2. DEFINATION
Antibiotics are chemical substance
elaborated by various species of micro-
organism such as fungi, actinomycetes and
bacteria. They suppress the growth of other
micro-organism and may ultimately destroy
them in low concentration.
4. Early history
3500 BC the Sumerian doctors would give patients
beer soup mixed with snakeskins and turtle shells.
Babylonian doctors would heal the eyes by using an
ointment made of frog bile and sour milk.
The Greeks used many herbs to heal ailments.
All of these "natural" treatments contained some sort
of antibiotic.
5. Modern history
Louis Pasteur was one of the first recognized
physicians who observed that bacteria could be used
to kill other bacteria.
In 1929 Sir Alexander Fleming a Scottish
bacteriologist, went on a vaction and left a petri dish
of staphylococci bacteria uncovered. When he
returned, he noticed that there was mold growing on
it. Upon further examination, he saw that the area
around the mold had no bacteria growing. He named
the mold Penicillium, and the chemical produced by
the mold was named penicillin, which is the first
substance recognized as an antibiotic.
6. Almost immediately after penicillin was introduced,
resistance in certain strains of staphylococci was
noticed.
In 1935, Domagkdiscovers synthetic antimicrobial
chemicals (sulfonamides).
During World War II, because of need for antibiotic
agents, penicillin was isolated and further tested by
injection into animals. It was found to be extremely
useful in curing infections, and to have extremely low
toxicity to the animals. Because of these findings, use
of penicillin greatly increased. This also spurred a
search of other chemical agents of similar use.
7. the late 1940's through the early 1950's, streptomycin,
chloramphenicol, and tetracycline were discovered
and introduced as antibiotics.
In 1953, during a Shigella outbreak in Japan, a certain
strain of dysentery bacillus was found to be resistant
to chloramphenicol, tetracycline, streptomycin, and
the sulfanilamides.
By the 1950's it was apparant that tuberculosis
bacteria was rapidly developing resistance to
streptomycin, which had commonly been used to
treat it.
9. Classification of antibiotics
Classification based on chemical structure & proposed
mechanism of actions as fallows
1. Agents that inhibits synthesis of bacterial cell wall
these includes
a) penicillin & cephalosporin which are structurally simillar
b) Cycloserine vancomycin bacitracine & the azole
antifungal agent ( e.g clotrimazole, fluconazole &
itraconazole which are structurally dissimilar agent
10. 2.Agent that act directly on the cell membrane of
the micro organism affecting permeablity &
leading to leakage of intercelluar compound
e.G polymyxin & polyene antifungal agent nystatin
Amphotericin B which bind to cell wall sterolls
11. 3 .Agent that affect the function of 30 s or 50 s
ribosomal subunit to cause or reversible inhibition of
protein synthesis
e.G chloramphenical
Tetracycline
Erythromycin
Clindamycin
12. 4 .agent that bind to 30s ribosomal subunit &alter
protein synthesis which eventually lead to cell death
E.g. aminoglycosides
5.agent that affect bacterial nucleic acid metabolism
such as rifamycin (e.g. rifampin ) which inhibit RNA
polymerase & the quinilones which inhibit
topoisomerase
13. 6 . agent that block essential enzymes of folate
metabolisum
E.g. trimethoprim& sulfonamide
7 . Antiviral agent which are of several classes including
e Nuclic acid analog such as acyclovir or gancyclovir
that selectively inhibit viral DNA polymerase and
zidovidine which inhibit reverse transcriptase
Non nucleoside reverse transcriptase inhibitors such
as nevirapine
r Inhibitor of other essential viral enzyme. E.g.
inhibitors of HIV protease or influenza neuraminidase
14. classification
According to spectra
1.Antibiotic effective against gram positive bacteria
a.For systemic infection, erythromycin, lincomycin,
novobiocin.
b. Those employed topically
e.g. bacitracin
2.Antibiotic mainly against gram negative bacteria
a.For sylstemic infection
e.g. strepomycin & other aminoglycosides
b.Those used locally in intestine
e.g.paromomycin
15. 3.Antibiotic mainly effective against gram –ve
& +ve bacteria
a.Used for systemic infection
e.g. ampicillin, amoxycillin, cephalosporin
b.For topical application
e.g. neomycin
4. Effective against rickettsial & chlamydia
e.g. tetracycline & chloramphenicol
5.Effective against acid fast bacilli
e.g. steptomycin, rifampicin & viomycin
16. 6.Effective against protozoa
e.g. paramomycin & tetracyclin
7.Effective against fungi
e.g.nystatine, amphotericin B
8.Effective against malignancy
e.g. actinomycin, mitomycin
18. Following are the points by which the clinician can
make a decision of when to use antibiotic, which are
to select, and how to use both therapeutic and
prophylactic situations. To do this one should atleast
know about the following
1. Bacterial flora causing most odontogenic
infections
2. The basic mechanism of host defenses
3. The variety of contemporary antibiotics and
principles to choose
19. Bacterial flora causing most
odontogenic infections
The indigenous microbial flora of the mouth is
bacteria, which are almost always the cause of
odontogenic infections. The usual flora is both
aerobes and anaerobes
20. The basic mechanism of host
defenses
Host defense mechanism is the most important factor
in the final outcome of a bacterial insult.Each patient
has many defenses against infections.
