All are true about ESBL except aEUR’
Correct Answer: Sensitive to carbapenems
Description: 3rd and 4th generation sensitivity is must Penicillins were the earliest antibiotics to be developed. Penicillins and their related group of antibiotics were called fi lactam antibiotics because they contained a .four carbon ring called )3 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 time bacterias developed resistance even against these organisms by producing fi lactamase. 13 lactamase are enzymes that break open the 13 lactam ring and deactivate the antibiotic. The fi lactamases hydrolyze penicillins and narrow spectrum cephalo- sporin, such as cephalothin or cefazolin, and are resistant to them. To counteract the problems against fi lactamases new classes of /3 lactams were developed. These are cephalosporins containing oxy- minio side chain e.g. ceftizoxime, cefotaxine, ceftazidime, ceftriaxone (broad spectrum cephalosporins). - Consequently, when these oxymino side chain containing corn- pounds were introduced they were effective against a broad group of otherwise resistant bacterias. - /3 lactamases 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 fi lactamase enzyme (ESBL). These bacterias are called ESBL bacterias Bucterias are classified as extended spectrum )3 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 13 lactam containing antibiotics which includes even the oxyminio 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 filactamase ESBLS are capable of efficiently hydrolyzing :- Penicillins Narrow spectrum cephalosporins Many extended spectrum cephalosporins Oxyimino group containing cephalosporins (cefotaxime, ceftazidime) Monobactams (aztreonams) Beta lactcunase inhibitors (clavulanic acid sulhactam) An impoant point None of the ESBLS described till to date are able to hydrolyze cephamycin or carbepenems (imipenem, 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. Laboratory diagnosis of ESBLs Detection of bacterias expressing ESBL is difficult. Although a paicular ESBL will typically confer resistance to at least one paicular extended spectrum cephalosporin or aztreonam, the minimum inhibitory concentration may not be high enough for the strain to be called resistant under current interpretations of the national committee for clinical laboratory standards. Because of the clinical significance of ESBL a specific guideline for the detection of ESBL expressing organisms were proposed in 1999 by NCCLS. The presence of an ESBL is suggested if :? - Bacterial growth is observed despite a concentration of I p g/ml of at least one of three extended spectrum cephalosporins (ceftazidime, ceftriaxone, cefotaxime) or Aztreonam or growth occurs despite a concentration of 4 p g/ml of cefpodoxime. Classification of fl lactamase The number of 13 lactamase enzyme is continuously increasing at an alarming rate. Various classifications have been proposed.for lactamases. The earliest classification by sawai was based on Antisera. /3 lactamases have also been classified based on substrate profile, "correlation of substrate and inhibitory propeies". A modern system of classification ambler is based on the "molecular" structure. Recently a new classification system has been developed by Bush Jacoby medeiors to integrate functional and molecular characteristics. This scheme puts 178 fi lactamases from naturally occurring bacterial isolates into four groups bused on substrate and inhibitor profiles. Treatment of ESBL'S Of all the available fl lactams carbepenents are the most effective and reliable as they are highly resistant to the hydrolytic activity of the iglactamase. - None of the ESBLS described till todate are able to hydrolyze cephamycin or Carbepenem (imipenem. nteropetzem) 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 clavulanic acid the only infections that may be treated safely with fi lactam /Q lactamase inhibitor combinations are those involving the urinary tract. - In this instance p lactamase inhibitor concentration is high enough to counteract the hydrolytic activity of ESBL'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 plactam antibiotics Non ,B lactam antimicrobial agents (aininoglycosides, fluoro- quinolones) may be beneficial however, coresistance rates against these agents are frequent.
Category:
Pharmacology
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