The discovery of penicillin nearly 90 years ago revolutionized the treatment of bacterial disease. Since that time, numerous other antibiotics have been discovered from bacteria and fungi, or developed by chemical synthesis and have become effective chemotherapeutic options. However, the misuse of antibiotics has lessened the efficacy of many commonly used antibiotics. The emergence of resistant strains of bacteria has seriously limited our ability to treat bacterial illness, and new antibiotics are desperately needed. Since the discovery of penicillin, most antibiotic development has focused on the discovery of new antibiotics derived from microbial sources, or on the synthesis of new compounds using existing antibiotic scaffolds to the detriment of other lines of discovery. Both of these methods have been fruitful. However, for a number of reasons discussed in this review, these strategies are unlikely to provide the same wealth of new antibiotics in the future. Indeed, the number of newly developed antibiotics has decreased dramatically in recent years. Instead, a reexamination of traditional medicines has become more common and has already provided several new antibiotics. Traditional medicine plants are likely to provide further new antibiotics in the future. However, the use of plant extracts or pure natural compounds in combination with conventional antibiotics may hold greater promise for rapidly providing affordable treatment options. Indeed, some combinational antibiotic therapies are already clinically available. This study reviews the recent literature on combinational antibiotic therapies to highlight their potential and to guide future research in this field.

Objective: Pittosporum angustifolium Lodd. is used to treat a variety of pathogenic diseases and inflammation by Australian aborigines. Practitioners of complementary medicine frequently use herbal medicines concurrently with conventional antibiotics. There is a need to evaluate their effects in combination. Methods: The bacterial growth inhibitory activity of P. angustifolium leaf extracts was assessed against a panel of pathogenic triggers of some autoimmune diseases by standard disc diffusion and liquid dilution minimum inhibitory concentration (MIC) methods. Combinational effects between the extracts and conventional antimicrobials were classified using the sum of the fractional inhibitory concentration. Synergistic interactions were further assessed across a range of ratios by isobologram analysis. The toxicity of the individual samples and combinations was evaluated by Artemia lethality and 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) human dermal fibroblast cell viability assays. Results: P. angustifolium leaf extracts strongly inhibited the growth of several bacterial triggers of autoimmune diseases. The methanolic, aqueous and ethyl acetate extracts were particularly good inhibitors of Proteus mirabilis and Klebsiella pneumonia growth (MIC = 26 and 57 µg/mL respectively). Some combinations of the extracts and conventional antibiotics significantly potentiated the combined inhibitory activity compared to the individual components. Of the 250 combinations studied, approximately 0.02% showed synergistic interactions, 49.6% were additive, 46.8% showed indifferent interactions and antagonism occurred in only 0.02% of the combinations. Interestingly, all of the synergistic and antagonistic combinations contained tetracycline as their antibiotic component. Conclusion: P. angustifolium leaf extracts inhibit the growth of pathogenic triggers of some autoimmune diseases. Some extracts also potentiated the activity of conventional antibiotics, without significantly affecting the toxicity of the combination.Please cite this article as: Blonk B, Cock IE. Interactive antimicrobial and toxicity profiles of Pittosporum angustifolium Lodd. extracts with conventional antimicrobials. J Integr Med. 2019; Epub ahead of print.

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