Pharmacy Council of Guyana CE Session Dr. Shamdeo Persaud Chief Medical Officer

Pharmacy Council of Guyana
CE Session
Dr. Shamdeo Persaud
Chief Medical Officer
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Background
- Antibiotics
Importance of appropriate use
Why overprescribe and Antibiotic Abuse
Rational use of Antibiotics
Indications for antibacterial therapy
What antibiotics
Factors considered while prescribing antibiotics
Methods of administration of antimicrobials
R i t
Resistance
tto A
Antimicrobial
ti i bi l Agents
A
t
Factors contributing to antimicrobial resistance
Control of use of antimicrobial agents
g
CMO, November 2010
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Antibiotics are considered as one of the
greatest discovery of the twentieth century.
In the p
pre-antibiotic era,, infectious diseases
accounted for significant morbidity and
mortality and invasive medical procedures
were fraught with the risk of infection.
Antibiotics are Life Saving drugs..
CMO, November 2010
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The first antimicrobials were discovered in the
mid-20's and many new molecules were
discovered between 1960 and 1980.
This 'golden era of antibiotics' saw a dramatic
fall in the mortality from infections.
Since the 80's, not many new class of molecules
have been discovered and the funding into
antimicrobial
i i bi l research
h iis on the
h d
decline
li
CMO, November 2010
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“The miracle seems to be
short lived.”
Irresponsible and erratic
use of these medicines
resulted in the
development of drug
resistance by many
organisms
i
and
d deaths
d th due
d
to hospital-acquired
infections is on the rise.
In the U
U.S.,
S mortality due
to nosocomial infections is
now 4 times that due to
road traffic accidents
CMO, November 2010
"Antibiotics have been ggiven
for everything from
headaches to ingrown
toenails; theyy are
swallowed, sucked,
injected and smeared; they
are ppainted on cuts,
dumped into wounds, fed
to the chickens and pigs
and spread
p
on the floors
f
off
the hospital wards."
Dr. Richard Novick
CMO, November 2010
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% of
70-80%
prescriptions for
antimicrobials are
probably
b bl written
itt
unnecessarily
Why do doctors overprescribe antibiotics?
p
CMO, November 2010
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y easy
y to scribble a p
p
It is very
prescription
but it takes
courage to avoid unnecessary prescriptions.
Inability to make a fairly accurate clinical diagnosis
Inability to convince the patient about the nature and
simplicity of the illness
Some doctors may harbour a notion that it is better to
give
i ""something
thi powerful“
f l“ (Shot
(Sh t Gun
G therapy).
th
)
The fact remains that most patients do not demand
any
yp
particular prescription
p
p
from their doctor and
many are indeed happy if they are explained about
their problem and prescribed as less drugs as
p
possible.
CMO, November 2010
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Some doctors may have
a fear
that
f
h if they
h do
d not
prescribe, their 'next
door' colleague may
prescribe
these
'powerful' drugs and
get all the credit for
'curing'
cu g tthee pat
patient.
e t.
To avoid this 'loss of
practice' they tend to
prescribe
p
these
'powerful'
remedies.
This is another face of
'defensive' practice.
CMO, November 2010
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Some patients with halfknowledge will insist on a
prescription for
antibacterials so as to "get
better at the earliest"
(because they are "very busy
and have no time to lie
down in bed") or to "avoid
any hassles", particularly in
cases of children and the
elderly.
It is the duty of the doctor to
resist any such pressures,
some doctors
d
may yield
i ld to
these pressures, often to
appease the patients and to
'save' their practice
CMO, November 2010
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With many pharmaceutical companies and medical
representatives,
it is
t ti
i natural
t
l to
t come under
d some pressure
for prescribing
Companies seem to mislead the doctors about the
indications suppress the facts on adverse effects and hide
indications,
the facts on cost of therapy.
dangerous trend of 'combining' antibacterials and
marketing
g them for imaginary
g
y diseases.
Many of the so called 'newer' antibiotics (which are in fact
nothing more than modifications of existing molecules)
are priced exorbitantly (even hundred times more than
their older congeners)
become rather fashionable to prescribe these drugs, with
many doctors feeling that 'costlier must be better'.
