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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.

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Background:Urinary tract infections (UTI) are one of the most common medical complications of pregnancy. The emergence of drug resistance and particularly the Extended-spectrum beta-lactamase production by Escherichia coli and methicillin resistance in Staphylococci, limits the choice of antimicrobials.Materials and Methods:Patients in different stages of pregnancy with or without symptoms of urinary tract infection attending the antenatal clinic of obstetrics and gynaecology were screened for significant bacteriuria, by standard loop method on 5% sheep blood agar and teepol lactose agar. Isolates were identified by using standard biochemical tests and antimicrobial susceptibility testing was done using Kirby Bauer disc diffusion method.Results:A total of 4290 (51.2%) urine samples from pregnant females showed growth on culture. Prevalence of asymptomatic bacteriuria 3210 (74.8%) was higher than symptomatic UTI 1080 (25.2%). Escherichia coli was the most common pathogen accounting for 1800 (41.9%) of the urinary isolates. Among the gram-positive cocci, coagulase negative species of Staphylococci 270 (6.4%) were the most common pathogen. Significantly high resistance was shown by the gram negative bacilli as well as gram positive cocci to the β-lactam group of antimicrobials, flouroquinolones and aminoglycosides. Most alarming was the presence of ESBL in 846 (47%) isolates of Escherichia coli and 344 (36.9%) isolates of Klebsiella pneumoniae, along with the presence of methicillin resistance in 41% of Staphylococcus species and high-level aminoglycoside resistance in 45(30%) isolates of Enterococcus species. Glycopeptides and carbepenems were the only group of drugs to which all the strains of gram positive cocci and gram negative bacilli were uniformly sensitive, respectively.Conclusions:Regular screening should be done for the presence of symptomatic or asymptomatic bacteriuria in pregnancy and specific guidelines should be issued for testing antimicrobial susceptibility with safe drugs in pregnant women so that these can be used for the treatment. For empirical treatment cefoperazone-sulbactum can be recommended, which is a safe drug, covering both gram positive and gram negative organisms and with a good sensitivity.