This document provides definitions and information about chemotherapy and antimicrobial agents. It discusses the history of chemotherapy beginning with Paul Ehrlich and the discovery of penicillin. It then classifies antibiotics according to spectrum of activity, type of action, organisms targeted, mechanism of action, chemical structure, and source. The document discusses drug resistance, combination therapy, chemoprophylaxis, superinfection, and principles of rational antibiotic use. It emphasizes the importance of proper antibiotic selection, dosage, duration and monitoring treatment to improve outcomes and reduce drug resistance.

1. Dr. Manoj Kumar
Asst. Prof Pharmacology
AMCH Mohri

2. Definitions
 Chemotherapy:
Chemo + therapy
 By Paul Ehrlich
 Treatment of systemic/topical
infection
 Drugs have selective toxicity
for an invading pathogen
without damaging host
tissues.
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Chemotherapeutic
agents
Antimicrobials
(AMAs)
Antibacterials
Antifungals
Antivirals
Antiprotozoals
Antihelminthics
Anticancer drugs

3. Antibiotics
 Chemical substances produced by microorganisms that kill
or suppress the growth of other microorganisms at very low
concentration
 Excludes antibodies, ethanol, lactic acid, H2O2
 Antimicrobial agent (AMA)
 Synthetic (antibacterial) & naturally obtained (antibiotics)
drugs that minimize microorganisms growth
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4. History
Modern era
 Domagk (1935): Prontosil for pyogenic infection
 Pasteur (1870): Anthrax bacilli inhibited by bacteria
 Fleming (1929): Penicillium mould could destroy Staph
culture
 Clinical use of Penicillin in 1941
 Waksman (1944): Discovered Streptomycin
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5. Classification of antibiotics
According to
1. Spectrum of activity
2. Type of action
3. Type of organisms against which active
4. Mechanism of action
5. Chemical structure
6. Type of source
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6. 1. Spectrum of activity
 Narrow spectrum
Penicillin G
Streptomycin
Erythromycin
 Broad spectrum
Tetracyclins
Chloramphenicol
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7. 2. Type of action
 Bacteriostatic
Sulphonamides
Tetracyclines
Chloramphenical
Linezolid
Erythromycin/Macrolides
 Bactericidal
Cotrimoxazole
Penicllins
Aminoglycosides
Rifampicin
Cephalosporins,
Metronidazole
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8. 3. Type of organisms
1. Antibacterial: Penicillins, Aminoglycosides, Erythromycin
2. Antiviral: Acyclovir, Amantadine B, Zidovudine
3. Antifungal: Griseofulvin, Amphotericin B, Ketoconazole
4. Antiprotozoal: Chloroquine, Pyrimethamine, Metronidazole
5. Anthelminthic: Mebendazole, Niclosamide, Diethyl
carbamazine

