just for you nina from sunsheroo

1. Bacteriology 1
Its only for you Ninaa

2. ..
Hrant Ourgandjian, M.D.
Medical Manager

3. Grouping (Micro-organisms)
Micro-organisms can be divided into 4
important groups:
 1. Bacteria
 2. Protozoa
 3. Fungi
 4. Viruses

4. Bacteria
 Size: variable depending on the species.
 Nucleus: no. Mass of DNA without nuclear
membrane, formed by a single chromosome.
 Cell wall: yes, formed of liposaccharides and
lipoproteins
DEFINITIONS

5. Bacteria
Bacteria are small single celled organisms that are
not visible to the naked eye and have a very
primitive structure.

6. Microscopic parasites
or Protozoan
 Kingdom : animal,
 Nucleus : true,
 Example : Entamoeba histolytica = Ameba
Amebiasis

7. Protozoa
Protozoa (eg amoeba) are more complex
than bacteria in structure.

8. Fungi
 Kingdom: vegetable,
 Size : a few microns,
 Nucleus : true.
 2 types : yeasts and
dermatophytes
 Example of yeasts : Candida albicans
Mycosis

9. FUNGI
Fungi resemble primitive plants and live on dead
organic matter they can exist as single cells (yeast) or as
many cells (called mycelium)

10. Virus
 Size: between 20 and 200 millimicrons
(visible under the electron microscope),
 Nucleus : no. Nucleic acid core
(DNA or RNA) contained in an
envelope (capsid).
 They invade the human, bacterial, plant or animal
cells to survive Example : Myxovirus = Flu virus

11. VIRUSES
Viruses are the smallest and simplest of all organisms
and can only be seen with powerful electron
microscopes. Viruses cannot multiply by themselves and
so have to invade host cells to allow multiplication.

12. Bacterial structure
 Constant Elements :
Bacterial "nucleus"
= chromosomic DNA
Cell wall
Cytoplasmic
membrane
Cytoplasm
Ribosomes
(synthesis of proteins and nutritive reserves of the bacterium)

13.  Optional elements :
Bacterial structure
Pili
(tissue binding,
transmission of plasmids)
Plasmid (DNA fragments carrying genes of resistance)
Flagella
(motility)
Capsule
(resistance to phagocytosis)

14.  Characteristics of all bacteria:
 All bacteria possess 5 basic components:
- Cell wall
- Cytoplasmic membrane
- Cytoplasm
- Ribosomes
- Nuclear material
 Some bacteria possess:
- Flagella
- Pili
- Capsules

16. Ribosome

17. Flagella, and pili

18. BACTERIOLOGY :
Identification of the bacterium ?
Metabolism
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19.  Bacterial classification
Difficulty in classification: Unlike higher
organisms, bacteria lack sufficient variations
in structure upon which normal classifications
can be made. Basic criteria Most of the
systems developed to classify bacteria utilise
these diagnostic criteria
- Shape (morphology) and culture
characteristics
- Staining – Gram Stain
- Culturing and biochemical tests
- Growth requirement for oxygen; i.e. aerobic or
anaerobic

20. Shapes of bacteria
1. Identification by shape

21. Cocci (spheres)

22. Bacilli (rods)

23. Vibrio (short curved rods)

24. Spirochetes (long twisting
filaments): syphilis, leptospirosis

25. GRAM STAIN

27. Gram staining
Gram + Gram -
BACTERIOLOGY :
2. Identification staining the cell wall
External membrane
Peptidoglycane
Cytoplasmic membrane
Pores
PBP
Optional capsule

28. BACTERIOLOGY:
3. Identification by metabolism
 METABOLISM
Strict aerobe Aero-anaerobe Strict anaerobe
(use oxygen to metabolise glucose) (use fermentation to metabolise glucose)
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29. BACTERIOLOGY:
Synthesis / Identification
Shape
Cocci
Bacillus
Stain Gram + Gram -
Bacillus + Bacillus -
Cocci + Cocci -

