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 aEUR’
Correct Answer: Change ceiftliaxone to Imipenem
Description: 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 ESBL'S 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.
Category:
Pharmacology
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