ANTIBIOTICS: GENERAL

CONSIDERATION
Chemotherapy v/s Antibiotics

𝗈 CHEMOTHEAPY : Term used to describe

any treatment that utilizes the introduction
of chemical agents to kill or retard the rapid
growth of cells and bacteria. This treatment
is used for cancer or similar ailments.
𝗈 ANTIBIOTICS: Substances produced by
microorganisms which selectively suppress
the growth or kill the microorganism.
Basis of chemical structure Mechanism of action

Classification types
Source
Type of action

Type of org. against

active Type of spectrum
CLASSIFICATION OF
ANTIBIOTICS:
Antibiotics are classified in many ways:
1. On the basic of chemical structures
𝗈 Sulphonamides and related drugs:
Sulphadiazine, dapson, p- amino
salicylic acid(PAS)

� Diaminopyrimidines: Trimethoprim,
� Pyrimethamine
𝗈 Nitrobenzene derivative.
: Chloramphenicol

𝗈 Beta lactum: Penicillins,

Cephalosporins, monobactams,
Carbapenems
𝗈 Aminoglycoside:
Streptomycin, Gentamicin,
Neomycin,tobramycin etc.
Macrolide antibiotics:
Erythromycin, Clarithromycin,etc.
𝗈 Oxytetracycline,
Tetracyclines:
doxycycline

𝗈 Lincosamide: lincomycin
, clindamycin etc.
𝗈 Glycopeptide:
Vancomycin, Teicoplanin
o Nicotinic acid dvt. :
Isoniazid, Ethionamide

o Azole dvt.:
Ketoconazole,Clotrimazole
𝗈 Quinolones: Nalidixic acid
Norfloxacin,Ciprofloxacin,etc.

𝗈 Others :Rifampin, Viomycin , Cycloserine etc

2. On the basis of mechanism of action:
� Inhibition of cell wall synthesis: Penicillins,
�
Cephalosporins, Vancomysin
𝗈 Cause leakage from cell membrane:
Polymyxins, hamycin
𝗈 Inhibit protein synthesis :
Tetracyclines, Chloramphenicol,
Erythromycin, Clindamycin
𝗈 Cause misreading of m-RNA and affect
permeability: Streptomycin, Gentamicin,
etc.
𝗈 Inhibit DNA gyrase : Ciprofloxacin
𝗈 Interfere with DNA funct.: Rifampin
𝗈 Interfere with intermediary metabolism :
3. Type of organism against which
primarily active:
𝗈 Antibacterial: Penicillin,
Aminoglycoside, Erythromycin,etc.
𝗈 Antifungal :
Griseofluvin,Ketoconazole,etc.
𝗈 Antiviral : Acyclovir , Amantadine, etc.
𝗈 Antiprotozoal : Chloroquine,
Metronidazole, Pyrimethamine, Diloxanide,
etc.
𝗈 Antihelmintic :
Niclosamide, Mebendazole,
etc.
4. Based on spectrum of activity :
� NARROW SPECTRUM :
�
Penicillin G, Streptomycin, Erythromycin
� BROAD SPECTRUM :
�
Tetracyclin, Chloramphenicol
5. On the basis of type of action:
𝗈 Primarily bacteriostatic :

Sulphonamides,Tetracyclines,Chloramphenicol
, Erythromycin, Clindamycin, etc.
𝗈 Primarily bactericidal :

Penicillins, Aminoglycoside, cephalosporins,

Vancomycin, Isoniazid, Rifampin,
Ciprofloxacin, Cotrimoxazole
6. BASED ON THE
SOURCE:
� FUNGI: Penicillin, Griseofluvin,
�
Cephalosporin
� BACTERIA: PolymycinB ,
�
Colistin, Bacitracin, Aztreonam
� ACTINOMYCETES : Aminoglycoside,
�
Tetracycline, Chloramphenicol, Macrolides
PROBLEMS THAT ARISE
WITH THE USE OF AMA’s :
1. TOXICITY:
� Local irritancy:
�
*Exerted at the site of administration
*Gastric irritation, pain,abscess formation
in i.m injection
*eg. Erythromycin, Tetracycline , some
Cephalosporins, Chloramphenicol
� Systemic toxicity:
�
* High therapeutic index: Doses upto
100 fold range may be given without
apparent damage to host cells .. Eg
Penicillins, Erythromycin, some
Cephalosporins