30. BACTERIOLOGY:
Classification of Bacteria
 Anaerobes
Cocci Bacillus
+ +
- -
 Aerobes
Cocci Bacillus
+ +
- -

31.  Genus :
Haemophilus Streptococcus
 Species :
influenzae para influenzae pneumo- b hemolytic group B
coccus group A group C
group D etc.
 Serotypes :
a, b, c, d, etc etc. 23F,9, 6,14 etc.
(+ of 80 different serotypes) (+ of 80 different serotypes)
 The bacterial strain is a colony resulting from a sample and a
particular serotype, obtained from sucessive subcultures ("clones").
BACTERIOLOGY:
Concept of bacterial strain

32. Aerobic Pathogens
COCCI +
• Staphylococcus:
– aureus
– epidermidis
• Streptococcus:
– S. pneumoniae
– S. group A b hemolytic
– S. group B
– S. viridans
– S. group D = S. foecalis
COCCI -
• Neisseriae:
– meningitidis
– gonorrhae
• Moraxella catarrhalis

33. BACILLI +
• Corynebacterium
diphteriae
• Listeria monocytogenes
• Haemophilus
influenzae
• Pseudomonas
aeruginosa
• Vibrio cholerae
• Brucella
• Acinetobacter
• Helicobacter
• Mycobacteria
Aerobic Pathogens
BACILLI -
ENTEROBACTERIA:
• Escherichia coli
• Proteus
• Serratia
• Klebsiella
• Enterobacter
• Citrobacter
• Salmonella
• Shigella
• Yersinia

34. COCCI +
• Peptococcus
• Peptostreptococcus
COCCI -
• Veillonella
BACILLI +
• Clostridium :
– C. difficile
– C. botulinum
– C. perfringens
– C. tetani
• Propionobacterium
– Corynebacterium acnes
BACILLI-
• Bacteroides fragilis
• fusobacterium
Anaerobic Pathogens

35. Pathogens with intra-cellular
development
• Mycoplasmae :
– Mycoplasma pneumoniae
• Chlamydiae :
– Chlamydia pneumoniae
• Legionella
• Rickettsiae
Miscellaneous pathogens
Spirochaetas
• Treponema pallidum
• Theptospires
• Mycobacterium
tuberculosis (KB)

36. DEFINITIONS
 INFECTION =
A sequence of repercussions which result in an attack on
a living organism by a ± virulent pathogen.
Endogen or exogen
Infection involves 3 actors :
PATHOGEN
HOST THERAPY

37. DEFINITIONS
INFECTION
2 types of clinical sign:
Typical symptoms Local symptoms
The symptoms indicate
the illness and
the pathogen responsible.
An organ is suffering.
Experience points
to a pathogen.

38. Streptococcus pneumoniae
Gram + Cocci
 HABITAT: Commensal (organism that derives
food or other benefits from another organism
without hurting or helping it (50 % of individual
carriers, and more in winter).
 PATHOGENIC POWER: Very virulent
(capsule),
– leader as regards mortality of bacterial origin,
– responsible for the majority of cases of acute
lobar pneumonia, otitis, adult meningitis,
sinusitis

39. Gr A b hemolytic streptococcus
Gram + Cocci
 HABITAT: Strictly human bacterium.
Commensal
 PATHOGENIC POWER: Very virulent (capsule, toxin etc.),
responsible for ENT (tonsillitis, otitis etc.) and cutaneous
infections (impetigo, erysipelas etc.)
COMPLICATIONS: rheumatic fever, glomerulonephritis, endocarditis

40. Staphylococcus aureus
Gram + Cocci
 HABITAT: Human, soil, air, water.
 PATHOGENIC POWER: Very virulent (capsule, toxins,
enzymes, etc.), responsible for cutaneous, osseous, pulmonary
and cerebral infections, and for superinfection after
severe burns. Responsible for septicemia and endocarditis.

41. Haemophilus Influenzae
Gram - Bacillus
 HABITAT: Flora of upper respiratory tract. 75% of children under
5 are healthy carriers.
 PATHOGENIC POWER: 35 to 50% of otitis, sinusitis,
rhinopharyngitis, superinfection of chronic bronchitis or of viral
illnesses. Meningitis and septicemia are due to encapsulated forms
(H.i.b.). A vaccine against encapsulated Haemophilus exists.
The vaccination must be performed at the age of 3 to 4 months
with a booster at 14 or 16 months to be effective.

