ANTIBIOTIC RESISTANCE

ANTIBIOTIC RESISTANCE
Rashid.K
Asst. Professor
Dept. of Pharmacology

• Antibiotics are medicines used to prevent and treat bacterial
infections. Antibiotic resistance occurs when bacteria change in
response to the use of these medicines.
• Bacteria, not humans or animals, become antibiotic-resistant.
These bacteria may infect humans and animals, and the infections
they cause are harder to treat than those caused by non-resistant
bacteria.
• Antibiotic resistance leads to higher medical costs, prolonged
hospital stays, and increased mortality.
INTRODUCTION

0 10 20 30 40 50 60
………. Age……….
Animals: pets, food Crops: food
Otitis, Tonsilitis Cystic fibrosis PCOD
Trauma: Pneumonia
Mother/ child birth
sepsis
Post surgical…
Prostheses;
STD’s
Cancers;
Neonatal
TB/ AIDS related infections
Antibiotic Use Over Life Time…..

Status of Antibiotic Consumption, 2000-2010

Mortality, due to Antibiotic Resistance Vs other Causes….

Emergence of ABR: A Timeline of events

Why ABR a global concern?
• New resistance mechanisms emerge and spread globally
threatening our ability to treat common infectious diseases,
resulting in death and disability of individuals who until
recently could continue a normal course of life.
• Without effective anti-infective treatment, many standard
medical treatments will fail or turn into very high risk
procedures.

Antibiotic Resistance…..?
Micro-organisms that are not
inhibited by usually achievable
systemic concentration of an
antimicrobial agent with normal
dosage schedule and / or fall in the
minimum inhibitory concentration
(MIC) range.

 Antibiotic resistance is one of the biggest threats to global health,
food security, and development today.
 Antibiotic resistance can affect anyone, of any age, in any country.
 Antibiotic resistance occurs naturally, but misuse of antibiotics in
humans and animals is accelerating the process.
 A growing number of infections – such as pneumonia, tuberculosis,
gonorrhoea, and salmonellosis – are becoming harder to treat as the
antibiotics used to treat them become less effective.
 Antibiotic resistance leads to longer hospital stays, higher medical
costs and increased mortality.
Key Facts…..

 For example, 70 to 80 percent of diarrhea is caused by viral pathogens, for which
antibiotics are not effective. But nevertheless, around 40 percent of these cases are
attempted to be treated with antibiotics.
 Patients insisting on antibiotics and physicians prescribing them as they do not have time
to explain why they are not necessary. Another cause can be physicians not knowing
when to prescribe antibiotics or being overly cautious for medical or legal reasons.
 A third of people believe that antibiotics are effective for the common cold, and the
common cold is the most common reason antibiotics are prescribed even though
antibiotics are useless against viruses.
Key Facts…..

Types of Antimicrobial Resistance
 Natural drug resistance:
 Acquired drug resistance:
 Adaptation (tolerance) :
 Mutation and selection :
 Single step chromosomal mutations :
 Transmissible drug resistance :
 Transferred resistance:

Natural drug resistance:
In this case, even before the introduction of the drug, there is a
resistance produced by the entire bacterial species to an antibiotic. It
may transpire as a result of the lack of suitable cell wall target site,
penetration of drug through the cell wall and susceptibility to
naturally produced agent that destroys the antibiotics.
e.g.; S. Pyrogens resistant to Neomycin.

Acquired drug resistance:
In this type of resistance is associated with two types of mechanisms, the main
mechanisms involving intrinsic type of resistance and drug destroying enzymes e.g.
Methicillin resistance acquired by the microbe S. Aureus species of strains.
The development of resistance in a microbe in this case are due to the development
of misrepresented binding of penicillin on the receptors of microbes.
Eg. MRSA

Adaptation (tolerance) :
There are many chances of a laboratory isolated organism becoming
adapted to the environment and grow gradually in the presence of
low concentration of the drug. But it has no further importance
clinically. e.g. it is easier to treat gonococcal strains by enormous
use of penicillin.

Mutation and selection :
Within a population of bacteria, mutants that are resistant to an
antibiotic arise spontaneously. When the bacteria are exposed to
the antibiotic, the sensitive organisms will be eliminated and the
resistant forms will proliferate. This selection pressure particularly
occurs in hospitals where initially it might be observed as the
microbes being sensitive to antibiotic and later on when tested it
might show the particular resistance to the drug.

