antimicrobes

1. Antibiotics: An Introduction
Dr Ravi Kant Agrawal, MVSc, PhD,
Senior Scientist (Veterinary Microbiology)
Food Microbiology Laboratory
Division of Livestock Products Technology
ICAR-Indian Veterinary Research Institute
Izatnagar 243122 (UP) India

2. Antibiotics and Antimicrobials
• Antibiotics: Greek words anti (against) and biotikos (concerning
life) refers to substances produced by microorganisms, which
selectively suppress the growth of or kill other microorganisms
at very low concentration.
• Chemotherapeutic agents: The use of drugs (chemical entity)
with selective toxicity against infections/ viruses, bacteria,
protozoa, fungi and helminthes.
• Antimicrobials: derived from the Greek words anti (against),
mikros (little) and bios (life) and refers to all agents of natural,
synthetic or semi-synthetic origin which at low concentrations
kill or inhibits the growth of microorganisms but causes little or
no host damage. Antimicrobials include both chemotherapeutic
agent + Antibiotics.

3. Antibiotics
• OLD: An antibiotic is a chemical substance produced by various
species of microorganisms that is capable in small
concentrations of inhibiting the growth of other
microorganisms.
• NEW: An antibiotic is a product produced by a microorganism
or a similar substance produced wholly or partially by chemical
synthesis, which in low concentrations, inhibits the growth of
other microorganisms.
• An antibiotic is a selective poison.
• It has been chosen so that it will kill the desired bacteria, but
not the cells in your body. Each different type of antibiotic
affects different bacteria in different ways.

4. History
 Use of substances with antimicrobial properties is known to have been
common practice for at least 2000 years.
 Ancient Egyptians and ancient Greeks used specific molds and plant extracts
to treat infection.
 Although, for centuries preparations derived from living matter were applied
to wounds to destroy infection, the fact that a microorganism is capable of
destroying one of another species was not established until the latter half of
the 19th cent when Pasteur noted the antagonistic effect of other bacteria
on the anthrax organism and pointed out that this action might be put to
therapeutic use.
 Microbiologists such as Louis Pasteur and Jules Francois Joubert observed
antagonism between some bacteria and discussed the merits of controlling
these interactions in medicine.
 Before Ehrlich Period:
 Chaulmoogra oil by hindus in leprosy.
 Cinchona bark for fever.
 Mouldy curd by chinese for boils.
 Chinese used artemisia for malaria treatment (1970-isolated Artemisinin).
 Mercury by Paracelsus for syphilis.
 Jordan people- used red soils to treat skin infections- isolated Actinomycetes
and many other antibiotic producing bacteria.

5. History……
Paul Ehrlich (Ehrlich Period – 1900-1930)
• The German chemist Paul Ehrlich developed the idea of selective
toxicity: that certain chemicals that would be toxic to some
organisms, e.g., infectious bacteria, would be harmless to other
organisms, e.g., humans.
• Paul Ehrlich - derived from finding that dyes used in
histochemistry became bound to cell-specific receptors. He
asked “Why can’t such dyes be toxic for specific organisms?”
• Paul Ehrlich, Alfred Bertheim and Sahachiro Hata (1910) looking
for something to target Treponema pallidum, developed
hundreds of organo-arsenic compounds from highly toxic drug
Atoxyl and 606th
compound tested was effective against syphilis.
• Hoechst - Salvarsan (Arsphenamine).
• First documented case of a chemical that could selectively kill
pathogens w/o permanently harming the human host.
• The concept of chemotherapy to treat microbial diseases was
born.
• Coined the term ‘CHEMOTHERAPY’
• NOBEL: 1908
• FATHER OF CHEMOTHERAPY
• He used the term ‘MAGIC BULLETS’
• MOA- still not known.

6. Post Ehrlich Period: 1930- till date
• Over the next 20 years, progress was made against a variety of
protozoal diseases, but little progress was made in finding
antibacterial agents untill introduction of Proflavine in 1934.
• Proflavine is a yellow coloured amino-acridine structure which
is particularly effective against deep wound bacterial infections.
• Used in world war II.
• Interesting drug as it targets bacterial DNA rather than protein.
• Despite success of this drug, it was not effective against
infections in Bloodstream and there was urgent need for agents
which could fight systemic infections.
History……
Proflavine

