ANTIMICROBIAL

 AGENTS/  ANTIBIOTIC  

Kuntaman
kuntaman@fk.unair.ac.id
Department Microbiology
FMAU/RSUD Dr. Soetomo Surabaya
 Source of A.M.

!  Product  by  M.O.  

!  Chemical  SyntheAc  
!  SEMI-­‐SyntheAc:  PROD.  M.O.  à  Change  
chemically  
 Paul  Ehrlich  

•  SelecAve   Toxicity  
•  IsnaniyanA,  isnaniyanA.fajrin@gmail.com,  
089652181075.  Ceiterakan  penemuan   Ehrlich  
 Mechanism  of  AnAmicrobial  drug  
1.  Compe))ve  Antagonism  

SULFONAMIDE Similar PABA

formula
NH2 NH2
Tahapan
sintesis DNA, PABA (name)
. Bacterial
Metabolism

COOH SO2NH
Animal Cell: Folic Acid
Folic Acid from
externalSources Purine DNA
 2. Cell Wall Inhibition
Penicillin/Cephalosporin (Beta Lactam)

Bind and Inhibit Transpeptidase enzyme

# Peptidoglycan Synthesis
Activation of Autolytic enzyme
[+] in Bact Cell Wall
[-] in Animal Cell Wall
Cell Killed
Proses sintesis dinding sel bakteri, & Anatomi dd sel bakteri
Gram Pos dan Gram neg, manusia, Engat Shofia Yuthi,
engat.shofia@icloud.com, 081803694649
 Penicillin   Cephalosporin  
•  Penicillin  G   ! Ceph-­‐1st  gen  
•  Ampicillin   ! Ceph-­‐2nd  gen  
•  Amoxycillin   ! Ceph-­‐3rd  gen  
! Ceph-­‐4th  gen  

Carbapenem  
•  Meropenem  
•  Imipenem  
•  Doripenem  
3.  Cell  Membrane  Inhibi)on  
 
Polymixin  à  bind  to  PhosphaAdil-­‐Ethanolamine  
         (Bacterial  cell  membrane)  
 
Polyeneà  bind  to  STEROL  (Fungi  Cell  Membrane)  

Bacterial / Fungi Cell Killed

Jelaskan komposisi cell membrane mikroba dan
manusia, Muziburrahman,
muziburrahman600@gmail.com, 081918006468
4. Protein Synthesis Inhibition
Bacteria

RIB.30S RIB.50S
tRNA

Tetracyclin Chloramphenicol
Aminoglycoside Lincomycin
Erythromycin
Oleandomycin
PROTEIN
Synthesis
 Ribosome  
•  Prokaryotes  have    
•  70  S  ribosomes,  each  consis)ng  of  a  small  (30S)  and  a  large  (50S)  
subunit.  Their  small  subunit  has  a  16S  RNA  subunit  (consis)ng  of  1540  
nucleo)des)  bound  to  21  proteins.  The  large  subunit  is  composed  of  a  5S  
RNA  subunit  (120  nucleo)des),  a  23S  RNA  subunit  (2900  nucleo)des)  
and  31  proteins.[15]  Affinity  label  for  the  tRNA  binding  sites  on  the  E.  
coli  ribosome  allowed  the  iden)fica)on  of  A  and  P  site  proteins  most  
likely  associated  with  the  pep)dyltransferase  ac)vity;  labelled  proteins  
are  L27,  L14,  L15,  L16,  L2;  at  least  L27  is  located  at  the  donor  site,  as  
shown  by  E.  Collatz  and  A.P.  Czernilofsky.[16][17]  Addi)onal  research  
has  demonstrated  that  the  S1  and  S21  proteins,  in  associa)on  with  the  
3'-­‐end  of  16S  ribosomal  RNA,  are  involved  in  the  ini)a)on  of  transla)on.
[18]  
•     
5. Nucleic Acid Synthesis Inhibition
Actinomycin
Rifampicin Quinolon
DNA
DNA Dep RNA
Polymerase
à rpo gene DNA gyr
RNA

DNA
PROTEIN
 Quinolon  
•  Ciprofloxacin  
•  Levofloxacin  
•  Moxifloxacin  
Jelaskan pola mutasi DNA pd resistensi Quinolon,
name

Jelaskan perbedaan mekanisme kerja

Siprofloksasin dan Rifampicin dalam menghambat
sintesis DNA, Isnani
 PABA
Sulfonamid
Folic Acid
Trimethoprim
DNA DNAgyr Quinolon
DNA
DNA Dep.RNA Pol Rifampicin
mRNA
Pol:jenis&penggunaa
Chloramphenicol n -Engat)
Macrolide
Aminoglycoside B-Lactam
Rib 50S
Glycopeptide
30S Lincosamid
tRNA Tetracycline
Polymixin
Protein Cell Membr Cell Wall
 Effect  of  An)bio)c  Combina)on  

