This is a brief study on antibiotic resistance, which is obviously a woe in the modern-day health care system.

1. UNDER GUIDENCE OF- ASSOCIATE PROFESSOR DR.GOURANGA NANDI
B.C.D.A COLLEGE OF PHARMACY AND TECHNOLOGY
78,jessore road,Hridaypur,Barasat,Kolkata-700124

2. Introduction
 Throughout history there has been a continual battle between human beings and
multitude of micro-organisms that cause infection and disease.
 Here comes Antibiotic to our rescue- “Antibiotics are medicines that fight bacterial
infections, either by killing or inhibiting bacteria from reproduction.”
 In pre-antibiotic era, even simple bacterial infections like cholera was epidemic,
surgeries were riskier to perform.
 But life is not so simple as it seems, bacteria are getting resistant to present antibiotics
and it seems to get impossible to treat them with present antibiotics.

3. HISTORY
 In 1928 Sir Alexander Fleming discovered first antibiotic, Penicillin.
 The Introduction of penicillin in 1940 ignited a total new era of
treatment and the time period of 1940-1962 is considered as “golden
era” of antibiotics.
Sir Alexander Fleming won Nobel Prize for discovery of Penicillin in 1945
and in his 1945 Nobel Prize lecture, Fleming himself warned of the danger
of resistance –“It is not difficult to make microbes resistant to penicillin in
the laboratory by exposing them to
concentrations not sufficient to kill them, ……and by exposing this
microbes to non-lethal quantities of the drug make them resistant.”

4. TIMELINE OF ANTIBIOTICS

5. ANTIMICROBIAL RESISTANCE
Antimicrobial resistance happens when microorganism (such as
bacteria, fungi, viruses, and parasites) change when they are
exposed to antimicrobial drugs (such as antibiotics, antifungals,
antivirals, antimalarial, and anthelmintic). Microorganisms that
develop antimicrobial resistance are sometimes referred to as
“superbugs”.
As a result, the medicines become ineffective and infections persist
in the body, increasing the risk of spread to others.

7. WHY RESISTANCE IS CONCERN ?
 Resistant organisms lead to treatment
failure.
 Increased mortality.
 Resistant bacteria may spread in
Community.
 Low level resistance can go undetected.
 Added burden on healthcare costs.
 Threatens to return to pre-antibiotic era.
 Selection pressure during prescribing.

8. Mechanism of action of antibiotics

9. EVOLUTION OF ANTIBIOTIC RESISTANCE
 Some microorganisms may ‘born’ resistant, some ‘achieve’ resistance by
mutation or some have resistance ‘thrust upon them’ by plasmids.
Antibiotic Resistance
Natural
(Intrinsic)
Acquired
Chromosomal Methods
Mutations
Extra Chromosomal Methods
Plasmids
Classification of antibiotic resistance mechanism

10. INTRINSIC RESISTANCE:
(Natural Resistance)
1.Lack target :
• No cell wall;
2. Innate efflux pumps:
• does not achieve adequate
internal concentration
3. Drug inactivation:
• Cephalosporinase in
Klebsiella
Acquired resistance
(Mutations)
• refers to the change in
DNA structure.
• Occurs in one per ten
million cells.
• Often mutants have
reduced susceptibility
Plasmids
• Extra chromosomal genetic element, replicate
independently and freely in cytoplasm.
• Plasmids carry r-genes
• These r-genes readily transferred from R-plasmid to
another plasmid or to chromosome.
• mostly observed
THE SUPER
BUG
BIRTH OF The sUPER BUG

11. SOME ANTIBIOTICS AND HOW THEY GOT RESISTANT
DRUG MECHANISM OF ACTION
Penicillin &
Cephalosporin
B Lactamase cleavage of the β-lactam ring
Aminoglycosides Modification by phosphorylating, adenylating
and acetylating enzymes
Chloramphenicol Modification by acetylation
Tetracycline Reduced uptake / increased export
Sulphonamides Active export out of the cell & reduced affinity
of enzymes
Erythromycin Change in receptor by methylation of r RNA

