Antimicrobial Drug Resistance

A 37-year-old male admitted for
pneumonia continues to present with the

same complaints even on the third day od
admission, inspite of the fact that he had
been compliant regarding the prescribed
antibiotics and their dosage
Antimicrobial
Drug Resistance
LO’s
At the end of this session students should be able to
• Write the four major mechanism responsible for
mediating bacterial resistance
• Write in detail about the two types of resistance
• Write the genetic and non genetic basis of disease
• Define Antibiogram, minimal inhibitory concentration ,
minimal bactericidal concentration
• Enlist the conditions of use of antibiotic combinations
Drug resistance
The ability of bacteria and other

microorganisms to resist the effects of
an antibiotic/drug to which they were
once sensitive
Mechanisms that mediate
antibiotic resistance
1. Production of enzymes
2. Modified targets
3. Reduced bacterial permeability
4. Efflux pumps/ MDR pumps
Mechanism of Drug resistance
1. Production of enzymes
Inactivation of the drug
Example
β-lactamase enzyme inactivates penicillin and
cephalosporins by breaking the β-lactam ring
2. Modified drug target in bacteria
drug has reduced effects
Example
Mutations in penicillin binding proteins
(PBPs)
3. Reduced permeability
to an extent that the effective drug
concentration inside the cell is not achieved
Example
Changes in porins can reduce the penicillin
entering the bacterium
4. Export of drug
Efflux pumps or multidrug-resistance
(MDR)pump
Example
The pump imports protons and exports
antibiotics such as tetracyclines
Types of Drug resistance
1. High level resistance

2. Low level resistance
Types of Drug Resistance
High level resistance
► mediated by enzymes
► cannot be overcome by increasing the dose of
antibiotics
► A different antibiotic from another group has to be
used
► Most commonly hospital acquired infections
Examples
1. β-lactamase as it destroys the drug completely
2. Penicillinase producing strains of Neisseria gonorrheae -
cannot be treated completely with penicillin G
Why in hospitals???
► wide spread and indiscriminate use of antibiotics
► Hospital strains are often resistant to multiple

antibiotics due to acquisition of plasmids
Examples
MRSA – Methicillin resistant Staphylococcus aureus
VISA – Vancomycin intermediate Staph.aureus
VRSA - Vancomycin resistant Staph.aureus
VRE - Vancomycin resistant Enterococcus
MDR TB – Multidrug resistant tuberculosis
Low level resistance
► Mediated by mutations in the genes
► can be over come by increasing the drug dose
► Although altered, but targets can still bind
some drug
Example
1. Penicillinase producing strains of Neisseria
gonorrheae exhibit high level resistance
against penicillin G
2. Strains of Neisseria gonorrheae that produce
altered PBPs exhibit low level resistance
Causes of Drug Resistance
1. Genetic basis
► Chromosome mediated resistance
► Plasmid mediated resistance
► Transposon mediated resistance
2. Non-genetic basis
Genetic basis of drug resistance
1. Chromosome mediated resistance
► Less frequent and less problematic than
plasmid mediated resistance
► Mutation in the gene which codes for either

target of the drug or transport system in the
membrane responsible for controlling its uptake
► Two or more antibiotics can be given in certain

conditions as the organism can be resistant to
one, but can be treated by another
2. Plasmid mediated resistance
► Causes high level resistance and is very
important from clinical point of view
1. Occurs in many different species especially
Gram negative rods
2. Frequently mediates resistance to multiple drugs
3. Has high rate of transfer from one cell to another
by conjugation
► Plasmids(R factors) carry the genes for a variety
of enzymes which can degrade antibiotics and
modify the transport systems
► May carry one antibiotic resistance gene or two
or more genes
R factor---- mediated resistance
Important properties of plasmids/R factor
► Can replicate independently of the bacterial
chromosome – multiple copies
► Can be transferred not only to the same
species, but also to other species
► In addition to antibiotic resistance they confer
resistance to metal ions (e.g., they code for an
enzyme that reduces mercuric ions to elemental mercury)
► Resistance to certain bacteriophages by
coding for enzymes that destroy their DNA
Transposon/jumping gene mediated
resistance
► Small pieces of DNA (genes) that are
transferred within or between larger
pieces of DNA i.e. between bacterial
chromosomes and plasmid
► They carry drug resistance genes . Many
R plasmid carry one or more
transposons
Non Genetic Basis
There are several non genetic reasons
1. No effective penetration of drugs in case of an
abscess where the bacteria are walled off
How to treat an abscess???
2. Bacteria in resting phase – they become insensitive
to cell wall inhibitors like penicillin & cephalosporins
Bacteria when dormant in tissues for years -
Mycobacterium tuberculosis
3. Survival as protoplast under certain circumstances
4. Presence of foreign bodies like catheters,
surgical implants can make successful
antibiotic treatment difficult
5. Artifacts
Prescribing a wrong drug
Prescribing wrong dose
Failure of a drug to reach a specific site
Non compliance
Overuse/misuse of antibiotics
1. Unnecessary use of multiple antibiotics when one is
enough
2. Prescribing prolonged course of antibiotics
3. Using antibiotics where they are not needed as in self
limited infections
4. Overuse for prophylaxis before and after surgery
5. Indiscriminate use of antibiotics e.g. availability of
antibiotics over counter
6. Use of antibiotics in animal feed to prevent infections
and promote growth – may contribute to the pool of
resistant organisms in humans
Antibiotic sensitivity testing
Q1- What is an Antibiogram?
Q2- How many ways to do it?

1. Kirby Bauer disc diffusion method
2. Tube dilution method
Antibiotic sensitivity testing
Antibiogram of vancomycin
resistant Enterococci (n=22)
Antibiotic disc used Number of resistant isolates Resistance (%)
Linezolid 0 0
Chloramphenicol0 0
Ampicillin 19 86.36
Erythromycin 18 81.81
Gentamicin 15 68.18
Tetracycline 8 36.36
Minocycline 6 27.27
Antibiotic sensitivity
Minimum Inhibitory Concentration(MIC)

Minimum concentration of a drug that
inhibits the growth of bacteria
Minimum Bactericidal concentration(MBC)

Minimum concentration of a drug that kills
the bacteria completely
Antibiotic Combinations
Single best antibiotic is to be selected to minimize
the side effects, but a combination of antibiotics are
commonly given
1. To treat serious infections before culture and
sensitivity report is received
2. To achieve synergistic inhibitory effect on the
bacteria
3. To prevent the emergence of resistant
organisms
MCQ
Bacterial drug resistance is a problem faced worldwide in
routine medical practice which spreads most commonly
by
1. Programmed rearrangement
2. Translation
3. Conjugation
4. Transduction
5. Transfection

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A 37-year-old male admitted for

pneumonia continues to present with the

The ability of bacteria and other

1. High level resistance

► Hospital strains are often resistant to multiple

► Mutation in the gene which codes for either

► Two or more antibiotics can be given in certain

Q2- How many ways to do it?

Antibiotic disc used Number of resistant isolates Resistance (%)

Minimum Inhibitory Concentration(MIC)

Minimum Bactericidal concentration(MBC)

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