2. Overview
Germ Theory of Disease
Timeline of Antibiotic Drug Discovery
Antibiotics Vs Antimicrobial Agents
Classification of AMAs
Type of Antimicrobial therapy
Principles of Antibiotic dosing
Factors affecting the choice of AMAs
Problems with the use of AMAs
Schedule HX
Conclusion
3. Germ Theory of Disease
Microorganisms known as pathogens or "germs" can lead to disease.
6. Antibiotics Vs Antimicrobial agents
Antibiotics
- Antibiotics are the substances which are obtained from one microorganism and
prove fatal for other microorganism in low concentration
Antimicrobials
- Broad term
- Includes all the natural, semisynthetic and synthetic agents which inhibit or kill
the micro-organism.
7. Antibiotics Vs Antimicrobial agents
All the antibiotics are antimicrobial agents but all anti microbial agents
are not the antibiotics.
8. Classification of AMAs
On the basis of type of organism against which they are active
- Antibacterial
- Antiviral
- Antifungal
- Antiprotozoal
On the basis of chemical structure
- Sulfonamide, Tc, FQs, Polyene
14. Minimum Inhibitory Concentration(MIC) and
Minimum Bactericidal Concentration (MBC)
MIC- Lowest antibiotic concentration that prevents the growth of microorganism
after a 24 hr incubation period with a standard organism inoculation (104 to 105
cfu/ml)
16. Minimum Inhibitory Concentration(MIC) and
Minimum Bactericidal Concentration (MBC)
Bactericidal drug- Difference between MBC and MIC is minimal
Bacteriostatic drug- Difference between MBC and MIC is large
19. Types of Antimicrobial therapy
Prophylaxis therapy
• A single, effective, non toxic drug* is successful in preventing infection by specific
organism.
• The main principle behind prophylaxis is targeted therapy
20. Types of Antimicrobial therapy- Prophylactic
Therapy
1) Prophylaxis given in HIV-AIDS patients or in post transplantation
2) Chemoprophylaxis to prevent wound infection after surgery
3) Post exposure prophylaxis- people who are in close contact to cases
4) Nevirapine is used in pregnancy to prevent vertical transmission
21. Types of Antimicrobial therapy- Pre Emptive Therapy
Pre- emptive therapy- Goal of pre-emptive therapy is to abort the impending disease.
23. Types of Antimicrobial therapy- Empirical
Therapy
1) Is there need of antibiotic therapy or the disease is self limiting
2) When to start the antibiotic therapy
• Starting therapy immediately after appearance of symptoms, without taking
appropriate culture can misdiagnosed the disease.
• Cost of waiting
• Broad spectrum drugs
24. Types of Antimicrobial therapy- Definitive
Therapy
Definitive Therapy- Once a pathogen has been isolated and the susceptibilities
results are available.
25. Types of Antimicrobial therapy- Definitive
therapy
Monotherapy is preferred to decrease the risk of antimicrobial toxicity and
selection of antimicrobial resistant pathogens.
Proper antimicrobial doses and dose schedules are crucial to maximize efficacy
and minimizing toxicity.
27. Combination Therapy
To enhance the therapeutic efficacy by synergistic interaction.
Cotrimoxazole- FDC of trimethoprim 80 mg + sulphamethoxazole 400 mg
(1:5)
1) Reduces the MIC of both the agents
2) Widens the spectrum
3) Reduces the chances of development of resistance
28. Combination Therapy
Combination of two bacteriostatic or bactericidal drug is synergistic
Combination of bactericidal and bacteriostatic drug is Irrational if
organism has high sensitivity to cidal drugs.
29. Combination Therapy
Reduce toxicity
In cryptococcal meningitis- Combination of amphotericin B and Flucytosine
shortens the duration of treatment.
30. Irrational FDCs available in Indian Market
Amoxycillin + Cloxacillin
Norfloxacin + Tinidazole
Ofloxacin + Ornidazole
Fluconazole+ Tinidazole
Roxithromycin + Ambroxol
Gatifloxacin + Ambroxol
32. Type of Antimicrobial Therapy
Post treatment suppressive therapy
Given after the disease is controlled by antimicrobial agents, at lower dose.
Reason
Because infection is not completely eradicated and the immunological or anatomical
defect that led to the original infection is still present.
Example- AIDS and Post transplant patients
33. Principles of Antibiotic Dosing
Two important characteristics that have a significant influence on the
frequency of dosing are-
1) Concentration Dependent killing (CDK)
2) Time Dependent killing (TDK)
34. Principles of Antibiotic Dosing- CDK
In concentration dependent killing, the outcome of treatment depends on
the peak antimicrobial concentration at the site of infection in relation to
MIC.
Higher peak concentration/MIC ratio – more bacterial killing.
Single large dose of such drugs produce better effect in comparison to same
amount in divided dose.