7. Post Ehrlich Period: 1930- till date
• Ehrlich approach of systematic screening of compounds became
the cornerstone of the pharma industry.
• This approach led to the discovery of Sulfonamidochrysoidine
(KI-730) – synthesized by Bayer chemists Josef Klarer and Fritz
Mietzsch and tested by Gerhard Domagk for antibacterial
activity.
• Marketed under the brand name Prontosil.
• Effective against streptococcal infections invivo.
• Prontosil was a prodrug and its active compound sulfanilamide
was not patentable as had been in use in dye industry.
• Cheap to produce, off-patent and easy to modify – many
companies started producing sulfonamide derivatives.
• NOBEL: 1939
History……

8. History….
Alexander Fleming
• In 1928, Sir Alexander Fleming, a Scottish
biologist, observed that Penicillium
notatum, a common mold, had destroyed
staphylococcus bacteria in culture.
• Fleming unable to purify compound
• NOBEL: 1945
• Penicillin was isolated in 1939 by Oxford
chemists Howard Florey and Ernst Chain.
• 1940: first clinical trials of penicillin were
performed.
• Mass production of penicillin started from
1945 and used during WWII.

9. Selman Waksman
• Soil Streptomyces make antibiotics
• Comes up with definition of antibiotic
• In 1944, Selman Waksman and Albert Schatz,
American microbiologists, isolated
streptomycin and a number of other
antibiotics from Streptomyces griseus.
• NOBEL: 1952
History……

10. • 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.
• 1960 onwards second
generation antibiotics like
Methicillin were discovered.
• Following this, semi synthetic
derivatives of older antibiotics
with more desirable properties
and different spectrum of
activity were produced e.g.
Fluoroquinolones,
Oxazolidinones etc.

11. 1900 1920 1940 1960 1980 2015
1900- Paul
Ehrilich
Chemotherapy
Animal model
developed
1908- Discovery
of Arsphenamine
1932- Prontosil-
First sulfonamide-
Bayer’s Laboratory
Gerhard Domagk 1939-
Sulfonamidochrysoidine
(Prontosil)
Alexander Fleming 1928-
Penicillin
1943- Nitrogen
mustard in
lymphomas
1948- Anitfolates
1951- Thiopurines
1958- Methotrexate
1957- 5-Fluorouracil
1959- Antitumor
antibiotics
1963 to 1970-
Treatment for
Hodgkin’s disease
1962- nalidixic acid
1997- Monoclonal
antibody approved
for the treatment of
tumor.
2005- Tyrosine kinase
inhibitors
2007- Target specific
screens
1996- Imatinib
Paul
Ehrilich
Father of
Chemotherapy
Timeline history of chemotherapy development
1944- Waksman et
al., discovered
streptomycin.
1963-
Vinca alkaloids

12. Between 1962 and 2000, no major classes of
antibiotics were introduced
Fischbach MA and Walsh CT, Science 2009
Methicillin

13. Timeline of antibiotic resistance
Penicillin
Penicillin resistant
S.aureus
Methicillin
MRSA
VRE VRSA
Vancomycin
Pencillin:1943, Resistance in 1947
within 4 years
Methicillin: 1959, resistance in 1961
Vancomycin: 1958
VRE:1987
VRSA:2002

14. The Ideal Drug*
1. Should have powerful action against MOs.
2. Selectively kill or inhibit the growth of pathogens - cause no damage to
the host - greater harm to microbes than host, done by interfering with
essential biological processes common in bacteria but not human cells.
3. Therapeutic index (the lowest dose toxic to the patient divided by the
dose typically used for therapy). High TI are less toxic to the patient.
4. Should not be inactivated rapidly by tissue enzymes or GI microflora
5. Should have good oral bio-availability
6. Should penetrate efficiently to various body tissues and fluids - reach
target site in body with effective concentration remain in specific tissues
in the body long enough to be effective
7. Favorable pharmacokinetics - drug interactions, how drug is distributed,
metabolized and excreted in body (unstable in acid, can it cross the
Blood-brain barrier, etc)
• Drugs differ in how they are distributed, metabolized and excreted
• Important factor for consideration when prescribing
• Rate of elimination of drug from body expressed in half-life -Time it
takes for the body to eliminate one half the original dose in serum
• Half-life dictates frequency of dosage
• Patients with liver or kidney damage tend to excrete drugs more slowly

