principle of antimicrobials

1. GENERAL PRINCIPLES OF
ANTIMICROBIAL THERAPY
Dr.Tarup Gokia
International school of
Medicine

2. The specific questions include the
following:
1. Is an antimicrobial agent indicated on the basis of
clinical findings?
2. Have appropriate clinical specimens been obtained to
establish a microbiologic diagnosis?
3. What are the likely etiologic agents for the patient's
illness?
4. What measures should be taken to protect individuals
exposed to the index case to prevent secondary
cases, and what measures should be implemented to
prevent further exposure?
5. Is there clinical evidence (eg, from clinical trials) that
antimicrobial therapy will confer clinical benefit for the
patient?

3. Once a specific cause is identified, the
following further questions should be
considered:
1. If a specific microbial pathogen is identified, can a
narrower-spectrum agent be substituted for the initial
empirical drug?
2. Is one agent or a combination of agents necessary?
3. What is the optimal dose, route of administration,
and duration of therapy?
4. What specific tests (eg, susceptibility testing) should
be undertaken to identify patients who will not
respond to treatment?
5. What adjunctive measures can be undertaken to
eradicate the infection?

4. Empirical Antimicrobial Therapy
• Antimicrobial agents are frequently used
before the pathogen responsible for a
particular illness or the susceptibility to a
particular antimicrobial agent is known. This
use of antimicrobial agents is called empirical
(or presumptive) therapy and is based upon
experience with a particular clinical entity.

5. Approach to Empirical Therapy
• Formulate a Clinical Diagnosis of Microbial Infection.
Using all available data, the clinician should conclude
that there is anatomic evidence of infection (eg,
pneumonia, cellulitis, sinusitis).
• Obtain Specimens for Laboratory Examination
• Examination of stained specimens by microscopy or
simple examination of an uncentrifuged sample of
urine for white blood cells and bacteria may provide
important etiologic clues in a very short time.
• Formulate a Microbiologic Diagnosis.

6. Approach to Empirical Therapy
• Determine the Necessity for Empirical Therapy
• Institute Treatment
Selection of empirical therapy may be based
upon the microbiologic diagnosis or a clinical
diagnosis without available microbiologic clues. If
no microbiologic information is available, the
antimicrobial spectrum of the agent or agents
chosen must necessarily be broader, taking into
account the most likely pathogens responsible for
the patient's illness.

7. Choice of Antimicrobial Agent
• Selection from among several drugs depends
upon host factors which include the following:
(1) concomitant disease states (eg, AIDS, severe chronic
liver disease);
(2) prior adverse drug effects;
(3) impaired elimination or detoxification of the drug (this
may be genetically predetermined but more frequently
is associated with impaired renal or hepatic function
due to underlying disease);
(4)age of the patient;
(5) pregnancy status.

8. Choice of Antimicrobial Agent
• Pharmacologic factors include
(1) the kinetics of absorption, distribution,
and elimination;
(2) the ability of the drug to be delivered to
the site of infection;
(3) the potential toxicity of an agent;
(4) pharmacokinetic or pharmacodynamic
interactions with other drugs.

9. Empiric Antimicrobial Therapy Based
on Microbiologic Etiology

11. Empiric Antimicrobial Therapy
Based on Microbiologic Etiology

12. Empiric Antimicrobial Therapy
Based on Microbiologic Etiology

13. Empiric Antimicrobial Therapy
Based on Microbiologic Etiology

14. Empiric Antimicrobial Therapy Based
on Microbiologic Etiology

15. Empiric Antimicrobial Therapy Based
on Microbiologic Etiology

16. Empiric Antimicrobial Therapy Based
on Microbiologic Etiology

17. Empiric Antimicrobial Therapy Based
on Site of Infection

18. Empiric Antimicrobial Therapy Based
on Site of Infection

20. Antimicrobial Therapy of Infections
with Known Etiology
• Interpretation of Culture Results
The lack of a confirmatory microbiologic diagnosis may be due to
the following:
(1) Sample error, eg, obtaining cultures after antimicrobial agents
have been administered.
(2) Noncultivable or slow-growing organisms, (Histoplasma
capsulatum, bartonella species), where cultures are often
discarded before sufficient growth has occurred for detection.
(3) Requesting bacterial cultures when infection is due to other
organisms.
(4) Not recognizing the need for special media or isolation
techniques.

