Farrukh Sobia

The use of successive generations of beta-lactams has selected successive generations of beta-lactamases including CTX-M ESBLs, AmpC beta-lactamases, and KPC carbapenamases in Enterobacteriaceae. Moreover, this cephalosporin resistance, along with rising resistance to fluoroquinolones, is now driving the use of carbapenems and unfortunately the carbapenem resistance has emerged markedly, especially in Acinetobacter spp. due to OXA- and metallo-carbapenemases. The industry responded to the challenge of rising resistance and recently developed some novel beta-lactams such as ceftobiprole, ceftaroline etc. and many beta-lactam compounds, including beta-lactamase-inhibitors, such as BMS-247243, S-3578, RWJ-54428, CS-023, SMP-601, NXL 104, BAL 30376, LK 157, and so on are under trials. This review provides the comprehensive accounts of the developments in penicillins, cephalosporins, carbapenems, and beta-lactamase-inhibitors, and the insight about medicinal chemistry, mechanism(s) of action and resistance, potential strategies to overcome resistance due to beta-lactamases, and also the recent advancements in the development of newer beta-lactam compounds; some of which are still under trials and yet to be classified. This review will fill the gap since previously published reviews and will serve as a comprehensive update on the current topic.

Histamine, a biological amine, is considered as a principle mediator of many pathological processes regulating several essential events in allergies and autoimmune diseases. It stimulates different biological activities through differential expression of four types of histamine receptors (H1R, H2R, H3R and H4R) on secretion by effector cells (mast cells and basophils) through various immunological or non-immunological stimuli. Since H4R has been discovered very recently and there is paucity of comprehensive literature covering new histamine receptors, their antagonists/agonists, and role in immune regulation and immunomodulation, we tried to update the current aspects and fill the gap in existing literature. This review will highlight the biological and pharmacological characterization of histamine, histamine receptors, their antagonists/agonists, and implications in immune regulation and immunomodulation.

OBJECTIVE: To delineate the frequency of occurrence of bla(CTX-M), bla(TEM), and bla(SHV) in Enterobacteriaceae from North-Indian tertiary hospital. METHODS: A random collection of a subset of 45 Escherichia coli (E. coli) and 28 Klebsiella pneumoniae (K. pneumoniae) that was resistant to a third generation cephalosporin and obtained during 2007-2008 was selected for detailed screening for bla(CTX-M), bla(TEM), and bla(SHV) by monoplex PCRs. The isolates demonstrating the presence of bla(CTX-M) alleles were characterized for the specific CTX-M-genogroup by using a multiplex PCR. RESULTS: Resistance to cefoperazone, ceftazidime, ceftriaxone, cefotaxime, cefoxitin and piperacillin was 100% each in K. pneumoniae isolates, whereas these resistance-rates for E. coli isolates were 93.1%, 83.8%, 91.9%, 93.6%, 97.3% and 97.1%, respectively. Concomitant resistance to aminoglycosides, quinolones and aztreonam was also noticed. Presence of any of the bla genes (bla(CTX-M), bla(TEM), and bla(SHV)) was noticed in a total of 28 (38.4%) isolates of the 73 isolates studied. Many isolates demonstrated occurrence of these genes in various combinations. bla(CTX-M), bla(TEM), and bla(SHV) were noticed in 28.8%, 10.9% and 13.7% isolates, respectively. Multiplex PCR in bla(CTX-M) harboring isolates demonstrated the presence of CTX-M-Genogroup-1 and sequencing for the specific CTX-M-type revealed presence of CTX-M-15 type. RAPD typing showed wide diversity in isolates. CONCLUSIONS: This is amongst the premier report describing the simultaneous occurrence of bla(TEM), bla(SHV), and bla(ampC) in Indian Enterobacteriaceae and that wider dissemination of these genes, as demonstrated by diversity of isolates, raises concern and emphasizes a need for extensive search for the presence of these gene pools in Indian subcontinent.

Pasteur and Joubert, in 1877, were among the first to recognize the potential of microbial products as therapeutic agents and demonstrated that common microorganisms could inhibit the growth of Anthrax bacilli. However, the milestone in the field of antimicrobial agents was the advent of penicillin, in 1928, by Alexander Fleming from a strain of the mold Penicillium. Since then, the fungi and higher plants have been searched for the production/preparation of novel antibacterial compounds, including cephalosporins and aminoglycosides. However, due to increasing usage and selection pressure, bacteria have started expressing resistance to these compounds. Hence, there is an urgent need to review and search for newer antibacterial compounds derived from plant species. In this review, the potential of plant species to yield newer antibacterial agents will be illustrated with an emphasis on compounds exclusively isolated in very recent years. Some of the issues pertinent to this area will be briefly reviewed and it is hoped that this would definitely stimulate further discussions and research on this important aspect. Keywords: Plant-derived, antibacterial, antimicrobial resistance

Cefoxitin-resistant Escherichia coli (n = 109) and Klebsiella pneumoniae (n = 16) isolates collected from patients in India in 2009 to 2010 were screened for bla(ampC) families and mobilizing elements (ISEcp1, IS26, ISCR1, and sul-1-type class 1 integrons) and their association with bla(ampC) and for the occurrence of class A beta-lactamases (BLs) (CTX-M, TEM, and SHV). The concurrent occurrences of two distinct AmpC families (bla(CIT) and bla(EBC)) and of class A with class C beta-lactamase were observed. All but one of the isolates harboring CTX-M extended-spectrum BLs (ESBLs) were carrying bla(CTX-M) genogroup 1; the remaining isolate carried bla(CTX-M) genogroup 9. The mobilizing elements occurred in different combinations in the study isolates.