ICU patient having fever since 1 week.

A patient in the ICU having fever since 1 week. He empirically started on a ceftriaxone AND amikacin. the pus sent for culture after 48 hours blood culture report showed klebsiella with ESBL, what is the next step –

 

  1. Increasing the dose of the same antibiotics
  2. Change amikacin to quinolone
  3. Change cerfirtaxone to Imipenem
  4. Change ceftriaxone to cefiazidime

Ans. is ‘c’ i.e., Change ceftriaxone to Imipenem [Ref: Harrison I S/e (new edition) p. 1247-1248]

  • >Penicillins were the earliest antibiotics to be developed.
  • >Penicillins and their related group of antibiotics were called 13 lactam antibiotics because they

contained a four carbon ring called 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 we

introduced.

  • They remained first line antibiotics for several years.
  • Over a period of time bacterias developed resistance even against these organisms by

producing beta -lactamase. (3 lactamase are enzymes that break open the 13 lactam ring and deactivate the antibiotic.

  • The 13 lactamases hydrolyze penicillins and narrow spectrum cephalo- sporin, such as

cephalothin or cefazolin, and are resistant to them.

 

  • To counteract the problems against 13 b- lactamases new classes of lactams were developed

these are cephalosporins containing oxyiminio side chain e.g. ceftizoxime, cefotaxime,

ceftazidime, ceftriaxone (broad spectrum cephalosporins).

 

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  • Consequently, when these oxyimino side chain containing com- pounds were introduced they

were effective against a broad group of otherwise resistant bacterias.

 

  • 13 b- lactamases cannot hydrolyze higher generation cephalosporins with an oxyimino side chain

(cefotaxime, ceftizoxime, ceftazidime).

 

  • But not long ago after these cephalosporins came into use strains ofKlebsiella pneumonia

were discovered which were resistant even to oxyimino containing cephalosporins e.g.

(cefotaxime, ceftazidime, ceftriaxone)

 

  • The mechanism of this resistance was production of extended spectrum lactamase enzyme

(ESBL).

 

These bacterias are called ESBL bacterias

o Bacterias are classified as extended spectrum 13 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).

 

o As a result of the mutation, organisms, are able to produce novel beta lactamases that can

hydrolyze all the b-lactam containing antibiotics which include even the oxyimino group

containing cephalosporins (ceftizoxime, cefotaxime, ceftazidime, ceftriaxone), Aztreonam

and all the older b-lactam drugs.

 

o Because of their greatly extended substrate range these enzymes were called extended

spectrum b-lactamase

 

ESBLS are capable of efficiently hydrolyzing

 

  •  Penicillins
  • Narrow spectrum cephalosporins
  • Many extended spectrum cephalosporins
  • Oxyimino group containing cephalosporins (cefotaxime, ceftazidime)
  • Monobactams (aztreonams)
  • Beta lactamase inhibitors (clavulanic acid sulbactam)

 

An important point

  • None of the ESBLS described till to date are able to hydrolyze cephamycin or carbapenems

(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 Mith ESBL are klebsiella

(Klebsiella pneumonia predominantly) and E. coli.

 

Treatment of ESBL’S

  • Of 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 todate 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 / 13 lactamase inhibitor combinations are those involving the urinary

tract.

 

– In this instance 13 lactamase inhibitor concentration is high enough to counteract the hydrolytic

activity of ESBL’s clavulanic acid appears more emcient than sulbactam (It takes about eight

times more sulbactam to obtain a protection similar to that given by clavulanic acid).

 

Non 13 lactam antibiotics

Non 13 lactam antimicrobial agents (aminoglycosides, fluoro- quinolones) may be beneficial

however, co resistance rates against these agents are frequent.

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