CMO, November 2010
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Most Common Situations
Fever: It is a manifestation of hundreds of diseases,
infective and non-infective. Antibacterials DO
NOT have any beneficial effects in cases of fever
due to non-bacterial causes. Self-limiting viral
infections are the commonest infectious causes for
fever and antibacterials have no role to play in
their management
CMO, November 2010
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y the commonest illness
Sore throat: It is p
probably
where antibacterials are misused the most.
Although it accounts for 13% of all office visits, it
h been
has
b
found
f
d in
i various
i
studies
t di that
th t only
l 8 to
t
20% of persons with a sore throat make a visit to
a general practitioner (and in the other 80
80-90%
90% it
cures spontaneously!).
Sore Throat Score 1. Tonsillar exudate 2. Swollen
anterior cervical nodes 3. A history of a fever of
more than 380 C. 4. Lack of a cough.
T
Two
or more – Throat
Th t swab
b and
d antibotics
tib ti
CMO, November 2010
Diarrhoea:
Š It is another condition where antibacterials
are often over-prescribed.
p
Š While there are many causes for diarrhoea,
infective and non-infective, the fact remains
that most of them are self-limiting and
require only adequate rehydration.
Š In all doubtful cases, a stool examination
should be done for ova, cyst, blood and
h
hanging
i drop
d
if cholera
h l
is
i suspected.
t d
CMO, November 2010
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Antibiotics are the most
important weapons in our
hands.
Each one of them have been
invented after spending
considerable
id bl amount off time,
i
energy and money.
Therefore, we cannot afford
to lose them.
We
must
exercise
considerable restraint in
prescribing
antibacterials
and restrict their use to only
certain definite indications.
CMO, November 2010
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Definitive therapy: This is for proven
bacterial infections
Empirical
p
therapy:
py Strong
g indication in
critical cases
Prophylactic
p y
therapy:
py Indicated and p
proven to
prevent an infection for which a treat exist
CMO, November 2010
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This is for p
proven
bacterial infections.
Antibiotics are drugs to
tackle
bacteria
and
hence
should
be
restricted
for
the
treatment of bacterial
i f ti
infections
only.
l
Based on the reports, a
narrow spectrum, least
toxic
toxic,
easy to
easy-toadminister and cheap
drug
should
be
prescribed.
CMO, November 2010
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Should be restricted to
critical cases
When time is inadequate for
identification and isolation
off th
the b
bacteria
t i and
d
reasonably strong doubt of
bacterial infection exists:
ƒ septicemic
p
shock// sepsis
p
syndrome
ƒ immunocompromised
patients with severe
y
infection
systemic
ƒ hectic temperature,
neutrophilic leukocytosis,
raised ESR etc.
CMO, November 2010
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Antimicrobial prophylaxis is administered to
susceptible patients to prevent specific infections
that can cause definite detrimental effect.
These include antitubercular prophylaxis,
prophylaxis anti
rheumatic prophylaxis, anti endocarditis
prophylaxis and prophylactic use of
antimicrobials in invasive medical procedures
etc.
In all these situations, only narrow spectrum and
specific drugs are used.
used
It should be remembered that there is NO single
prophylaxis to 'prevent all' possible bacterial
infections.
infections
CMO, November 2010
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There are more than 100 antibacterials available
today, and each one has its own spectrum of
activity, adverse effect profile and cost.
The doctor should consider many factors
before prescribing an antibacterial agent so as
to make the treatment most effective with least
adverse effects and cost.