15. 8. Desired Spectrum of activity: broad vs. narrow
• broad spectrum – wide
• Narrow spectrum - narrow range (pathogen must be ID’d)
9. Bactericidal vs. bacteriostatic
• Bacteriostatic drugs rely on host immunity to eliminate pathogen
• Bacteriocidal drugs are useful in situations when host defenses cannot be
relied upon to control pathogen
10. Should have a long elimination half life and not rapidly excreted by kidney
or bile
11. Should not interfere the host immune mechanism
12. Should not show adverse drug interactions with other antimicrobial drugs
Combination some times used to treat infections
When action of one drug enhances another, effect is synergistic
When action of one drug interferes with another, effect is antagonistic
When effect of combination is neither synergistic or antagonistic, effect said
to be additive
13. Should have no/short withdrawl time in food producing animals.
14. Little resistance development- Should not favour bacterial resistance and
show cross resistance with other antimicrobial agents
15. Stable when stored in solid or liquid form
16. Affordable and easily available
17. Lack of “side effects” allergic, toxic side effects, suppress normal flora
• Allergic reactions: Allergies to penicillin
• Toxic effects: Aplastic anemia- Body cannot make RBC or WBC
• Suppression of normal flora
• Antibiotic associated colitis
* There is no perfect drug

16. Classification of antimicrobials
A. Chemical structure
B. Mechanism of action
C. Type of organisms (against which primarily active)
D. Spectrum of activity
E. Type of action (bacteriostatic and bactericidal)
F. Source of antibiotics

17. A. Chemical structure
• Sulfonamides and related drugs: Dapsone (DDS), Sulfadiazine,
Paraaminosalicylic acid (PAS)
• Diaminopyrimidines: Trimethoprim, Pyrimethamine
• Quinolones: Nalidixic acid, Norfloxacin, Ciprofloxacin
• Beta lactam antibiotics: Penicillins, Cephalosporins
• Tetracyclines: Oxytetracycline, Doxycycline
• Nitrobenzene derivative: Chloramphenicol
• Aminoglycosides: Streptomycin, Gentamycin, Amikacin,
Neomycin
• Macrolides antibiotics: Erythromycin, Clarithromycin,
Azithromycin
• Lincosamide antibiotics: Clindamycin
• Glycopeptide antibiotics: Vancomycin
• Polypeptide antibiotics: Polymyxin-B, Bacitracin, Tyrothricin
• Nitrofuran derivatives: Nitrofurantoin
• Nitroimidazoles: Metronidazole, Tinidazole
• Nicotinic acid derivatives: Isoniazid, Pyrezinamide, Ethionamide
• Polyene antibiotics: Amphotericin-B, Nystatin, Hamycin
• Azole derivatives: Miconazole, Clotrimazole, Ketoconazole,
Fluconazole
• Others: Rifampin, Ethambutol, Griseofulvin

18. B. Mechanism of action
THFA
PABA
Ribosomes
cell
membrane
metabolism
Cell wall synthesis m-RNA code
protein
synthesis
DNA gyrase

19. B. Mechanism of action
THFA
PABA
Ribosomes
Inhibition of
protein
synthesis
Inhibition of DNA
gyrase
Inhibition of
metabolism
Inhibition of
Cell wall synthesis
Sulfonamides
Sulfones
Trimethoprim
PAS
Pyrimethamine
Ethumbutol
Beta-lactams
Cephalosporins
Vancomycin
Tetracyclines
Aminoglycosides
Macrolides
Clindamycin
Chloramphenicol
Fluoroquinolones
Inhibition of Cell
Membrane
Leakage form cell
membrane
Polypeptides - Polymyxines,
colistin.
Polyenes- Amphotericin B,
Nystatin, Hamycin
Fluoroquinolones
Rifampin
Misreading of
m-RNA code
Aminoglycosides-
Streptomycin,
Gentamicin

20. C. Type of organisms (against which primarily active)
• Antibacterial: Penicillins, Aminoglycosides, Erythromycin, etc.
• Antiviral: Acyclovir, Amantadine B, Zidovudine, etc.
• Antifungal: Griseofulvin, Amphotericin B, Ketoconazole, etc.
• Antiprotozoal: Chloroquine, Pyrimethamine, Metronidazole,
etc.
• Anthelminthic: Mebendazole, Niclosamide, Diethyl
carbamazine, etc.

21. D. Spectrum of activity
Narrow-spectrum
Penicillin G, Streptomycin,
Erythromycin
Broad-spectrum
Tetracyclines,
Chloramphenicol
effective against specific
type of bacteria
either gram-positive or
gram-negative
effective against a wide
range of bacteria,
both gram-positive and
gram-negative

22. D. Type of action
(bacteriostatic and bactericidal)
Bacteriostatic:
Inhibit the growth of Bacteria.
E.g.: Sulfonamides, Tetracyclines,
Chloramphenicol, Erythromycin,
Ethambutol
Bactericidal:
Kill the microbes.
E.g.: Penicillins, Aminoglycosides,
Polypeptides, Rifampin, Isoniazid,
Vancomycin, Ciprofloxacin, Metronidazole,
Cotrimoxazole
Note: Some b’static drugs may act as
bactericidal at high concentration
(Sulfonamides, nitrofurantion)

