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Farmakologi Antibiotik
Farmakologi Antibiotik
ANTIBIOTIK
NASRUHAN ARIFIANTO
STIFAR SUNAN GIRI
PONOROGO
Drug
concentration
must
remain
constantly above the minimum inhibitory
concentration (MIC)
-lactams, vancomycin
Concentration-dependent
Wall
Folic Acid Synthesis
Nucleic Acid Synthesis
Ribosome
Cell Membrane
Fig. 1.1 Simplified scheme of bacterial cell wall synthesis showing site
of action of cell wall-active antibiotics. (Reproduced from Medical
Microbiology, 16th Edition by David Greenwood (2003), with
permission from Elsevier
Penicillins
Cephalosporins
Monbactams
Carbapenems
Glycopeptides
10
-Lactam Subtypes
All
Penicillins
Cephalosporins
Monobactams
Carbapenems
11
Penicillin Classifications
Narrow-spectrum
penicillins
Penicillinase-resistant penicillins
Extended-spectrum penicillins
12
Narrow-Spectrum
Penicillins
Penicillin
G (Pfzierpen)-IM, IV, PO
More active
anaerobes
Penicillin
against
Neiserra
and
V (Pen-Vee K, Veetids)-PO
activity
against
Gram
{+}
cocci
Anaerobic
activity
(except
Bacteroides)
Drug of choice for syphilis, gas
13
Penicillinase-Resistant
Agents
Cloxacillin
(Cloxapen)
Dicloxacillin (Dynapen)
Methacillin (Staphcillin)
Discontinued in US
Nafcillin
(Nafcil)
Oxacillin (Prostaphlin)
14
Extended-spectrum PCNs
Aminopenicillins
Carboxypenicillins
Ureidopenicillins
15
Aminopenicillins
Agents
Carboxypenicillins
Agents
Carbenicillin (Geopen)
Ticarcillin (Ticar)
More
coverage
aminopenicillins
than
the
Enterobacter
Carbenicillin
urine
concentrates rapidly in
17
-Lactamase Inhibitors
Chemicals
with no antibacterial
activity
that
irreversibly
inactivate -lactamase
Sulbactam
With ampicillin (Unasyn)
Tazobactam
With pipercillin (Zosyn)
Clavulanate/Clavulanic acid
With amoxicillin (Augmentin)
With ticarcillin (Timentin)
18
Cephalosporins
Spectra
of activity (generation)
Anaerobic activity (Cephamycins)
Anti-pseudomonal activity
Methyltetrazolethiomethyl side-chain
Metabolism/elimination
Cerebrospinal fluid penetrance
19
(Ancef, Kefzol)
Cefadroxil (Duricef)
Cephalosporin analog of amoxicillin
Cephalexin
(Keflex)
(Keflin)
Cephapirin (Cefadyl)
Cephradine (Anspor, Velosef)
20
1st Generation
Cephalosporins
Great
(Ceclor)
Cefamandole (Mandol)
Cefmetazole (Zefazone)
Cefoxitin (Mefoxin)
Cefotetan (Cefotan)
Cefonicid (Monocid)
Cefprozil (Cefzil)
Cefuroxime (Ceftin, Zinacef,
Kefurox)
22
2nd Generation
Cephalosporins
More
H. influenzae
Enterobacter* (rapid resistance occurs)
Neisseria
Proteus
E. coli
Klebsiella
23
3rd Generation
Cephalosporins
Have
25
4th Generation
Cephalosporins
Cefepime
(Maxipime)
26
The Generation
Progression
As
one
moves
up
in
cephalosporin generation, more
Gram {-} activity is seen
Consequently, Gram {+} activity
is
decreased
advancing
in
generation
4th generation has Gram {-}
activity without sacrificing Gram
{+} activity
27
Anti-Pseudomonal
Cephalosporins
3rd
Generation
Cefoperazone
Ceftazidime
4th
Generation
Cefepime
The
Cephalosporin Elimination
For
29
CSF penetrance
2nd
Generation
Cefuroxime
3rd
Generation
Cefotaxime
Q6-8 dosing
Agent of choice in neonatal meningitis (along
with ampicillin)
Ceftriaxone
Q12-24 dosing
Agent of choice for adult meningitis
Causes kernicterus in neonates
30
Monobactams
Aztreonam
(Azactam)
Resistant to most Gram {-} lactamases
Activity
Only Gram {-} coverage (spectrum
resembles aminoglycosides)
Excellent
activity
against
P.