42. Moraxella catarrhalis
Gram - Cocci
 HABITAT: Commensal of the respiratory mucus.
 PATHOGENIC POWER: Superinfection of chronic bronchitis,
otitis, sinusitis

43. Neisseriae gonorrhoeae
Gram - Cocci
 HABITAT: Human parasite
 PATHOGENIC POWER: Blennorrhagia, salpingitis,
pharyngeal gonococci

44. Salmonella
Gram - Bacillus (enterobacteria)
 HABITAT: Parasite of the human and animal digestive tract.
Contamination by oral route.
 PATHOGENIC POWER:
 Digestive forms : Toxi-infections (gastro-enteritis)
 Septicemic forms : Typhoid (S.typhi) or paratyphoid
(S.paratyphi) fever
The septicemic forms can become complicated (pulmonary, meningeal,
osseous, digestive infections etc

45. Shigella
Gram - Bacillus (enterobacteria)
 HABITAT: Human digestive tract. Contamination through food, or
water contaminated with fecal matter.
 PATHOGENIC POWER: Infectious colitis, gastro-enteritis
(children). Bacillary dysentery (army on march).

46. Escherichia Coli
Gram - Bacillus (enterobacteria)
 HABITAT: Normally found in human digestive tract.
 PATHOGENIC POWER:
 Intestinal infections: Infectious diarrhea
 Urinary infections: Responsible in up to 90%
 Abdominal infections: Peritonitis, salpingitis,
cholecystitis
 Meningeal infections: Meningitis in infants or elderly
patients

47. Mycoplasma pneumoniae
 HABITAT: Micro-organisms without cell wall, intracellular or
associated to cells; vegetable, animal, and human parasite.
 PATHOGENIC POWER:
 Atypical pneumonia : Young adults, particularly in fall
and winter.

48. Intracellular
Chlamydia
 HABITAT: Strict intracellular parasite of small size.
 3 SPECIES: Chlamydia pneumoniae
Chlamydia psittaci
Chlamydia trachomatis
 TREATMENT: Macrolides, fluoroquinolones
 Non specific urethritis (50% of cases)
 Post-gonococcal urethritis (20 to 60% of cases)
 Cervicitis, salpingitis, rectitis
 Pneumonias in newborn babies
 Conjunctivitis in newborn babies and adults

49. Intracellular
Legionella pneumophila
 HABITAT: Bacterium of the environment (lake water, air
conditioning). The entry port for the infection is pulmonary.
 PATHOGENIC POWER:
 Acute pneumonia: pseudo-flu state, dry cough, gastro-
intestinal disorders etc.
Especially in debilitated subjects of + 50 ans (tabacco, alcohol,
immunodepression)
Pathology fatal without treatment: 20% of cases

50. • Specific pathogenic
bacterium
• Opportunistic pathogenic
bacterium
..
The different types of
pathogenic bacteria

51. What are the opportunities for a
bacterium to become pathogenic ?
Migration
Immunodepression
Antibiotic
Physiological
change
..

52. 1/ Endogenous infectious illness =
rupture of the bacterial ecosystem (saprophyte flora) and
proliferation of a bacterial species.
2/ Exogenous infectious illness =
 penetration of pathogens within
 proliferation the organ
 How do they proliferate?
 How are they pathogenic?
 How do they penetrate?
How is bacterial infection or
pathogenesis triggered?

53. 1/ How do they proliferate?
In favorable environments :
• in presence or in absence of oxygen,
• in presence of nutrients and space,
• humidity,
• optimal temperature
By mitosis

54. 2/ How are they pathogenic ?
Pathogenic power or "Virulence"
 2 principal factors of virulence
1. Invasion
+ or - rapid
2. Toxicity
Secretion of
sometimes fatal
toxins S
S
S
S
S
S
S S
S
S
S
SS
S
S
S
S
S
Exotoxins Endotoxins

55. Other factors of bacterial
virulence
Bacterium Host
Pili Capsule
Enzymes - extreme age
- weakened
general state,
- iatrogenic factors ,
- entry port: wound or
surgery.

56. 3/ How do they penetrate ?
The entry ports
Skin
Mucus
Respiratory
tract
Digestive
tract

57. Program of bacterial
"excursions"
 Surface infection: the pathogens multiply on the surface of
mucus,
 Infectious site: the pathogens multiply in the tissues close to the
entry port,
 Targeting of organ: tropism relative to certain organs,
 Bacteriemia: passage of pathogens into the blood or the lymph
system with no morbid effect,
 Septicemia: massive passage of pathogens into the blood
Infestation of the whole organism, multiple sites of infection.

