This document discusses multiple drug resistance (MDR) in bacteria. It begins by defining drug resistance and how bacteria can develop resistance through natural mechanisms or by acquiring resistance over time when exposed to antibiotics. The key points are: - Bacteria can become resistant through mutations or gene transfer that make antibiotics unable to bind or enable the bacteria to destroy or pump out antibiotics. - Multiple drug resistance (MDR) occurs when bacteria resist many different drug classes through various mechanisms like altered cell walls or target sites. - Common MDR bacteria include MRSA, VRE, and ESBL-producing gram-negative bacteria. - MDR-TB is also discussed, which is TB resistant to at least is

1. Multiple drug
resistance
Abdullah Memon and Divyesh Zala
S.Y.B.Sc Semester III

2. content
 What is drug resistance?
 Multiple drug resistance
 History of antimicrobial agents and resistant bacteria
 Mechanism in attaining multi drug resistance
 Common multiple drug resistant organisms
 MDR-TB

3. What is Drug resistance?
 It is tolerance of microorganisms to inhibitory action of
antimicrobials.
 Natural Resistance:
Some microbes have always been resistant to certain AMAs(anti
microbial antibodies .
 They lack metabolic process or target site that is affected by
specific drug.
Eg: gram-ve bacilli are not affected by penicillin G.

4. Acquired resistant:
• It is development of resistant by an organism due to use
of an AMA over a period of time
• This can happen with any microbes & is major clinical
problem However ;development of resistant depend on
microorganism as well as drug .
• Resistance may be developed by mutation or gene
transfer.

5. Resistant organisms can be:
 Drug tolerant:-loss of affinity of the target biomolecule
of the organism for a particular AMA(anti microbial
antibodies) ,
 Eg; resistant Staph.Aurus & E-Coli develop a RNA
polymerase that does not bind to Rifampicn.
 Drug destroying:- The resistant microbe elaborates an
enzyme which inactivates the drug
 Eg B- lactamases are produced by staphylococcus
Hymophylus ,which inactivates Penicillin G.

6.  Drug impermeable:- Many hydrophobic antibiotics gain access
in to the bacterial cell through specific channels formed by
proteins called porins or need specific transport mechanism .
 Active efflux based resistant has been detected by the bacteria
may also acquire plasmid directed inducible energy dependent
efflux protein in their cell membrane which pump out
tetracycline.
 Cross-resistance: Acquisition of resistance to AMA confirming
resistant to another AMA ,to which the organism is not to been
exposed is called cross resistant. some times unrelated drugs
show partial cross-resistant
 Eg between tetracycline & chloramphenicol.

8. Hey kid wana be a MDR…? Stick some of this
into your genome…
Even Penicillin won’t be able to harm you….

10.  Multiple drug resistance or Multidrug resistance is a
condition enabling a disease-causing organism to
resist distinct drugs or chemicals of a wide variety of
structure and function targeted at eradicating the
organism.
 Organisms that display multidrug resistance can be
pathologic cells, including bacterial and neoplastic
cells.
 Multidrug-Resistant Organisms (MDROs) are
defined as microorganisms that are resistant to one
or more classes of antimicrobial agents.

12. Mechanisms in attaining multidrug
resistance:
 No longer relying on a glycoprotein cell wall
 Enzymatic deactivation of antibiotics
 Decreased cell wall permeability to antibiotics
 Altered target sites of antibiotic
 Efflux mechanisms to remove antibiotics
 Increased mutation rate as a stress response

14. Common multi-drug-resistant
organisms (MDROs)
 MDROs are microorganisms, predominantly bacteria,
that are resistant to one or more classes of
antimicrobial agents
Methicillin-resistant Staphylococcus aureus (MRSA)
Vancomycin-resistant enterococcus (VRE)
MDR-TB
(ESBLs) producing Gram-negative bacteria

15. MRSA
VR
E
Gram negative
bacilli

16. Every year, over 2 million people in the United
States become infected with bacteria that are
resistant to antibiotics, and around 23,000 people
die as a result of these infections (CDC, 2013a).
Multidrug-resistant organisms, are bacteria that
are resistant to current antibiotic therapy and,
therefore, difficult to treat.
MDROs can cause serious local and systemic
infections that can be severely debilitating and even
life-threatening.
In the past, these infections were usually
controlled by penicillin.

17. The most serious concern with antibiotic resistance
is that some bacteria have become resistant to almost
all of the easily available antibiotics.
For example, Staphylococcus aureus (‘golden
staph’) and Neisseria gonorrhoeae (the cause of
gonorrhoea) are now almost always resistant to
benzyl penicillin.
These bacteria are able to cause serious disease
and this is a major public health problem.