23. E. Source of antibiotics
• Fungi: Penicillin, Griseofulvin, Cephalosporin
• Bacteria: Polymyxin B, Tyrothricin, Colistin, Aztreonam,
Bacitracin
• Actinomycetes: Aminoglycosides, Macrolides, Tetracyclines,
Polyenes, Chloramphenicol

24. Principles of antimicrobial therapy
• Diagnosis: Site of infection, responsible organism,
sensitivity of drug
• Decide- chemotherapy is necessary: Acute
infection require chemotherapy whilst chronic infections
may not. The chronic abscess respond poorly, although
chemotherapy cover is essential if surgery is undertaken
to avoid a flare-up of infection.
• Select the drug: Specificity (spectrum of activity,
antimicrobial activity of drug), pharmacokinetic factors
(physiochemical properties of the drug) , patient related
factors (allergy, renal disease)

25. Principles of antimicrobial therapy
Cont.,
• Frequency and duration of drug administration: Inadequate dose
may develop resistance, intermediate dose may not cure infection,
optimize dose should be used for therapy.
• Continue therapy: Acute infection treated for 5-10 days. But some of
the bacterial infection exceptions to this. E.g.: Typhoid fever, tuberculosis
and infective endocarditis (after clinical cure, the therapy is continued to
avoid relapse).
• Test for cure: After therapy, symptoms and signs may disappear before
pathogen eradicated.
• Prophylactic chemotherapy: To avoid surgical site infections.

26. Choice of an antimicrobial agents
Patient related factors
Drug factors
Organism-related considerations

27. Choice of an antimicrobial agents
Patient related factors:
• Patient age (chloramphenicol produce gray baby syndrome in
newborn; Tetracyclines deposition in teeth and bone-below the
age of 6 years)
• Renal and hepatic function (aminoglycoside, vancomycin- renal
failure; erythromycin, tetracycline- liver failure)
• Drug allergy (History of known AMAs allergy should be obtained) .
– Syphilis patient allergic to penicillin – drug of choice is tetracycline
– Fluoroquinolones cause erythema multiforme
• Impaired host defense

28. Choice of an antimicrobial agents
Cont.,
Drug factor:
• Pregnancy
– All AMAs should be avoided in the pregnant
– many cephalosporins and erythromycin are safe, while safety data on
most others is not available.
• Genetic factors
– Primaquine, sulfonamide, fluoroquinolones likely to produce haemolysis
in G-6-PD deficient patient)
• Spectrum of activity (Narrow/ broad spectrum)
• Type of activity (bactericidal/ bacteriostatic)
• Sensitivity of the organism (MIC)
• Relative toxicity
• Pharmacokinetic profile
• Route of administration
• Cost

29. Choice of an antimicrobial agents
Cont.,
Organism-related considerations:
• A clinical diagnosis should first be made, and the choice of the
AMAs selected
• Clinical diagnosis itself directs choice of the AMA
• Choice to be based on bacteriological examination (Bacteriological
sensitivity testing)

30. Problems with AMAs
Toxicity
Hypersensitivity
reaction
Drug
resistance
Superinfection
Drug tolerant

31. Toxicity
Local irritancy:
• exerted site of administration e.g. Gastric irritation, pain and abscess formation at the
site of i.m. inection, thrombo-phlebitis of injected vein.
Systemic toxicity:
• Dose related organ damage.
– High therapeutic index agents may not damage host cells, E.g.: penicillin,
erythromycin.
– The agent which have low therapeutic index exhibits more toxicity.
– Very low therapeutic index drug is used when no suitable alternative AMAs
available. E.g.: Vancomycin - hearing loss, kidney damage, “red man’ syndrome;
polymyxin B - neurological and renal toxicity
aminoglycosides
(renal and CNS toxicity)
tetracycline
(liver and renal toxicity)
chloramphenicol
(bone marrow depression)

32. Hypersensitivity reaction
• All AMAs are capable to causing hypersensitive reaction, and
this this reactions are unpredictable and unrelated to dose. E.g.:
Penicillin induced anaphylactic shock (prick skin testing)
Inj. Penicillin induced
anaphylactic shock
To avoid
Perform sensitivity test before
administering penicillin Inj.

