lactams Inhibition of Cell wall synthesis Penicillins Cephalosporins

ﻣکﺎﻧیﺴﻢ ﺍﺛﺮ آﻨﺘی ﺑیﻮﺗیک ﻫﺎ βlactams Inhibition of Cell wall synthesis Penicillins Cephalosporins Carbapenems Glycopeptides Protein synthesis Macrolides Chloramphenicol Tetracycline Aminoglycosides DNA synthesis Fluoroquinolon es RNA synthesis Rifampicin Folic acid synthesis Sulfonamides Trimethoprim

ẞ-lactams

Penicillins � Natural penicillins: benzylpenicillin (penicillin. G), phenoxymethyl penicillin (penicillin V) � Penicillinase – resistant penicillins methicillin, naficillin, oxacillin, cloxacillin Ø Active against all ß- hemolytic streptococci, meningococci and most G(+) anaerobes, poor activity against G( -) rods. Ø Similar to natural penicillins , except enhanced activity against Staphylococci

� Broad-spectrum penicillins : aminopenicillins (ampicillin , amoxicillin , carbenicillin, ticarcillin), ureidopenicillins (piperacillin) � ß-Lactam with ß-lactamase inhibitor: ampicillin/sulbactam , amoxicillin/clavulanate , ticarcillin/clavulanate , piperacillin/tazobactam Ø Ø Activity against G(+) cocci , active against some G(-) rods with piperacillin the most active Activity similar to natural ß-lactams, plus improved activity against ß-lactamase producing Staphylococci and selected G(-) rods, not all ß-lactamases are inhibited , piperacillin/tazobactam is most active

Cephalosporins and cephamycins � Narrow spectrum : (Cephalosporin I) cephalexin, cephalothin, cefazolin, cephapirin, cephradine � Expanded-spectrum cephalosporins : (Cephalospoin II) cefaclor, cefuroxime Ø Activity equivalent to oxacillin against G(+) bacteria , some G(-) activity (E. coli, klebsiella, p. mirabilis, …) Ø Activity equivalent to oxacillin against G(+) bacteria, improved G( -) activity (Enterobacter, Citrobacter, Proteus)

Cephalosporins and cephamycins � Expanded- spectrum cephamycins : cefotetan, cefoxitin � Broad spectrum : ( cephalospoin III) cefexime, cefotaxime, ceftriaxone, ceftazidime � Extended spectrum: (cephalosporin IV) cefepime, cefpirome Ø Ø Ø Activity similar to expanded-spectrum cephalosporins but less susceptible to ßlactamase Activity equivalent to oxacillin against G(+) bacteria, improved G(-) activity to include Pseudomonas Activity equivalent to oxacillin against G(+) bacteria, marginally improved G(-) activity

Action of a b-lactamase S O H 2 O N Inactive penicilloate COOH S Active penicillin O HN OH COOH

ESBLs ﺍﻧﺘﺸﺎﺭ � 1963 Ampicillin; 1 st broad spectru penicillin � 1965 TEM -lactamases in E. coli � 1969 TEM -lactamase in P. aeruginosa � 1974 TEM in H. influenzae & N. gonorrhoeae TEM in 30 -60% E. coli & enterobacteria & in 5 -20% of H. influenzae & gonococci � Now

Extended Espectrum Beta-Lactamases � K. oxytoca � K. pneumoniae � E. coli � P. mirabilis � Enterobacter � E. ESBLs ﺑﺎﺳیﻞ ﻫﺎی گﺮﻡ ﻣﻨﻔی ﺗﻮﻟیﺪ کﻨﻨﺪﻩ cloacae aerogenes � Serratia marcesens � Citrobacter diversus � Providencia stuartii � Proteus mirabilis � Salmonella typhimurium � Pseudomonas aeruginosa � Burkholderia cepacia � Acinetobacter �

Double Disk Synergy Test (DDST)

Etest for ESBLs Cefotaxime + clavulanate

ESBLs ﻣﻘﺎیﺴﻪ آﺰﻣﺎیﺸﺎﺕ ﺗﺎییﺪی Pro Contra Double disc Cheap Best disc spacing varies with strain Combination disc Cheap, sensitive & specific Batch variation; Sensitive More expensive; False +ve's with K 1 in K. oxytoca Etest Internally controlled Controls critical