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1. Chemotherapy :
General Consideration
Dr. Archana Dhavalshankh
Prof & Head, Dept of Pharmacology
D Y Patil Medical College, Kolhapur

2. CHEMOTHERAPY
General Consideration
PART I
• Definition/ Terminology
• Classifications of Antimicrobials
• Problems that arise with the use of
antimicrobial agents (AMAs)
PART II
• Antimicrobial Resistance
• Choice of an AMAs
• Combined use of AMAs
• Prophylactic use of AMAs

4. Definition / Terminology
 Chemotherapy:
 Treatment of systemic/topical
 infections/infestations
 with specific drug that
 kill/suppress the
 invading pathogen (living or multiplying)
 without significantly affecting the host.
 Selective toxicity: A drug that kills harmful
microbes without damaging the host

6. Definition / Terminology
 Antimicrobial agent :
Drugs effective against micro-organisms,
Naturally or synthetically derived
 Antibacterial agent:
Drugs effective against bacteria
 Antibiotics :
Obtained from fermentation of microorganisms
 Commensals :
Micro-organisms that are parasites without
causing disease (may cause disease if host is
immuno-compromised)

8. Classification I-
[Type of organism against which primarily active]
Antimicrobial Agents
Anti- Bacterial agents – Sulfonamide, Fluro-quinolone,
Penicillin, Cephalosporin, Macrolide,
Aminoglycoside, Tetracycline,
Choramphenicol
Antibiotic- Penicillin, Cephalosporin. Macrolide
Anti- viral agents- Acyclovir, Amantadine, Zidovudine, Nevirapine
Anti- protozoal agents- Metronidazole, Diloxanide, Chloroquine
Anti- fungal agents- Amphotericin-B, Griseofulvin, Ketoconazole
Anti- helminthic agents- Mebendazole, Niclosamide, Pyrantel

9. Higher forms
Gram + ve, branching filamentous
• Actinomycetes
A. Israelli- Cervico-facial, abdominal
Nocardia- Pulmonary, brain abscess
• Streptomycetes
Non pathogenic
Useful as source of antibiotics
Lower forms
1 µm size, Gram + ve or - ve
• Cocci -Spherical
Stapylococci (cluster)
Streptococci (chain)
Diplococci (pair)
• Bacilli
Straight rod shape
• Vibrios
Curved cylindrical rod
• Spirilla
Elongated spiral shape
My. Tuberculosis My. Avium intracellularae
My. Kansasii My. Leprae
Special
group
No gram stain ,
Koch stain +ve
BACTERIA

10. Spirochetes Rickettsiae Chlamydiae Atypical
No rigid cell wall
Contractile cell
Stain by silver
impregnation
Rigid cell wall
Gram - ve
Rigid cell wall
Gram – ve
Posses DNA RNA
Grow only in
other cell
Mycoplasma
pneumonae
Ureaplasma
Pneumocystitis
cariini
Tr. Pallidum
Borellia
Leptospira
Rickettasia
Coxiella
Chl. Trachomatis
Chl. Pneumonae
Smallest cellular
organism
No rigid cell wall
Acquire variety
of structures
Plasma memb.
Has cholesterol
RNA or DNA
present

11. Gram + ve
Cocci Infections occur
Staph.
aureus
Abscesses. Septicemia,
Bacteremia, Osteomyelitis,
Endocarditis
Strep.
pyogens
Pharyngitis, Sinusitis, Otitis
Media, Rheumatic Fever,
Glomerulonephritis,
Septicemia
Strep.
viridans
Bacterial Endocarditis,
Bacteremia
Strep.
facealis
Endocarditis, Bacteremia,
Urinary Tract Infection
Peptostrept
ococcus
Brain, Lung, Puerperal &
Dental Abscess
Strep.
pneumonae
Pneumonia, Meningitis,
Sinusitis
Bacilli Infections occur
Clstr. tetani Tetanus
Clstr.
perfingens
Gas gangrene
Clstr. difficile Pseudomembranous
colitis
Clstr.
botulinum
Botulism/ food poisoning
Corne.
diphatheriae
Diphtheria
Listeria
monocytoge
ns
Meningitis, bacteremia
Bacillus
anthracis
Pneumonia, anthranx

12. Gram - ve
Cocci Infections occur
Neisseria
gonorrhoeae
Gonorrhoea
Neisseria
Meningitidis
Meningitis
morexella Pneumonia, sinusitis,
otitis media
Bacilli Infections occur
E.Coli UTI, dysentery
Salmonella
typhi
Typhoid & paratyphoid
fever, food poisoning
Shigella Gastroenteritis, bacillary
dysentry
Klebsiella Hosptal asso. Pneumonia,
UTI
Proteus UTI
Enterobacte
raerogenes
UTI
H.pylori Peptic ulcer
Coliform
bacteria
Encephalopathy in liver
failure

13. OTHERS
Organism Infections occur
H. influenzae Sinusitis, bronchitis,
pneumonia, meningitis
H. ducreyi chancroid
Ps. aeruginosa Pneumonia, UTI,
hospital aq infections
Yer. pestis plague
Brucella
abortus
Brucellosis
Francisella
tuleransis
Tularemia
Legionella
pneumonae
Legionnarie’s disorders
Campylobacter Gastroenteritis
Vibrio chlerae Cholera
Organism Infections occur
Bordetella
pertusis
Whooping cough
Acinetobacter Nosocomial
opportunistic infection
Serratia Nosocomial
opportunistic infection
Fusobacterium Alveolar, lung abscess,
gingivitis
Bacteroides
fragilis
Oral,lung, brain,
pharyngeal infection
Porphyromon
as
Acute Orofacial infections
Prevotella Acute Orofacial infections
Burkholderia
pseudomallei
Melioidosis