!   C  =<  A  +  B  =  Indifferent  
!   C  =  A  +  B      =  Adi)ve  
!   C  >  A  +  B      =  Synergism  
!   C  <  A  +  B      =  Antagonism  

!   DRUG  DEPENDENT:    à    require  A.B.  for  life  

–  STREPTOMYCIN  DEP.  MENINGOCOCCI  
–  For  growth  à  BUTUH  STREPTOMISIN    ??  
 ‘BACTERICIDAL’ &‘BACTERIOSTATIC’
Bactericidal: Bacteriostatic
- Irreversible cell damage *  Cell Cleavage inhibition
- MBC slightly upper MIC *  Bacterial cell not killed & not
growth
*  MBC significantly upper MIC

Ex: Ex:
- Penicillin - Aminoglyco -  Chloram * Sulfonamid
- Cephalosporin - Quinolon -  Clindamycin
- Cotrimoxazole - Rifampisin -  Tetracyclin
- Metronidazol - Vancomycin -  Erythromycin

MIC, MBC, metodologi dilution tube;Muzibur

MIC, MBC, metodologi E-test; Isnani
 Group-­‐1  of  anAbioAcs  
•  Target  site:  PepAdoglycan  synthesis  of  cell  
wall  
–  Penicilin  
•  Narrow  Spectrum,  Penicillin  G  and  Pen  V,  Nafcillin,  Oxacillin  
•  Penicillin  Broad  Spectrum  :  Ampi,  Amox,  Piperacillin  
–  Cephalosporin:  
•  Narrow  spectrum:  Ceph-­‐1  
•  Broad  Spectrum:  2,3,4th  Cephalosporin  
–  Aztreonam  
–  Carbapenem  (Meropenem,  Imipenem,  
Doripenem)  
q   Vancomycin  
 
 Group-­‐1-­‐1  of  anAbioAcs  
•  Penicilin  
•  Narrow  Spectrum,  Penicillin  G  and  Pen  V,  
Nafcillin,  Oxacillin  
•  Penicillin  Broad  Spectrum    
–  (Ampi/Amoxicillin),      
»  some  Ame  used  in  combinaAon  with  Pen  Inhibitor  
(Clavulani  acid)  
»  SynergisAc  with  Aminoglycoside  
»  AcAve  against  Enterococci,  Enterobacteriaceae,  Moraxella  
–  Piperacillin  and  Ticarcillin  
»  AcAve  also  against  Pseudomonas  and  Enterobacteriaceae  
»  Good  combinaAon  with  Pen  Inhibitors  

 
 Group-­‐1-­‐2:  Cephalosporin  
•  Mostly  parenteral  route  
•  Mostly  secreted  via  urine;  BUT  cefoperazone  
mostly  via  bile/Liver  
•  More  resistant  to  penicillinase,  than  pencillin  
group  
 Group-­‐1-­‐2-­‐1:  Cephalosporin  
•  1st  gen:  cefazolin  (parenteral),  cephalexin  
(oral)  
–  Use  for  Gram  Pos  
–  Many  Gram  Neg,    
–  BUT  not  for    
•  mostly  Gr  Neg  and    
•  Enterococci,    
•  Gram  Neg  Cocci  
•  MRSA  (kecuali  SATU,  coba  jelaskan)  
 Group-­‐1-­‐2-­‐2:  Cephalosporin  
•  2nd  gen:  Cefotetan,  CefoxiAn,  Cefamandole,  
Cefuroxim,  Cefaclor  
–  Extended  coverage  for  Gram  Neg  
–  Less  coverage  for  Gram  Pos  
–  BUT  not  for  MRSA  
•  Less  penetrate  to  CSF  
 Group-­‐1-­‐2-­‐3:  Cephalosporin  
•  3rd  gen:  Cefotaxime,  Cefriaxone,  Cefazidime,  
Cefixime  (CAZ  à  anA  Pseudomonas)  
–  Usually  parenteral  
–  More  Extended  coverage  for  Gram  Neg  (included  
Neisseria  spp)  and  Pseudomonas  
–  Enter  to  CSF  (exept:  cefoperazone,  Cefixime)  
–  BUT  not  for  MRSA  
–  Mostly  excreted  via  Urine,  exept  Cefriaxone  
•  ESBL  producers  are  mostly  resistant  against  
3rd  gen  Ceph  (Engat)  
 Group-­‐1-­‐2-­‐4:  Cephalosporin  
•  4th  gen:  Cefepim  
–  Parenteral  
–  Expands  coverage  for  Gram  Neg  (as  3rd  gen  ceph)  
and  also  to  Gram  Pos  (as  1st  gen  ceph)    
–  Used  for  Beta-­‐Lactamase  producing  Gram  Neg  
–  BUT  not  for  MRSA  
–  Mostly  excreted  via  Urine,  
 Group-­‐1-­‐4:  Carbapenem  
•  Meropenem  and  Imipenem  &  Doripenem  
–  AcAve  against:  Gram  Pos,  Gram  Neg  Rod  (included  
Pseudomonas)  and  Anaerobic      
–  Imipenem  is  inacAvated  by  renal  
dehydropepAdase  
–  Resistant  to  ESBLs;  as  a  drug  of  choice  for  ESBLs  
producers  
–  BUT  not  for  MRSA  
–  Mostly  excreted  via  Urine,  
 Group: 1-5: Vancomycin  
•  For MRSA: Policy: Van hanya untuk MRSA
•  Bactericidal glycoprotein
•  inhibiting cell wall formation
•  Binds D-Ala-D-Ala pentapeptide side chain to prevent
transpeptidation in growing peptidoglycan
•  Resistance in VRE and VRSA is due to change of one D-ala to
D-lactate
•  Narrow spectrum of use
–  Mainly for MRSA, penicillin-resistant pneumococcus and C. difficile
•  Eliminated unchanged in urine.
•  Not absorbed from gut so only used orally for C. difficile
•  S.E.: Nephrotoxic, ototoxic, RED MAN syndrome with rapid
infusion (Jelaskan ???, name)
 Group 2-1a: Tetracycline
Tetracyclines:
Mode of Action: Reversible binding to 30S
ribosome subunit blocking aminoacyl-tRNA access to
acceptor site (A site)
Mostly excreted via Bile

