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Recent advances antibiotics.ppt s.pdf
1. Recent Advances to overcome
Antibiotic Resistance
Dr.Akhilesh
M-5698
M.V.Sc Scholar
VETERINARY MEDICINE
2. Contents
Introduction
History
Common causes
Common modes of AR
Most resistant pathogens
Newer antibacterials
New Targets for the Next Generation of Antimicrobial drugs
Possible Solutions for Antibiotic Resistance
3. Introduction
Antimicrobial resistance (AMR) is the ability of a
microorganism to stop an antimicrobial from working against
it. As a result, standard treatments become ineffective,
infections persist and may spread to others.
Antibiotic / Antimicrobial resistance is the ability of microbes
to resist the effects of drugs.
The ability of pathogens that works against the antibiotics, is
termed Antibiotic Resistance.
[1]
(1. www.who.int/drugresistance/en/)
4. Superbug
An informal term for a bacterium that has become resistant
to antibiotics that usually are used to treat it.
Ex:Methicillin-resistant Staphylococcus aureus (MRSA)
Vancomycin-resistant Enterococcus (VRE)
(Rakel RE and Rakel D,2015 )
(Fri, Sep 16,2016)
5. History
PAUL EHRLICH
Coined the term “CHEMOTHERAPY”
Discovered Salvarsan (for Syphilis)
FATHER OF CHEMOTHERAPY
He used the term ‘MAGIC BULLETS’
(Stefan H. E. Kaufmann,2008)
7. …..history
Domagk discovered “Sulphonamides”
Selman Waksman discovered
“Streptomycin”
In 1947, “chloramphenicol” was first used
clinically to treat Typhus
G.Brotzu discovered “Cephalosporins”
Benjamin M. Duggar isolated
“Chlortetracycline” from a mud sample
obtained from a river in Missouri.
8. …..history
1960 onwards second generation
antibiotics like “Methicillin” were
discovered
Following this, semi synthetic derivatives
of older antibiotics with more desirable
properties & different spectrum of activity
were produced
e.g. Fluroquinolones, Oxazolidinones etc.
16. Why do we need newer antimicrobials
Bacterial resistance to antimicrobials-
health and economic problem
Chronic resistant infections contribute to
increasing health care cost
Increase morbidity & mortality
with resistant microorganisms
[D.M. Livermore ,Clinical Microbiology & Infection
Volume 10, Supplement 4, Pages 1-36 (2004)]
17.
18. Oxazolidinones
Considered to be the first truly new
class of antibacterial drugs introduced in
the past 3 decades
Linezolid
Approved for adults use in 2000
Approved for pediatric
use in 2005
20. Mechanism of Resistance to
older Oxazolidinones
Occurs due to mutations in ribosomal RNA
(rRNA)
Resistance overcome by:
Newer oxazolidinones by additional
hydrogen bond interactions with 23S rRNA
(Jaswant Rai et al, 2013)
21. Newer glycopeptides
Vancomycin & Teicoplanin are already in
use
Recently APPROVED DRUG
Telavancin :Approved in 2009 for complicated
skin and skin structure infections(MRSA)
DRUGS IN PIPELINE
Oritavancin : Phase III trial
Dalbavancin : Phase III trial
22. Mechanism of resistance to older
glycopeptides.
Synthesis of low-affinity precursors in
which C-terminal D-Ala residue is replaced
by:
D-lactate (D-Lac) or by D-serine (D-Ser)
Resistance overcome by:
High binding affinity for both substrates
(D-Ala-D-Lac precursor substrate OR D-
Ala-D-Ser) due to presence of
hydrophobic side chain. (Mandeep Kaur et al,2014)
23. Ketolides
Drug resistance in community acquired
respiratory tract infections discovery
and development of ketolides.
Carbonyl group at the C3 position, responsible for
sensitivity to macrolide resistant strains.