33. Drug Tolerance
• Loss of affinity of target biomolecule of the microorganism with
particular AMAs, E.g.: Penicillin resistance to Pneumococcal
strain (alteration of penicillin binding proteins)
Drug target site Change in protein
configuration - loss of
affinity

34. Superinfection (Suprainfection)
• A new infection occurring in a patient having a preexisting infection.
• Development of superinfection associated with the use of broad/
extended-spectrum of antibiotics, such as tetracyclines, chloramphenicol,
ampicillin and newer cephalosporins.
• Superinfections are more common when host defense is compromised.
• Superinfections are generally most difficult to treat.
– bacterial superinfection in viral respiratory disease
– infection of a chronic hepatitis B carrier with hepatitis D virus
– Piperacillin-tazobactam may cause superinfection with Candida

35. Superinfection
Cont.,
• Treatment for superinfection
– Candida albicans: Monilial diarrhoea, Candidal vulvovaginitis or vaginal
thrush (an infection of the vagina's mucous membranes) treat with
nystain or clotrimazole
– Resistant Staphylococci: treat with coxacillin or its congeners
– Pseudomonas: Urinary tract infection, treat with carbenicillin, piperacillin
or gentamicin.
• Superinfections minimized by
– using specific (narrow-spectrum) AMA (whenever possible)
– avoid using (do not use) antimicrobials to treat self limiting or
untreatable (viral) infection
– avoid prolong antimicrobial therapy.

36. Resistance
• Unresponsiveness of a microorganism to an AMA, and is similar
to the phenomenon of drug tolerance.
– Natural resistance
– Acquired resistance
• Natural resistance: Some microbes have resistant to certain
AMAs. E.g.: Gram negative bacilli not affected by penicillin G; M.
tuberculosis insensitive to tetracyclines.
• Acquired resistance: Development of resistance by an organism
(which was sensitive before) due to the use of AMA over a period
of time. E.g.: Staphylococci, tubercle bacilli develop resistance to
penicillin (widespread use for >50 yr). Gonococci quickly
developed resistant to sulfonamides in 30 yr.

37. COMMON MODES OF ANTIMICROBIAL RESISTANCE
e.g.
Penicillins
e.g. aminoglycosides
, chloramphenicol &
penicillins
e.g.tetracyclines
e.g. aminoglycosides &
tetracyclines

38. Acquired Resistance
Cont.,
Development of resistance
•Resistance mainly developed by mutation or gene transfer.
•Mutation: Resistance developed by mutation is stable and
heritable genetic changes that occurs spontaneously and randomly
among microorganism (usually on plasmids).
•Mutation resistance may be single step or multistep.
– Single gene mutation may confer high degree of resistance. E.g.:
enterococci to streptomycin
– Multistep mutation may modify the more number of gene that will
decreases the sensitivity of AMAs to pathogens.

39. • Development of resistance
• Gene transfer (Infectious resistance): From one organism to
another organism.
– Conjugation
– Transduction
– Transformation
Transposon
donor
a
b
a a a
b
b b
Plasmid
cointegrate
Transfer of resistance genetic elements within the bacterium
Resistance
Cont.,

40. Gene transfer - Conjugation:
• cell-to-cell contact; transfer of chromosomal or
extrachromosomal DNA from one bacterium to another
through sex pili.
• The gene carrying the resistance or ‘R’ factor is
transferred only if another “resistance transfer factor”
(RTF) is present.
• This will frequently occurs in gram negative bacilli.
• The nonpathogenic organisms may transfer ‘R’ factor to
pathogenic organisms, which may become wide spread by
contamination of food and water.
•The multidrug resistance has occurred by conjugation.
– Chloramphenicol resistance to typhoid bacilli
– Penicillin resistance to Haemophilus, gonococci
– Streptomycin resistance to E. coli
Resistance
Cont.,

41. Development of resistance Gene
transfer - Transduction:
•Transfer resistance gene through
bacteriophage (bacterial virus) to
another bacteria of same species.
– E.g.: Transmission of resistance gene
between strains of staphylococci and
between strains of streptococci.
Resistance
Cont.,

42. Development of resistance
Gene transfer - Transformation:
• It will occur in natural conditions.
• Bacteria taking up naked DNA form its environment and
incorporating it into its genome through the normal cross-over
mechanism.
Resistance
Cont.,

43. Combined use of antimicrobials
• To achieve synergism, Rifampin+ isoniazid for tuberculosis
•
• To reduce severity or incidence of adverse effects, Amphotericin
B + rifampin (rifampin enhance the antifungal activity of
amphotericin B)
• To prevent resistance (Concomitant administration of rifampin
and ciprofloxacin prevents Staph. aureus resistance
ciprofloxacin)
• To broaden the spectrum of antimicrobial action (cotrimoxazole:
Trimethoprim/sulfamethoxazole)

