ANTIBIOTIC AGENTS
Antimicrobial agents
1. Antibiotics
2. Antivirals
3. Antifungals
4. Antiparasitics
PRINCIPLE USE OF ANTIBIOTICS
Antimicrobial agents are among the most
commonly used and misused of all drugs.
The antibiotic-resistant pathogens
increasing need for new drugs
Reducing inappropriate antibiotic use is
thought to be the best way to control
resistance.
Actions of antibacterial drugs on
bacterial cells
Mechanisms of Action
(1) Agents that inhibit synthesis of bacterial cell walls
eg. b-lactam class and other agents such as vancomycin, penicillin,
amoxicillin, cephalosporin
(2) Agents that act directly on the cell membrane to increase permeability
and cause leakage of intracellular compounds
e.g., aminoglycosides, tetracyclines, erythromycin, and clindamycin
(4) Agents that bind to the 30S ribosomal subunit and alter protein
synthesis
e.g., the aminoglycosides
(5) Agents that affect bacterial nucleic acid metabolism by inhibiting RNA
polymerase (e.g., rifampin) or topoisomerase (e.g., the quinolones)
Pharmacological aspect
When a drug enters the body, the body begins immediately to work
on the drug: absorption, distribution, metabolism (biotransformation),
and elimination.
Pharmacokinetics
The drug also acts on the body, an interaction to which the concept
of a drug receptor is key, since the receptor is responsible for
the selectivity of drug action and for the quantitative relationship
between drug and effect
Pharmacodynamics
PK-PD
The location of the infection may dictate the choice of drug
and the route of administration
There is an evidence to suggest that even subinhibitory
concentrations of antibiotics may enhance phagocytosis
Pharmakokinetic aspect
Pharmacodynamic properties can be used to divide antibiotics into
two major classes based on their mechanism of bactericidal action:
(1) concentration-dependent drugs,
such as aminoglycosides and fluoroquinolones
- the higher the drug concentration, the faster the eradication of
pathogens.
(2) concentration-independent drugs, e.g. the -lactams
- peak concentrations are relatively unimportant
- time-dependent drugs
.
Pharmacodynamic aspect
The postantibiotic effect (PAE):
is the phenomenon of continued suppression of bacterial
growth after a short exposure of bacteria to antimicrobial
agents
This effect is probably the result of:
nonlethal damage caused by the antibiotic and
continued persistence of the drug at the bacterias drug-
binding site for a time after drug is removed
Advantage
- The simultaneous use of two or more antimicrobial agents is recommended in specifically
defined situations based on pharmacological rationale
- However, selection of an appropriate combination requires an understanding of the potential
for interaction between the antimicrobial agents. Interactions may affect either the
microorganism or the patient
Disadvantages
- increased risk of toxicity from two or more agents,
- selection of multiple-drug-resistant microorganisms,
- eradication of normal host flora with subsequent superinfection,
- increased cost to the patient
The addition of a bacteriostatic drug to a bactericidal drug frequently results in a
bacteriostatic effect, antagonism between antibiotics probably is relatively
unimportant when host defenses are adequate e.g. Penicillin - Chlortetracycline
IMPROPER DOSAGE
Excessive dosing can result in significant toxicities, while too low a
dose may result in treatment failure and is most likely to select for
antibiotic resistance.
INAPPROPRIATE RELIANCE ON ANTIBIOTICS ALONE
Infections complicated by abscess formation or the
presence of necrotic tissue or a foreign body often cannot
be cured by antibiotic therapy alone.
Drainage, debridement, and removal of the foreign body
are at least as important as the choice of antibiotic agent.
Reaksi toksik antibiotik ini juga tergantung pada jenis obat dan faktor pada
tubuh pasien.
Contoh tetrasiklin bisa mengganggu pertumbuhan jaringan tulang
termasuk gigi bila diberikan pada anak-anak.