12. WHY BACTERIA ARE GETTING RESISTANT ?
The followings can be stated as main reasons for antibiotics
resistance-
• The diagnosis is incorrect.
• Over prescription of antibiotics
• Patients not finishing the entire course of anti-biotic
• Overuse of antibiotics in livestock and fish farming.
• Poor infection control in Health care settings.
• Poor hygiene and sanitation
• Absence of new antibiotics

13. FACTORS AFFECTING ANTIBIOTIC RESISTANCE
1.Environmental Factors.
 Huge populations and overcrowding.
 Rapid spread by better transport facility.
 poor sanitation.
 Infective infection control programme.
 huge use of antibiotic in agriculture ,
animal-husbandary and medical cleansing.

14. 2.Drug related.
 Over the counter availability
of antimicrobials.
 Soaring use of antibiotics.
 Irrational fixed dose combination
of antimicrobials.

15. 3.Patient Related:
 Poor adherence of dosage regiments.
 Poverty.
 Lack of education.
 Self medication.
 Misconception.

16. 4.Prescriber related.
 Inappropriate use of available drug.
 Overuse of antimicrobials.
 Inadequate dosing.
 Lack of current knowledge and training.

17. SOME DANGEROUS ANTIBIOTIC RESISTANT BACTERIA
1. Mycobacterium tuberculosis
2. Staphylococcus aureus (MRSA)
3. Pseudomonas aeruginosa
4. Streptococcus pyrogenes
5. Escheria coli
6. Neisseria gonorrhoea

18. DRUG RESISTANT TUBERCULOSIS
• Tuberculosis is a potentially serious lung disease
spread by Mycobacterium tuberculosis
• The most effective way to treat tuberculosis is
Antibiotic treatment-
Isoniazid, Rifampicin, Pyrazinamide, Ethambutol
and Streptomycin are considered as first line drug
to treat Tuberculosis.
• But due to mismanagement of these drugs to
treat tuberculosis is nearly impossible now by
single first line treatment.

19. TYPES OF DRUG RESISTANT TUBERCULOSIS
Mono-resistance: resistance to one first-line anti-TB drug only.
Poly-resistance: resistance to more than one first-line anti-TB drug,
Multidrug resistance (MDR): resistance to both isoniazid and rifampicin.
Extensive drug resistance (XDR): resistance to fluoroquinolone, and at
least one of three second-line injectable drugs (capreomycin, kanamycin
and amikacin).
Rifampicin resistance (RR): resistance to rifampicin.

20. TREATMENT OF DRUG RESISTANT TUBERCULOSIS
• WHO recommendations aim to speed up detection and improve treatment
outcomes for multidrug resistant tuberculosis (MDR-TB) through use of a
novel rapid diagnostic test and a shorter, cheaper treatment regimen.
• During the last few years, two new drugs have emerged from the research are
bedaquiline and delamanid, these are indicated for the treatment of drug-
resistant TB.
Group 1 - First-line drugs: Isoniazid, rifampicin, ethambutol, pyrazinamide
Group 2 - Injectable agents: Kanamycin, amikacin, capreomycin,streptomycin
Group 3 - Fluoroquinolones: Levofloxacin, moxifloxacin, ofloxacin
Group 4 - Oral bacteriostatic agents: Ethionamide, cycloserine,
para aminosalicylic acid (PAS), prothionamide, terizadone
Group 5 – Unclear role: Clofazamine, linezolid, amoxicillin/clavulanate,
Imipenem/cilastatin, thioacetazone, high-dose isoniazid, clarithromycin,

21. METHICILIN RESISTANT STAPHYLOCOCCUS AUREUS
Introduction:
 MRSA or methiciline-resistant difficult to diagnose be Staphylococcus aureus,is a
bacterial infection.
 The infection causes skin infections in non-hospitalizied people.
Symptoms of MRSA:
 MRSA can be difficult to diagnose because when it first appears, it looks mimic those
of other skin infections reddish bumps or blisters.
 While other rashes gets worse more rapidly.
 Develop a fever and skin around the area may become tender to touch.
 Depending on where MRSA is located generalized swelling of the surrounding tissue.

