ANTIBIOTICS

Done by Basel Mohammad Aljarhy

730398
31/3/2012
 Antibiotic is a chemical substance produced by
a microorganism that inhibits the growth of or
kills other microorganisms.
 Antimicrobial agent is a chemical substance

derived from a biological source or produced

by chemical synthesis that kills or inhibits the
growth of microorganisms.
SOURCES OF ANTIBACTERIAL AGENTS
 Natural :mainly fungal sources(Benzylp. &Genta.)
Organisms develop resistance faster to the natural
antimicrobials because they have been pre-exposed to
these compounds in nature.
 Semi-synthetic :chemically-altered natural
compound(Ampicillin and Amikacin)
 Synthetic : chemically designed in the lab
(Moxifloxacin and Norfloxacin)
 There is an inverse

relationship between
toxicity &effectiveness as
you move from natural
to synthetic antibiotics
 WHICH DRUGS KILL & WHICH DRUGS
MAIM??
 Bacteriostatic = only inhibits bacterial growth, then the
host’s immunity system does the killing;
So, don’t use it in patients with defective immune
system(cancer , AIDS , DM..) or in overwhelming infections
 Minimal Inhibitory Concentration = MIC:
[antibiotic] which prevent growth on the cuture

 Bactericidal = kills bacteria;

 Minimal Bactericidal Concentration = MBC
[antibiotic] that kills the bacteria

Serum bactericidal titer: [antibiotic] in the patient serum

that is capable to kill the pathogen.
 Organisms that differ significantly from human
cells are easier to selectively kill
 What you have to know about antibiotics?

 Mechanism of action, chemistry, spectrum of

activity, toxicity(the most common side effects as
well as un common but sever),administration ,&
distribution(know which drugs penetrate the
BBB, joint capsules, the eye, testes & abscess
wall;poor antibiotic pearmeability)drugs that fail
to leave the GIT, or those that concentrate in
urine
 TARGETS:
 Bacterial cells differ from human cells in:
(1) cell wall (2) ribosomes(30S & 50S)
(3)Unique metabolic pathway(enzymes)

 Drugs like penicillins have few side effects

because they attack bacterial structures that are
absent in human cells have high selective
toxicity(good therapeutic index)
 Drugs like amphotericin are toxic to human cells
at therapeutic doses poor selective toxicity(bad
therapeutic index)
 If the identity of the pathogen is unknown,
empirical therapy (best guess) is initiated

 The site of infection , Gram stain , & latex

agglutination provide clues about the organism
identity ,but culture is the gold standard for
identification of organism.. Then empiric therapy
should be changed to narrow spectrum
KEEP YOUR EMPIRIC THERAPY ARSENAL
SMALL
 Each practitioner should thoroughly understand a
small # of antibiotics that are frequently used for
empirical therapy .so, take Hx , know infection
location & do rapid identification test
 If the presumed organisms are :
(1)Gram(+) :we need to (a)decrease cell wall synthesis
(b)to cover most Gram (+) (c)choose drugs that are not
destroyed by penicillinase
Nafcillin (IV) or dicloxacillin(po) Or
Vancomycin

 Skin infections..(cephalexin)..skin penetration

 amoxicillin(or 2nd generation cephalo.)is frequently
used for otitis media & other URTI
(2)Gram (-) :3rd generation cephalosporines
(ceftriaxone , cefotaxim)not destroyed by
cephalospornase & can penetrate BBB
Trimethoprime-sulfamethoxazole is active against
most UTIs
Cephalo.& penicillins enhance activity of
aminoglycosides against Gram(-)
A combination of “Amp & Genta” provides a very
good coverage of both Gram (+) &(-)
(3)Pseudomonas: Ticarcillin, ceftazidime,Imipenem
,Meropenem, or Tobramycin
(4)Anerobs: metronidazole , or clindamycin (licomycine
derivatives)
(5)Mycoplasma: Macrolids
Macrolids can also cover other organisms that cause
community acquired pneumonia
+less side effects (not as aminoglycosides)

(6)Systemic fungi :most frequently due to broad

spectrum antibiotics that have destroyed the
endogenous bacteria , allowing fungal overgrowth
amphotericine
WHEN TO USE MORE THAN ONE
ANTIBIOTIC???