44. Prophylactic use of antimicrobials
• Prophylaxis against specific organisms (Cholera: tetracycline
prophylaxis; Malaria: for travelers to endemic area may take
chloroquine/ mefloquine)
• Prevention of infection in high risk situations
• Prophylaxis of surgical site infection

45. Failure of antimicrobial therapy
• Improper selection of AMAs, dose, route or duration of
treatment.
• Treatment begun too late
• Failure to take necessary adjuvant measures
• Poor host defense
• Trying to treat untreatable (viral) infections
• Presence of dormant or altered organisms which later give risk
to a relapse

46. 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

47. A Changing Landscape for
Numbers of Approved Antibacterial Agents
Bars represent number of new antimicrobial agents approved by the FDA during the period listed.
0
0
2
4
6
8
10
12
14
16
18
Number
of
agents
approved
1983-87 1988-92 1993-97 1998-02 2003-05 2008
Infectious Diseases Society of America. Bad Bugs, No Drugs. July 2004; Spellberg B et al. Clin Infect Dis. 2004;38:1279-1286;
New antimicrobial agents. Antimicrob Agents Chemother. 2006;50:1912
Resistance

48. Common side effects with
chemotherapeutics agents
Think before dispensing
Thank U

50. Antimicrobials Targets
z

51. Disinfection
Disinfection is the process that reduces the number of
potential pathogens on a material until they no longer
represent a hazard.
• Disinfection is complex of measures that are directed
to prevention spread of microorganisms which can be
agent of disease.
• Disinfection, refers to the use of a physical process or a
chemical agent (a disinfectant) to destroy vegetative
pathogens but not bacterial endospores. It is
important to note that disinfectants are normally used
only on inanimate objects because, in the
concentration required to be effective, they can be
toxic to human and other animal tissue.

52. Asepsis
asepsis refers to any practice that prevents the
entry of infectious agents onto sterile tissues
and thus prevent infection
• Aseptic techniques commonly practiced in
health care range from sterile methods that
exclude all microbes to antisepsis.

53. Antisepsis
is the complex of procedures of growth inhibition and
reproduction potential pathogenic microorganisms
on skin of mucous membrane
• In antisepsis, chemical agents called antiseptics are
applied directly to exposed body surfaces (skin and
mucous membrane), wounds, and surgical incisions
to destroy or inhibit vegetative pathogens. Examples
of antisepsis include preparing the skin before
surgical incision with iodine compounds

54. Microbial
Sources of
Antibiotics

55. Administration of Antibiotics

56. MECHANISMS OF ACTION
• Inhibitors of cell wall synthesis
• Inhibitors of protein synthesis
• Inhibitors of nucleic acid (replication/transcription/other
mechanism)
• Drugs altering cell membranes
• Anti-metabolites

57. Antibiotics: Mechanisms of Action
Transcription
Translation
Translation
Alteration of
Cell Membrane
Polymyxins
Bacitracin
Neomycin

58. Categories antimicrobial agents based
on their application
Term Description Examples
Disinfec-
tant
Agent that kills microorganisms on
inanimate objects
Hypochlorite,
formaldehyde
Antiseptic Agent that kills of prevents the growth of
microorganisms on lining tissues
Soap, hydrogen
peroxide, iodine,
ethanol
Sanitizer A disinfectant that is used to reduce
numbers of bacteria to levels judged safe
by public health officials
Ethanol
Preserva-
tive
Agents that prevents microbial growth:
often added to products such as foods and
cosmetics to prevent microbial growth
Lactic acid,
benzoic acid,
sodium chloride
Antibiotic Agent produced by microorganisms that
inhibits or kills other microorganisms
Penicillin,
tetracycline

59. The action of antimicrobial agents
Term Action Examples
Bactericide Agent that kills bacteria Chlorhexidine,
ethanol
Biocide Agent that kills living organisms Hypochlorite
Fungicide Agent that kills fungi Ethanol
Germicide
(microbicide)
Chemical agent that specifically
kills pathogenic
microorganisms
Formaldehyde,
silver, mercury
Sporicide Agent that kills bacterial
endospores
Glutaraldehyde
Virucide Inactivates viruses so that they
lose the ability to replicate
Cationic detergents

60. Antimicrobial agents
Disinfectants and
antiseptics
Can kill or inhibit growth and
development majority of
microorganisms in space around
patient, and microorganisms that are
on human body surface
Chemotherapeuti
c medicines
Can kill or inhibit reproduction of
agents of disease in the patient
organism. Have selective influence
upon microorganisms.

