Ans. is 'd' i.e., 3rd and 4th generation sensitivity is must Penicillins were the earliest antibiotics to be developed.Penicillins and their related group of antibiotics were called b lactam antibiotics because they contained a four carbon ring called b lactam ring.Within a few years of introduction of penicillin, bacterias started acquiring resistance against penicillins by producing penicillinase.To overcome this problem penicillinase resistant penicillins came into picture.Shortly 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 b lactamase.b lactamase are enzymes that break open the b 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 b lactamases new classes of b lactams were developed. These are cephalosporins containing ox imino side chain e.g. ceftizoxime, cefotaxime, ceftazidime, ceftriaxone (broad spectrum cephalosporins).Consequently, when these ox imino side chain containing com- pounds were introduced they were effective against a broad group of otherwise resistant bacterias.b lactamases cannot hydrolyze higher generation cephalosporins with an ox imino 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 ox imino containing cephalosporins e.g. (cefotaxime, ceftazidime, ceftriaxone)The mechanism of this resistance was production of extended spectrum b lactamase enzyme (ESBL).These bacterias are called ESBL bacteriasBacterias are classified as extended spectrum b 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 b lactam containing antibiotics which includes even the ox imino group containing cephalosporins (ceftizoxime, cefotaxime, ceftazidime, ceftriaxone), Aztreonam and all the older b lactam drugs.Because of their greatly extended substrate range these enzymes were called extended spectrum b lactamaseESBLS are capable of efficiently hydrolyzingPenicillinsNarrow spectrum cephalosporinsMany extended spectrum cephalosporinsOxyimino group containing cephalosporins (cefotaxime, ceftazidime)Monobactams (aztreonams)Beta lactamase inhibitors (clavulanic acid sulbactam)An important pointNone of the ESBLS described till to date are able to hydrolyze cephamycin or carbapenems (imipenem, meropenem)ESBL producing organisms are associated with gram negative bacterias and most of these organisms are in the family. Enterobacteriaceae and has been discovered in almost all members of the Enterobacteriaceae family.The Enterobacteriaceae species most commonly associated with ESBL are Klebsiella (Klebsiella pneumonia predominantly) and E. coli.Laboratory diagnosis of ESBLsDetection of bacterias expressing ESBL is difficult.Although a particular ESBL will typically confer resistance to at least one particular 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 1 m g/ml of at least one of three extended spectrum cephalosporins (ceftazidime, ceftriaxone, cefotaxime) or Aztreonam or growth occurs despite a concentration of 4 m g/ml of cefpodoxime.Classification of b lactamaseThe number of b lactamase enzyme is continuously increasing at an alarming rate.Various classifications have been proposed for b lactamases.The earliest classification by sawai was based on Antisera.b lactamases have also been classified based on substrate profile, "correlation of substrate and inhibitory properties".A modern system of classification by 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 b lactamases from naturally occurring bacterial isolates into four groups based on substrate and inhibitor profiles.Treatment of ESBL'SOf all the available b lactams carbapenems are the most effective and reliable as they are highly resistant to the hydrolytic activity of the b lactamase.None of the ESBLS described till to date are able to hydrolyze cephamycin or Carbapenem (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 clavulanic acid the only infections that may be treated safely with b lactam /b lactamase inhibitor combinations are those involving the urinary tractIn this instance b lactamase inhibitor concentration is high enough to counteract the hydrolytic activity of ESBL's clavulanic acid appears more efficient than sulbactam (It takes about eight times more sulbactam to obtain a protection similar to that given by clavulanic acid).Non b lactam antibioticsNon b lactam antimicrobial agents (aminoglycosides, fluoro- quinolones) may be beneficial however, coresistance rates against these agents are frequent.