Molecular characterization of extended spectrum ß -lactamases enterobacteriaceae causing lower urinary tract infection among pediatric population.

Background: The ß-lactam antibiotics have traditionally been the main treatment of Enterobacteriaceae infections, nonetheless, the emergence of species producing ß- Lactamases has rendered this class of antibiotics largely ineffective. There are no published data on etiology of urinary tract infections (UTI) and antimicrobial resistance profile of uropathogens among children in Qatar. The aim of this study is to determine the phenotypic and genotypic profiles of antimicrobial resistant Enterobacteriaceae among children with UTI in Qatar. Methods: Bacteria were isolated from 727 urine positive cultures, collected from children with UTI between February and June 2017 at the Pediatric Emergency Center, Doha, Qatar. Isolated bacteria were tested for antibiotic susceptibility against sixteen clinically relevant antibiotics using phoenix and Double Disc Synergy Test (DDST) for confirmation of extended-spectrum beta-lactamase (ESBL) production. Existence of genes encoding ESBL production were identified using polymerase chain reaction (PCR). Statistical analysis was done using non-parametric Kappa statistics, Pearson chi-square test and Jacquard's coefficient. Results: 201 (31.7%) of samples were confirmed as Extended Spectrum ß -Lactamases (ESBL) Producing Enterobacteriaceae. The most dominant pathogen was E. coli 166 (83%) followed by K. pneumoniae 22 (11%). Resistance was mostly encoded by bla CTX-M (59%) genes, primarily bla CTX-MG1 (89.2%) followed by bla CTX-MG9 (7.7%). 37% of isolated bacteria were harboring multiple bla genes (2 genes or more). E. coli isolates were categorized into 11 clusters, while K. pneoumoniae were grouped into five clonal clusters according to the presence and absence of seven genes namely bla TEM, bla SHV, bla CTX-MG1, bla CTX-MG2, bla CTX-MG8 bla CTX-MG9,bla CTX-MG25. Conclusions: Our data indicates an escalated problem of ESBL in pediatrics with UTI, which mandates implementation of regulatory programs to reduce the spread of ESBL producing Enterobacteriaceae in the community. The use of cephalosporins, aminoglycosides (gentamicin) and trimethoprim/sulfamethoxazole is compromised in Qatar among pediatric population with UTI, leaving carbapenems and amikacin as the therapeutic option for severe infections caused by ESBL producers.

Polymeric micelles: Basic research to clinical practice.

Rapidly developing polymeric micelles as potential targeting carriers has intensified the need for better understanding of the underlying principles related to the selection of suitable delivery materials for designing, characterizing, drug loading, improving stability, targetability, biosafety and efficacy. The emergence of advanced analytical tools such as fluorescence resonance energy transfer and dissipative particle dynamics has identified new dimensions of these nanostructures and their behavior in much greater details. This review summarizes recent efforts in the development of polymeric micelles with respect to their architecture, formulation strategy and targeting possibilities along with their preclinical and clinical aspects. Literature of the past decade is discussed critically with special reference to the chemistry involved in the formation and clinical applications of these versatile materials. Thus, our main objective is to provide a timely update on the current status of polymeric micelles highlighting their applications and the important parameters that have led to successful delivery of drugs to the site of action.

Hydrolyzed polyacrylamide grafted maize starch based microbeads: application in pH responsive drug delivery.

The present study details the synthesis, characterization and pharmaceutical application of hydrolysed polyacrylamide grafted maize starch (HPam-g-MS) as promising polymeric material for the development of pH responsive microbeads. Different grades of graft copolymer were synthesized by changing the net microwave irradiation time, while keeping all other factors constant. Acute oral toxicity study performed in rodents ensured the bio-safety of graft copolymer for clinical application. Various batches of aceclofenac loaded microbeads were prepared by ionic gelation method using synthesized graft copolymers and evaluated for formulation parameters. FTIR spectroscopy confirmed the chemical compatibility between drug and graft copolymer. Results of in vitro release study (USP type-II) carried out in two different pH media (pH 1.2 acid buffer and pH 7.4 phosphate buffer) showed that release rate of drug from developed microbeads was a function of both: (a) surrounding pH and (b) the matrix composition. The drug release was relatively higher at alkaline pH as compared to acidic pH and this feature is desirable from viewpoint of site specific drug delivery. A direct correlation was observed between percentage grafting and microbeads performance and it presents a scope for further research on application and optimization of HPam-g-MS based microbeads as drug delivery carriers.

Hydrolyzed polyacrylamide grafted carboxymethylxyloglucan based microbeads for pH responsive drug delivery.

The present study investigates the pharmaceutical application of hydrolyzed polyacrylamide grafted carboxymethylxyloglucan (HPam-g-CMXG), as promising polymeric material for the development of pH responsive microbeads. The graft copolymer was synthesized by conventional free radical polymerization method and saponified to enhance its functionality and characterized. An acute oral toxicity study ensured the bio-safety of developed copolymer for clinical application. Various batches of pH responsive spherical microbeads were developed and evaluated for the effect of process parameters on their overall performance. Result of in vitro drug release study (USP Type-II, paddle method) carried out in two different pH media (pH 1.2 and pH 7.4) showed a triphasic drug release pattern in all the formulations. Both the drug release and swelling of microbeads were significantly higher in simulated intestinal (alkaline) pH compared to simulated gastric (acidic) pH and this nature is desirable for targeted drug delivery. A strong correlation was observed between the process parameters and matrix composition and it directly influenced the drug transport mechanism. In conclusion, the hydrolyzed polyacrylamide grafted carboxymethylxyloglucan holds an immense potential to be explored pharmaceutically as new matrix material for the design of targeted drug delivery system.