CMO, November 2010
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Site of infection
Type of infection
Severity of infection
Isolate and its sensitivity
Source of infection
Host factors
Drug related factors
CMO, November 2010
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Rule Of The Thumb, infections above the diaphragm Cocci and Gram (+); infections below - Bacilli and
Gram (-)
()
Above the diaphragm: Upper respiratory tract infections
like pharyngitis
B l the
Below
th diaphragm:
di h
E
Examples
l include
i l d urinary
i
tract
t t
infection
Certain sites where the infection difficult to treatment:
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Meningitis
M
i iti (i
(impenetrable
t bl bl
blood-brain
db i b
barrier),
i )
Chronic prostatitis (non-fenestrated capillaries),
Intra-ocular infections (non-fenestrated capillaries),
Abscesses (thick wall, acidic pH, hydrolyzing enzymes etc.),
Aardiac and intra
intra-vascular
vascular vegetations (poor reach and penetration)
penetration), Osteomyelitis (avascular sequestrum) etc.
Higher dose, more frequent administration, longer duration and
antibacterial combinations may have to be used.
CMO, November 2010
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Infections can be localised or extensive;;
mild or severe;
superficial
p
or deep
p seated;
acute, sub acute or chronic
extracellular or intracellular.
For extensive, severe, deep seated, chronic
and intracellular infections, higher and more
frequent dose,
dose longer duration of therapy
therapy,
combinations, lipophilic drugs may have to
be used.
CMO, November 2010
Life threatening and rapidly fatal infections.
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Bacteremia
/ septic
B t
i / pyemia
i / sepsis
i syndrome
d
ti shock;
h k
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Abscesses in lung/ brain/ liver/ pelvis/ intra-abdominal;
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Meningitis/ endocarditis/ pneumonias/ pyelonephritis/ puerperal
sepsis;
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Severe soft tissue infections / gangrene and hospital acquired
infections)
g
In such situations the drug
absorption, distribution and excretion could be altered due to tissue
hypoxia, changes in hemodynamics, renal and hepatic perfusion, GI
absorption etc.
g dynamics
y
can also be altered due to acidosis,, altered p
permeability,
y,
The drug
presence of hydrolysing enzymes at the site of infection etc.
In such situations, possibility of infection with multiple organisms and of
drug resistance make the choice difficult
CMO, November 2010
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g
y significant
g
Ideal management
of any
bacterial
infection requires culture and sensitivity study of
the specimen.
If the situation permits,
permits antibacterials can be
started only after the sensitivity report is
available.
Narrow spectrum, least toxic, easy to administer
and cheapest of the effective drugs should be
chosen.
If the patient is responding to the drug that has
already been started, it should not be changed
even if th
the in
i vitro
it reportt suggests
t otherwise
th
i
CMO, November 2010
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y acquired
q
Community
infections are less
likely to be resistant
whereas
h
hospital
h
it l
acquired infections
are likely to be
resistant and more
difficult to treat (e.g.
P d
Pseudomonas,
MRSA
etc.).
CMO, November 2010
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g of the p
Age
patient
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Infants: Chloramphenicol (can cause grey baby
syndrome) and sulfa (can cause kernicterus) are
contraindicated.
Below the age of 8 years: Tetracyclines are
contraindicated because they are known to discolour the
teeth.
B l
Below
the
h age off 18 years: All fluoroquinolones
fl
i l
are
contraindicated because they are known to cause
arthropathy by damaging the growing cartilage.
Elderly: In the elderly
elderly, achlorhydria may affect
absorption of antibacterial agents. Drug elimination is
slower, requiring dose adjustments. Ototoxicity of
aminoglycosides may be increased in the aged
CMO, November 2010
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immune status
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In patients with extremes of age, HIV infection,
diabetes mellitus, neutropenia, splenectomy, using
corticosteroids or immunosuppressants,
immunosuppressants patients
with cancers / blood dyscrasias, ONLY bactericidal
drugs should be used.
It iis iindeed
d dd
debatable
b t bl whether
h th antibacterials
tib t i l should
h ld
be used to treat infections like aspiration pneumonia,
UTI, catheter infections, infections through life
supportt systems,
t
pressure sores etc.
t iin patients
ti t who
h
are terminally ill (brain dead, patients with massive
stroke, terminal cancers, advanced age, terminal
AIDS etc.).
t )
CMO, November 2010
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p
g
y and lactation
pregnancy
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Drugs with known toxicity or un-established safety like
tetracyclines, quinolones, streptomycin, erythromycin
estolate and clarithromycin
y
are contraindicated in all
trimesters and sulfa, nitrofurantoin and chloramphenicol
are contraindicated in the last trimester. Drugs with
limited data on safety like aminoglycosides,
azithromycin,
ih
i clindamycin,
li d
i vancomycin,
i metronidazole,
id
l
trimethoprim, rifampicin and pyrazinamide should be
used with caution when benefits overweigh the risks.
