<prompt> A patient in the ICU having fever since 1 week. Heempirically staed on a ceftriaxone amikacin, the pus sent for culture after 48 hours blood culture repo showed klebsiella with ESBL, what is the next step aEURIncreasing the dose of the same antibioticsChange amikacin to quinoloneChange ceiftliaxone to ImipenemChange ceftriaxone to ceftazidime  <response>: Change cerftriaxone to Imipenem Penicillins were the earliest antibiotics to be developed. Penicillins and their related group of antibiotics were called fl lactam antibiotics because they contained a four carbon ring called fi lactam ring. Within a .few years of introduction of penicillin, bacterias staed acquiring resistance against penicillins by producing penicillinase To overcome this problem penicillinase resistant penicillins came into picture. Sholy afterwards, the broad spectrum penicillin and first gene- ration cephalosporins were introduced. They remained, first line antibiotics. for several years. Over a period of tune bacterias developed resistance even against these organisms by producing filactamase. fi lactamase are enzymes that break open the fi lactam ring and deactivate the antibiotic. The ,B lactamases hydrolyze penicillins and narrow spectrum cephalo- sporin, such as cephalothin or cefazolin, and are resistant to them. To counteract the problems against fl lactamases new classes of I lactams were developed. These are cephalosporins containing oxy- minio side chain e.g. ceftizoxime, cefotaxine, ceftazidime, ceftriaxone broad spectrums cephalosporins. - Consequently, when these oxymino side chain containing com- pounds were introduced they were effective against a broad group of otherwise resistant bacterias. - f3luctamases cannot hydrolyze higher generation cephalosporins with an oxymino side chain cefotaxime, ceftizoxime, ceftazidime. But not long ago after these cephalosporins came into use strains of klebsiella pneumonia were discovered which were resistant even to oxyimino containing cephalosporins e.g. cefotaxime, cefazidime, ceftriaxone The mechanism of this resistance was production of extended spectrum 3 lactanzase enzyme ESBL. These bacterias are called ESBL bacterias -Bacterias are classified as extended spectrum fl lactamase ESBL producing bacteria, when a simple point mutation occurs in genes normally responsible .for beta lactamase mediated resistance. The mutation usually responsible is TEM. - As a result of the mutation, organisms, are able to produce novel beta lactamases that can hydrolyze all the fi lactam containing antibiotics which includes even the ox-pninio group containing cephalosporins ceftizoxime, cefotaxime, ceftazidime, ceftriaxone, Aztreonam and all the older fi lactam drugs. Because of their greatly extended substrate range these enzymes were called extended spectrum 13 lactamase ESBLS are capable of efficiently hydrolyzing :- -Folic illins - Narrow spectrum cephalosporins - Many extended spectrum cephalosporins - Oxyimino group containing cephalosporins cefotaxime, ceftazidime - Monobactams aztreonams - Beta lactatnase inhibitors clavulinic acid sulbactam An impoant point None of the ESBLS described till to date are able to hydrolyze cephamycin or carbepenems imipenenz, meropenems ESBL producing organisms are associated with gram negative bacterias and most of these organisms are in the family. Enterobacteriaeae and has been discovered in almost all members of the enterobacteriaceae family. The enterobacteriacea species most commonly associated with ESBL are klebsiella Klebsiella pneumonia predominantly and E. coli. Treatment of ESBLS Of all the available fllactams carbepenenzs are the most effective and reliable as they are highly resistant to the hydrolytic activity of the fl lactamase. - None of the ESBLS described till todate are able to hydrolyze cephamycin or Carbepenem imipenem, meropenem Meropenem is the most active with MIC generally lower than those of imipenem. Beta lactamase inhibitors Clavulanic acid, sulbactam, Tazobactam Although ESBL activity is inhibited by clavulinic acid the only infections that may be treated safely with b lactam f3lactamase inhibitor combinations are those involving the urinary tract. - In this instance i3lactamase inhibitor concentration is high et,ough to counteract the hydrolytic activity of ESBI:.s clavulinic acid appears more efficient than sulbactam It takes about eight times more sulbactam to obtain a protection similar to that given by clavulinic acid. Non 13 lactam antibiotics Non fi lactam antimicrobial agents amino glycosides, fluoro- quinolones may be beneficial however, coresistance rates against these agents are frequent. 