9. 4. Based on site of action
1. Inhibit cell wall synthesis Penicillins, cephalosporins,
carbapenems, monobactam, vancomycin, cycloserine.
2. Damage cell membranes Polymyxins, amphotericin B, nystatin
3. Bind to ribosomes & inhibit protein synthesis
50S—erythromycin, chloramphenicol clindamycin, linezolid
30S—tetracyclines, aminoglycosides
4. Inhibit DNA gyrase Fluoroquinolones
5. Inhibit DNA function Rifampicin
6. Interfere with metabolic steps Sulfonamides, trimethoprim,
pyrimethamine
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10. 5. Chemical structure
1. Sulfonamides & related drugs
Sulfadiazine, Sulfamethoxazole
Sulfones – Dapsone, PAS
2. Diaminopyrimidines
Trimethoprim, Pyrimethamine
3. Quinolones
Nalidixic acid, Norfloxacin
4. Beta lactam antibiotics
Penicillins Monobactams
Cephalosporins Carbapenems
5. Tetracyclines
Oxytetracycline Doxycycline
6. Nitrobenzene derivatives
Chloramphenicol
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11. Chemical structure cont..
7. Aminoglycosides
Streptomycin Gentamycin
8. Macrolides
Erythromycin Azithromycin
9. Polypeptide antibiotics
Polymixin B Bacitracin
Colistin Tyrothricin
10. Glycopeptides
Vancomycin Teicoplanin
11. Oxazolidinones
Linezolid
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12. Chemical structure cont..
12. Nitrofuran derivatives
Nitrofurantoin Furazolidone
13. Nitroimidazoles
Metronidazole Tinidazole
14. Nicotinic acid derivatives
Isoniazid, Ethionamide , Pyrazinamide
15. Polyene antibiotics
Nystatin, Hamycin, Amphotericin B
16. Others
Rifampin, Cycloserine, Lincomycin, Ethambutol,
Griseofulvin, Clindamycin, Thiacetazone, Spectinomycin
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13. 6 Source
1. Fungi
Penicillin, Tetracyclin, Cephalosporin
2. Bacteria
Polymixin B, Bacitracin, Colistin
3. Actinomycetes
Aminoglycosides, Tetracyclins, Macrolides
4. Synthetic
Linezolid
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14. 14

15. Drug resistance
 Unresponsiveness of a microorganism to an antimicrobial agent
 Types
 Natural (genetically determined)
 Lack target site/ metabolic process affected
 Gram negative bacilli by Penicillin G
 M. tuberculosis to tetracyclins
 Acquired
 Development of resistance due to its use over a period of
time
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16. 16
Gene Transfer
Acquired resistance by R-plasmids
Staph, Strepto

17. Mechanism of drug resistance
1. Antibiotic degrading enzymes
Lactamases: by S.aureus, N. gonorrhoea, H. influenzae
Acetyltranferases
2. Prevention of drug accumulation
No influx, Promoting efflux (E.coli, P. aerugenosa, S. typhi)
3. Modification/Protection of target site
S. pneumoniae: Alteration of PBPs for penicillin resistance
M. tuberculosis: Alteration of one amino acid in RNA
polymerase for Rifampicin resistance
4. Use of alternate pathways for metabolic/ growth requirements
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18.  .
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1
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19. Drug resistance
 Cross resistance
 Acquisition of resistance to one AMA conferring resistance to
another AMA, to which the organism is not exposed
 Related chemically
 Same mechanism of action
 β-Lactam antibiotics
 Multidrug resistance
 Serious & difficult to treat
 M.tuberculosis
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20. Consequences of resistance
 ↑ Mortality
 ↑ Morbidity
 ↑ Cost
 Limited solution
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21. Facilitation of development of resistance
 Improper dosage
 Improper dose interval
 Insufficient duration of therapy
 Inappropriate selection of AMA
 AMAs used when not needed

22. Prevention of drug resistance
1. Rational use
Avoid indiscriminate, inadequate, unduly prolonged use
2. Use narrow spectrum drugs
3. Combination therapy whenever prolonged therapy required:
TB, HIV
4. Intensive therapy for infections known to develop quick
resistance: S. aureus

23. Principles of antimicrobial therapy
1. Diagnosis: Site of infection, responsible organism, sensitivity of
drug
2. Decide- chemotherapy is necessary: acute or chronic
infection, deferent time of pride
3. Select the drug:
 Specificity (spectrum of activity, antimicrobial activity of drug)
 Pharmacokinetic factors (physiochemical properties of the drug)
 Patient related factors (allergy, renal disease)

24. Principles of antimicrobial therapy Cont…
4. Frequency & duration of drug administration:
Inadequate dose may develop resistance,
Intermediate dose may not cure infection,
optimize dose should be used for therapy.
5. Continue therapy: Acute infection treated for 5-10 days. E.g.
Sore throat, Typhoid fever,
Chronic infection treat for a logger pride e.g tuberculosis & HIV.
6. Test for cure: After therapy, symptoms & signs may disappear
before pathogen eradicated.
7. Prophylactic chemotherapy: To avoid surgical site infections.

