ABSTRACT
Octapeptin has strong antibacterial activity against Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, while it also has activity against some Gram-positive bacteria. This study used natural octapeptin A3 and B3 as lead compounds for structural modification. Twenty-one peptide derivatives (including A3 and B3) containing eight amino acid residues were prepared by solid-phase synthesis, and evaluated for antibacterial activity and renal cytotoxicity. Among them, three compounds 6, 7 and 17 exhibited broad-spectrum antibacterial activity and significantly enhanced the activity for Gram-positive bacteria while maintaining the activity of Gram-negative bacteria. Several compounds improved the activity for Pseudomonas aeruginosa. Compound 7 was active against all test strains and had relatively low renal cytotoxicity. The results provide a basis for the further development of novel polypeptide antibiotics.
ABSTRACT
Meropenem is a broad spectrum antibacterial drug from the carbapenem family. It is commonly used as an empirical antimicrobial in severe infections like pneumonia, intra-abdominal infections, septicaemia, meningitis etc. Severe adverse effects with meropenem are rare (<1 %) which include hypersensitivity and hematologic adverse effects. In the literature, few cases have been reported of meropenem induced thrombocytopenia that has shown the immune mechanism by which thrombocytopenia occurs. Drug induced thrombocytopenia (DITP) can be a life threatening condition if not diagnosed and managed properly. As meropenem is being widely used in hospitals nowadays, it is important to be aware of the rare but serious adverse effects it causes.