No abstract

Discovery of novel drugs with new mechanisms of action and without cross-reaction with current therapeutic agents is crucial in the management of infections caused by multi-drug resistant (MDR) bacteria. The aim of the present study was to investigate effects of carvacrol and thymol on biofilm formation and antimicrobial activity against different carbapenemase-producing Gram negative bacilli. The antimicrobial and antibiofilm effect of thymol and carvacrol was investigated against strains harboring different genes related to carbapenemase resistance. Antimicrobial resistance was examined by an agar dilution method and antibiofilm effect was evaluated by microtiter plate assay and staining by crystal violet. Thymol and carvacrol had antibacterial effects ranging from 200-1600 μg/mL and 62-250 μg/mL respectively, and antibiofilm effect from 125-500 and 400-1600 μg/mL respectively. Seoul imipenemase- (SIM) producing isolates had the highest sensitivity, and NDM (New Delhi metallo-beta-lactamase) producing isolates had the lowest sensitivity to these components. Findings of the present study indicated a potential role of carvacrol and thymol in controlling carbapenemase-producing gram negative bacterial infections. These findings helped to develop herbal drugs for replacing antibiotics. In addition, their antibiofilm effects showed that carvacrol and thymol inhibit biofilm formation of carbapenemase-producing strains.

Bacterial antimicrobial resistance mediated by the production of extended-spectrum β-lactamases (ESBLs) is considered a major threat for treatment of Salmonella and Shigella infections. This study aimed to investigate antibiotic resistance patterns of Salmonella and Shigella spp. and presence of CTX-M from three teaching hospitals in Iran. In the present study, 58 clinical Shigella and 91 Salmonella isolates were recovered between 2009 and 2013 from 3 teaching hospitals in Iran. After culture and antimicrobial susceptibility testing, ESBL-positive isolates were subjected to further investigations. These included polymerase chain reaction (PCR) amplification and DNA sequencing of blaCTX-M-15 encoding plasmid. In both genera, high sensitivity to gentamicin and amikacin, but high resistance to ampicillin, tetracycline, and trimethoprim–sulfamethoxazole, was found. Molecular investigation showed that 31.8% isolates of Salmonella spp. and 34.48% isolates of Shigella spp. were CTX-M positive and all of them were also positive for ISEcpI. Protein translation, comparing with reference sequences, showed that all CTX-M isolates belong to CTX-M-15. The present study suggests that the resistance of ESBLs-producing Salmonella and Shigella spp. in Iran hospitals is very serious. Therefore, strategies to minimize the spread of ESBL-producing isolates should be implemented.

Carbapenemase inhibitors play a critically important role in prevention of carbapenem resistance. In the current review, based on studied articles from PubMed, Google Scholar and Scopus, we summarize the current state of carbapenemase inhibitors and their importance in clinical use. Clavulanic acid, sulbactam and tazobactam are traditional β-lactam\class A carbapenemase inhibitors. Avibactam; relebactam and boronic acid-based inhibitors including PRX7009, β-lactamase inhibitory protein II, Zinc01807204 and Zinc02318494 compounds are also novel and non-β-lactam\class A carbapenemase inhibitors. In the case of metallo-β-lactamase inhibitors, EDTA, thioester derivatives, propionic acid, maleic acid, succinic acid and phthalic acid derivatives are reputed inhibitors. There are limited oxacillinase (OXA) inhibitors because of the variability in amino acid sequence of OXAs. Boronic acid-based compounds and penicillin sulfone derivatives are promising candidates for the development of OXA-carbapenemase inhibitors. Although the prospect for non-β-lactam inhibitors is better, but the available inhibitors are mostly developed against plasmid-mediated carbapenemases, and other clinically important carbapenemases are increasing throughout the world. Despite in-vitro activity of aforementioned inhibitors, few of them are in clinical use. Side effects followed by inhibitors and also carbapenemase inhibitor resistance indicate the clinical need for development of novel, effective and nontoxic inhibitors to overcome carbapenemase-mediated resistance in bacteria.

Background: Gastroenteritis is known as the leading cause of morbidity and mortality in children worldwide. Diarrhea is the second leading cause of infant death in the developing countries. Identification of gastroenteritis-causing pathogens helps to control fecal-oral transmission and prevents further outbreaks.