouse, some basic amides were more active than the parent teicoplanins when administered subcutaneously. Some of those of CTA were also slightly more effective than teicoplanin by oral route.

The mechanism of action of rifampicin, an antibiotic which inhibits in vitro the polycondensation of ribonucleotides by ribonucleic acid (RNA) nucleotidyltransferase, was studied in vivo in Escherichia coli . It is argued that the inhibition of RNA nucleotidyltransferase represents the primary lesion and is responsible for the bactericidal effect. This conclusion is based on (i) the correlation between concentrations of the antibiotic which block in vivo incorporation of labeled uracil and the bactericidal concentrations, (ii) the evidence that the loss of viability of the cells immediately follows the block of RNA synthesis, and (iii) the observation that the reversal of the inhibition of RNA synthesis goes together with a reversal of the loss of viability.