Activities of derivatives of dehydrodicaffeic acid dilactone (DDCAD) to inhibit catechol-O-methyltransferase (COMT), cyclic AMP phosphodiesterase (PDE) and DOPA decarboxylase(DDC) were examined. Among those tested, 2, 6-bis-(5', 6'-dibromo-4'-hydroxy-3'-methoxyphenyl)-3, 7-dioxabicyclo-[3, 3, 0]-octane 4, 8-dione was found to be the strongestinhibitor of both COMT and PDE. There were no derivatives which showed a strongerinhibition against DDC than the original compound, DDCAD.
A new antifungal antibiotic, named ileumycin, was isolated from culture broth of StreptomycesH 698-SY2, which was identified as S. lavendulae. The antibiotic was recovered from the culture filtrate by adsorption on Amberlite XAD-II and elution with aqueous methanol and was further purified by ion-exchange column chromatography on SE-cellulose and followed by partition chromatography on silica gel. The antibiotic was named ileumycin, because isoleucine was detected in the acid hydrolyzate of the antibiotic. Ileumycin exhibited antimicrobial activity against only a few species of fungi.
The effects of pretreatment with colistin (polymyxin E) on the sensitivity of Proteus mirabilis, P. vulgaris and P. morganii strains to tris and sodium deoxycholate (DOC) have been studied. Pretreatment of two P. mirabilis strains (NCTC 60 and 4199) with low concentrations (0.25-1μg/ml) of colistin rendered them sensitive to lysis by tris (0.05 M) or DOC (250-1, 000μg/ml) although DOC induced lysis of control (non colistin-treated) suspensions also. In contrast, the other P. mirabilis strains, as well as the P. vulgaris and P. morganii strains were little affected by tris (0.2 M) or DOC (10, 000μg/ml) even after exposure of the cells to high colistin concentrations (up to 500μg/ml). Colistin-pretreated or control cells of P. mirabilis NCTC 60 rapidly lost viability when suspended in water but not when held in 0.16 M sodium chloride solution. Ethylenediamine tetraacetate-pretreated cells of strains 60 and 4199 were fairly sensitive to tris, although the extent of the lysis was less than when colistin was used as pretreating agent. One strain of P. vulgaris (NCTC 4175) became sensitive to tris and to DOC following exposure of the cells to ampicillin.
Twenty clinical isolates of Serratia sp. were tested against netilmicin, gentamicin, carbenicillin and cefamandole alone (broth and agar dilution) and in combination (agar dilution). Broth and agar dilution minimal inhibitory concentrations agreed to within a two-fold dilution in 96% of the tests. Overall, 95% of the isolates were susceptible to netilmicin regardless of susceptibility to gentamicin or carbenicillin. Netilmicin-carbenicillin synergy was seen in 55% of the strains and netilmicin-cefamandole in 70%. These results indicate that combinations of netilmicin with carbenicillin or cefamandole may be clinically useful.
The synergistic activities of netilmicin, gentamicin and amikacin combined with carbenicillin, ticarcillin, azlocillin and mezlocillin were investigated against 32 Serratia marcescens isolates. Synergy could be demonstrated by killing curve technique, isobologram plots as well as susceptibility data with any of the aminoglycosides and penicillins combinations. No antagonism was shown with any of the combinations. The majority of the isolates were resistant to the aminoglycosides and penicillins. Combination of either ureido-penicillin or carbenicillin with gentamicin or netilmicin did not reduce the MIC values to levels achievable in serum but did reduce the MIC levels of both agents to those achievable in urine. The combination of ureido-penicillins or carbenicillin and ticarcillin with amikacin reduced the inhibitory levels of all isolates to levels achievable in both serum and urine.
Eight sensitive strains (two Staphylococcus aureus, two Escherichia coli, two Pseudomonas aeruginosa and two Klebsiella pneumoniae) and four resistant Pseudomonas aeruginosa strains were used to study uptake of sisomicin and gentamicin by the bacterial cells. In eleven out of the twelve organisms studied employing (methyl-14C)-sisomicin and (methyl-14C)- gentamicin, uptake of the former was found higher than that of the latter. In one organism, the uptake of the two antibiotics was similar. This higher uptake of sisomicin may help explain the superior potency of the antibiotic in relation to gentamicin.
Antifungal action of di- and triacetyl derivatives of mycobacillin is not antagonised by cholesterol or lecithin which antagonise the action of its heptamethyl derivative. Considering the reactive groups of mycobacillin, the antagonism may involve the tyrosine hydroxyl groups of the antibiotic and the 3-hydroxyl group of cholesterol or the oleic acid component of lecithin having unsaturation at the 9: 10 position with cis-configuration.
Binding of aminoglycoside antibiotics to acidic mucopolysaccharides has been studied by means of physicochemical methods. Reactivity was affected markedly by the ionic environment, e.g. pH and ionic strength of the medium, the concentrations and the molar ratios of the constituents. The ionic character of binding was further confirmed by gel chromatography. The reduction of metachromasis by an aminoglycoside was also observed. Theiraffinity is correlated with localization of the aminoglycosides in vivo. According to reactivity, the following descending order of affinity was obtained for each family: neomycin, gentamicin, sagamicin, kanamycin and streptomycin; heparin, chondroitin sulfate and hyaluronic acid. This sequence of aminoglycosides corresponds to the extent of oto-, nephro- and neuro-(acute)toxicity, suggesting that their affinity for acidic mucopolysaccharides contribute to their tissue toxicity.