Broad spectrum
Ulcerative Colitis
Sulfonamides for Topical Use
Sulfacetamide
Good penetration in eye
Non-irritating
Silver sulfadiazine
Prevention and
treatment of burn wound
infections
Bacterial corneal
infection
Long Acting
Sulfonamide
Sulfadoxine
Serum half-life is
measured in days rather
than minutes or hours
Combined with
Pyrimethamine to treat
malaria
Plasmodium
vivax
Therapeutic Uses
of Sulfonamides
Urinary tract infections
Nocardiosis:
Nocardia asteroides
Nocardia brasiliensis
Toxoplasmosis (avoid
using in pregnant women)
Nocardia asteroides
Toxicity/Contraindications
of Sulfonamides - UT
Crystallization in acid urine
Common to uncommon depending on drug
Alkalize urine or increase hydration
Toxicity/Contraindications
of Sulfonamides - blood
Acute hemolytic anemia
Rare to extremely rare
Associated with glucose-6-phosphate
dehydrogenase activity in RBC
Therapeutic Uses of
Quinolones
Respiratory tract
All work well against atypical pneumonia
agents (eg, chlamydia, mycoplasma, and
legionella),
New agents for strep. Pneumonia
Respiratory fluoroquinolones: Levofloxacin,
gatifloxacin, gemifloxacin, and moxifloxacin.
are effective and used increasingly for
treatment of upper and lower respiratory
tract infections.
Therapeutic Uses of
Quinolones
Bone, joint, soft tissue
Ideal for chronic
osteomylitis
Resistance
developing in
S. aureus, P.
aeruginosa, and S.
marcesens
Good against polymicrobial
infections like diabetic foot
ulcers
Therapeutic Uses of
Quinolones
Ciprofloxacin for
anthrax and tularemia
(Francisella tularensis)
Pulmonary
Anthrax
Toxicity/Contraindications of
Quinolone
Nausea, vomiting, abdominal discomfort (common)
Diarrhea and antibiotic-associated colitis
(uncommon to rare)
CNS side effects
Mild headache and dizziness (common to rare)
Hallucinations, delirium, and seizures (rare)
May damage growing cartilage and cause an
arthropathy. Thus, these drugs are not routinely
recommended for patients under 18 years of age
(common)
Quinolones not given to children unless benefits
outweigh the risks
Leukopenia, eosinophila, heart arrhythmias (rare)
The Beta-Lactams
Penicillins
Penicillium notatum
produces the only
naturally occuring
agent penicillin G or
benzylpenicillin
P. chrysogenum
produces 6-
aminopenicillanic acid,
raw material for
semi-synthetics
Penicillins
Spectrum of activity based on R groups
added to 6-aminopenicillanic acid core
Mechanisms of resistance
Alter affinity of transpeptidase
Enzymatically cleave the beta-lactam ring
Efflux pumps
Poor penetration into cell
Penicillins
Administered orally, intramuscularly, or
intravenously depending on agent
R groups determine
spectrum of activity and
pharmacological properties
Mechanism of
action/resistance and class
pharmacology essentially
the same as penicillins
First Generation
Cephalosporins
Cefazolin, cephalexin, cephadroxil
Excellent against susceptible staph and strep
Modest activity against G-
Cefazolin given parentally, others orally
More than half of the drug is bound to plasma
proteins
Excreted by kidneys unmetabolized
Good for staph and strep skin and soft tissue
infections
Second Generation
Cephalosporins
Cefaclor, cefuroxime, cefprozil, cefotetan,
cefoxitine, cefamandole
Modest activity against G+, increased
activity against G-, works against anaerobes
Cefaclor and cefprozil given orally
Absorption and excretion same as first gen.
Good for treating
respiratory tract infections
intra-abdominal infections
pelvic inflammatory disease
diabetic foot ulcers
Third Generation
Cephalosporins
Cefotaxime, ceftriaxone, cefoperazone, cefpodoxime, cefixime
Broad spectrum killers
Drugs of choice for serious infections
No effect against Listeria and beta-lactamase producing
pneumococci
Cefpodoxime and cefixime are given orally, others parentally
Most excreted by kidney
Therapeutic uses
Bacterial meningitis
(2 exceptions cefoperazone, cefixime)
Lyme disease
Life-threatening G- sepsis
Fourth Generation
Cephalosporin
Cefepime
Same antimicrobial spectrum as third
generation but resists more beta-lactamases
Parenteral administration
Ertapenem:
has longer half-life
Less effective against pseudomonas
Causes pain at site of injection
Aztreonam a monobactam
Works only on G-, including
Pseudomonas aeruginosa