58. How does the human
organism defend itself ?
 1st line:
• Physical resources,
• Chemical resources,
• Bacteriological resources,
 After introduction:
• Non specific reaction: inflammatory reaction,
• Specific reaction: immune system
immune reaction
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59. 1/ A hermetic barrier = the skin
Sebaceous gland
Sweat
Sebum
Sweat gland
Keratinous
cells

60. 2/ A physico-chimique barrier =
the mucus
Hairs
Mucus
Lysozyme
Transferrine (Igs)

61. 3/ A bacteriological barrier:
the saprophyte flora
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Stop
infection ..
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Down with
pathogens
e.g.: Lactobacillus, Doderlein's bacilli in the vagina

62. Vulvo-vaginal flora
• Lactobacilli,
• Staphylococcus,
• Streptococcus,
• Bacteroides,
• Peptostreptococcus
Skin : Cutaneous
flora
• Staphylococcus,
• Streptococcus,
• Corynebacterium,
• Fungi.
3/ A bacteriological barrier :
the saprophyte flora
Oro-pharyngeal flora :
Mouth - nose - throat
• Staphylococcus,
• Streptococcus,
• Peptococcus,
• Peptostreptococcus,
• Fusobacterium,
• Bacteroides
Intestinal flora
• Lactobacilli,
• Bifidobacterium,
• Bacteroides,
• Clostridium,
• Colibacille,
• Proteus,
• Streptococcus,
• Staphylococcus,
• Yeasts

63. What if the threshold is crossed ?

64. 1/ The non specific
inflammatory reaction
1/ VASODILATATION
2/ PLASMA LEAK
.
. .
. .
.
3/ FORMATION OF
FIBRINE MESH
4/ PHAGOCYTOSIS

65. 1/ The non specific inflammatory
reaction : PHAGOCYTOSIS
Two types of phagocytary cells:
 Polynuclear
 Macrophages
1/ Chemotaxis
2/ Adhesion
3/ Invagination 4/ Digestion

66. 2/ The specific immune reaction
LYMPHOCYTES =
immunocompetent cells
B
T Action on contact
Circulating antibodies
Humoral immunity
Cellular
immunity

67. 2/ The specific immune reaction
Marrow and Thymus
lymph vessels
and glands
blood
vessels
Production
of lymphocytes
Transport by
During infection the glands swell and become painful
(adenopathy).

68. A- The humoral immune
reaction
. . . . B
B
Specific
antigen-antibody reaction
.
.
.
.
.
T4
PP
PP
PP
PP
Plasmocytes
antibodies

69. A- The humoral immune
reaction
. . . . B
B
.
.
.
.
T4
Bm
Memorization
= Immunity acquired
The lymphocytes which are not transformed into plasmocytes producing
antibodies keep the antigen and the antibody fabrication mode in memory.

70. B- The cellular immune
reaction
. . . . T
.
.
.
T4
T
Te
Te
Te
Tm
Memory
T4 lymphocytes
T lymphocyte "effectors"

71. The immune reaction: the T4
T4
T
B
Humoral immunity
Cellular immunity
B lymphocyte secreting
remote antibody
Cytotoxic
T lymphocyte
Preponderant role
of T4

72. Conclusion Cellular immunity

73. If the infection is triggered despite
the defenses...
 What is its origin ? What type of treatment?
 viral ? antiviral
 parasite ? antiparasite
 bacterial ? antibiotics
 mycotic ? antifungal
 Infections can be mixed: bacteria + fungi.
 The infections can be successive: bacterial superinfection of an
infection of viral origin

74. What is
bacterial superinfection?
"The virus prepares the bacterium's nest."
Alteration of healthy cells by the virus
Tissue lesions Inflammatory Inflammatory
tissue response pathology
Disturbance of functions (e.g. cold)
+ Alteration of defense mechanisms
Invasion by bacteria
Bacterial superinfection Aggravation of tissue lesions

76.  Definition:
An antibiotic is a substance produced by micro-
organisms, or which can be reproduced
synthetically, which possesses the property of
destroying bacteria or of inhibiting the growth
of bacteria.
Study of an
ANTIBIOTIC