18. Methicillin-Resistant Staphylococcus
aureus

20.  MRSA now accounts for more than 50% of hospital-
acquired staph infections.
 According to the CDC, almost 1,00,000 cases of
invasive MRSA occurred in 2005, with 18% of these
individuals dying during their hospitalization.
 These infections account for more than 5,000 deaths
each year which are directly attributable to MRSA.
 Specifically, MRSA has an attributable mortality rate
of 6.9% at 30 days and 16.7% at 1 year.
 The additional cost of MRSA alone is 39,000$ per
case in patients with a MRSA surgical-site infection
 Mortality rates were 13% higher in patients with
MRSA infection, regardless of mechanism of death.

22. Vancomycin Resistant
Enterococci(VRE)
 This are bacterial strains of genus vancomycin that are resistant to
antibiotic vancomycin
 Vancomycin-sensitive enterococci typically obtain new DNA in the
form of plasmid or transposons which encode genes that confer
vamcomycin resistance.
 Six different types of vancomycin resistance are shown by
enterococcus : Van-A, Van-B, Van-C, Van-D, Van-E and Van-G.
 A swab from samples of the blood, spinal fluid, sputum or
infectious tissue is taken and cultured in a petridish using the right
medium.
 Diagnosis requires culturing the organism. VRE can be easily
cultured in a laboratory.

23. • Lactobacillus rhamnosus GG (LGG), a strain of L.
rhamnosus, was used successfully for the first time
to treat gastrointestinal carriage of VRE.
• Some of the current drugs include combinations
of teicoplanin (Teichomycin) and amoxicillin or a
combination of ampicillin imipenem, and
vancomycin (Vancocin).

24. Extended spectrum beta-lactamase
producers (ESBLs)

25. Beta-lactam resistance

26. Drug resistance facts
 Drug resistance occurs when microbes survive and
grow in the presence of a drug that normally kills or
inhibits the microbe's growth.
 The history of drug resistance began with the
development of antimicrobial drugs, and the
subsequent ability of microbes to adapt and develop
ways to survive in the presence of antimicrobials.
 Diagnosis of antimicrobial drug resistance is performed
by lab tests that challenge the isolated microbes to
grow and survive in the presence of the drug.

27.  Treatment of antimicrobial drug resistance depends
on the type of infection and what the patient and
their doctor decide.
 Prevention of antimicrobial drug resistance is aided
by preventing the overuse and misuse of
antimicrobials; infections can be reduced by a
healthy lifestyle, hand washing, and other good
hygiene methods
 Antimicrobial resistance is a growing health issue
because more resistant microbes are being
detected and societal pressures often result in
overuse.

28. Multiple drug resistant
Tuberclousis
 What are the main types of drug resistant TB?
There are two main types of drug resistant TB, MDR TB and
XDR TB. Another type of drug resistant TB, variously
referred to as totally drug resistant TB, XXDR TB or TDR TB
has also now been detected.
What is the difference between the types MDR TB and
XDR TB?
MDR (multi drug resistant) TB is the name given to TB when
the bacteria that are causing it are resistant to at least
isoniazid and rifampicin, two of the most effective TB
drugs.

29. MDR & XDR TB
 WHO describing strains of TB, referred to as XDR TB,
that were resistant not only to isoniazid and rifampicin
(that is they were MRD TB) but they were also resistant
to at least three of the six classes of second line anti TB
drugs.
 In 1980 50% of TB bacilli were resistant to 1 drug.
 Multi-drug resistant TB (MDR-TB) began to emerge.
There are now an estimated 1.5million MDR cases
worldwide.
 Extreme drug resistance (XDR-TB) was reported in
2006.

32.  The first completely drug resistant (CDR-TB) case was
reported in Italy in 2007.
 MDR-TB has emerged and spread due to the
inadequacy of treatment. Today, treatment for drug-
resistant TB can take up to two years, and is so
complex, expensive, and toxic that a third of all MDR-
TB patients die.
 WHO treatment standards require that at least four
drugs be used to treat TB in order to avoid the
development of further resistance.
 According to the WHO, Eastern Europe's rates of MDR-
TB are the highest, where MDR-TB makes up 20% of
all new TB cases.
 In some parts of the former Soviet Union, up to 28% of
new TB cases are multidrug-resistant.

