ABSTRACT
Background: With the global epidemic of sepsis on the rising trend and gram negative sepsis being one of the most commoncause of increasing morbidity and mortality in developing nations like India, it becomes imperative to understand the role ofcombination antibiotics in controlling this burden. Aim and Methodology: In this study, we recognized the potential therapeuticrole of Meropenem combined with EDTA against a clinical endemic isolate of multi-drug resistant extended spectrum betalactamases (ESBLs) producing pathogens was investigated. The E-test strips studied the antimicrobial susceptibility of thepathogens and were applied to check for in-vitro sensitivity to Meropenem and combination of Meropenem and Ca-EDTA. Result:The MIC value of Meropenem-EDTA (0.25) was less than 50% of that of Meropenem (2.45) in sensitive isolates. Conclusion:Meropenem in unification with EDTA can exhibit more potent antimicrobial activity against ESBL producing pathogens thanjust Meropenem or EDTA alone.
ABSTRACT
Polymyxin B and polymyxin E (colistin) are increasingly used as last-resort drugs for treatment of infections caused by multidrug-resistant gram-negative pathogens. Unfortunately, the application was limited due to the serious side effects, especially nephrotoxicity. Very recently, the need for developing more tolerated and more effective polymyxin analogues has grown. This study details the design, synthesis, and evaluation of two classes of polymyxin B analogues with varying hydrophobicity and bulkiness at the N-terminal fatty acyl chain or position 6 amino acid. 20 polymyxin B analogues were synthesized and the chemical structures of the analogues were confirmed by HR-MS and 1H NMR spectra. Compounds 7e (MIC: 0.5-4 μg·mL-1) and 7l (MIC: 0.25-2 μg·mL-1) showed similar or better antimicrobial activity against both susceptible and resistant strains of Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa compared to polymyxin B (MIC: 0.5-2 μg·mL-1). Besides, compound 7l (CC50: 217.1±13.2 μg·mL-1) displayed noticeably decreased renal cytotoxicity compared to polymyxin B (CC50: 120.3±6.0 μg·mL-1). This work establishes the base of further study on the structure-activity relationship of polymyxin B.
ABSTRACT
Increase in the mortality and morbidity in pleural infection is a concern worldwide due to increasing resistant Gram negative pathogens like Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella species. Rise of pneumonia due to K. pneumoniae, is more likely observed in alcoholics, diabetics, hospitalized and patients receiving mechanical ventilation. In the present study, we discuss a case of a 59 year old male patient with pulmonary effusion infected with extended spectrum beta-lactamases (ESBL) producing K. pneumoniae with co-morbidities of uncontrolled Type II diabetes mellitus (DM), hypertension and coronary artery disease (CAD), treated with a newer antibiotic adjuvant entity: Elores (ceftriaxone/sulbactam/disodium edetate) and recovered well.