61. Classification of disinfectants based on
their mode of action
Mode of action Type of disinfectant
Coagulate proteins Formaldehyde,
glutaraldehyde, alcohols,
dyes, mercurials, acids
Oxidize proteins Halogens: iodine, iodophors,
chlorine, chlorine compoynds
Destroys cell membrane Phenolics, quaternary
ammonium compounds
(surface-active agents)

62. Chemotherapy
is a method of therapy of infectious disease
and cancer with chemical agents –
chemotherapeutic medicines

63. Chemotherapeutic index
Maximal tolerated dose is the most quantity of drug
that not cause harmful effect in a patient.
Minimal curative dose is the least dose of drug that
kill of inhibit reproduction of microorganisms
Maximal tolerated dose
Minimal curative dose
> 3

64. Paul Ehrlich’s principles of chemotherapy
Paul Ehrlich have provided principled of chemotherapy.
Receptor interaction of drug and microorganism
Changing of chemical structure of drug causes change of its
activity
Changing of drug structure can occur in microorganism’s cell,
therapeutic effect can slacken or intensify during it
Microbes can develop drug resistance to medicine
The drug can be used only if its chemotherapeutic index is not
less three.

65. Community
interactions
Mutualism
Commensalism
Parasitism
Antagonism
(competition)
Synergism
Predation

66. Antagonism (ammensalism)
Antagonism is a form interaction between
organisms when one microorganisms inhibits
development of others
Mechanisms of antagonism:
Competition for nutrient substrate (different spread of
growth)
Excretion of acids, alcohols, ammonia by microorganisms-
antagonist
Excretion antibiotics, bacteriocines by microorganisms-
antagonist
Predation

67. Antibiotic
Chemotherapeutic preparation produced by
living organisms or their synthetic analogs
that can selectively inhibit disease agents or
inhibit growth tumor cells in patient organism

68. Characteristics of successful
antimicrobial drugs
Great activity against microbes
Selectively toxic to the microbe but nontoxic to host cells
Microbicidal rather than mocrobistatic
Relatively soluble and functions even when highly diluted
in body fluids
Remains potent long enough to act and is not broken down
or excreted prematurely
Not subject to the debelopment of antimicrobial resistance
Complements or assists the activities of the host’s
defenses
Remains active despite the presence of large volumes of
organic materials
It is readily delivered to the site of infection
Does not disrupt the host’s health by causing allergies or
predisposing the host to other infections

69. Classification based on type of
antibiotic action
Microbistatic (bacteriostatic,
fungistatic) agents prevent the growth of
microorganisms (bacteria, fungi)
Microbicidal agent (bactericide,
virucide, fungicide) kills microorganisms
(bacteria, viruses, fungi)

70. Categories based on group of organisms
that produce of antibiotics
Producers Antibiotics
Bacteria Polmyxyn
Fungi Penicillin, cephalosporin
Actinomycetes Streptomycin, tetracycline
Plants Imanin, salvin,
Animals Lysocim

71. Classification of antibiotics based on
spectrum of action
Narrow-spectrum agents are effective against a
limited array of different microbial types (examples:
bacitracin inhibit certain gram-positive bacteria)
Broad-spectrum agents are active against a wider
range of different microbes (example – tetracycline that
affect upon gram-positive and gram-negative bacteria,
rickettsias, mycoplasmas)

72. Principles of antimicrobial therapy

73. Classification of antimicrobials

74. Classification of antimicrobials
A. Chemical structure
B. Mechanism of action
C. Type of organisms (against which primarily active)
D. Spectrum of activity
E. Type of action (bacteriostatic and bactericidal)
F. Source of antibiotics

75. A. Chemical structure
• Sulfonamides and related drugs: Dapsone (DDS), Sulfadiazine,
Paraaminosalicylic acid (PAS)
• Diaminopyrimidines: Trimethoprim, Pyrimethamine
• Quinolones: Nalidixic acid, Norfloxacin, Ciprofloxacin
• Beta lactam antibiotics: Penicillins, Cephalosporins
• Tetracyclines: Oxytetracycline, Doxycycline
• Nitrobenzene derivative: Chloramphenicol
• Aminoglycosides: Streptomycin, Gentamycin, Amikacin, Neomycin
• Macrolides antibiotics: Erythromycin, Clanthromycin, Azithromycin

76. A. Chemical structure
Cont.,
• Lincosamide antibiotics: Clindamycin
• Glycopeptide antibiotics: Vancomycin
• Polypeptide antibiotics: Polymyxin-B, Bacitracin, Tyrothricin
• Nitrofuran derivatives: Nitrofurantoin
• Nitroimidazoles: Metronidazole, Tinidazole
• Nicotinic acid derivatives: Isoniazid, Pyrczinamide, Ethionamide
• Polyene antibiotics: Amphotericin-B, Nystatin, Hamycin
• Azole derivatives: Miconazole, Clotrimazole, Ketoconazole, Fluconazole
• Others: Rifampin, Ethambutol, Griseofulvin