77. Mechanism of action
Process inhibition by antibiotics.
Antibacterial agents act by effecting one or
more of the following processes taking place
inside bacterial cells:
 The synthesis of the cell wall.
 The functioning of the cell membrane
 The synthesis of proteins
 The synthesis of nuclear material (DNA)
 Metabolic transformations

78. Study of an
antibiotic
Chemical Mode Effects Spectrum Indications Pharmacokinetics
structure of action & toxicity

80.  Spectrum of activity
This is the range of bacteria that are
sensitive to the antibiotic (inhibited or
killed)
Study of an
antibiotic
Cocci +
Cocci -
Bacillus +
Bacillus -
Cocci + Narrow spectrum
Broad spectrum

81.  Activity : determined in laboratory
in a number of ways:
Antibiogram Dilution method
by diffusion
with disks
on agar
Study of an
antibiotic
Several antibiotics can
be studied at the same
time
One antibiotic can be
studied at a time

82.  Activity : determined by identifying the MIC and MBC for
each common pathogen
 MIC = Minimum Inhibiting Concentration
the minimum concentration of antibiotic capable of stopping the
culture of a given strain in a medium
Study of an
antibiotic
X quantity of germs
in the inoculum
X quantity of germs
after culture

83.  MBC = Minimum Bactericidal Concentration
the minimum antibiotic concentration destroying 99.99 %
of a bacteria population
after 18 hours of contact at 37°
Study of an antibiotic
X quantity of germs
in the inoculum
< 1 pathogen alive
out of 10 000

84. Dilution method:
determining the MIC
MIC = Minimum Inhibiting Concentration
the minimum concentration of antibiotic capable of stopping
all culture of a given strain in a medium (37° for 24 hours)
MIC
Control 0,25 0,50 1 2 4 8 16 32 mg/ml

85. Dilution method:
determining the MBC
4 8 16 32 mg/ml
Culture
from an MIC tube
on agar
MBC
T1 T2 T3 T4
T1
T2
T3
T4

86. MBC
1/10 000 = 10
102
105
104
103
106
107
108
109
2 4 6 8 10 12 14 18
8 mg
4 mg
2 mg
1 mg
0,5 mg
Control
0,25 mg
Number of
bacteria / ml
Time
(hours)
Inoculum
MBC
MIC
C
o
n
c.
of
A
B
T

87. Agar diffusion method

88. Agar diffusion method: THE
ANTIBIOGRAM
5 antibiotics tested Inhibition diameter
37° for a period of
18 hours

89. BACTERIOSTATIC ANTIBIOTIC
stop
. .
B
T4
Eradication
Stimulation

90. BACTERICIDAL ANTIBIOTIC

91. THE ANTIBIOGRAM
the laboratory response
A B
C
A: Sensitive
B: Moderately sensitive
C : Resistant

92. Study of an antibiotic
 Pharmacokinetics :
study of the behavior and fate of an antibiotic in the organ from
administration to elimination
AbsorptionMetabolization
Diffusion
Elimination

93.  Pharmacokinetics
are dependent on the route of administration
Oral
Parenteral
I.M.
I.V.

94.  Pharmacokinetics
Absorption
Distribution or Diffusion
Elimination
Metabolization

95.  Pharmacokinetics: definitions
• absorption: % of the dose of active principle administered
passing through the intestinal mucus into the blood.
• metabolization: the transformation of the active principle
into active or inactive metabolite, principally in the liver.
• effect of first hepatic passage: presence of hepatic
metabolism.
• bioavailability: the result of the previous 2 criteria; the %
of the quantity of active principle administered arriving in
the blood stream.

96. Pharmacokinetics : example
 administration via oral route of 100 mg of active principle,
 absorption = 80 % 80 mg,
 metabolization (hepatic first pass) = 20 % into inactive
metabolite 16 mg,
64 mg will reach the target
Bioavailability will therefore be 64 %

97. Pharmacokinetics : definitions
 distribution or diffusion: passage of the active compound from
the blood stream into the tissues (site of the infection ?).
 binding to plasma proteins:
% of the active compound circulating binding to proteins.
Plasma protein
TRANSPORTER

98. Pharmacokinetics: distribution
 Passage into the CSF:
Not all the products reach the C.N.S.
 Passage through the placenta barrier:
Harmful effects on fetus ?

