1. DEPARTMENT OF SURGERY
AND DIAGNOSTIC IMAGING
A S S I G N M E N T O F A N T I B I OT I C T H E R A P Y
P R O F. N AM E : D R . K U L I D I P S I N G
S T U D E N T N AM E : J I M C A L E ( D R . A S H R A F )
Mekelle university
college of veterinary medicine
2. overview of antibiotic therapy
A. introduction
B. classification of antibiotic therapy
C. mechanism of action
D. drug resistance mechanism
3. INTRODUCTION
Antimicrobial agents, or more simply
antimicrobials, are chemical compounds that kill or
inhibit the growth of microorganisms.
They are naturally produced by microorganisms
such as fungi (e.g. penicillin) and bacteria (e.g.
tetracycline and erythromycin), or can be
synthetically (e.g. sulfonamides and
fluoroquinolones) or semi-synthetically
produced (e.g. amoxicillin, clarithromycin and
doxycycline).
4. INTRODUCTION
According to the original definition by the Nobel laureate
S. A. Waksman, the term antibiotic only refers to natural
compounds of microbial origin. However, the term is often
used as a synonym for any antimicrobial agent by both
professionals and lay-persons alike.
Antimicrobials targeting bacteria are generally referred
to as antibacterial agents; although some of them (e.g.
sulfonamides and tetracyclines) are also active against
protozoa.
Some antimicrobial agents affect bacterial and human or
animal cells equally due to lack of selective toxicity, and
can therefore only be used on inanimate objects
(disinfectants) or on external surfaces of the body
(antiseptics).
5. CLASSIFICATION OF ANTIMICROBIAL
DRUGS
Antimicrobial drugs are classified in a variety of
ways, based on their basic features.
a. Class of target microorganism
b. Antibacterial activity
c. Bacteriostatic or bactericidal activity
d. Time or concentrated dependent activity
6. a. Class of target microorganism
Antiviral and antifungal drugs generally are active
only against viruses and fungi, respectively.
7. b. Antibacterial activity
Some antibacterial drugs are also considered narrow
spectrum in that they inhibit only gram positive or
gram negative bacteria, where as broad spectrum
drugs inhibit both gram positive and gram negative.
8. c. Bacteriostatic or bactericidal activity
An antibacterial agent that exhibits a large dilution
difference between inhibitory and cidal effects is
considered to be Bacteriostatic drug. On the other
hand, an antibacterial agent that kills the bacterium
at or near the same drug concentration that inhibits
its growth is considered to be a bactericidal drug.
9. d. Time /concentration dependent
activity
Antimicrobial agents are often classified as exerting
either time-dependent or concentration-
dependent activity depending on their
pharmacodynamic properties.
10. Continuee….
Some drugs exit characteristics of both time - and
concentration- dependent activity. The best
predictor of efficacy for these drugs is the 24-hour
AUC/MIC ratio.
. Glycopeptides, rifampin and, to some extent
fluoroquinolones fall within this category.
11. Mechanism of Action of Antimicrobial Drugs
1. ANTIBACTERIAL DRUGS
The mechanism of action of antibacterial fall into five
categories:-
A. Inhibition of cell wall synthesis: - those
antibacterial that inhibit cell wall synthesis are for
example: beta-lactams antibiotics, bacitracin, and
vancomycin.
12. B. Damage of cell membrane functions:
Those antibacterial that inhibit cell membrane
function are for example: polymyxins.
13. C. Inhibition of nucleic acid synthesis
Those antibacterial that inhibit nucleic acid
synthesis are for example: nitroimidazoles,
nitrofurans, quinolones, rifampin
14. D. Inhibition of protein synthesis
Those antibacterial that inhibit protein synthesis
function are for example: aminoglycosides,
chloramphenicol, lincosamides, macrolides,
streptogramins, pleuromutilins, tetracyclines, and
oxazolidinones.