14. Classification II- [Type of action]
Primarily Bacteriostatic
• Sulfonamide
• Tetracycline
• Chloramphenicol
• Erythromycin (Macrolide)
• Clindamycin
• Ethambutol
• Linezolid
Primarily Bactericidal
• Penicillin
• Cephalosporin
• Aminoglycoside
• Fluroquinolone
• Co-trimoxazole
• Rifampicin
• Isoniazid
• Pyrizinamide
• Metronidazole

15. Static [Bacteriostatic, Fungi-static ]
• Drugs that arrest the growth / replication of micro-
organism (bacteria or fungi)
• Thus arrest or limit the spread of infection
• These agents are adequate or sufficient to deal with
(to treat) uncomplicated infections. (Here host
defenses usually help to eradicate organisms).
• But in neutropenic individual, bacteriostatic drugs
are ineffective.
• Sulfonamide, Macrolide, Tetracycline,
chloramphenicol

16. Cidal [Bacteriocidal, fungicidal]
• Drugs that kill or irreversibly damage the multiplying
organisms (bacteria or fungi).
• Thus total number of viable organisms decreases.
• These drugs are preferred for the management of
complicated infections. (Tuberculosis, meningitis,
endocarditis)
• Preferred for treating the infection when host
defense is impaired.
• Penicillin, cephalosporin, aminoglycosides, co-
trimoxazole,fluroquinolones

18. Chloramphenicol
Bacteriostatic Gram – ve rods
Pneumococci
Bacteriocidal
Sulfonamides
Trimethoprim
Bacteriostatic
Co- trimoxazole
Bacteriostatic
Sulfamethoxazole
Trimethoprim
Bacteriocidal
+

19. Classification III- [Sources of antibiotics]
Antibiotics are the drugs that are derived from one micro-
organism and effective against another micro-organism.
Fungi
• Penicillin
• Cephalosporin
• Griseofulvin
Bacteria
• Polymyxin –B
• Colistin
• Bacitracin
• Tyrothricin
• azetreonam
Actinomycetes
• Aminoglycoside
• Tetracycline
• Chloramphenicol
• Macrolides
• Polyenes

20. Penicillin Penicillum notatum
Penicillum chrysogenum
Cephalosporin cephalosporium
Griseofulvin Penicillum griseofulvum
Aminoglycoside Streptomyces
Micromonospora
Tetracycline Streptomyces
Aureofaciens
Chloramphenicol Streptomyces
venezuelae
Macrolides Streptomyces
erythreus
Polymyxin –B Bacillus polymyxin
Colistin B colistinus
Bacitracin Bacillus subtilis

22. Classification IV- [Spectrum of activity]

23. Antimicrobial Spectrum
Narrow Spectrum
• Antimicrobial agents that are
active against single or
limited group of pathogens
are said to have Narrow
spectrum.
• Anti-tubercular drugs are
effective against M. tuberculae.
• Penicillin G & cloxacillin
effective against gram + ve
organisms.
Broad Spectrum
• Antimicrobial agents that are
active against a wide range of
pathogens (Gram +ve, Gram –ve,
Spirochetes, Chlamydia, Rickettsia)
are said to have Broad
spectrum.
• Broad spectrum antibiotics
likely to cause super
infections.
Extended spectrum – Drugs effective against Gram +ve & Gram – ve
Ex- Amoxicillin , Ampicillin

25. Classification V- [Mechanism of action]

31. Classification VI- [Chemical Structure]

34. Problems arise with the use of AMAs
Local irritancy /systemic Toxicity
Hypersensitivity reactions
Drug Resistance
Super infection
Nutritional deficiencies
Masking of an infection

35.  Practically all AMAs are capable of producing
Hypersensitivity Reactions.
 Sometimes unpredictable and unrelated to
dose
 Occurs in wide range from rash to
anaphylactic shock
 Commonly involved – penicillin,
cephalosporin, sulfonamides, fluroquinolone

36.  Some of the B complex group vitamins & Vit K
is synthesized by intestinal flora (gut flora) is
utilized by man
 Prolonged use of antimicrobials alter this
flora result in vitamin deficiencies
 Neomycin causes morphological
abnormalities in the intestinal mucosa which
can produce diarrhea and malabsorption
syndrome.

37.  A short course of AMAs may be sufficient to treat
one infection but only briefly suppress another
one contracted concurrently.
 The other infection will be masked initially, only
manifest later in sever form
 Syphilis masked by single dose of penicillin
which is sufficient to treat gonorrhoea.
 Tuberculosis is masked by short course of
streptomycin – sufficient for a minor respiratory
infection.

38.  The native indigenous bacterial flora present in
GIT& oral cavity provides resistance to
colonization & limits the growth of other
pathogenic flora
 Antibiotic therapy markedly reduces this flora
allowing invasion by opportunistic organisms
such as proteus, staphylococci & pseudomonas
 This is termed as superinfecton.

39.  Superinfection manifests as antibiotic
induced diarrhea & colitis
 Common Superinfections
due to clostridium difficile or candida
lead to pseudomembranous colitis (PMC)-
bloody diarrhoea, abdominal distention, pain,
dehydration, blood leukocytosis.
 Drugs showing – amoycillin, third generation
cephalosporin, clindamycin.

40.  Treatment given for superinfection (PMC)
Metronidazole 500 mg oral tds x 10 days
OR
Vancomycin 125 mg qid x 10 days
OR
Probiotics (to re-establish colonic flora ie lactobacilli & S.
boulardii)