These are the drugs used to suppress the

growth or to kill various microorganism

Natural---penicillin
Semisynthetic-----amoxacilln
Synthetic---------
sulphonamides,quinolones,oxazolidinon
es
 ANTIBIOTICS

These are the drugs/ chemical substances produced by

various species of micro-organisms that kill or suppress
the growth of other micro-organisms or cancer cells at
very low concentrations
 Treatment of infections or cancer with specific
agents that selectively suppress the infecting
microorganism(cancer cells) without significantly
affecting the host
Biochemical reactions involved in Bact. Cell function:
Class I
Use of glucose & other “C” sources to produce simple
carbon comp. ATP & energy
Class II
Energy + class I comp → small molecules (amino acids,
nucleotides, sugars, Phospholipids)
Class III
Assembly of small mole to form proteins nucleic acids
& peptidoglycan
According to
1-Class & spectrum of microorganism it kills
i-antibacterial
ii-antiviral
iii-antifungal
2- Biochemical pathway it inhibits/interferes with
i-cell wall synthesis
ii-protien synthesis
iii-nucleic acid synthesis

 chemical structure of drug

Macrolides

Imidazoles

Polypeptides

Sulphonamides
:ii) Protein synthesis inhibionitIBITOR
Drugs
Tetracyclins
Chloramphenicol
Aminoglycosides
Erythromycin
Lincomycin
Clindamycin
Oleandomycin
Anti-bact. Chemotherapy
History
 Male fern & aztes chenopodium → anthalmintic (Greeks)

 Chaulmoogra → leprosy (Hindus)

 16th century → Mercury → Leprosy

 17th century → Cinchona brak →Malaria

 19th century → modern chemoth → pioneer → P. Ehrlich

 He used word “Chemotherapy” in 1906.

 Sulphonamides (1935) by Domagk.

 Penicillin (1928) by Alexander Fleming at St. Marry’s

hospital London

 Penicillin isolated & antibact. (1939) by Chain & Florey at Oxford & powerful
effects analyzed antibact. Activityshown infected mice

 1st Penicillin inj. (1941) to an old lady --- by Fletcher

 Extracted laboriously form culture of mould of Genus Penicillinum notatum in

laboratories of Dunn School of Pathology in Oxford
Antibacterial may be:
Bacteriostatic
Bactericidal
ANTIMICROBIALS MAY BE ANTIBIOTICS
• Synthetic anti bact:
• Principles of anti-bact. Therapy:
i) Diagnosis of infection
ii) Remove barriers
iii) Select best drug
 C&S
 Kinetics prop.
 Suitability
iv) Route of adm
 Severity of inf
 Compliance of Pt.
v) Duration of treatment
Combination Therapy:
To get potentiating eff. e.g. cotrimoxazole, Penicillin +
Gentamycin → enterococcal endocarditis
To delay dev. Of resistance (e.g TB)
To broaden the spectrum
Te reduce incidence & severity of side eff.

Disadvantages:
False sense of security
Broader suppression of normal flora
Increase in variety of side eff.
Self limiting disease ----no antimicrobials

No infection -------Prophylaxis

Infection (asymptomatic) -----Pre-empitive

Infection (symptomatic) ------Empiric

Definitive ----------- pathogen isolation

Suppressive-----------Resolution
 SELF LIMITING DISEASE

influenza

non specific diarrhea or Rota virus

 surgical dental

Vertical
postexposure
transmission

c
 Use of antimicrobial agents before the pathogen
responsible for a particular illness or the
susceptibility to a particular agent (C/S report)
 Indication
 APPROACHE TO EMPIRIC THERAPY

1-Formulate clinical diagnosis of microbial disease

2-Obtain specimens for lab exam

3-Formulate microbiological diagnosis

4-Determine the necessity of empiric therapy

5-institute treatment
 APPROACH TO EMPIRIC THERAPY
1- Formulate a clinical diagnosis(antatomical
evidence)
2-Obtain specimen for laboratory examination

staining &microscopic exam

Send cultures
non culture methods
antigen testing,PCR,serology

3)Formulate a microbiological diagnosis

( history, physical exam,&immediately
available results)
D)DETERMINE THE NECESSITY OF EMPIRIC
THERAPY
i-significant risk of serious morbidity
ii-public health reason e.g N gonnrhea,
chlamydia trachomatis
iii-immunocompromised /known risk
factors for poor outcome