Ex- Aminoglycosides, FQs
35. Principles of Antibiotic Dosing- PAE
The effect of antibiotic persist even if the antibiotic concentration falls below the MIC
OR
Bacterial growth occurs only after a lag period when kept in antibiotic free medium
The PAE is usually a result of disruption in bacterial ribosomal or DNA gyrase
functions whose resumptions requires time.
36. Principles of Antibiotic Dosing- TDK
The reduction in number of multiplying bacteria depends on the duration of length
of time the concentration remains more than MIC and not affected if
concentration of drug is increased many times in relation to MIC.
Examples: Beta lactams, Vancomycin
38. Factors affecting the choice of an AMAs
Age
Chloramphenicol in new born may cause Grey Baby Syndrome
Sulfonamides in new born may cause Kernicterus
Tetracycline are C/I in children <6 years
Pregnancy
All antibiotics pose risk to the fetus when used in pregnancy except Pn,
Cephalosporins and Macrolides
39. Factors affecting the choice of an AMAs
Impaired Host Defense
Bactericidal drugs are must in immunocompromised individual
Genetic Factors
Hemolysis in G-6PD deficiency
Chloroquine, Primaquine, Quinine, FQs etc
40. Factors affecting the choice of an AMAs
C/I In Renal failure C/I in liver failure
Nitrofurantoin Erythromycin estolate
Nalidixic acid Tetracycline
Tc Pyrazinamide
Pefloxacin*
41. Problems with the use of AMAs
Local Irritation
- Gastric irritation on oral administration- Ampicillin
- Pain on i.m injection- Streptomycin, Tc
Hypersensitivity/ Allergic Reaction
Pn, Sulfonamides, Chloramphenicol
Direct Systemic Toxicity
Aminoglycoside causes Nephrotoxicity
Streptomycin causes Ototoxicity
Chloramphenicol causes Bone marrow depression
42. Problems with the use of AMAs
Opportunistic Infection
- Pseudomembranous Colitis
Nutritional Deficiency
- Vitamin B complex and Vitamin K deficiency
Bacterial Resistance
43. Antimicrobial Resistance
It can be defined as insensitiveness of micro organism to a particular anti
microbial drug
Bacterial resistance is of great concern because if resistant strains are
developed then a very useful antibiotic becomes useless
46. Mechanism of AMR
Antimicrobial resistance can develop at any one or more of steps in the
process by which a drug reaches and combines with its target. Thus
resistance may develop due to
Mechanism of Resistance Drugs
Decrease permeability Aminoglycosides, Tetracyclines
Efflux pumps Tetracyclines, Erythromycin, FQs
Inactivating enzymes Aminoglycosides, Beta lactams
Chloramphenicol
Alternative metabolic pathway Sulfonamide
Decrease affinity for target MRSA, Vancomycin
49. Mutation
Is the alteration in the structure of chromosomal DNA that lead to development of
resistant genes.
Single mutation- Resistance develops rapidly
- Enterococci to streptomycin
- Staphylococci to Rifampicin
Multiple mutation- Resistance develops slowly over a period of time
- Erthromycin, Tc , Chloramphenicol
52. Horizontal Gene Transfer
Conjugation
• Responsible for MDR
• Imp for development of resistance chloramphenicol, streptomycin,
vancomycin
Transduction
• Staph aureus transfer plasmid of penicillinase production
• Imp for development of resistance chloramphenicol, Pn, Erythromycin
Transformation
• Pneumococci develop resistance to PnG
53. Misuse of Antimicrobial Agents
If use of AMAs is without justification and not following the principles of
chemotherapy then all such use is considered as misuse of drugs
54. Examples of Misuse of Antimicrobial Agents
Use of AMAs for non bacteriological infection
Pyrexia of unknown origin
Inadequate dose and duration of treatment
Relying only on chemotherapy
55. Failure of Antimicrobial Therapy
Clinician Factor
- R- Right Diagnosis
- R- Right Drug
- R- Right Dose
- R- Right Dosage
- R- Right duration
56. Failure of Antimicrobial Therapy
Drug Factor
- Drug Resistance
- Use of bacteriostatic drug in immunocompromised states
- Drug interactions with food
Patient Factor
- Poor Compliance
- Uncontrolled Diabetes, Immunocompromised states
57. Schedule HX
To prevent large scale misuse of antibiotics in the country.
While prescribing antibiotics, doctors have to issue two prescriptions to every
patient and one copy should be kept by the chemists for a period of two years.
The officials from the DCGI office or state regulatory authorities can, thus,
audit these prescriptions at any time.
Violations under the new Schedule may be punished with a fine of Rs. 20000
or up to two years of imprisonment.
58. Conclusion
Strongest weapon against many disease
Emergence of Resistance*
Control of Resistance
Think twice before prescribe