99. Pharmacokinetics: elimination
biliary route renal route
active form inactive form active form
other routes = pulmonary, cutaneous, salivary,
lacteous etc.

100. Pharmacokinetics:
The plasma concentration curve
Plasma
concentration
Time
Plasma peak
C max
T max
Drug

101. Pharmacokinetics :
The plasma elimination 1/2 life
Plasma
concentration
Time
Plasma peak
C max
T max T /
2
C / 2
1/2 life
elimination phase =
distribution, metabolization
and elimination
absorption
phase

102. Pharmacokinetics :
Notion of area under the curve
Plasma
concentratio
n
Time
Plasma peak
C max
T max
MIC
The larger the area below the serum concentration curve,
the better the impregnation of the organ by the antibiotic

103. Pharmacokinetics =
criteria of choice of an antibiotic
 maximum absorption,
 tissue diffusion at the site of the infection +++,
 intra-cellular diffusion +++,
 elimination in non-toxic active form via the
kidney or the bile depending on the infection,
 long half-life.

104. Criteria of choice of an antibiotic
 Bacteriology
 Pharmacokinetics
 Type of patient
 Side effects
 Compliance
 Ecology
 Economy
Major
criteria
Secondary
criteria

106. Bacteriology 106

107. 1. The B-LACTAMS

108. Mechanism of action
Beta lactam antibiotics inhibit cell wall
synthesis by binding to the Penicillin
Binding Proteins (PBP’s) on the outer
surface of the cytoplasmic membrane.
Once they bind to these PBP’s /
enzymes, they stop the process of cell
wall formation / division or replication
(depending on the PBP affected).

109. Mechanism of bacterial resistance
Bacteria can resist the action of beta lactam antibiotics in 3
main ways:
 Potential production of beta lactamase enzymes that will
hydrolyse (destroy) the beta lactam ring of the antibiotic
(mainly a problem with 1st generation penicillins and
cephalosporins against gram negative bacteria – the beta
lactamase enzymes can be concentrated in the periplasmic
space)
 Potential for porin channels in gram-negative bacteria to
resist entry to some types of beta lactam antibiotics by
altering their electrochemical charge
 Potential for alteration of the target binding sites (Penicillin
binding proteins may change so the antibiotics cannot
attach themselves to the site. Alternatively the bacteria
may produce alternate PBP's’ that the antibiotic will bind to
– the new PBP’s serve as decoys and have no function in
cell wall synthesis – this is a significant problem with many
gram positive bacteria and some gram negative bacteria)

110. Examples :
 Staphylococcus aureus
 Haemophilus influenzae
 Moraxella catarrhalis
 Escherichia coli
Bacterial resistance:
a / Production of enzymes : b Lactamases
Resistance can
be transmitted
with plasmids

111. Bacterial resistance:
b/ Impermeability
Outer membrane
Cytoplasmic membrane
Pores
too narrow ?
Only concerns Gram -

112. Bacterial resistance:
c/ Modification of the target
PBP
Modification of the PBP
-↑ in number MIC ↑
- In structure

113. 1- Betalactams:
USE
 Penicillins G: - rheumatic fever
- gonorrhoea
- syphilis
 Penicillins V : - strepto tonsillitis
 Penicillins M: - skin infections
 Penicillins A : - ENT, broncho-pulmonary, urinary
 C 1 G : - ENT, broncho-pulmonary
 C 2 G : - ENT, broncho-pulmonary, urinary
 C 3 G : - ENT, broncho-pulmonary, urinary

114. 2. THE AMINOGLYCOSIDES

115. Mode of action
 Interfere with protein synthesis and may
form transient holes in a cell wall to
disrupt the permeability function.

116. Mechanism of bacterial resistance
 Bacteria may defend themselves against aminoglycosides by some
combination of three mechanisms:
 Enzymatic modification: The bacteria has the potential to modify the
chemical structure of the aminoglycoside prior to it reaching the
ribosomes. The alteration renders the antibiotic useless by a process
of ATP-dependent phosphorylation of a hydroxy group or acetylation
of an amino group (enzymes break down the structure of the
antibiotic)
 Alteration in uptake: Potential alterations in the electrochemical charge
in the outer membrane will not allow the aminoglycoside to gain entry
 Altered ribosomal binding sites: This is the least common method that
bacteria may develop resistance. A mutation will alter the binding site
so that an aminoglycoside will not recognise the appropriate target
area on the ribosome.
Examples: Gentamicin, Neomycin, Streptomycin, and Amikacin.

