Potential synergistic activity of quercetin with antibiotics against multidrug-resistant clinical strains of Pseudomonas aeruginosa.

Development of drug resistance in opportunistic pathogens is one of the major healthcare challenges associated with infection management. Combination therapy has many advantages due to the simultaneous action of two drugs on two separate cellular targets. However, selection of the drugs should offer safety and synergistic interaction against most of the strains. Here, the efficacy of antibiotics in combination with quercetin, a natural flavonoid capable of targeting quorum sensing was tested against biofilm-forming Pseudomonas aeruginosa strains previously isolated from catheter associated urinary tract infection. Based on the antibiotic susceptibility pattern, synergistic effect of quercetin with selected antibiotics (levofloxacin, ceftriaxone, gentamycin, tobramycin and amikacin) was tested at the fractional concentrations of MIC by the checkerboard method and the fractional inhibitory concentration index (FICi) was calculated to estimate the synergistic effect. Effect of the synergistic combinations were further tested using time-kill assay, and against biofilm formation and biofilm cell viability. Cytotoxicity assays were performed using Human Embryonic Kidney 293T cells (HEK-293T) using the effective drug combinations with respective controls. The biofilm formation and biofilm cell viability were drastically affected with quercetin and selected antibiotics combinations with ≥80% inhibition. In vitro infection studies showed that all the strains could exert significant cell killing (68 to 85%) and the drug combinations decreased the infection rate significantly by reducing the cell killing effect of P. aeruginosa (p<0.05). The synergistic effect of quercetin is attributed to its quorum sensing inhibitory properties. These findings indicate that quercetin along with existing antibiotics can potentiate the treatment against P. aeruginosa infection and may reduce the selection pressure due to antibiotic overuse.

Laparoscopic pyelolithotomy as a monotherapy for the management of intermediate-sized renal pelvic stones.

INTRODUCTION: Renal calculi are one of the major reason leading to kidney failure or urinal obstructions. Percutaneous nephrolithotomy is considered as the major management option for intermediate to large renal pelvic stones. In the present study we compare Percutaneous nephrolithotomy vs laparoscopic pyelolithotomy procedures in the management of intermediate sized renal pelvic stones. METHODS: The time duration of study was between July 2012 and Jan 2014, 20 patients with solitary intermediate sized renal pelvic stones were selected and randomly divided into two groups; group one included 10 patients who were treated by laparoscopic pyelolithotomy and group two included 10 patients who were treated by PCNL. The differences in procedure time, blood loss, stone clearance and duration of hospital stay between the two procedures were compared and analyzed. RESULTS: There was no difference between the two groups regarding patient demographics and stone size. There was statistically significant difference between laparoscopic pyelolithotomy and PCNL regarding mean estimated blood loss (<50 mL vs. 180-250 mL), hospital stay (3-5 days vs. 4-6 days), mean time of postoperative analgesia (2.2 ± 0.9 days vs. 2 ± 0.9 days), and stone-free rate (100% vs. 95%). The operative time was significantly longer in the laparoscopic pyelolithotomy group (80-150 min vs. 45-75 min). CONCLUSION: Although PCNL is the gold standard for intermediate-sized renal pelvic stones of 2-4 cm, laparoscopic pyelolithotomy is a suitable surgical technique in selected cases.