33.  Among previously treated cases in the same region,
reported rates of drug resistance are commonly
above 50% and as high as 61%.
 During the late 1980s and early 1990s, outbreaks of
MDR-TB in North America and Europe killed more
than 80% of those who contracted the disease.
 During a major TB outbreak in New York City in the
early 1990s, one in 10 cases proved to be drug-
resistant.
 Today, drug-resistant TB is also quite common in India
and China —the two countries with the highest MDR-
TB burdens.
 Treatment for MDR-TB consists of what are called
second-line drugs. These drugs are administered

34.  Treatment for MDR-TB is commonly administered for
2 years or longer and involves daily injections
for six months. Many second-line drugs are toxic and
have severe side effects.
 The World Health Organization has issued a target of
treating 80% of MDR-TB cases by 2015.
 The cost of curing MDR-TB can be literally thousands
of times as expensive as that of regular treatment in
some regions.

36. Top MDR-TB High-Burden
Countries
1. China
2. India
3. Russian Federation
4. Pakistan
5. South Africa
6. Philippines
7. Nigeria
8. Bangladesh
9. Indonesia
10.Myanmar
11.Ukraine
12.Uzbekistan
13.Kazakhstan
14.Viet Nam
15. Democratic Republic of Congo
16. Ethiopia
17. Azerbaijan
18. Tajikistan
19. Republic of Moldova
20. Kyrgistan
21. Belarus
22. Georgia
23. Armenia
24. Bulgari
25. Lithuania
26. Latvia
27. Estonia

37. MDR & XDR TB is not
spread by
 Shaking someone’s hand
 Sharing food or drink
 Touching bed linens or toilet
seats
 Sharing toothbrushes
 Kissing
 Smoking or sharing cigarettes

39. Building a Treatment Regimen for
MDR-TB
Adapted from: Curry International Tuberculosis Center. Drug-resistant tuberculosis: a survival guide for
clinicians. Chang KC, et al. Respirology. 2013;18:8-21.
Step 1: Include any first-line
drugs to which the isolate is
susceptible
Injectables
Kanamycin
Amikacin
Capreomycin
Streptomycin
Step 2: Add a fluoroquinolone
Fluoroquinolone
Levofloxacin
Moxifloxacin
Gatifloxacin
First-line Drugs
Ethambutol
Pyrazinamide
Step 3: Include an
injectable agent
Oral Second-line Drugs
Ethionamide
Prothionamide
Cycloserine/terizidone
Para-aminosalicylic acid
Third-line Drugs
Clofazimine
Clarithromycin
Amoxicillin-clavulanate
Linezolid
Thiacetazone
Meropenem-clavulanate
Thioridazine
Other new drugs
Step 4: Include second-line
drugs until you have 4-6
drugs to which the isolate is
susceptible
Consider third-line drugs if
there are not 4-6 drugs to
which the isolate is
susceptible

40. 40
Step 3
Third line drugs
Imipenem Linezolid
Macrolides
Amoxicillin/Clavulanate
Consider use of these
If there are not
4-6 drugs
available
consider 3rd
line in consult
with MDRTB
experts
Step 1
Use any
available
Begin with any
First line agents to
Which the isolate is
Susceptible
Add a
Fluoroquinolone
And an injectable
Drug based on
susceptibilities
Fluoroquinolones
Levofloxacin
Moxifloxacin
Injectable
agentsAmikacin
Capreomycin
Streptomycin
Kanamycin
PLUS
One of
these
One of
these
First-line drugs
Pyrazinamide
Ethambutol
PLUS
Step 2 Pick one or more of these
Oral second line drugs
Cycloserine
Ethionamid
e PAS
Add 2nd line drugs until
you have 4-6 drugs to
which isolate is
susceptible (which have
not been used
previously)
BS

41. Prevent of MDR & XDR?
 Hand Hygiene – The Most Important Way to Prevent
Transmission of Microorganisms and Infection
 Use the appropriate
antimicrobial for an infection;
e.g. no antibiotics for viral
infections
 Identify the causative
organism whenever possible
 Select an antimicrobial which
targets the specific organism,
rather than relying on a
broad-spectrum antimicrobial

42.  Complete an appropriate
duration of antimicrobial
treatment (not too short and
not too long)
 Use the correct dose for
eradication; subtherapeutic
dosing is associated with
resistance, as demonstrated in
food animals.
 Minimize unnecessary
prescribing and overprescribing
of antibiotics.

43. TREATMENT
 Initial treatment with standardized regimens (HRZE)
 Directly observed therapy (DOT)
 Drug susceptibility testing for all retreatment cases
 Infection control precautions
 Monitor drug resistance through surveys
 Effective contact management

44. THANK YOU