E)INSTITUTE TREATMENT
if no microbial information available
broad spectrum antimicrobial which may cover
most likely pathogens
 The reflex action to associate fever with
treatable infections and prescribe antimicrobial
therapy without further evaluation is irrational
and potentially dangerous because

1-diagnosis may be masked

2- promotes selection of resistant strains

 Isolation of pathogen

Susceptibility testing

MIC & MBC

Specialized assay method

(Betalactamase assay,synergy studies etc )
 Antimicrobial therapy with known etiology

1-ISOLATION OF PATHOGEN
specimens properly obtained & processed
results properly interpreted
2- SENSITIVITY TEST
ADVANTAGES
dec chance of resistance,
narrow spectrum antibiotic
-when ever possible single antibiotic
BACTERIOSTATIC
They arrest the growth and replication of
bacteria at serum levels achievable in the
patient thus limiting spread of infection

BACTERICIDAL
They kill bacteria at drug serum levels
achievable in the patient
 surgical prophylaxis--wound infection after
surgical procedure in

i-dirty or contaminated surgical procedures

ii-insertion of a prosthetic implant

iii- complications of infection are so drastic

iv- high risk of endocarditis

dental procedures
only if there is manipulation of
gingival tissue
periapical region of teeth,
perforation of oral mucosa

 Post exposure prophylaxis ---

to protect healthy close contacts

i- rifampin --- meningococcal meningitis,

ii- macrolides -----after contact with pts of

pertussis

iii-gonorrhea or syphilis after contact,HIV

To prevent Mother-to-child transmission of dis

i)syphilis during pregnancy

ii)Anti-retroviral therapy for HIV

 after the initial disease control therapy is
continued at a lower dose if

i)infection is not completely eradicated

ii)immunological or anatomical defect that led

to the original infection is still present.(AIDS ,
post-transplant)
 Delivery of therapy prior to development of
symptoms (presymptomatic)

i-aborts impending disease

ii-Given for a short and defined period

iiiUsed as a substitute to universal prophylaxis

eg---cytomegalovirus after stem cell
transplant
 MIC
MBC

 RATE&EXTENT OF KILLING
CONC DEPENDENT KILLING
TIME DEPENDENT KILLING

 PAE
PALE
 Conc- Time-
dependent dependent
TIME DEPENDENT KILLING
The killing action continues only while blood
levels are maintained above MBC /MIC
e.g
beta-lactam, vancomycin

CONC DEPENDENT KILLING

The rate & extent of killing increase with
increased conc of drug
e.g
aminoglycosides
quinolones
POST ANTIBIOTIC EFFECT

Persistant suppression of bacterial growth after

limited exposure to an antimicrobial agent
or

Antibacterial effect that persists after drug conc

falls below MIC

PAE= T-C
T =time required for the viable count in the test
culture to inc 10 fold above the count
immediately before removal

C= time required for the viable count in the

untreated culture to inc 10 fold above the count
immediately after completion of same
procedure used on test culture
 Mechanism of post antibiotic effect
i-persistance of drug at binding site/
periplasmic space

ii-slow recovery after reversible non

lethal damage to cell structures

iii-time taken for synthesis of new enz

before growth can resume

iv-PALE (postantibiotic leukocyte

enhancement) in vivo
 ROUTE OF ADMINISTRATION

Depends upon site of infection

 pharmacokinetic properties of drug

1- Oral

2-Topical ,endopthalmitis ---ocular cavity

3-Parentral
I/V
i-critically ill,cannot take orally
ii-bacterial endocarditis& meningitis
iii-GIT problems----NVD, gastrectomy,any
disease severly impair abs
iv-very poor oral abs----aminoglycosides
 RATIONALE FOR COMBINATION ANTIMICROBIAL

