Antimicrobial Therapy

Principles of Antimicrobial Therapy

1. Make a diagnosis:
• As precisely as possible.
• Define the site of infection and the organism(s) responsible and their
sensitivity to drugs.
• All relevant biological samples should be taken before treatment.
Principles of Antimicrobial Therapy
2. Remove barriers to cure:
• Drain abscesses
• Replace infected IV cannula
• Clear blocked passages - respiratory, urinary
Principles of Antimicrobial Therapy
3. Decide the necessity of antimicrobials:
• Some of the acute infections are better managed symptomatically
than by antimicrobials e.g., Need of antibiotics for superficial wounds.
• Risks of adverse drug reactions
• Chronic wounds, chronic abscess or empyema respond poorly to
antibiotics alone.
Principles of Antimicrobial Therapy
4. Select the best drug:
• Consider the specificity – ideally the antimicrobial activity of the drug
should match that of the infecting organisms. Avoid broad spectrum
antibiotics – risk of resistance and opportunistic infections. At the
beginning – empirical/ best guess therapy.
• Consider the pharmacokinetic factors – the selected antibiotic should
reach the site of action in adequate amounts e.g., BBB, bones.
• Consider patient factors – allergies, renal/hepatic impairment.
Principles of Antimicrobial Therapy
5. Administering drugs:
• Optimum dose and frequency – inadequate dose may encourage
development of resistance.
• By the most appropriate route(s)
• Plasma concentration monitoring can be performed to optimize the
therapy and to reduce adverse drug reactions e.g., aminoglycosides,
Vancomycin.
Principles of Antimicrobial Therapy
6. Continuation of therapy:
• For most infections 5-7 days
• Longer for some infections in which relapse is possible long after the
apparent clinical cure e.g., Tuberculosis and infective endocarditis.
• Otherwise, prolonged therapy is to be avoided because it increase the
costs and the risks of adverse drug reactions.
Principles of Antimicrobial Therapy
7. Test for cure:
• Symptoms and signs disappear before organism has been eradicated
e.g., UTI.
• Microbiological culture must be done after the withdrawal of
antibiotics.
Concentration-dependent killing
• Show a significant increase in the rate of bacterial killing as the
concentration of antibiotic increases.
• Concentration-dependent killing is exhibited by once-a day bolus
infusions which achieves high peak levels favoring rapid killing of the
infecting pathogen.
• E.g., aminoglycosides, fluoroquinolones
Time-dependent killing
• Killing effect is best predicted by the time duration that the blood
concentrations of the antibiotic remain above the MIC.
• Increasing the concentration of antibiotic to higher the multiples of
the MIC does not significantly increase the rate of kill.
• E.g., Penicillin and Cephalosporins, Carbapenems
• Severe infections are best treated by continuous infusion of these
agents rather than by intermittent dosing.
Use of Antimicrobials
• Empirical therapy – Broad spectrum agent/s to cover all the likely
pathogens because the infecting organism(s) has not yet been
defined.
• Definitive therapy – Once the infecting microorganism is identified, a
narrow-spectrum, low-toxic agent can be used to complete the
course of treatment.
• Prophylactic therapy – Exposed to an agent and then to prevent
infection e.g., TB OR Following procedures likely to cause bacteremia
in susceptible people e.g., surgery.
• Combination Therapy – e.g., treatment of tuberculosis benefits from
drug combinations.
Combination Therapy
It is therapeutically advisable to treat patients with the single agent that is
most specific for the infecting organism. However, situations in which
combinations of drugs are employed do exist:
• To broaden the spectrum of antibacterial activity e.g., in a known mixed
infection etc.
• To obtain potentiation or synergy e.g., penicillin plus gentamicin.
• To enable reduction of the dose of one component and hence reduce the
risks of adverse drug reactions.
When a combination must be used blindly, it is theoretically preferable to
use two bacteriostatic or two bactericidal drugs, because a bacteriostatic
drug, by reducing multiplication, may protect the organism from a
bactericidal drug.
Complications of Antimicrobial Therapy
• Hypersensitivity e.g., Penicillin
• Direct toxicity e.g., aminoglycosides can cause ototoxicity
• Super infections – with broad-spectrum antimicrobials or
combinations of agents, can lead to alterations of the normal
microbial flora, permit the overgrowth of opportunistic organisms,
especially fungi.
• Resistance
• Masking of infections e.g., a course of penicillin adequate to cure
gonorrhea may prevent simultaneously infected syphilis from showing
primary and secondary stages.
To reduce the emergence of resistance
• Antibiotics Should use only when indicated
• Select most appropriate antibiotic
• Use the antibiotic for the total required duration
• Should not stop when symptoms disappear
• Use first line drugs whenever possible
Classification of Antimicrobials
According to the type of organism which they are active against:
• Antibacterial drugs
• Antiviral drugs
• Antifungal drugs
• Antiprotozoal drugs
• Anthelmintic drugs
Classification of Antimicrobials
According to the spectrum of activity:
• Narrow-spectrum antibiotics e.g., Isoniazid is active only against
mycobacteria
• Extended-spectrum antibiotics – antibiotics that are effective against
gram-positive organisms and also against a significant number of
gram-negative bacteria e.g., Ampicillin
• Broad-spectrum antibiotics – affect a wide variety of microbial species
e.g., tetracycline
Classification of Antimicrobials
According to the site of
action:
• Interference with
breakdown and extension
of the cell wall
• Interference with plasma
membrane
• Inhibit protein synthesis
• Interference with nucleic
acid synthesis
• Interference with DNA or
RNA replication/ repair
Classification of Antimicrobials
According to the chemical structure:
• Beta lactams
• Macrolides
• Quinolones
• Tetracyclines
• Aminoglycosides
• Sulfonamides
Antibiotics
• Antibiotics are chemicals
that enter and stick to
important parts of the
bacterial cell and
interfere with its ability
to survive and multiply.
• These important parts
include proteins/sugars
in the bacterial wall or
important enzymes that
make new bacterial DNA
or proteins.
Classification of Antibiotics
Bacteriostatic:
• Those that act primarily by
arresting bacterial multiplication.
• E.g., sulfonamides, tetracyclines
and chloramphenicol
Bactericidal:
• Those which act primarily by
killing bacteria.
• E.g., beta lactams,
aminoglycosides, quinolones
Classification of Antibiotics
Classification of Antibiotics
Classification of Antibiotics
Classification of Antibiotics