77. B. Mechanism of action
THFA
PABA
Ribosomes
cell
membrane
metabolism
Cell wall synthesis m-RNA code
protein
synthesis
DNA gyrase

78. B. Mechanism of action
Cont.,
THFA
PABA
Ribosomes
Inhibition of
protein
synthesis
Inhibition of DNA
gyrase
Inhibition of
metabolism
Inhibition of
Cell wall synthesis
Sulfonamides
Sulfones
Trimethoprim
PAS
Pyrimethamine
Ethumbutol Beta-lactams
Cephalosporins
Vancomycin
Tetracyclines
Aminoglycosides
Macrolides
Clindamycin
Chloramphenicol
Fluoroquinolones
Inhibition of Cell
Membrane
Leakage form
cell membrane
Polypeptides- Polymyxines,
colistin.
Polyenes- Amphotericin B,
Nystatin, Hamycin Fluoroquinolones
Rifampin
Misreading of
m-RNA code
Aminoglycosides-
Streptomycin,
Gentamicin

79. C. Type of organisms (against which primarily active)
• Antibacterial: Penicillins, Aminoglycosides, Erythromycin,
etc.
• Antiviral: Acyclovir, Amantadine B, Zidovudine, etc.
• Antifungal: Griseofulvin, Amphotericin B, Ketoconazole, etc.
• Antiprotozoal: Chloroquine, Pyrimethamine, Metronidazole,
etc.
• Anthelminthic: Mebendazole, Niclosamide, Diethyl
carbamazine, etc.

80. D. Spectrum of activity
Narrow-spectrum
Penicillin G, Streptomycin,
Erythromycin
Broad-spectrum
Tetracyclines,
Chloramphenicol
effective against specific
type of bacteria
either gram-positive or
gram-negative
effective against a wide
range of bacteria,
both gram-positive and
gram-negative

81. D. Type of action
(bacteriostatic and bactericidal)
Bacteriostatic:
Inhibit the growth of Bacteria.
E.g.: Sulfonamides, Tetracyclines,
Chloramphenicol, Erythromycin,
Ethambutol
Bactericidal:
Kill the microbes.
E.g.: Penicillins, Aminoglycosides,
Polypeptides, Rifampin, Isoniazid,
Vancomycin, Ciprofloxacin, Metronidazole,
Cotrimoxazole
Note: Some b’static drugs may act
b’cidal at high concentration
(Sulfonamides, nitrofurantion)

82. E. Source of antibiotics
• Fungi: Penicillin, Griseofulvin, Cephalosporin
• Bacteria: Polymyxin B, Tyrothricin, Colistin, Aztreonam,
Bacitracin
• Actinomycetes: Aminoglycosides, Macrolides, Tetracyclines,
Polyenes, Chloramphenicol

83. Choice of an antimicrobial agents
Patient related factors
Drug factors
Organism-related considerations

84. Choice of an antimicrobial agents
Patient related factors:
•Patient age (chloramphenicol produce gray baby syndrome in
newborn; Tetracyclines deposition in teeth and bone-below the
age of 6 years)
•Renal and hepatic function (aminoglycoside, vancomycin- renal
failure; erythromycin, tetracycline- liver failure)
•Drug allergy (History of known AMAs allergy should be
obtained) .
– Syphilis patient allergic to penicillin – drug of choice is tetracycline
– Fluoroquinolones cause erythema multiforme
•Impaired host defence

85. Choice of an antimicrobial agents
Cont.,
Drug factor:
•Pregnancy
– All AMAs should be avoided in the pregnant
– many cephalosporins and erythromycin are safe, while safety data on
most others is not available.
•Genetic factors
– Primaquine, sulfonamide fluoroquinolones likely to produce
haemolysis in G-6-PD deficient patient)

86. Choice of an antimicrobial agents
Cont.,
Organism-related considerations:
•A clinical diagnosis should first be made, and the choice of the
AMAs selected
•Clinical diagnosis itself directs choice of the AMA
•Choice to be based on bacteriological examination
(Bacteriological sensitivity testing)

87. Choice of an antimicrobial agents
Cont.,
Drug factor:
•Spectrum of activity (Narrow/ broad spectrum)
•Type of activity
•Sensitivity o f the organism (MIC)
•Relative toxicity
•Pharmacokinetic profile
•Route of administration
•Cost