Role antibiotics and

antiinflammatory

Mustofa
Bagian Farmakologi & Terapi
Fakultas Kedokteran UGM
 Antibiotic and
antimicrobial
Antibiotic : Chemical molecules
produced by a microorganism
that kills or inhibits the growth
of another microorganism
Antimicrobial agent : Chemical
molecules that kills or inhibits
the growth of microorganisms
 The anti-infective drugs
Anti-infective agents : drugs that
are developed to act selectively on
foreign organisms that have
invaded and infected the body.
Anti-infective drugs : range from
a. Antibiotics
b. Antifungals
c. Antiprotozoals
d. Antihelminthics
e. Antivirals
f. Antimycobacterial
Microbial Sources of Antibiotics
Antibiotic classification base on
their chemical sturcture

1.Beta-lactam antibiotics:
a. Penicillins
b. Inhibitors of beta-lactamases and
combined drugs,
c. Cephalosporins
d. Monobactams
e. Tienamycin (carbapenems).
2.Macrolides, azalides, streptogramins,
prystinamycines.
3.Linkozamides.
4.Tetracyclines.
5.Aminoglycosides.
6.Chloramphenicols.
7.Glycopeptides.
8.Cyclic polipeptides (polimixins).
Antibiotic classification base
on their spectrum activity

No antibiotic is effective against all microbes

Broad-spectrum:
Justifiable in life-threatening disease,
with unidentified organism
In general more expensive more likely
to resistance
More adverse effects than narrow
spectrum (increase superinfection)

Narrow spectrum:
Preferable if possible
Dangerous choice in life-threatening
disease unless organism (and
sensitivities) known
Antibiotic classification base on their activity
1. Bactericidal drugs kill bacteria directly
a. -lactam antibiotics
b. Cephalosporins
c. Vancomycin
d. Vancomycin
e. Aminoglycoside antibiotics
2. Bacteriostatic drugs prevent bacteria from
dividing
a. Tetracyclines
b. Sulfonamides
c. Spectinomycin
d. Trimethoprim
e. Macrolides
Modes of antimicrobial action
Principle antibiotics therapy
1. Susceptibility testing
2. Drug concentration in blood
3. Serum bactericidal titers
4. Route of administration
5. Monitoring of therapeutic
response
6. Clinical failure of antibiotics
therapy
1. Susceptibility testing
The results of susceptibility testing
establish the drug sensitivity of hte
organism
These results usually predict the MIC of a
antibiotics
Choosing of the most effective and the
2.least
Drug concentration
toxic in the blood
drug, in time administration
The measurement of drug concenctration
may be appropriate when using antibiotics
with low therapeutic index
(aminoglycosides & vancomycin)
It is also appropriate when investigating
poor clinicall response to a drug treatment
3. Route of administration
Parenteral administration is prefered in most
cases of serious microbacterial infections.
Chloramphenicol, the fluoroquinolones and
trimethoprim-sulfamethoxazole may be
effective orally.
5. Monitoring of therapeutic response
Therapeutic response should be monitored
clinically and microbiologically to detect
the development of resistance or
superinfection
The duration of therapy depend on the
pathogen (fungi or micobacterium), the
site of infection (endocarditis &
6. Clinical failure of antimicrobial therapy

Inadequate clinical or microbial response can

result from :
laboratory testing error,
problems the drug (incorrect choice, poor
tissue penetration, inadeqaute dose)
the patient (poor host defense, undrained
abcesses)
the pathogen (resistance or superinfection)
Factors influencing antibiotics use

1. Bacterial versus bacteriostatic

actions
2. Drug elimination mechanism
3. Special patients group
(pregnancy, neonate and
adult patients)
4. Drug interactions
1. Bactericidal versus bacteriostatic actions
For bacteriostatic drugs, the concentration
that inhibit growth are much lower than
those that kill bacteria.
For bactericidal drugs, there is little
difference between the concentration that
inhibit growth and those that kill bacteria.
Bactericidal drugs are preferred for the
treatment of infections in patients with
impaired defense mechanism
(immunocompromised patients)
Some bactericidal (aminoglycosides,
fluoroquinolones) cause concentration-
dependent killing maximing Cp increase
1. Bactericidal versus bacteriostatic actions (cont. )