50S
aa-tRNA
tRNA X
mRNA
P A
30S
Group 2-2: Macrolide
Block transpeptidase
 Group 2-3: Aminoglycosides
•  Broad spectrum
Gentamicin
Amikacin
Tobramycin
Netilmicin
Streptomycin
Kanamycin
Neomycin
Do not work alone on serious infections by enterococci or
streptococci but can Increase antimicrobial activity of other
drugs when used in combination for these
 Aminoglycoside  
•  Interfere aa-tRNA interacts with mRNA.
•  Distortion of ribosomal site by antibiotic
causes misreading of codons.
•  Interaction is within the 30S subunit
•  Generally given by i.v. or i.m. injection.
•  Mainly excreted in urine
•  High dose once a day is more effective and less
toxic than same amount split and administered
in 3 doses per day
•  Toxicity: Nephrotoxicity and ototoxicity
 Group  2-­‐5:  Clindamycin  
 

Clindamycin  (a  lincomycin)                

ü  Works  like  macrolides  
ü  Bacteroides,  several  anaerobes  
ü  Increased  danger  of  Clostridum  
 
difficile  coliAs  
 Group  3-­‐1:  Sulfonamide  
S.E.:
•  Steven-Johnson syndrome (<1% treatment
courses) (Jelaskan, Muziburrahman)
•  Crystalluria, hematuria (drugs precipitate at acid
pH)
•  Hematopoietic reactions
–  Hemolytic anemia or aplastic anemia
–  Granulocytopenia, thrombocytopenia, leukemoid
–  Glucose-6-DH deficiency – enhanced hemolytic
reactions
•  If given in late pregnancy
–  Kernicterus (brain damage due to excess jaundice)
 Group  3-­‐3:  Quinolones  
•  Interfere with DNA gyrase and DNA
topoisomerase IV

http://www.web.virginia.edu/Heidi/chapter30/chp30.htm
 Group  3-­‐3:  Quinolones  

! Indication for: Resp tract Inf & GI Inf

! Oral agents
–  inhibited up to 80% by coadministration with Al
and Mg-containing antacids
! Excreted in urine
–  except ciprofloxacin with 50% bile and 50% urine
 Group 3-4: Metronidazole
§  can be given orally
§  Effective on:
§  most obligate anaerobic bacteria:
§  anaerobic protozoa (Trichomonas, Giardia,
Entamoeba)
§  Activated after being reduced by ferredoxin
§  The reduced substance: can fragment DNA
§  Redox potential produced by aerobically growing
bacteria not low enough to activate the drug.
§  Clinical use of Metronidazole, dosing and
regiment,
33
 Group  4:  An)  mycobacterial  drug  
§  Problems  
ü Waxy  cell  walls  (inhibiAng  drug  diffusion)  
ü Bacteria  live  both  extracellular  and  intracellular  
ü Slow  growth  (drugs  must  be  used  for  long  periods)  
ü Many  drugs  only  work  for  one  or  a  few  species  
§  combinaAon  therapy  with  mulAple  
drugs  
§  Pilih  satu  jenis  anA  TB,  mekanisme  kerja  
(Isnani,  Engat,  Muzibur)