(1)Unknown microbeyou have to cover Gram(+),

(-), & anerobs
(2)To prevent resistance
(3)To achieve synergypenicillins work on the cell
wall & aminoglycosides work inside the cells
ENEMIES
(1)Gram (+) cocci
 Blue & round by microscopy; blue dye impermeable
through the wall
 Peptidoglycan cell wall (polypeptide + sugar)

 Drugs that inhibit cell wall synthesis…

(2)Gram(-)
 Thin peptidoglycan wall covered by protective
coat (lipopolysccharid) that is impermeable to
most penicillins & cephalosporins
 However , ampicillin & amoxicillin(broad
spectrum A.b.)& 3rd generation cephalosporins
are hydrophilic , allowing passage through
selective pores can penetrate the outer coat &
destroy the cell wall ; some gram(-) strains are
resistant also to these antibiotics because thy
produce beta lactamase (enzyme that destroy
penicillins). These enzymes are concentrated in
space between outer membrane & cell wall
GRAM (-) CAN BE DIVIDED INTO 4 GROUPS:
(1)Enerics (normally inhabit the GIT):E.coli, shigella,
salmonella , klebsiella, enerobacter, serratia, proteus..
(2)H.influenza red & elongated pneumonia & meningitis
(3)Neisseria paired red spheres
(4)Pseudomonas unipolar fagella +slime layer of
polysaccharidecan infect any site +hospital acquired
 The enterics are now responsible for the most nosocomial
infections
 Gram(-)meningitis ,pneumonia , badder infections ,UTI
,aspiration pneumonia , otitis media, sinus infections
 Neisseriathe only Gram (-) that are susceptible to
penicillin G;But Ceftriaxone has now replaced penicillin
due to emergence of penicillin resistent strains
(3)anerobes: can be Gram(+) or (-)
 Bacteroides fragilis, C.perfringens, C.difficile,
C.tetani ,C. botulinum
 Gram(+) &(-) work together, form abscess wall,
& produce foul smelling gas
 Normal flora in the mouth, GIT ,skin

 Ttt: metronidazole, clidamycin( lead to

pseudomembranous colitis) , chloramphenicole
ANTIBIOTIC CLASSIFICATION
Five functional groups cover most antibiotics
1. Inhibitors of cell wall synthesis
2. Inhibitors of protein synthesis
3.Anti-metabolites
4.Inhibitors of nucleic acid synthesis
5. Inhibitors of membrane function(Lipopeptides
& Polymyxins)
5 functional groups These are all functions
necessary for bacterial growth Targets for
antibiotics
1. INHIBITORS OF CELL WALL SYNTHESIS
 Beta-lactams
 Penicillins
 Cephalosporins
 Monobactams(Aztreonam)
 Carbapenems(Imipenem,Meropenem)
 Glycopeptides
 Bacitracin
 Fosfomycins

Bacteria are hyperosmolar .if we stop

synthesis of cell wall absorption of
water& exploding
(1) Inhibited by D-
cycloserine
(intracellular)

(2)Inhibited by
Vancomycine

(3)Inhibited by
Bacitracin

(4)Inhibited by any
beta lactame drug
PENICILLICS

 Was 1st isolated fro penicillum mold in 1949

 It remains an inexpensive & well tolerated drug of
choice against several infections
 4groups:

 (1) narrow spectrum (penicellinase sensitive)

 (2)group II narrow spectrum (penicellinase resistant)

 (3)group III broad spectrum (aminopenicillins)

 (4)extended spectrum (antipseudomona penicillin)