* Lower therapeutic index: Doses have

to watched eg.
#Chloramphenicol- bone marrow
depression
# Tetracycline- liver and kidney
damage
* Very low therapeutic index: use is
restricted to conditions where no suitable
alternative present eg.
#Vancomycin- hearing loss, kidney
damage
#Polymyxin B- neurologinal and
renal toxicity
2. HYPERSENSITIVITY REACTIONS :
* Unpredictable and unrelated to dose
* Reactions ranges from rashes to
anaphylactic shock
* Eg. Penicillins, Cephalosporins,
Sulfonamides, Floroquinolones
3. DRUG RESISTANCE:
Natural resistance:
Some microbes are naturally resistant to
some AMA’s . Because they lack the
metabolic process or the target site which
is affected by the particular drug.
Eg. # Gram negative bacilli are
unaffected by Penicillin G
# aerobic oragnisms are unaffected by
Metronidazole
# M.tuberculosis is insensitive to
Tetracyclines
Acquired resistance:
* Development of resistance by AMA’s
where overused. A major clinical problem.
*eg.of bacterias-Staphylococci , Tubercle
bacilli etc.
*Some like Strep.pyogenes and
Spirochetes have not developed resistant to
Penicillins despite of their use for more
than 40 years.
 Causes of resistance :
MUTATION:
*Stable and heritable genetic change .
*Sensitive population of microbes turns
resistant strain by the high conc. Of AMA’s
*Eg. When single antitubercular drug is used
Also called vertical transfer of resistance.
GENE TRANSFER:
(Infectious resistance)
*resistance causing gene is passed from
one to another organism.
*Also called horizontal transfer of
resistance
CROSS RESISTANCE:
� Acquisition of resistance to one AMA
�
conferring resistance to another AMA to which
org. has not been exposed.
𝗈 Resistance between Chemically or
mechanically related drugs: Sulfonamide and
others.
𝗈 Resistance between unrelated drugs:
between Tetracycline and Chloramphenicol
;Erythromycin and Lincomycin
4. SUPER/SUPRAINFECTION:
Infection caused as a result of antimicrobial therapy.
Use of most AMA’s causes alteration in normal
microbial flora of the body(contributes to host
defence from pathogens by elaborating subs. Called
bacteriocins)
#sites involved: oropharynx, intestinal, respiratory
and genitourinary tracts.

ORGANISM INVOLVED N DRUGS FOR

TREATING:
Candida albicans- Nystatin or Clotrimazole
Resistant staphylococci- Vancomycin
Clostridium difficile- Vancomycin and
Metronidazole
5. NUTRITIONAL DEFICIENCES :
B complex group of vitamins and vit.K
synthesised by the intestinal flora is altered by
the use of AMA’s causing vitamin deficiences.
eg. Neomycin causes abnormalities in intestinal
mucosa
CHOICE OF AMA :
PATIENT RELATED FACTORS:
1.
AGE:
Chloramphenicol conjugation and excretion
𝗈 in new born is inefficient hence cause gray
baby syndrome
� Tetracyclines deposit in developing teeth and
�
bones and hence discolours and weakens them.
� Sulfonamides displace bilirubin from protein
�
binding sites and hence cause kernicterus
(High level of bilirubin in blood) in neonates.
2. RENAL AND
HEPATIC FAILURE
(RENAL)
In mild failure- (HEPATIC)
Aminoglycosides
,Cephalosporins, To be reduced-
Vancomycin Talampicillin,
In Tetracycline,Erythromycin,
moderate/severef Pefloxacin
ailure- To be avoided-
Cotrimoxazole, Chloramphenicol,
Meropenem,Carbenicillin, Clindamycin,
clarithromycin
Tetracycline(except Metronidazole,
Doxycycline),Nitrofurantoin,
To be avoided- Isoniazid,Rifampin
Talampicillin
3. LOCAL FACTORS:
𝗈 Presence of pus and secretions decrease the
efficacy of AMA’s especially Sulphonamides ,
Aminoglycosides
𝗈 Presence of foreign body like implants,
catheters makes infection eradication almost
impossible because of bacteria adhering to
foreign body and forming biofilms.
𝗈 Lower pH at the site of infection
reduces the activity of Macrolide ,
Aminoglycosides
4. DRUG ALLERGY:
𝗈 History of patient exposure to AMA.
𝗈 If any AMA has caused allergic reaction, then
it is to be replaced eg. Patient allergic to
Penicillin can be given Tetracycline.
𝗈 Beta lactum, Sulfonamides,
Fluroquinolones, Nitrofurantoin causes
allergy.
5. PREGNANCY:
𝗈 Penicillins, many
Cephalosporins, Erythromycins are
somewhat safe in pregnancy.
𝗈 Tetracyclines are clearly contraindicated
in pregnancy because of liver and kidney
damage to mother and discoloration of teeth
and bone deformities of offspring.
𝗈 Aminoglycosides causes foetal ear
damage.
6. GENETIC FACTORS:
Chloramphenicol, Nitrofurantoin,
Sulfonamide, Fluroquinolones carry the risk
of producing haemolysis in G-6-PD deficient
factors.
DRUG RELATED FACTORS:

1. Spectrum of activity:
For definitive therapy a narrow spectrum
AMA is used but for empirical therapy a
broad spectrum antibiotic is used.
2. Type of activity:
𝗈 Several acute infections resolve better
with bactericidal than bacteriostatic drug,
because the cidal drug directly reduces the
no. of bacteria at the site of infection, while
the static drug only prevents the increase in
the no.
𝗈 With static AMA the bacteria starts
multipling when drug levels falls below the
MIC,resulting in relapse of infection.
3. Relative toxicity:
Less toxic is always preffered. Eg
� Beta lactum over Aminoglycoside
�
Erythromycin over Clindamycin
�
�
4. Route of administration :
For less severe infection oral antibiotic
is used but for serious infections eg. For
meningitis or septiceamias parentral
antibiotic is used.
5. Cost :
Lesser expensive drugs are to be
preffered.
6. Evidence of clinical efficacy :
Relative value of diff. AMA in treating an
infection ,optium dose regimen, duration of
treatment is desided on the basis of clinical
trials . So, reliable clinical trial data is the
final guide for the choice of AMA.
7. Pharmacokinetic profile:
𝗈

Fluoroquinolones,aminoglycoside,metronidazol
e produce concentrationdependent
inhibition i.e inhibitory effect depends on th
ratio of the peak con. To the MIC
𝗈 Beta lactums,glycopeptides,macrolides
produce time dependent inhibition i.e
action depends on the time the conc. Remains
above the MIC.
 PREVENTING EMERGENCE
OF RESISTANCE

WHY COMBINATION OF
ACHIEVING AMA’S USED? REDUCING
SYNERGISM SIDE EFFECTS

TO BROADEN THE SPECTRUM

OF ACTION
COMBINED USE OF
ANTIMICROBIALS
1. To achieve synergism:
Synergism may manifest of decreasing the
MIC of one AMA by the presence of
another ;or the MIC of both may be lowered
� If MIC of each AMA is reduced to 25% or less
�
the pair is synergistic
� 25-50% of each is considered to be additive
�
More than 50% of each is antagonism.
�
�
Eg.
𝗈 Penicillin + Streptomycin for SABE ,Penicillin
by acting on cell wall may enhance the
penetration of Streptomycin into the bacterium.
𝗈 Carbenicillin + Gentamycin in
pseudomonas infection
𝗈 Rifampin + Isoniazid in tuberculosis
2. To reduce severity or
incidence of adverse effects:
Only if the combination is synergistic so that the
doses can be reduced.
And for the low safety margin drug.eg.
𝗈 AmphotericinB +Rifampin (latter is with
no antifungal activity but enhances the
action of amphotericin)
𝗈 AmphotericinB+ Flucytosine (course
duration shortens)
3. To prevent the emergence of
resistance:
� for chronic infections needing prolonged
�
therapy eg. In tuberculosis,leprosy, malaria etc.
� Rifampin with Ciprofloxacin prevents the
�
developmnt of resistance to latter by
Staphy. Aureus.
4. To broaden the spectrum of
antimicrobial action:
� In mixed infection: Peritonitis , Diabetic foot
� infection , bedsores , gynaecological infections,
abscesses are mostly mixed infection. Aerobic
and anaerobic organisms sensitive to diff. drugs
are involved.
𝗈 Topically: generally AMA’s which are not
used systematically are poorly absorbed from
the local site and cover a broad range of gram
positive n negative bacteria are combined for
topical applications.
Eg Neomycin, PolymyxinB
𝗈 Initial treatment of severe infections
: For empirical therapy since bacterial diagnosis is
not known, gram positive and gram negative my
be given together eg.
Penicillin + streptomycin and
cephalosporin + erythromycin etc.
Rational combinations improve the certainity of
curing the infection in first attempt but should be
continued only till bacteriological data is available.
DISADVANTAGES OF ANTIMICROBIAL
COMBINATIONS
� Increased chances of superinfections.
�
Increased incidence and variety of adverse
�
� effects. Eg. Gentamycin+cephalothin =
exaggerated kidney failure
� If inadequate doses of nonsynergistic drugs
�
used then emergence of resistant can be
promoted.
� Higher cost of therapy.