25. Principles of antibiotic dosing
Goal of antibiotic therapy
 To aid body’s defences to clear the tissues of microbial
pathogens by achieving antibiotic levels in the infected area
equal to or greater in MIC
 MIC
Lowest concentration of the antibiotic that prevents visible
growth after 24 hours
 MBC
Lowest concentration that causes destruction 99.9% organisms
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26. Combination therapy
Advantages
 Synergism
 Penicillin + Streptomycin in Bacterial endocarditis
 Trimethoprim + sulphamethoxazole in PCP
 β-lactam inhibitors (sulbactam) + β-lactam antibiotics
 Prevent resistance: TB, leprosy
 Prevent adverse effects: ↓ doses
 For mixed infections: Intra-abdominal infections, brain
abscess, genito-urinary infections
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27. Combination therapy
 Disadvantages
 Antagonism
 Penicillin + Tetracycline for meningitis
 ↑ Risk of adverse effects: Anti-TB drugs are hepatotoxic
 Multi drug resistance
 ↑ Cost
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28. Chemoprophylaxis
 Use of AMAs to prevent infection
 Advantages
 Protect healthy persons
 Pn G for post exposure prophylaxis in gonorrhoea, syphilis
 Chloroquine prophylaxis in malaria
 Protect high risk patients
 Neutropenia, AIDS
 FQs, cotrimoxazole
 Burns
 Surgical prophylaxis
 Abdomen surgery, surgeries > 2hrs
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29. Superinfection
 New infection resulting from use of AMAs
 Normal bacterial flora
 Inhibit growth of pathogenic organisms
 Bacteriocins, competing for nutrients
 Causes
 Broad spectrum AMA
 Immuno-compromised patient
 Sites
 Oropharynx, GIT, respiratory, genito-urinary
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30. Superinfection cont..
 Antibiotic induced diarrhoea, colitis
 Pseudomembranous colitis
 Bloody diarrhoea, abdominal distension, pain, dehydration,
leucocytosis
 Often seen with Amoxycillin, 3rd generation, cephalosporins,
Clindamycin etc.
 T/t: Metronidazole (500 mg TDS x 10 d),
Vancomycin (125 mg QID x 10d), re-establishment of colonic
flora with probiotics
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31. Antimicrobial stewardship program
 Promote appropriate use of antimicrobials by the prescriber
 To reduce their overuse & prevent resistance.
 To control & supervise the use of antibiotics
 ↓ emergence & spread of infections due to MDR organisms.
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32. Choice of an antimicrobial agents
 Patient related factors
 Drug factors
 Organism-related considerations

33. Patient related factors
Age (chloramphenicol produce gray baby syndrome in newborn
Tetracyclines deposition in teeth & bone-below the age of 6 years)
Renal & hepatic function (aminoglycoside, vancomycin- renal
failure; erythromycin, tetracycline- liver failure)
Drug allergy (History of known AMAs allergy should be obtained)
Syphilis patient allergic to penicillin – drug of choice is tetracycline
Fluoroquinolones cause erythema multiform

34. Immune system
Pregnancy & lactation – AMAs should be avoided in the
pregnant – many cephalosporins & erythromycin are safe.
Genetic factors – Primaquine, sulfonamide, fluoroquinolones
likely to produce haemolysis in G-6-PD deficient patient)

35. Drug factor
 Spectrum of activity (Narrow/broad spectrum)
 Type of activity
 Sensitivity o f the organism (MIC)
 Relative toxicity
 Site of infection (BBB, Lipid solubility, Mw, P. Binding)
 Pharmacokinetic profile
 Route of administration
 Cost

36. Organism-related considerations:
 A clinical diagnosis should first (sample of blood, staining ) &
the choice of the AMAs selected
 Clinical diagnosis itself directs choice of the AMA
 Choice to be based on bacteriological examination
(Bacteriological sensitivity testing)