24. Newer ketolides
APPROVED DRUG
Telithromycin –Approved in 2004
DRUGS IN PIPELINE
Cethromycin- Phase III trails
Solithromycin – Phase III trails
26. Glycylcyclines
New class of antibiotic derived from
tetracycline
Designed to overcome two common mechanisms
of tetracycline resistance
Resistance mediated by acquired efflux pumps
Ribosomal protection
Only one glycylcycline antibiotic for
clinical use : TIGECYCLINE
(Frampton JE & Curran MP, Tigecycline Drugs,2005)
27. Newer Carbapenems
Beta-lactum antibiotics with a broad
spectrum of antibacterial activity
NEWER CARBAPENEMS :
Ertapenem : Approved in 2001
Doripenem : Approved in 2007
DRUG IN PIPELINE :
Razupenem : Phase II clinical trail
(Livermore DM, Mushtaq S, Warner M, 2009)
28. Newer Cephalosporins
Approved Cephalosporins
Ceftaroline: Approved in 2010
For the treatment of
o Community – acquired pneumonia
o Complicated skin and soft – tissue
infections
Drugs in pipeline
Ceftobiprole : awaiting FDA approval
(Saravolatz LD et al, 2011)
29. New Targets for the Next
Generation of Antimicrobial drugs
Targeting virulence factors
Targeting bactericidal functions of
bacterial proteins
Modulating host response pathways
Peptides derived from vertebrates,
invertebrates and microorganism.
(Gurpreet Kaur Randhawa et al, 2013)
30.
31.
32.
33.
34.
35.
36. Possible Solutions for Antibiotic
Resistance
Stop unnecessary antibiotic prescriptions.
Finish antibiotic prescriptions.
Use the right antibiotic in an infectious situation
as determined by antibiotic sensitivity testing.
Use antibiotics in rotation.
Use combination of antibiotics if necessary.
Promote Vaccine recommendations.
Implement infection control measures, such
as hand washing, isolation precautions, and
immunization.
Improve communication, education and training.
37. Conclusion
There is a great need of newer antibiotics
because of increasing microbial resistance
Because of increase cost of development
and increasing resistant, only few drugs
are in pipeline
Some of the newer agents are effective
against resistant strains
Programs like Antibiotic stewardship can
be helpful to combat the resistance
Rational use of antibiotics remains the
most important measure.
38. References
www.who.int/drugresistance/en/
www.cdc.gov › Antibiotic / Antimicrobial Resistance › U.S.
Activities to Combat AR
http://www.sciencedaily.com/articles/a/antibiotic_resistanc
e.html
Andrea Gyyot, Graham Layer,2006 MRSA Bugbear of a surgical
practice reducing the incidence of MRSA surgical site infection,
Ann R Coll Surg Engl: 88: 222-223.
Archibald L(1997).Antimicrobial resistance in isolates from
inpatients and outpatients in the United States: increasing
importance of the intensive care unit. Clinical Infectious Diseases.
24(2):211-215
Ceasr A, Arias, M.D. and Balbara E. Murray, M.D.N., 2009.
Antibiotic resistant Bugs in the 21st Century. A clinical super
challenge. Eng. J. Med.: 360: 439-443
39. Microbiology, A clinical Approach -Danielle Moszyk-Strelkauskas-
Garland Science 2010
Jaswant Rai, Gurpreet Kaur Randhawa, and Mandeep Kaur,
Recent advances in antibacterial drugs, Int J Appl Basic Med
Res. 2013 Jan-Jun; 3(1): 3–10.
D.M. Livermore ,Clinical Microbiology & Infection Volume
10, Supplement 4, Pages 1-36 (2004)
Vikas Manchanda, Sinha Sanchaita, and NP Singh J. Glob
Infect Dis. 2010 Sep-Dec; 2(3): 291–304.
Losee L. Ling et al, A new antibiotic kills pathogens without
detectable resistance, Journal Nature 517, 455–459 (22 January
2015)