Recent advances in the development of antibacterial potentiators / 中华检验医学杂志

Multidrug-resistant bacteria that can′t be treated with any common antibacterial drugs have become a global medical crisis. Therefore, there is an urgent need for new antibacterial potentiators to restore the sensitivity of bacteria to the antibacterial drug. This review elaborates on the novel antibacterial synergistic methods and their underlying mechanisms, clinical experimental data and efficacy, and the progress of drug research and development. This review aims to raise awareness about antibacterial potentiators among the public.

Antibacterial and antibiotic potentiating capabilities of extracts isolated from Burkillanthus malaccensis, Diospyros hasseltii and Cleisthanthus bracteosus against human pathogenic bacteria

@#Antibiotics which once a boon in medicine and saved millions of lives are now facing an ever-growing menace of antibacterial resistance, which desperately needs new antibacterial drugs which are innovative in chemistry and mode of action. For many years, the world has turned to natural plants with antibacterial properties to combat antibiotic resistance. On that basis, we aimed to identify plants with antibacterial and antibiotic potentiating properties. Seventeen different extracts of 3 plants namely Burkillanthus malaccensis, Diospyros hasseltii and Cleisthanthus bracteosus were tested against multi-drug resistant Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Methicillinresistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA). Antibacterial activity of hexane, methanol and chloroform extracts of bark, seed, fruit, flesh and leaves from these plants were tested using, disk diffusion assay, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Antibiotic potentiating capabilities were tested using time-kill assay. B. malaccensis fruit chloroform extract showed the biggest zone of inhibition against MRSA (13.00±0.0 mm) but C. bracteosus bark methanol extract showed the biggest inhibition zone against MSSA (15.33±0.6 mm). Interestingly, bark methanol extract of C. bracteosus was active against MRSA (8.7±0.6 mm), MSSA (7.7±0.6 mm) (Gram-positive) and A. baumannii (7.7±0.6 mm) (Gram-negative). Overall, the leaf methanol and bark methanol extract of C. bracteosus warrants further investigation such as compound isolation and mechanism of action for validating its therapeutic use as antibiotic potentiator importantly against MRSA and A. baumannii.

Ivacaftor in cystic fibrosis: the first disease modifying agent.

The exact magnitude of cystic fibrosis (CF) in India is not known, as it is often misrepresented and underdiagnosed. CF is caused by a mutation in the gene that encodes for the CF transmembrane conductance regulator (CFTR) protein whose dysfunction leads to multiorgan manifestations. Most CF mutations either reduce the number of CFTR channels at the cell surface or impair the channel function. Current treatments (mucolytics, antibiotics and anti-inflammatory agents) target the secondary effects of CFTR dysfunction and help to ameliorate the symptoms but do not address the basic defect of the disease. Ivacaftor is a first-in-class oral CFTR potentiator that increases the CFTR channel opening. In clinical trials, ivacaftor has shown improved pulmonary function, normalization of sweat chloride concentration, substantial weight gain as well as acceptable safety profile. The most frequent adverse effects associated with ivacaftor include headache, oropharyngeal pain, upper respiratory tract infection, nasal congestion, abdominal pain and nasopharyngitis. FDA has approved this agent for the treatment of CF in patients aged 6 years or older with at least one copy of the G551D mutation in the CFTR gene. Searches of medline, cochrane database, medscape, SCOPUS and clinicaltrials.org were made for terms like CFTR potentiator, cystic fibrosis, and ivacaftor. Relevant journal articles from last 5 years were chosen.