Single step chromosomal mutations :
If it is there in an infective strain, there is chances of developing
resistance during the course of the treatment if a single drug is being
used. It may particularly apply in case of staphylococci to
streptomycin, rifampicin and erythromycin. The development of
resistant mutants occur at a high frequency in the case of above
drugs.

Transmissible drug resistance :
Plasmids are extra chromosomal packets of DNA which may code
for antibiotic resistance which will be transferred to a sensitive
strain from an antibiotic resistant strain, which makes the sensitive
strain also to become an antibiotic resistant strain as that of the
previously resistant strain.

Mechanism of Antimicrobial Resistance

Enzymatic inactivation of the antibiotic:
When a microbe which is capable to produce an enzyme, that digests
or breakdown the antibiotics referring to degradation of the active
molecule is termed as enzymatic inactivation e.g. the production of
penicillinase which belong to beta-lactamase class

Absence of a metabolic pathway required to activate the
antibacterial agent:
The microbes changes the pathway which is required to activate
an drug to show its action.

Alteration of the target:
Here the microbes changes the
receptor to which an antibiotic
attaches to produce an action.
Due to this change the drug
does not bind to the microbe
and thus doesn’t produce any
action e.g. in case of
erythromycin.

Altered transport of the antibiotic to its site of action:
The process involve the change in transportation mechanism and
where by the drug does not reach the active receptor to produce an
action.

Reduced cellular uptake:
The resistant microbes does not allow the drug to get inside the
microbe there by reducing the efficacy of the drug. This process
makes the drug incapable to produce any effect e.g. in case of
tetracycline.

Increased efflux Pumps:
It’s a process of self-defence adopted by an microbe, where there is
an reverse pumping of antibiotic which has gained access into the
microbes, so that its thrown out of the cell and this process
ultimately results in ineffectiveness of the medicament e.g. in case
of tetracycline.

Impact of antibiotic resistance
Clinical: A proportion of people who will be infected with the
resistant strain and thus will be difficult to treat the same with
the drugs normally used to treat the infections.
Financial: Financial burden on the patient and bed
occupancies in a hospital it was recorded that the resistance
strain of microbes where hard to treat and thus required more
number of days to treat it when compared to that of sensitive
microorganisms.

 Patient undergoing cancer chemotherapy, where after the chemo their white
blood cell count goes down and an infection at this stage becomes life
threatening due to decreased self-immunity.
 The patients undergoing complex surgeries like cardiac bypass, joint
replacements etc. are prone to surgical site infections which can be of severe
type and cause fatality or increased length of stay in the hospital by prolonging
the recovery time.
 Patients with rheumatoid arthritis where their immune system weakens due to
various medications used as well as the disease factor itself, can lead to
infectious outbreak in them. Thus it is necessary that an antibiotic is potent
enough to counter the infectious agents.
 Patients undergoing dialysis always have chance of getting infection into the
blood and it is one of the most leading causes of mortality among the renal
failure patients.
High Risk Population

Disadvantages of Antibiotic Combination
 Increase risk of toxicity
 Increase MDR-pathogens
 Increase cost
 Increase antagonism (bacteriostatic + bactericide)

GUIDELINES FOR RATIONAL USE OF ANTIBIOTICS
 Use antibiotics only when indicated.
 Where appropriate, specimen for gram stain, culture and sensitivity testing
should be obtained before commencing antibiotic therapy
 Choice of agent based on causative organism, safety, previous clinical
response, cost, ease of use and potential.
 Adequate dose and duration of treatment is essential.
 History of allergy or other ADR should be considered.
 Prophylactic use of antibiotic should be restricted.

Role of Pharmacist in Combating Resistance:
To promote awareness among the population, for ethical or proper safe use of
antibiotics.
The pharmacist should also make it sure that a Judicious use of available antibiotics is
done at all times and it is only given or dispensed when they are recommended and
prescribed
The pharmacist’s role might be increased from mere dispensing to reviewing of
antibiotic orders, helping physicians with drug selection and deciding on duration of
therapy
If the virulence of the disease is high, the pharmacist should always advice on proper
hygienic precautions to be considered, by which we can control the cross-transmission
of resistant strains from persons to person can be avoided.

Rashid. K, M.Pharm
Asst. Professor
Dept. of Pharmacology
JSPC, Pulikkal
raashkpharma@gmail.com

ANTIBIOTIC RESISTANCE

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