aeruginosa
Superb Enterobacteriaceae activity
No Gram {+} or anaerobic activity
31
Carbapenems
More
Carbapenem Agents
Agents
Ertapenem (Invanz)
Imipenem (Primaxin)
Meropenem (Merrem)
Ertapenem
33
Glycopeptides
Vancomycin
(Vancocin)
Teicoplanin (Targocid)
34
Vancomycin Spectrum
Gram
{+} aerobes
MRSA
Penicillin-resistant
pneumococcus
35
38
Inhibit
dihydrofolate
reductase,
an
enzyme necessary for thymidine synthesis
Both
are bacteriostatic
39
Stevens-Johnson syndrome
Angioedema
Hemolytic
anemia
Nephrotoxicity
Via precipitation of crystals of the inactive
metabolite
Crosses
the placenta
Kernicturus
Should be avoided in pregnancy and in children
under 2 months of age
41
Nucleic Acid
Synthesis Inhibitors
42
Fluoroquinolones
Inhibit
gyrase)
Bacteriostatic
Divided into generations; reverse of
the reverse of cepholosporins (actual
classification varies between sources)
Cephalosporins progress from Gram {+}
to Gram {-} activity, but loses Gram {+}
Fluoroquinolones progress from Gram {-}
to Gram {+} activity, but retains Gram
{-}
43
Acid (NegGram)
Gram {-} coverage only
Enterobacteraceae
E. Coli
Klebsiella
Proteus
44
Cinoxacin (Cinobac)
Enoxacin (Penetrex)
Pulled from market
Lomefloxacin (Maxaquin)
Norfloxacin (Noroxin)
Increased
45
Ciprofloxacin (Cipro)
Ofloxacin (Floxin)
Has
46
Gatifloxacin (Tequin)
Grepafloxacin (Raxar)
Pulled from market
Levofloxacin (Levaquin)
L-isomer
of Ofloxacin
Sparfloxacin (Zagam)
Temafloxacin (Omniflox)
Pulled from market
Same
Gemifloxacin (Factive)
Moxifloxacin (Avelox)
Trovafloxacin (Trovan PO)
Limited market availability d/t toxicity
Same
FQ Side Effects
Complexes
with cations
Photosensitivity
CYP450 interactions
Renal elimination
QT prolongationTorsades de Pointes
Hepatic failure (Trovan)
Tendon rupture
Do not give if <18yo
49
Ribosomal Inhibitors
51
Inhibitors
Tetracyclines:
55
Tetracyclines
Demeclocycline
(Declomycin)
Doxycycline (Vibramycin)
Minocycline (Minocin)
Tetracycline (Sumycin)
56
Tetracycline Spectrum
Gram
{+} Bacilli
Gram {-} Rods
Gram {-} Bacilli
H. influenzae, Vibrio cholera
Spirochetes
Borrelia burgdorferi
pallidum (syphilis)
(Lyme
dz),
treponema
Chlamydia
Rickettsia
rickettsii
(Rocky
Mt.
Spotted
Fever)
57
Tetracycline SE
Chelates
with cations
upset
Phototoxicity
Demeclocycline
Never used as an antibiotic because it can
induce nephrogenic diabetes insipidus
Used in treatment of SIADH
58
Aminoglycocides
Amikacin
(Amikin)
Gentamicin (Garamycin)
Netilmycin (Netromycin)
Neomycin (Mycifradin)
Kanamycin (Kantrex)
Streptomycin
Tobramycin (Nebcin)
60
Aminoglycocide Spectrum
Aminoglycocide SE
Highly
hepatic failure
Streptomycin-used in TB
62
Macrolides
Azalides:
Azithromycin (Zithromax)
Ketolides:
Telithromycin (Ketek)
Macrolides:
Clarithromycin (Biaxin)
Dirithromycin (Dynabac)
Erythromycin (Ery-Tab)
64
Macrolide Spectrum
Chlamydia
(Erythro drug of
choice in pregnancy)
Mycoplasma pneumoniae
Ureaplasma urealyticum
Legionella
pneumophila
Treponema pallidum (Syphillis)
Gram (+) cocci
Gram (+) bacilli
65
Macrolide Spectrum
Clarithro>erythro
Staph, Strep
Azithro>erythro
66
Macrolide SE
Erythro
concentrates in
neutrophils, macrophages,
fibroblasts
Erythro Azithro=hepatic;
clarithro=renal
SE:
NVD, cholestatic jaundice (estolate
salt-erythro), Erythro & clarithro go
through CYP450
67
Lincomycins
Clindamycin
(Cleocin)
Lincomycin (Lincocin)
70
Lincomycin Spectrum
Gram
{+} aerobes
Gram {+} anaerobes
Gram {-} anaerobes
NO gram {-} aerobic coverage
Think of these as 2nd-line
penicillins
71
Lincomycin SE
Rash
Neutropenia
Thrombocytopenia
Erythema
multiforme (rare)
Pseudomembranous colitis
72
Chloramphenicol
Broad
Cell Membrane
Inhibitors
74
(Cubicin)
Unique mechanism of action that it
binds to bacterial membranes and
causes a rapid depolarization of
membrane potential which leads to
inhibition of protein, DNA, and RNA
synthesis
Used in antibiotic resistant MRSA,
VRE, and linezolid-resistant strains
Can cause myalgias
75
Selamat belajar.