22. Diagnosis:
• Diagnostic microbiology laboratories and reference laboratories are key for
identifying outbreaks of MRSA. Normally the bacterium must be cultured
from blood, sputum, urine or other body fluids in “Quantitative PCR”
procedures.
• Another common laboratory test is Rapid Latex Agglutination test that
detects PBP2a protein.
Transmission of MRSA:
• MRSA is mainly transmitted via skin to skin contact. It can also spread by objects.
MRSA can live on towel, bench, and other objects for some times.

23. Treatment:
• If one is diagnosed with MRSA ,he/she will be put on a course of
antibiotics that are known to have an effect on the infection. If the
symptoms doesn’t resolve then the antibiotic will be given via IV route
or may be admitted to hospital.MRSA can be serious illness and must
be treated as such.
Drugs Used:
• Vancomycin, Teicoplanin (but several newly discovered strains of MRSA
show antibiotic resistance to these drugs also)
• Thus nowadays Linezolid is used to treat MRSA.

24. ANTIBIOTIC RESISTANT MALARIA
In humans, malaria infection is caused by four species of
intracellular protozoan parasite Plasmodium falciparum, P. vivax,
P. ovale, and P. malariae
drug resistance has only been documented in two of the four
species, P. falciparum and P. vivax.
Diagnosis:
• Clinical diagnosis
• Dip-stick test
• Molecular test
• Serology

25. DRUGS AVAILABLE FOR TREATMENT
Chloroquineremainsthedrugofchoicefor
treatmentofnon-falciparuminfectionsand
nonseverefalciparuminfections
Quinine,eitheraloneorincombination
withtetracyclines,ormefloquinetendtobe the
drugsof choiceformultidrug-resistantmalaria,
Artemisininisananotherimportantdrug.

26. PREVENTION FROM ANTIBIOTIC RESISTANCE
1.Ask healthcare professionals if there are any other steps you can take
without prescribing antibiotics.
2.Take antibiotics exactly how the professional prescribed.
3.Discard any leftover medication.
4.Never skip doses.
5.Avoid antibiotics for a viral infection, cold or flu.
6.Never save antibiotics for the next time you get sick.
7.Never take antibiotics prescribed for someone else.

27. SOME NEWER ANTIBIOTICS
• Linezolid: targets 50s ribosomes.
• Tigecycline: targets 30s ribosomes.
• Dalbavacin: inhibits cell wall synthesis.
• Iclaprin: inhibits dihydrofolate reductase.

28. CONCLUSION
• Antibiotics are medicines that help stop infections caused by bacteria.
• The successful outcome of the therapy would depend very much on the choice of
antibacterial agent.
• Thus if antibiotics are administered without proper diagnosis or choice of antibiotic
is incorrect or the route of administration is wrong. Then the bacteria gets resistant
to those antibiotics and can cause antibiotic-resistant infections.
• That can lead to serious disability or even death. Thus rational use of antibiotics
should be used to treat the bacterial infections easily in a safe manner.

29. References
 Essentials of Medical Pharmacology, K.D.Tripathi, 7th Edition, Antimicrobial Drugs:
General Considerations, Page-688
 Rang and Dale’s Pharmacology, H.P Rang, M.M.Dale, J.M.Mitter, R.J.Flower,
G.Henderson,7th Edition, Basic principles of antimicrobial chemotherapy, page:617
 “WHO treatment guidelines for drug resistant tuberculosis (2016 update)”, WHO,
Geneva, 2016,
http://www.who.int/tb/areas-of-work/drug-resistant-tb/treatment/resources/en/
 Wollina, U (2017). "Microbiome in atopic dermatitis". Clinical, Cosmetic and
Investigational Dermatology. 10: 51–56. doi:10.2147/CCID.S130013. PMC 5327846
. PMID 28260936.