117. 3. THE TETRACYCLINES

118. TETRACYCLINES:
Mode of action
On the
ribosomes:
fraction 30 S
Inhibition of
protein synthesis
bacteriostatic

119. Mechanism of resistance
 There are 3 main resistance mechanisms:
 Decreasing the influx into the bacterial cell: The gram-negative
bacteria may alter the outer membrane charge to prevent entry
to some tetracyclines
 Increasing the efflux of the antibiotic out of the cell: Once inside
the cell some bacteria have developed mechanisms that act as
pumps to export the antibiotic from the cytoplasm before it can
exert its mechanism of action
 Alteration of the ribosomal binding site: Some bacteria may
alter the ribosomal binding site so that the antibiotic will have no
target to affect.
Examples: Tetracyclines: Doxycycline (Doryx, Vibramycin),
Minocycline

120. TETRACYCLINES: Spectrum
Doxycyclin, minocyclin, tetracyclin.
Cocci -
Gonococcus
Miscellaneous Bacillus -
Chlamydia, Mycoplasma, Haemophilus, Brucella,
Treponema, Borellia, Vibrio cholerae
Rickettsia, Leptospires
Anaerobes
+) P. acnes

121. TETRACYCLINES :
USES
 Brucellosis
 Acne
 STD

122. 4. The QUINOLONES

123. Mode of action
 Interfere with the synthesis of DNA
(gyrase and topoisomerase IV)

124. QUINOLONES :
Mode of action
On the
DNA
INHIBITION
of DNA synthesis
bactericidal
the bacterium
can no longer
multiply,
or live.

125. Mechanism of resistance
Bacteria acquire resistance to quinolones by
2 methods:
 Spontaneously occurring mutations in
chromosomal genes that either alter the
target enzymes or DNA
 Alteration of the drugs permeation across
bacterial cell membranes
Examples: Ciprofloxacin (Ciproxin),
Moxifloxacin (Avalox), Ofloxacin (Oflocet),
Grepafloxacin (new molecule)

126. Bacterial resistance:
Modification of the target of the antibiotic
Modification
of the DNA

127. FLUOROQUINOLONES:
Spectrum
Ciprofloxacin, gatifloxacin, gemifloxacin, levofloxacin,
moxifloxacin, ofloxacin
Cocci + Cocci -
Staphylococcus Gonococcus
Meningococcus
Bacillus -
E.coli, Proteus vulgaris
Klebsielle (IS), Salmonella
Citrobacter (IS), P.mirabilis
Campylobacter, Pseudomonas aeruginosa(IS), Serratia (IS).
Intracellular,
Mycoplasma () Legionella Chlamydia,Rickettsia
Haemophilus,
S
P
E
C
T
R
U
M
W
I
D
E

128. QUINOLONES: USES
 1st generation: urinary infections
 Fluoroquinolones :
» high and low urinary infections, prostatitis
» STD caused by Gonococci, Chlamydia, Mycoplasma
» Atypical pneumonia caused by Legionella, Chlamydia,
Mycoplasma
» Digestive infections: salmonellosis, typhoid fever
 Aminofluoroquinolones:
» pneumopathies, superinfections of chronic bronchitis
» acute purulent sinusitis

129. 5. MACROLIDES

130. Mode of action
 Binds to the 50S ribosomal subunit
resulting in blockage of transpeptidation.
(Binds to ribosome to stop amino acid
chains – proteins being produced inside
the bacteria).