1-rapid killing of microbe

2-Provide broad-spectrum

3-empiric therapy in seriously ill patients

4-To treat polymicrobial infections

5-dec dose-related toxicity

6- synergism

7-dec development of resistance

SYNERGISM(potentiation)
Inhibitory or killing effects of two or more
antimicrobials used together are significantly
greater than expected from their effects when
used individually

MECHANISM
Inc of antimicrobial agent uptake

1) penicillin+gentamycin (G -ive)

2) amphotericin B + flucytosine
 2) Blockade of sequential steps

 e.g trimethoprim & sulphamethoxazole

3)INHIBITION OF ENZYMATIC ACTIVATION

inhibition of beta lactamases e.g sulbactam

ANTAGONISM
It occurs when the combined inhibitory or killing
effects of two or more antimicrobial drugs are
significantly less than observed when the drugs
are used individually
e.g bacteriostatic & bactericidal
MECHANISM OF INHIBITION
Inhibition of cidal activity with static drugs

Penicillins & tetracyclines

 Induction of enzymatic activity

Ampicillin &piperacillin
How bacterial develop resistance:-
a) Natural resistance --- by natural selection
b) Acquired resistance:-
i) Chromosomal muation
 MRSA, mycobact, T.B mycobact. leprac

ii) Through the genetic material

 Gene of resistance is tranferred by:
 Plasmid
 Transponsons
 Gene casettes & intergron
Mechanisms for transfer of resistance Gene:-
a) Conjugation:-
b) Transduction: (Bacteriophage)
c) Transformation:-
Taking naked DNA from enviroment carrying gene for
resistance
Biochemical mechanism of resistance
a) Enzymatic inactivation
i) b-lactamase:
Penicillins
Cephalosporins
Genes → on plasmid → transduction
Staph →Enz in inducible
G –ve bact. chromosomal gene → (Enz inducible)
Plasmid gene (Enz constitutively)
Many b lactamases are encoded by transposons
 ii) Chloramphenicol acetyl trasferase
Plasmid mediated (G +ve → inducible & G –ve
→ constitutive)
iii) Aminoglycoside inactivation
(Through plasmid & transposons → G +ve & G –ve
bact.)
Phosphorylation
Adenylation
Acetylation
b) Alteration of target / binding site
Decr. binding of DNA gyrase → Fluoroquinolones
Alt. of protein on 30 s subunit by chromosomal
mutation (Aminoglycoside)
Alt. of protein on 50 – s plasmid →
(Erythromycin)
Alt. of DNA dependent RNA polymerase →
(Rifampicin)
Alt. penicillin binding proteins → Methicilhin
resistant staph aureus
c) Impaired drug accumulation
Tetracyclins
d) Development of alternative pathway
Sulphonamides
Trimethoprim
e) Impaired penetration through outer membrance
(porins)
b lactam drugs in G –ve org e.g. Ampicillin
f) Efflux pump
Some b – lactam anti-biotic
Tetracyclines
Macrolides
Anti-cancer drugs
Classification of Anti-microbials:
i) According to structure:
b lactams
Aminoglycosides
Tetracycline
Macrolides
Imidazoles
Polypeptides
Sulphonamides
ii) According to mechanism of action
a) Inhibiting bact. Cell wall synth:
Penicillins
Cephalosporins
Monobactams --- aztreonam
Carbapenems --- Imipenem
 Meropenem
Extapenem
Vancomycin
Bacitracin
Cycloserine
c) Inhibiting proteins synth:
Broad spectrum
• Tetracyclines
• Chloramphenicol
Aminoglycosides
Macrolides
• Erythromycin
• Oleandomycin
Mis
• Lincomycin
• Clindamycin
• Spectinomycin
d) Inhibitors of nucleic acid synth:
i) Inhibit RNA synth
Rifampicin
Rifamycin
ii) Inhibit DNA synth
Nalidixic acid
Oxolinic acid
Other Quinolones & Fluoroquinolones
Actinomycin
Mitomycin
Acyclovir (inhib. DNA – polymerase in herpes virus only)
Inhibiting nucleotide s ynth:
Sulphonamides
Sulphones
PAS
Trimethoprim
Pyrimethamine