15. E. Inhibition of folic acid synthesis:
Those antibacterial that inhibit folic acid synthesis
function are for example: sulfonamides,
trimethoprim.
16.
17. 2. ANTIFUNGAL DRUGS
Most currently used systemic antifungal drugs
(polyenes, azoles) damage cell membrane function
by binding ergosterols that are unique to the fungal
cell membrane.
18. 3. ANTIVIRAL DRUGS
Antiviral drugs act only during viral replication;
newer analogs are targeted at inhibition of
penetration of viruses into the cell or inhibition of
their assembly and release. The distinction between
deoxyribonucleic acid (DNA) and ribonucleic acid
(RNA) viruses is important in antiviral therapy.
19.
20. Resistance mechanism
Antimicrobial resistance can be classified into four main
categories:
1. The antimicrobial agent can be prevented from reaching
its target by reducing its penetration into the bacterial
cell.
2. General or specific efflux pumps may expel antimicrobial
agents from the cell.
3. The antimicrobial agent can be inactivated by
modification or degradation, either before or after
penetrating the cell.
4. The antimicrobial target may be modified so that the
antimicrobial cannot act on it anymore, or the
microorganism’s acquisition or activation of an alternate
pathway may render the target dispensable.
21. Reference
S.Giguers, J.F. Prescott, J.D. Baggot, R.D.Walker,
P.M.Dowling ( ANTIMICROBIAL THERAPY in veterinary
medicine) fourth edition.
The Danish Small Animal Veterinary Association, SvHKS,
Nov. 2012
Lessons from the Danish Ban on Feed-grade Antibiotics,
Dermot J. Hayes and Helen H.Jensen, Center for Agricultural
and Rural Development, Iowa State University, June 2003,
http://www.card.iastate.edu/publications/dbs/
pdffiles/03bp41.pdf
Veira, A. R. and others. Foodborne Pathogens and Disease
2011, 8(12): 1295-1
Cox, L. A and Singer, R. S. Foodborne Pathogens and Disease,
2012 9(8), 776
22. Aarestrup, F.M. (2006). The origin, evolution and global dissemination of
antimicrobial resistance. In Antimicrobial Resistance in Bacteria of
Animal Origin (ed. Aarestrup, F.M.). ASM Press, American Society for
Microbiology, Washington DC, pp. 339–60.
Guardabassi, L. and Courvalin, P. (2006). Modes of antimicrobial action
and mechanisms of bacterial resistance. In Antimicrobial Resistance in
Bacteria of Animal Origin (ed. Aarestrup, F.M.). ASM Press, American
Society for Microbiology, Washington DC, pp. 1–18.
Kruse, H. and Sorum, H. (1994). Transfer of multiple drug resistance
plasmids between bacteria of diverse origins in natural microenvironments.
Appl. Environ. Microbiol. 60: 4015–21.
Hasman, H., Kempf, I., Chidaine, B. et al. (2007). Copper resistance in
Enterococcus faecium, mediated by the tcrB gene, is selected by
supplementation of pig feed with copper sulphate. Appl. Environ.
Microbiol. 72: 5784–9.
23. Barug, D., de Jong J., Kies, A.K. and Verstegen, M.W.A. (eds.)
(2006). Antimicrobial Growth Promoters: Where Do We Go
From Here? Wageningen Academic Publishers, The
Netherlands.
Schwarz, S. and Chaslus-Dancla, E. (2001). Use of
antimicrobials in veterinary medicine and mechanisms of
resistance. Vet. Res. 32: 201–25.
Anonymous (2005). DANMAP 2004 – Use of antimicrobial
agents and occurrence of antimicrobial resistance in bacteria
from food animals, foods and humans in Denmark. Statens
Serum Institut, Danish Veterinary and Food Administration,
Danish Medicines Agency and Danish Institute for Food and
Veterinary Research; Copenhagen. Available at http://
www.danmap.org/pdfFiles/Danmap_2004.pdf