CLINICAL USE OF ANTIMICROBIAL

DRUGS
Introduction:
-use of antimicrobial drugs continues to
rise
2005 these agents accounted for an
expenditure
of approximately 26 billion.
UK, prescribing in general practice
accounts for approximately 90% of all
antibiotics and largely involves oral and
topical agents
Hospital use accounts for the remaining
10% of antibiotic prescribing, with a much
heavier use of injectable agents
Antimicrobial Chemotherapy
Advantages:
Self evident
BUT led to a significant problem in
ensuring that they are always used
properly
Principles use of Antimicrobial Drugs
Susceptibility of infecting organism
- against drug selection
- some organisms may be predictably
susceptible to a microbial agent.
Host Factors:

In vitro susceptibility testing

Does not always predict clinical
outcome
Even though it is effective,
because of host factor: 1) ADME
Plays important role
Infections can progress rapidly in
patients suffering from either an
absolute or functional deficiency of
phagocytic cells.
applies particularly to those
suffering
from
various
haematological malignancies, such
as the acute leukaemias, where
phagocyte function is impaired
both by the disease and also by
the use of potent cytotoxic drugs
which destroy healthy, as well as
malignant, white cells.
essential to select agents that are
bactericidal,
as
bacteriostatic
drugs, such as the tetracyclines or
sulphonamides, rely on host

phagocytic
bacteria.

activity

to

clear

Pharmacological Factors
>Influenced by:
1) Satisfactory Drug Concentrations
- Very specific
2) Absorption,
Distribution,
Metabolism
And
Excretion
(ADME)
3) Presence
of
Food,
Drug
Interactions

oral absorption may be inappropriate

in patients who are vomiting or have
undergone recent surgery; under these
circumstances a parenteral agent will be
required and has the advantage of providing
rapidly effective drug concentrations
4) Anatomical Site of Infection
-presence of inflammation may
affect drug penetration into the
tissues
Drug Resistance
Antibiotics susceptible to organisms
Antibiotic Resistance Organisms

Natural
- Organism is resistant from the start
may
be
chromosomal
or
transferable on transposons or
plasmids.
- * Plasmid mediated resistance has
been
increasingly
recognized
among Gram - negative enteric
pathogens

Acquired
- Because of some factors, there are
some organisms that became :
susceptible
resistant
Due to:
1) Mutation
2) Adaptation
3) Gene Transfer
Multidrug Resistance
Epidemic and worldwide
Weak to strong antibiotics
That is why DOCTORS do not give the best
medicine when you have simple disease.
Main problem:

Nobel drugs
ex. M. tuberculosis . Staph. AureusMRSA (known as meticillin
resistant)

 Enterococcus (Van)
- in particular, E. faecium Resistance
to the glycopeptides
has again been a problem among
patients in high - endency units.
Four different phenotypes are
recognized (VanA, VanB, VanC
and VanD). VanA - phenotype is
resistant to both glycopeptides,
while the others are sensitive to
teicoplanin but demonstrate highn
(VanB) or intermediate (VanC)
resistance to vancomycin; VanD
resistance has only recently been
described
and
remains
uncommon.
Extended Spectrum B
- Lactamase (ESBL)
- Producing
Gram
negative
organisms are an increasing
problem
in
hospitals,
and
occasionally seen as a cause of
urinary tract infection in primary
care;
- can hydrolyse most cephalosporins
and penicillins, limiting therapeutic
options
to
carbapenems
or
aminoglycosides. - ESBLs can be
chromosomally mediated
*** Tuberculosis is on the increase
after decades in which the
incidence had been steadily falling.
Drug resistant strains have
emerged
largely
among
inadequately treated or non compliant patients.

Drug Combinations
- two drugs to have greater
effect
-Combining two antibiotics may
result in:
1) Synergism
may enable the use of toxic agents
where dose reductions are possible
Positive effect
Higher effect
2) Indifference
Effect is STILL EQUAL TO ONE
DRUG
3) Antagonism
DO NOT work harmoniously

Adverse Reactions
-Side effects:
hypersensitvity
negative effect is TOLERABLE
more benefits, less harm
more frequent in patients with
previous allergic
diseases such as childhood
eczema or asthma
-Toxicity:
Lethal dose
Often dose related
Happens when drug is taken
beyond recommendation
Ex.
chloramphenicol - induced bone
marrow suppression. This effect
is generally reversible with dose
reduction or drug withdrawal.
This dose related toxic
reaction of chloramphenicol
should be contrasted with
idiosyncratic
bone
marrow
toxicity which is unrelated to
dose.
Superinfections
Anti - infective drugs not only affect
the invading organism undergoing
treatment but also have an impact on
the normal bacterial flora, especially of
the skin and mucous membranes.
Normal bacteria flora (anti- infective
drugs)
- Ex. development of
pseudomembranous colitis from
the overgrowth of toxin - producing
strains of Clostridium difficile
present in the bowel flora following
the use of clindamycin or broad spectrum antibiotics, though any
antimicrobial can precipitate this
condition
Chemoprophylaxis
- Antimicrobial agent to prevent
infection in surgery exposed
to environment
- Perioperative Period

First dose one hour before

surgery
- relate to the predictability of
infection for a particular

surgical procedure, in terms of

its occurrence, microbial
aetiology and susceptibility to
antibiotics
Clinical Use

Antibiotic Policies
Rationale
Number of antimicrobial drugs
- Excessive use of antimicrobial agents
- Susceptibility of microorganism must
be CONTROLLED

Free Prescribing
More than number of agents in use
Lesser drug resistance will emerge

Restricted Prescribing
Limited range Tests of agent against
bacterial isolation
Allows clinician to use agents with
greater confidence

Unrestricted Prescribing
Drugs that can easily be get
Always available