Penicillins cephalosporins,
Penicillins,
cephalosporins INH and ethambutol are safe
in pregnancy. In lactating mothers sulfa, tetracyclines,
metronidazole, nitrofurantoin and quinolones are
contraindicated
CMO, November 2010
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Associated conditions like renal failure, hepatic failure, epilepsy etc.
should be considered in choosing the antibacterial agent.
agent
Renal failure:
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Tetracyclines are absolutely contraindicated; aminoglycosides,
cephalosporins, fluoroquinolones and sulfa are relatively
contraindicated;
t i di t d
penicillins, macrolides, vancomycin, metronidazole, INH,
ethambutol and rifampicin are relatively safe.
It is better to avoid combinations of cephalosporins
p
p
and
aminoglycosides in these patients because both these classes of
drugs can cause nephrotoxicity.
Hepatic failure:
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N drugs
No
g are absolutely
y contraindicated;; chloramphenicol,
p
,
erythromycin estolate, fluoroquinolones, pyrazinamide,
rifampicin, INH and metronidazole are relatively contraindicated
Penicillins, cephalosporins, ethambutol and aminoglycosides are
safe.
CMO, November 2010
1.
2.
3.
4.
Hypersensitivity: in patients with prior history of
hypersensitivity
h
iti it the
th concerned
d antibacterial
tib t i l agentt should
h ld
be avoided.
Adverse reactions: Certain adverse reactions warrant
discontinuation of therapy and the doctor should
adequately educate the patients on these adverse effects.
Interactions: Interactions with food and other concomitant
drugs
g should be considered before instituting
g antibacterial
therapy so as to maximize efficacy and minimize toxicity.
Cost: The cost of therapy should be considered in choosing
the antibacterial agent. It should always be remembered
that just because a particular drug is expensive,
expensive it need not
be superior than the cheaper ones. For example, cheaper
drugs like doxycycline or co-trimoxazole would be as
effective as the costlier cephalosporins in the management
g
off LRTI.
CMO, November 2010
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Route of administration
Dosage
Frequency and duration of administration
Combinations
CMO, November 2010
The route of administration depends on the site, type and severity of the
infection and the availability of a suitable drug.
drug
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Oral route - most preferred, easy and cheap, but it may not be reliable in
all circumstances, particularly in patients with severe infections, noncompliant patients, in the presence of vomiting etc. Certain drugs like the
aminoglycosides and most 3rd generation cephalosporins are not
available for oral administration.
Š
Intramuscular route - generally restricted for the administration of
procaine and benzathine penicillin and single shot of ceftriaxone; the
p
is not very
y reliable and it is p
painful and disliked by
y the
absorption
patients.
Š
Intravenous route - best for the management of severe and deep-seated
infections since it ensures adequate serum drug levels. Procaine penicillin
and benzathine penicillin should never be given I.V. However, some
d
drugs
are not available
il bl ffor parenterall use (e.g.
(
most macrolides,
lid sulfa,
lf
tetracyclines).
Š
Topical: Antibacterials are also used topically, but drugs used for
systemic administration should not be used in skin ointments.
CMO, November 2010
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p
Dose depends
on:
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age of the patient
weight of the patient
associated conditions like pregnancy
renal and hepatic failure and site
type and severity of infection.
Generally the dose should be higher in cases of
severe, deep-seated infections and in pregnancy
and lower in cases of renal failure.