131. MACROLIDES :
Site of action
On the
ribosomes:
fraction 50 S
Inhibition of
protein synthesis
Dependent on
concentration in situ
bactericidal bacteriostatic
Inhibition of
translocase

132. Mechanism of resistance
Bacteria can develop resistance to macrolides in
two ways:
 Promotion of efflux pumps within the cell to expel
the antibiotic prior to exerting the mechanism of
action. Some of these bacteria will remain
susceptible if higher doses are given.
 Alteration in the ribosomal target binding site.
Changing the target for the antibiotic so that it has
no binding potential.
Examples: Erythromycin, Roxithromycin (Rulide) and
Clarithromycin

133. Bacterial resistance:
Modification of the target of the antibiotic
Ribosomes

134. MACROLIDES :
Spectrum
 erythromycin, azithromycin,
clarithromycin, dirithromycin
Cocci + Cocci -
Staphylococcus Meti S Gonococcus
Gr A b hemolytic streptococcus Meningococcus
Pneumococcus(IS) Moraxella
Intracellular Bacillus +
Mycoplasma Listeria, diphtheria B.
Chlamydia, Legionella Bacillus -
Helicobacter, Vibrio cholerae
Anaerobes: (+) Clostridium perfringens,
P. acnes, Peptostreptococcus., Actinomyces.
Protozoan
Toxoplasma

135. 6. KETOLIDES:
Site of action
On the
ribosomes:
fraction 50 S
• Stops protein synthesis, then
bacterial lysis
2 components act in synergy:
• the first binds to the bacterial ribosome,
• the 2nd then binds in turn

136. KETOLIDES:
telithromycin
 Cocci + Cocci -
Staphylococcus Gonococcus
Streptococci Meningococcus
Streptococcus D (Enterococcus)(IS) Moraxella
Pneumococcus
Intracellular
Chlamydia, Legionella, Bacillus +
Mycoplasma C.diphteriae. , Listeria
Anaerobes Bacillus -
(-) Bacteroides Haemophilus

137. KETOLIDES
TOXICITY : 0 to + + occasional hepatic toxicity
SIDE EFFECTS : + to + + occasional hepatic toxicity
RESISTANCE : + to + + +
CONTRA-INDICATIONS : + +
PHARMACOKINETICS :
 BIOAVAILABILITY : 40 to 80%
 TISSUE DIFFUSION : very good
 ELIMINATION : biliary in active or inactive form

138. KETOLIDES
 ENT: tonsillitis, sinusitis
 broncho-pulmonary: typical and atypical
pneumonia, bronchitis

139. 7. SULFONAMIDES
Mode of action
On DNA
INHIBITION
of synthesis
of folic acid
bacteriostatic
the bacterium
no longer multiplies

140. 7. SULFONAMIDES: spectrum
Cocci + Bacillus -
Streptococcus(IS) E. coli, Proteus, Citrobacter
Pneumococcus(IS) Salmonella, Shigella,
Staphylococci (IS) Haemophilus,
Bacillus + Serratia (IS), Klebsiella (IS)
Listeria Enterobacter (IS)
Protozoans Miscellaneous
Pneumocystis corini Vinbrio cholerae
Toxoplasma*

141. SULFONAMIDES
 Trimethoprime
+ Sulfamethoxazole........

142. 8. NITRO-IMIDAZOLES
Mode of action
On DNA
Attacks the DNA
Bactericidal

143. 8. NITRO-IMIDAZOLES :
Spectrum
 e.g. Metronidazole (Flagyl)
Anaerobes Protozoans
Bacteroïds Trichomonas vaginalis
Fusobacterium Giardia lamblia
Clostridium Entamoeba histolitica
Peptostreptococcus (IS)
Peptococcus (IS)
+ Helicobacter pylori

144. Intrinsic and Acquired Resistance
 Intrinsic resistance
- Intrinsic resistance means that the bacterium has always
been resistant to a particular antibiotic or that particular
antibiotic has no intrinsic activity against the bacterium. For
example, E.coli has intrinsic resistance to Rulide and
Chlamydia has intrinsic resistance to Amoxycillin.
 Acquired resistance
- Acquired resistance means that the bacteria used to be
sensitive to a particular antibiotic but it has now developed a
mechanism to prevent the antibiotic from killing it. It’s a bit
like Charles Darwin’s theory of evolution, in that only those
organism that are able to evolve in order to survive will be
around in the future. MRSA has acquired resistance to
Methicillin, H.flu has acquired resistance to amoxycillin.

145. Mechanisms of resistance transfer

146. Which drug to choose ?
b Lactams ?
Macrolide ?
Cocci + ?

147. Bacteriology 147
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