This presentation was used for lecture class of BSN 1st year. Here we have discussed the general considerations for antimicrobial therapy.

1. Antimicrobial Therapy:
General Considerations
Dr. Pravin Prasad
M.B.B.S., MD Clinical Pharmacology
Lecturer, Lumbini Medical College
14 February 2019 (2 Falgun 2075), Thursday

2. By the end of the class, BSN 1st Year
students will be able to:
➢Differentiate the terms antibiotic and antimicrobial
agents (AMAs)
➢Understand the basis of classification of AMAs
➢List the factors governing choice of AMA
➢Explain the rationale of combining AMAs
➢Identify the conditions requiring prophylactic use of
AMAs
➢List the adverse effects and causes of failure of AMA
therapy

3. Differentiating the terms
➢Antibiotics:
✓Substances
produced by micro-
organisms, which
selectively supress
the growth or kill the
micro-organisms at
very low
concentrations
➢Antimicrobial agents:
✓Synthetic as well as
naturally obtained
drug that attenuate
microorganisms

4. Basis of classification of AMAs
➢Type of organism against which primarily active
✓Antibacterial, antifungal, antiviral, antiprotozoal,
anthelminthic
➢Spectrum of activity
✓Narrow spectrum, Broad spectrum
➢Type of action
✓Primarily bacteriostatic or bactericidal

5. Basis of classification of AMAs
➢Mechanism of Action:
✓Inhibit cell wall synthesis
✓Cause leakage from cell membranes
✓Inhibit protein synthesis
✓Cause misreading of m-RNA code and affect permeability
✓Inhibit DNA gyrase
✓Interfere with DNA Function
✓Interfere with DNA function
✓Interfere with intermediary metabolism

6. Choice of an Antimicrobial Agent
Organism
related
Drug
related
Patient
related

7. Patient Factors affecting the choice
of an Antimicrobial Agent
➢Age
➢Renal or Hepatic Function
➢Local factors
➢Drug Allergy
➢Impaired Host Defence
➢Pregnancy
➢Genetic Factors

8. Patient Factors affecting the choice
of an Antimicrobial Agent
➢Age
✓Chloramphenicol in new born-grey baby syndrome
✓Tetracycline are C/I in children below 6 years
✓Half life of aminoglycosides is prolonged in the elderly
➢Pregnancy
✓All antibiotics pose risk to the fetus when used in pregnancy.
Penicillins, most cephalosporins and macrolides appear safe.
➢Impaired host defence
✓Bactericidal drugs are must in immunocompromised patients.

9. Patient Factors affecting the choice
of an Antimicrobial Agent
➢4.Renal failure
Drugs Contraindicated Dose reduction required
in renal failure
Cephalothin Aminoglycosides
Cephaloridine Amphotericin B
Nitrofurantoin Vancomycin
Nalidixic Acid Ethambutol
Tetracyclines
(Except Doxycycline)
Penicillin, Rifampicin: No Dose Adjustment Required

10. Patient Factors affecting the choice
of an Antimicrobial Agent
➢Liver function
Drugs C/I in liver
disease
Dose reduction required in
liver failure
Erythromycin estolate Chloramphenicol
Tetracyclines Isoniazid
Pyrazinamide Rifampicin
Pefloxacin Clindamycin

11. Patient Factors affecting the choice
of an Antimicrobial Agent
➢Genetic Factors:
✓Antimicrobials producing hemolysis in G6PD
deficient patients are:
• Primaquine, Chloroquine, Quinine
• Dapsone, Sulphonamides
• Chloramphenicol, Nitrofurantoin,
Fluoroquinolones,

12. Choice of an Antimicrobial Agent:
Organism Related Considerations
➢Clinical Diagnosis itself directs the choice of the AMA
➢A good guess can be made
➢Choice based on bacteriological examination
✓Bacterial services are not available
✓Bacterial services are available but treatment
cannot be delayed: Emperical Therapy
✓Bacterial services are available and treatment can
be delayed

13. Choice of an Antimicrobial Agent:
Organism Related Considerations
➢Emperical Therapy:
✓Refers to initiation of antibiotics depending
upon knowledge and experience of physician
before result of culture and sensitivity test is
available
✓Broad spectrum antibiotics started
✓After sending sample for C/S
• In serious infections like meningitis &
septicaemia

14. Choice of an Antimicrobial Agent:
Drug Factors
➢Spectrum of activity
➢Type of activity
➢Sensitivity of organism
➢Relative toxicity
➢Pharmacokinetic profile
➢Route of administration
➢Evidence of clinical efficacy

15. Combined Use of Antimicrobial
Agents
➢To achieve synergism
➢To reduce severity of adverse effects
➢To prevent emergence of resistance
➢To broaden the spectrum of antimicrobial action
➢Disadvantages??

16. Combined Use of Antibiotics
➢Two bacteriostatic agents: additive effect
✓Clavulanic acid with amoxicillin.
➢Two bactericidal agents: additive
✓Penicillin and Aminoglycosides
Static Cidal
Static Additive ?
Cidal ? Additive

17. Combined Use of Antibiotics
➢Combination of a bactericidal with a bacteriostatic
drug:
✓Additive if the organism has low sensitivity to
the cidal drug
• Streptomycin + Tetracycline for brucellosis
✓Antagonistic if the organism has high sensitivity
to cidal drug
• Penicillin + tetracycline for pneumococci.

18. Prophylactic Use of Antimicrobials
➢Use of AMAs before the clinical disease has
occurred
✓Prevent the setting in of an infection
✓Suppress contacted infections

19. Prophylactic Use of Antimicrobials
Type of Prophylaxis Example
Prophylaxis against specific
organisms
Rheumatic fever
(Penicillin G)
Prevention of infection in
high risk situations
Malaria (Chloroquine)
Prevention of infection in
general
Prior to surgical
procedures

20. Problems that arise with use of
AMAs
➢Toxicity
✓Local irritancy
✓Systemic toxicity
➢Hypersensitivity
reactions
➢Superinfection
➢Drug Resistance
✓Natural
✓Acquired
➢Nutritional deficiencies
➢Masking of an infection

21. Mechanism of Resistance
➢Decrease affinity for the target
✓Pneumococci, Staphylococci: Altered penicillin binding
proteins
➢Development of alternative metabolic pathway
✓Sulfonamides resistant organisms start utilizing
performed folic acid in place of synthesizing it from PABA.
➢Drug resistance by inactivating enzymes
✓Aminoglycosides, Beta-lactams, Chloramphenicol
➢Development of efflux pumps
✓Tetracyclines, Erythromycin, Fluoroquinolones

22. Superinfection (Suprainfection)
➢A new infection occurring in a patient having a pre-
existing infection
➢Most difficult to treat

23. Failure of AMA Therapy
➢Causes
✓Improper selection of drug, route, dose or
duration of treatment
✓Delayed commencement of treatment
✓Poor host defense eg; Neutropenia, Leukemia
✓Failure to take necessary adjuvant measures
• Drainage of abscess, removal of renal stone or
other foreign bodies, control of DM

24. Conclusion
➢Antibiotics are naturally obtained from micro-
organisms
➢Classification of AMAs can be done on different
basis
✓Based on mechanism of action important
➢Choice of AMA depends on patient related,
organism related and drug related factors

25. Conclusion
➢AMAs can be combined for multiple advantages
➢AMA prophylaxis is started before the clinical
manifestation of disease has occurred
➢Drug resistance is one of the dreadful complication
of AMA
➢Failure of AMA therapy can occur due to some
avoidable situations

26. Any queries?
They are not the same