Other bactericidal (beta lactam,

vancomycin) cause time-dependent
killing their killing is independent of drug
concentration and continous only while
blood concentration are maintained > MBC.
Inhibition of bacterial growth that continues
after antibiotic blood concentration have
fallen to low level is called the
postantibiotic effect (PAE).
PAE is another factor contribute to the
effectivenes of once daily administration of
aminoglycosides and clinical efficacy of the
fluoroquinolones.
 2. Drug elimination mechanism
Change in hepatic and renal function influence
pharma-cokinetics of antibiotic & necessite
dosage modifications.
In anuria (creatinine Cl < 5mL/min) the
t1/2 necessiting major reduction in drug
dosage.
Erythromycin, clindamycin, chloramphenicol,
rifampicin, ketokonazole no change in dosage
in renal failure.
Patients with biliary dysfunction &cirrhosis,
reduction in dosage is required for drug
undergo hepatic elimination.
Dialysis/hemodialysis decrease the plasma
3. Special patients group
Antibiotics therapy in special group
(preganancy, nonate & elderly) requires
special conciderations.
Aminoglycosides may cause neurologic and
renal damage.
Tetracucline casue tooth enamel dysplasia and
inhibiton of bone growth.
Sulfonamide displaces bilirubin from serum
albumin and causes kernicterus in the
neonate.
Chloramphenicol may cause gray baby
syndrome.
Other antibiotics should be used with extreme
4. Drug interaction
Interaction sometimes occure between
antibiotics and other drugs.
Aminoglycosides with diuretics, vancomycin
or cisplatin enhanced nephrotoxicity &
ototoxicity
Sulfonamide with sulfonylurea
hypoglycemic
Sulfonamides with warfarin
hypoprothrombinemia
Dilsufiram-like reactions to ethanol occur
with metronidazole, with TMP-SMX & with
4. Drug interaction (cont. ..)
Erythromycin inhibits the hepatic
metabolism of a number of drugs :
clozapine, lidocaine, loratidine, phenytoin,
quinidine, sildenefil, theiphylline and
warfarin.
The azole antifungal (ketoconazole)
inhibits metabolims of caffeine,
carmazepine, cyclosporine, HMG-CoA
inhibitor, methadone, oral contraceptives,
phenytoin, sildenafil, verapamil and
zidovudine.
Rifampicin decreases the effect of digoxin,
ketoconalzole, oral contraceptive,
Antimicrobial drugs combination indication

1. Emergency situations
2. To delay resistance
3. Mixed infections
4. To achieve synergistic effects
1. Emergency situations
In seveval infections (sepsis and meningitis),
combinations of antimicrobial drugs are used
empirically to supress all of the most likely
pathogens.
2. To delay resistance
The combined use of drugs is valid when the
rapid emergence of resistance impairs the
chances for cure.
Combined drug therapy is especially
important in the treatment of TBC, malaria,
virus infection.
3. Mix infections
Multiple organims may be involved in some
infections.
Peritonial infections may be caused by
several pathogens a combiantion drug
may be required.
Skin infections are often due to mixed
4. To achieve synergistic effect
bacterial, fungal or viral pathogens.
The use combination may result in an effect
greater than a single drug.
Examples :
Penicillins + gentamicin in enterococcal
endocarditis
Penicillin + aminoglycoside in Pseudomonas
infections
 Mechanism antimicrobial drugs combination

1. Sequential blockade H
N C
O H
N SO2 NH2
H OH
H

combination P-aminobenzoid Sulfonamides

acid
may cause Folic acid
H
N C
O

inhibition of Dihydropteroate
H2C NH
H

synthase HOOC CH

2 or more
H N N CH2

HOOC CH2

Dihydro folic acid (DHF) N OH

steps in a H2N
N
H3CO
OCH3
OCH3

metabolic DHFReductase CH2

pathway. N

N
NH2

Tetrahydro-folic acid
H2N

Example : H
N
Trimethorprim
TMP+SMX
H2C
H

Human cell
H N N

N OH

N
H2N

Synthesis of purine
bases & thymidine Parasite
Mechanism antimicrobial drugs combination (cont. ..)
2. Blockade of drug-inactivating
enzymes
Clavulanic acid, sulbactam and
tazobactam inhibit penicillinases and
are often combined with penicillinase-
sensitive beta-lactam drugs.
3. Enhanced drug uptake
Increase permeability to
aminoglycosides after exposure of
certain bacteria to cell wall-inhibiting
antimicrobacterial (e.g. beta-lactams)
Antimicrobial chemoprophylaxis
General priciples :
a. Prophylaxis should always be
directed toward a specific
pathogen (TBC, malaria, influenza,
hepatitis, polio, ect.)
b. No resistance should develop
during the period of drug use
c. Prophylaxis drug use should be of
limited duration
d. Conventional therapeutic doses
should be employed
e. Prophylaxis should be used only