21. Guiding to Antimicrobial Therapy of
Established Infections
• Susceptibility Testing
Tests measure the concentration of drug
required to inhibit growth of the organism
(minimal inhibitory concentration [MIC]) or to
kill the organism (minimal bactericidal
concentration [MBC]).
• Specialized Assay Methods
1. Beta-Lactamase Assay
2. Synergy Studies

22. Monitoring Therapeutic Response:
Duration of Therapy
•The duration of therapy required for cure depends on
the pathogen, the site of infection, and host factors
(immunocompromised patients generally require longer
courses of treatment).
• In many situations, duration of therapy is determined
empirically. For serious infections, continuing therapy for
7–10 days after the patient has become afebrile is a good
rule of thumb.
• For recurrent infections (eg, sinusitis, urinary tract
infections), longer courses of antimicrobial therapy are
frequently necessary for eradication.

23. Bacteriostatic Versus Bactericidal
Activity

24. Bacteriostatic Versus Bactericidal
Activity
• For agents that are primarily bacteriostatic,
inhibitory drug concentrations are much lower
than bactericidal drug concentrations.
• Bactericidal agents are required for treatment
of acute infections (endocarditis and other
endovascular infections, meningitis, and
infections in neutropenic cancer patients).
• Bacteriostatic agents are preferable in chronic
reccurent infections.

25. Pharmacokinetic Considerations
• Route of Administration
The intravenous route is preferred in the following
situations:
(1) for critically ill patients;
(2) for patients with bacterial meningitis or
endocarditis;
(3) for patients with nausea, vomiting,
gastrectomy, or diseases that may impair oral
absorption;
(4) when giving antimicrobials that are poorly
absorbed following oral administration.

26. Pharmacokinetic Considerations
• Drug Concentrations in Body Fluids.
Most antimicrobial agents are well distributed
to most body tissues and fluids. Penetration
into the cerebrospinal fluid is an exception.

27. Conditions That Alter Antimicrobial
Pharmacokinetics
• Impairment of renal or hepatic function may
result in decreased elimination.
• The pharmacokinetics of antimicrobials are
also altered in the elderly, in neonates, and in
pregnancy.

28. Conditions That Alter Antimicrobial
Pharmacokinetics

29. Monitoring Serum Concentrations of
Antimicrobial Agents
• To justify routine serum concentration
monitoring, it should be established
(1) that a direct relationship exists between drug
concentrations and efficacy or toxicity;
(2) that substantial interpatient variability exists in
serum concentrations on standard doses;
(3) that a small difference exists between
therapeutic and toxic serum concentrations;
(4) that the clinical efficacy or toxicity of the drug is
delayed or difficult to measure;
(5) that an accurate assay is available.

30. Management of Antimicrobial Drug
Toxicity
• Allergic reactions
• Cross reactivity
• Adverse reactions to antimicrobials occur with
increased frequency in several groups,
including neonates, geriatric patients, renal
failure patients, and AIDS patients.
• Polypharmacy

31. Rationale for Combination
Antimicrobial Therapy
• Antimicrobial combinations should be selected for
one or more of the following reasons:
(1) To provide broad-spectrum empirical therapy in
seriously ill patients.
(2) To treat polymicrobial infections such as intra-
abdominal abscesses.
(3) To decrease the emergence of resistant strains.
(4) To decrease dose-related toxicity by using reduced
doses of one or more components of the drug regimen.
(5) To obtain enhanced inhibition or killing.