37. Prophylactic use of antimicrobials
 Prophylaxis against specific organisms (Cholera: tetracycline;
Malaria: for travelers to endemic area take chloroquine/
mefloquine)
 Prevention of infection in high risk situations
 Surgical site infection
 Prophylaxis against specific organisms

38. Failure of antimicrobial therapy
 Improper selection of AMAs, dose, route or duration of
treatment.
 Treatment begun too late
 Failure to take necessary adjuvant measures
 Poor host defence
 Trying to treat untreatable (viral) infections

39. .

40. Definition
Prescribing right drug, in adequate dose for the sufficient
duration & appropriate to the clinical needs of the patient at
lowest cost
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41. Criteria’ for Using antibiotics
1. Right patient
2. Right patient information
3. Right indication
4. Right drug
5. Right cost
6. Right dosage and duration
7. Right administration
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42. Reasons for Irrational use of antibiotics
1. Lack of information
2. Role models – Teachers or seniors
3. Lack of diagnostic facilities/Uncertainty of diagnosis –
medicine for all possible causes
4. Demand from the patient
5. Patient load
6. Promotional activities of pharmaceutical industries
7. Drug promotion & exaggerated claim by companies
8. Defective drug supply system & ineffective drug regulation
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43. Absolutely Irrational Use
1. Injudicious use of antimicrobials: Antibiotics in Viral fever &
diarrhea
2. Unnecessary combinations
3. Use of drugs not related to diagnosis
4. Incorrect route
5. Incorrect dosing – under or overdose
6. Incorrect duration – prolong or short term use
7. Unnecessary use of expensive medicines
8. Unsafe use of corticosteroids
9. Polypharmacy
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44. Risk of Irrational Use
1. Ineffective & unsafe treatment
2. over-treatment of mild illness
3. Inadequate treatment of serious illness
4. Exacerbation or prolongation of illness
5. Distress & harm to patient
6. ↑ Cost of treatment
7. ↑ Drug resistance - misuse of anti-infective drugs
8. ↑ Adverse Drug Events
9. ↑ Morbidity & mortality
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45. Steps of rational drug use…
Step:- I Identify the patient’s problem based on symptoms &
recognize the need for action
Step:- II Diagnosis of the disease – define the diagnosis
Step:- III List possible intervention or treatment (drug or no
drug) – Identify the drug
Step:- IV Start treatment by writing an accurate & complete
prescription e.g. name of drugs with dosage forms, dosage
schedule & total duration of treatment
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46. …contd.
 Step:-V Give proper information, instruction & warning
regarding the treatment e.g. side effects (ADR), dosage
schedule & dangers/risk of stopping the therapy suddenly
 Step:-VI Monitor the treatment to check, if the particular
treatment has solved the patient’s problem.
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47. General Guidelines use of Antibiotics
1. Start antibiotics if there is evidence of infection
2. Antibiotics should not be started in response to patients
pressure
3. No antibiotics use- viral infections like Common cold or
diarrhea to satisfy the patients
4. Antibiotics used given for sufficient long period, Inadequate
duration & dose of therapy
5. Do not change an antibiotic before giving the current
antibiotic a fair trial
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48. General Guidelines use of Antibiotics cont..
6. Cost effectiveness of therapy should be considered especially
while changing the antibiotics
7. Calculating the full duration of treatment.
8. Possible culture sensitivity of the sample should be seen before
the antibiotic treatment started
9. Avoid using too many AMAs & drug combinations as it
encourages diagnosis & its mismanagement
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49. General Guidelines use of Antibiotics
10. Avoid use of multiple antibiotics, except -TB
11. Provide acquire adequate information their efficacy & side
effects
12. Get a full drug & allergy history to chosen antibiotics, before
starting the antibiotics
Thank you
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