 Early penicillins was acid labile, ineffective
against gram (-) & can be destroyed by beta
lactamase.
 Each of these limitations has been overcome in
newer penicillins due to alterations of the
chemical structure or development of the adjunct
agents such as probenicid & clavulanic acid
SIDE EFFECTS
(1)Hypersensitivity: due to pencilloic acid,
 Ranging from maculopapular rash to angioedema &
anaphylaxis
 Cross allergic reactions occur among the beta lactam
antibiotics. virtually all patients who are truly
allergic to one form of penicillin will be allergic to
other penicillins
(2)Diarrhea
(3)Acute interstitial nephritis(mithicillin)
(4)Neurotoxicity (seizures)
(5)hematology:decreased coagulation &eosinophelia
neutropenia
(6)Increase the Na+ & K+
CEPHALOSPORINS
 Share with penicillins a common mechanism,
susceptibility to beta lactamases, &similar side
effects
 Perhaps the greatest problem is that their names
sound alike
 Concentrate on the commonly used agents 1st
 Each generation has only one preferred oral
preparation..usually referred to by the trade
names:
 (1)Keflexcephalexin (1st generation)
 (2)Ceclorcefaclor (2ndgeneration)
 (3)supraxcefixime (3rd generation)
VANCOMYCIN,BACITRACIN, MONOBACTAMS,
CARBAPENEMS
 Cross allergenesity between cephalosporins &
pinicillins occurs in 10-15% of patients.
 MRSAvancomycin
 VRSALinezolid(BM suppression +peripheral
neuropathy)

 New Anti- MRSA Cephalosporins:

 Ceftobiprole
 Ceftaroline
 NewLipoglycopeptide:
 Dalbavancin,Oritavancin ,Telavancin
,Teicoplanin
 Fosfomycins: Inhibits the first step of the
peptidoglycan synthesis processurinary tract
infections due to E.coli and E.faecalis.
 Cell wall inhibitors(explosion of bacteria) can’t
kill all types of bacteria because some lack cell
wall & others have unique structures.

 So other vital unique bacterial features are

effective in eliminating these infections
 These drugs have mechanism of action similar to
those used to combat viral , protozoal ,& some
fungal infections
 Fluoroquinolones are a growing class of
antimicrobial agents
 The newest Fluoroquinolones :Trovafoxacin
,sparfloxacin , & levofloxacine, have improved
activity against Gram(+).This combine with their
excellent Gram(-) covarage & excellent tissue
penetration broaden their list of indications to
include skin , bone , joint ,GIT , & respiratory
infections
 Additionally ,quinolones can be used for sexually
transmitted disease(gonorrhea & chlamydia)
QUINOLONES ,FLUROQUINOLONES ,&
METRONIDAZLE

 Disruption of a microb’s genetic code & inhibition

of DNA replication provide common targets for
anti-infectious agents.

 Druges that target DNA are mutagenic or

carcinogenic because they can damage the
eukaryotic DNA
ANTIMETABOLITES
(1)SULFONAMIDES
(2)TRIMETHOPRIM
PROTEIN SYNTHESIS INHIBITORS
 Good selective toxicity because bacterial
ribosomes (site of protein synthesis) consist of
50s & 30s subunits
 Proteins are built from a.a.

 Codon=3 nucleotidsone a.a.

 mRNA(ribonuclic acid)

 Reading of mRNA by ribosmes

 tRNA bear the next a.a. & enter fro A site

(acceptor)
 Growing peptid
PROTEIN BUILDING

 Step (1) :binding of t-RNA to A site this step is

inhibited by
tetracyclines (tetracycline, doxycycline ,minocycline
,& tigecycline)&
aminoglycosidses(gentamicin, tobramycin
,amikacin ,streptomycin , & neomycin)
Step(2):transpeptidation;the growing peptide that
present in P site is transferred to A site to attach
the a.a. of tRNA this step is inhibited by
Chloramohenicol
 Step(3)the growing peptide is translocated to P
site this step is inhibited by Macrolides &
streptogramins(against Gram+;reserved for
MRSA)

 Gram (+) bacteria are more sensitive than

Gram(-)bacteria to erthromycin because they
accumulate about 100X more drugs
PROTEIN SYNTHESIS INHIBITORS
(1) Aminoglycosidses
(2) Tetracyclines
(3) Chloramohenicol
(4) Macrolides
(5) Linezolid
(6) Lincosamides(clindamycin & Lincomycin)