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Quantitative and qualitative determinations of the combined effect of tetracycline and oleandomycin. II. In vivo effect.

The combination effect of tetracycline (TC) and oleandomycin (OM) on acute infection of mice with four strains of Staphylococcus aureus including TC or OM resistant ones was examined by the quantitative determination of protective potencies of single and combined drugs. The grade of synergism was expressed by the synergistic ratio (SR), a ratio of experimentally determined potency of the combined drug over a hypothetical potency in which additive effect of the both drugs is assumed. With 3 out of the 4 strains of S. aureus synergism between TC and OM or triacetyloleandomycin (TAO) was demonstrated by the determination of the 50% effective dose and by statistical examination of the SR. The grade of synergistic protection by these drugs varied with the strains infected and it did not depend upon the sensitivity to antibiotics or grade of synergism in vitro. There was no synergistic enhancement of acute toxic action in the combined administration of TC and OM to mice.

Animals↗

Nonantibiotic effects of macrolide antibiotics of the oleandomycin-erythromycin group with special reference to their "steroid-sparing" effects.

Certain macrolide antibiotics, such as troleandomycin (TAO), oleandomycin, and erythromycin estolate (Ilosone), can lower the maintenance dose of glucocorticoids required by severely asthmatic patients. These effects were postulated to be caused by an as yet undefined steroid-sparing effect. In this study, TAO in combination with methylprednisolone, when compared with methylprednisolone alone, was demonstrated to significantly increase liver glycogen deposition in adrenalectomized mice, intact mice, and adrenalectomized rats; protect histamine-sensitized mice following beta adrenergic blockade or adrenalectomy; further decrease the steroid-lowered glucose tolerance of mice and significantly increase the plasma corticosteroid levels in rats. TAO alone did not have these effects. TAO plus betamethasone, and erythromycin estolate plus methylprednisolone also increased liver glycogen deposition. However, TAO did not appear to potentiate the effects of hydrocortisone. Erythromycin stearate and to a lesser degree erythromycin ethylsuccinate when combined with methylprednisolone also decreased histamine lethality in mice. Leucomycin and tetracycline did not enhance the effects of methylprednisolone. TAO, alone or with methylprednisolone, did not alter serum glutamic oxaloacetic transaminase (SGOT) levels in rats. Thus, TAO and some other macrolides did not exert their effects on corticosteroids as antimicrobial agents, adrenocorticotropic hormone (ACTH)--like compounds, or quasisteroids, but as steroid-sparing agents by some undefined mechanism.

Anaphylaxis↗

Oviedomycin, an unusual angucyclinone encoded by genes of the oleandomycin-producer Streptomyces antibioticus ATCC11891.

Our investigations on the discovery of novel natural metabolites using type II polyketide synthase gene probes (actI/III) yielded an unusual angucyclinone, oviedomycin (2), when applied to the oleandomycin (1) producer Streptomyces antibioticus ATCC11891. The novel natural product was produced using S. albus R(-)M(-) as a host strain, into which a cosmid containing the oviedomycin gene cluster was transformed. Its structure was elucidated by NMR spectroscopy and mass spectrometry.

Aminoglycosides↗

[Is triacetyl oleandomycin-ergotamine tartrate combination dangerous?].

The authors report a case of ischaemia of all four limbs in an adolescent following the simultaneous ingestion of triacetyl oleandomycin and ergotamine tartrate in low dosage. Two cases involving this same association of medications have appeared in the literature and attention is therefore drawn to the possible danger of use of these two drugs together.

Adolescent↗