While unnecessary overdosage only adds to the
cost and adverse effects, there should not be any
compromise
i on adequate
d
t dose.
d
CMO, November 2010
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q
y of administration: The drug
g should be
Frequency
administered 4-5 times the plasma half-life to
maintain adequate therapeutic concentrations in
the serum throughout the day.
day Frequency can be
increased in cases of severe, deep seated and
sequestrated infections and reduced in cases of
renal and hepatic failure.
failure
Duration: Duration of therapy depends on the site,
type
yp and severity
y of infection. ((e.g.
g Tonsillitis-10
days; bronchitis-5-7 days; UTI-single shot to 21
days; lung abscess-2-8 weeks; tuberculosis-6-24
months etc.).
etc )
CMO, November 2010
Antibacterial combinations can be useful in the following situations:
1.
To sharpen the effect: Synergistic combination of two static drugs
- e.g. Combination of Trimethoprim and Sulfamethoxazole - CoTrimoxazole
2.
Treatment of infections with multiple organisms: Mixed
infections in lung abscess, peritonitis, soiled wounds etc., naturally
require multiple antibiotics for complete clearance of the infection
- Penicillins (for gram positive and certain anaerobes) +
Aminoglycosides (for gram negative); metronidazole for
bacteroides etc.
3.
To prevent resistance: The classic example is the antitubercular
therapy.
h
4.
To overcome resistance: Examples include Penicillins + b
lactamase inhibitors/b lactamase resistant penicillins for S. aureus;
/ p
p
+ aminoglycosides
gy
for Pseudomonas etc.
Penicillins/cephalosporins
Š
The following combinations are irrational, not useful or even
harmful:
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Combinations of bactericidal with bacteristatic drugs (e.g.
(e g Penicillins with tetracyclines);
Combinations of drugs with similar toxicity (e.g. chloramphenicol and sulfa)
Combining drugs for non-existing ‘mixed infections’ (e.g. tablets of ciprofloxacin + metronidazole
CMO, November 2010
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Resistance to antimicrobial agents is one of the
greatest problems faced by the medical
community.
These powerful weapons, developed by
spending millions of dollars and years of
dedicated research, have been rendered less
effective or totally ineffective only because of
our own negligence and complacence
complacence.
CMO, November 2010
Organism
Resistance
Gram Positive cocci Methicillin resistant Staph.
p aureus and coagulase
g
negative Staphylocci, penicillin resistant
Pneumococci, macrolide resistant Streptococci,
vancomycin resistant Enterococci
Gram negative
cocci
Gram negative
bacilli
A id fast
Acid
f t bacilli
b illi
Penicillin, quinolone resistant gonococci
Enterobacteriaccae resistant to B lactams and B
lactamase inhibitors, multi drug resistant pathogens
include Shigella, E. Coli, Salmonella.
M lti d
Multi
drug resistant
i t t M.
M tuberculosis
t b
l i
CMO, November 2010
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yap
p
Antimicrobial resistance,, initially
problem in hospitals
and developing countries, today affects the world at
large.
The WHO reports that the antimicrobial agents are used
by too many people to treat the wrong kind of infection in
the wrong dosage and for the wrong period of time.
Increase in poverty, over crowded living areas, crowded
day care centers have all contributed in spreading the
resistant bacterial infection.
The tremendous increase in the size of the high risk
populations because of immunocompromise, the
increased frequency of invasive medical interventions
and prolonged survival of patients with chronic
debilitating disease have
amplified
the problem
CMO, November
2010
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Inability of the drug to reach the organisms
Inactivation of the drug
Alteration in the target
Resistance may be acquired by mutation and
passed onto the next generations.
It may also be acquired by horizontal transfer
from a donor cell by
y transformation,,
transduction or conjugation.
CMO, November 2010
g methods can be used to control
The following
the use of antimicrobial agents in hospitals:
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Education programmes like staff conferences, lectures and
audiovisual programmes
Availability
l b l off clinical
l
l pharmacist consultants
l
Control of contact between pharmaceutical representatives and
staff physicians and of various sponsorships from companies
Restriction of hospital formulary to minimum number of agents
needed for most effective therapy
Availability of diagnostic microbiology laboratory sensitivity
tests and appropriate selection of sensitivity tests for organism
and site
Automatic stop orders for specific high-cost agents and written
justification for high-cost agents
CMO, November 2010
Thank You!
CMO, November 2010
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