Ferulic acid derivative inhibits NorA efflux and in combination with ciprofloxacin curtails growth of MRSA in vitro and in vivo.

A series of ferulic acid (FA) derivatives were synthesized and evaluated for its ability to inhibit NorA efflux in methicillin resistant Staphylococcus aureus (MRSA), by in silico docking analysis. Based on prediction from glide scores and ability to reduce EtBr MIC, two of the ten derivatives S3- [4-((E)-2-(diethylcarbamoyl)vinyl)-2-methoxyphenyl acetate] and S6- [(E)-methyl 3-(4-((p-tolylcarbamoyl)methoxy)-3-methoxyphenyl)acrylate] were chosen as putative efflux pump inhibitors (EPI's). Time dependent accumulation studies revealed that S6 caused enhanced EtBr accumulation relative to standard NorA efflux inhibitor reserpine, in clinical isolate of MRSA (CIMRSA) and in NorA overexpressed strain of S. aureus (SA1199B). S6 also exhibited synergy with Ciprofloxacin (CPX) against NorA overexpressed strain (SA1199B) of S. aureus but not in NorA knock out strain (K1758). MIC reversal studies showed that S3 in CIMRSA and S6 in NorA overexpressed strain of S. aureus (SA1199B), caused a 4 fold reduction in CPX MIC. In vitro time kill studies revealed that both S3 and S6 with sub MIC of CPX caused a significant 4 log CFU decline in CIMRSA. A decline of >3 log fold CFU by time kill assay implies synergy between FA derivatives and CPX. When tested in vivo in infected muscle tissue of zebrafish both S3 and S6 with CPX caused >3.2 log decline in CIMRSA cell counts relative to CPX treatment alone. Of the two potent derivatives, S6 probably acts through NorA whereas S3 might exert its effect through pump other than NorA. Greater in vitro and in vivo efficiency of FA derivatives implies its potential to be used as an adjuvant along with CPX to curtail MRSA infection in higher animal models.

A study on isolation rate and prevalence of drug resistance among microorganisms isolated from multiorgan donor and donor corneal rim along with a report on existence of bla NDM-1 among Indian population.

PURPOSE: To study the rate of isolation and prevalence of drug resistance among bacteria isolated from conjunctival swabs collected from multiorgan donor and Donor corneal rim specimens obtained from a tertiary eye hospital in South India. METHODS: Donor corneal rims (DCR) and conjunctival swabs from multiorgan donors collected over a period of 6 months were screened for the prevalent species of bacteria and drug resistance associated with them against the first line of antibiotics by phenotypic methods and multidrug resistant isolates were further subjected for genotypic analysis. RESULTS: Seventy-six DCR specimens were screened out of which 46 (60.5%) specimens showed bacterial growth, the predominant isolate being Coagulase negative Staphylococci, the rest 30 (39.5%) did not show any culture growth. All 42 (100%) conjunctival swabs collected from multiorgan donors were positive for bacterial culture, the prevalent species once again, being Coagulase negative Staphylococci. Among the other gram positive bacterial genus encountered were Streptococci, Bacillus, Diphtheroids and the gram negatives were Enterobacteriaceae and nonfermentors. Antibiotic resistance was significantly high among gram positive group. Seven (29.1%) gram negative isolates were positive for Extended Spectrum Beta Lactamases (ESBL's) by conventional and molecular method. A blaNDM -1 carrying Acinetobacter baumannii was isolated from a multiorgan donor. CONCLUSION: Preexcision culture in multiorgan donor is necessary to prevent postoperative endophthalmitis. Preexcision culture and antibiotic susceptibility testing of bacterial isolates of DCR will aid in understanding antibiotic pattern as institution of correct antibiotic will prevent the emergence of postoperative endophthalmitis. Molecular methods help in reducing the turn-around time for understanding the drug resistance genotypes.

Systemic melioidosis presenting as suppurative parotitis.

A 3 year old child was brought with fever, left parotid swelling and altered sensorium. Cultures from blood, pus and throat swab grew Burkholderia pseudomallei. A diagnosis of septicemic melioidosis with encephalopathy was made. She recovered following treatment with parenteral ceftazidime for 14 days, and 6 months of oral co trimoxazole and amoxycillin clavulanate. She is doing well on follow-up.