MRSA

A burn is a wound in which there is coagulative necrosis of the tissue, majority of which are caused by heat. Burn injury is a major public health problem in many areas of the world. Infection in burn wounds is the second most common cause of mortality in burn cases after pneumonia. Burns predispose to infection by damaging the protective barrier function of the skin, thus facilitating the entry of pathogenic microorganisms. Burn itself is an immunocompromised condition. The present study was therefore undertaken to isolate and identify the aerobic bacterial flora in burn patients and its antibiotic susceptibility pattern. A total of 100 patients admitted with different degree of burns were studied. Wound swabs were taken with aseptic precautions by dry sterile cotton swab sticks. These swabs were transported to the microbiology laboratory and isolates were identified by standard microbiological methods. Antibiotic susceptibility was done by Kirby Bauer’s Disk Diffusion method as per CLSI (Clinical and Laboratory Standards Institute ) guidelines. A total of 120 bacterial pathogens were isolates from 100 patients. Out of them 70  are monomicrobial in and 20 are polymicrobial in nature. The most frequent cause of infection was found to be Staphylococcus aureus (33.33%), followed by Pseudomonas aeruginosa (29.67%), Klebsiella pneumoniae (17.5%), E.coli (13.33%)  Citrobacter spp (4.1%) and Proteus spp. (2.94%). Out of the total Staphylococcus aureus isolates, 55% were Methicillin sensitive and 45% were Methicillin resistant (MRSA). All the MRSA strains were 100% sensitive to Vancomycin and Linezolid. The Pseudomonas aeruginosa isolates were most sensitive to Imipenem (97%), Amikacin (57%), Pipercillin (57%) , Ciprofloxacin (54%) and Ceftazidime (34% ) Staphylococcus aureus and Pseudomonas aeruginosa were major causes of infection in burn wounds. Therefore it is necessary to implement urgent measures for restriction of nosocomial infections, sensible limitation on the use of antimicrobial agents, strict disinfection and hygiene.

Efflux inhibition is proven bacterial machinery responsible for removal of bacterial wastage including antibiotics. Recently, efflux inhibitors (EI) have been tested with encouraging results as an adjuvant therapy for treatment of various bacterial invasions especially methicilline-resistant Staphylococcus aureus (MRSA). Although, EI have emerged as innovative approach of treatment for several multi drug resistant bacterial infections including tuberculosis, toxicity profile limits their wider use. To address this issue, we have attempted synthesizing hybrid molecules those results by combining known EI and triazole. This synthesis was aimed to arrive at structure that possesses pharmacophore from known EI. Synthesized molecules were evaluated as growth inhibitors (GI) and Efflux inhibitor of S. aureus. Pharmacologically active compounds were then tested for their cytotoxicity to further narrow down search. Most active compounds 209, 210, 217 & 228 were then tested for their GEI action against MRSA. We arrived at compound 210 as most potent dual inhibitor.

Efflux inhibition is proven bacterial machinery responsible for removal of bacterial wastage including antibiotics. Recently, efflux inhibitors (EI) have been tested with encouraging results as an adjuvant therapy for treatment of various bacterial invasions especially methicilline-resistant Staphylococcus aureus (MRSA). Although, EI have emerged as innovative approach of treatment for several multi drug resistant bacterial infections including tuberculosis, toxicity profile limits their wider use. To address this issue, we have attempted synthesizing hybrid molecules those results by combining known EI and triazole. This synthesis was aimed to arrive at structure that possesses pharmacophore from known EI. Synthesized molecules were evaluated as growth inhibitors (GI) and Efflux inhibitor of S. aureus. Pharmacologically active compounds were then tested for their cytotoxicity to further narrow down search. Most active compounds 177, 178, 187 and 196 were then tested for their GEI action against MRSA. We arrived at compound 145 as most potent dual inhibitor.