1. Physiologic depression of host defence,
Shock
Disturbances of circulation caused by advanced
age Obesity
Fluid imbalance
2. Diseases and disease state that may inhibit host
defense
Malnutrition syndrome
Patient with cancer and leukemia
21. 3 Congenital defect which causes defective host
mechanism
Agammaglobulinemia
Multiple myeloma
Total body radiation therapy
Children who have had splenectomy
4. Therapeutic drugs that impares host defense
mechanism
Cytotoxic drugs
Immunosuppressive drugs
22. principles to choose
Antibiotics
Once the decision has been made to use antibiotics as
an adjunct to treating infection the antibiotics should
be properly selected. The followingguide lines are
useful
1. Identification of causative organism
2. Determination of antibiotic sensitivity
3. Choice of antibiotics
23. 1. Identification of causative organism
Causative organism can be isolated from pus
blood, or tissue fluids. Based upon the knowledge of
pathogenesis and clinical presentation of specific
infection,antibiotic therapy will be either initial or
definitive depending upon whether or not the
organism is diagnosed previously.
24. 2. Determination of antibiotic sensitivity
When treating an infection that has not
responded to initial antibiotic therapy or when
treating a postoperative wound ,the causative agent
must be previously identified and the antibiotic
sensitivity must also be determined.
25. 3 Choice of antibiotics
Upon receipt of the culture and sensitivity report,
there may be a choice of four or five antibiotics.
Selection should be based on consideration of several
factors like
1. Patients previous history of allergy
2. Antibiotics with narrow spectrum
3. Drug that cause fewest adverse reactions.
4. Drug which is least toxic
5. The well established still effective antibiotics
6. Bactericidal rather than bacteriostatic drug
7. The less expensive still effective antibotic
8. Combination antibiotics
26. 1. Patient`s history of allergy
Allergic reaction to drugs should be considered
first. When it exists, alternative drugs must be used.
Example erythromycin or clindamycin is usually use if
the patient is allergic to penicillin
27. 2. Antibiotics with narrow spectrum
The only majour indication for use of broad
spectrum antibiotics coverage is in severe life
threatening infection where identification of causative
agent is obsure. Each time bacteria are exposed to
antibiotics, the opportunity for development of
resistant strains is present. If narrow spectrum
antibiotics is used ,fewer organisms have the
opportunity to become resistant.
28. 3. Drug that cause fewest adverse reactions
The goal of antibiotic therapy is to provide an
effective Drug that causes least problem to the patient
4. Drug which is least toxic
Toxicity reactions are those that occur as a result
of excessive dose or duration of therapy, but can
occur in individual patients with normal doses.
29. 5. The well established still effective antibiotics
Since its initial availability, penicillin, has been
used for oral infection and it has been very effective,
with low incidence of adverse reaction. Newer
antibiotics should be used only when they have
proved advantage over the older ones .
30. 6. Bactericidal rather than bacteriostatic drug
Bactericidal drugs are effective during the log
phase of bacterial growth the time . If growth is
slowed or brought to stop,cidal drugs have a greately
diminished effect. As a result, in these situations,
when combination drug therapy is to be used,cidal
and static combination should not be used in
combination.
31. 7. The less expensive still effective antibotic
Most effective but less expensive drug should be
considered first.
8. Combination antibiotics
There are situations in which the use of
antibiotic combination is clearly indicated. Example is
when it is necessary to increase the antibacterial
spectrum in patients with life threatening sepsis of
unknown cause.
33. Selection of antibiotics
When an antibiotic is indicated the goal is to
choose a drug that is selectivley active for the
most likely infecting micro-org.& that has least
potential to cause toxicity or allergic reaction in
individual being treated.
Antibiotic are used in three general ways
as empirical therapy
as definative therapy
As prophylactic or preventive therapy
34. Pharamacokinetic factor that
affect the selection of antibiotic
Location of the infection
access of antibiotic to sites of infection
e.g. if the infection in the CSF the drug must
pass the blood brain barrier
35. Host factors
Host factor for the selection of antibiotics
Host defense mechanisms
action in the immunocompetant host can be
cure mearly by halting multiplication of micro
organism { bacteriostatic effect}
if host defense are impaired bacteriostatic
activity may be inadequate and a berteriocidal
agent may be required for cure
e.g. pt with bacterial endocarditis
pt with AIDS
36. Local factors
Antimicrobial activity may be significantly
reduces in pus
Large accumulation of Hb in infected
hematomous cab bind penecillin and
tetracycline & thus may reduce the
effectiveness of other drug
Penetration of antibiotic into infected areas
such abscess is imparied because vascular
supply is reduce
37. Genetic factors
A no. of drug (e.g. sulfanamides,
chloramphenicol and nalidixic acid )
may produces acute hemolysis in pt
with glucose 6- phosphate
dehydrogenase deficiency
38. pregnancy
Pregnancy may impose an increased risk of
reaction to antibiotic for both mother &
fetus
Hearing loss in child with administration of
streptomycin to the mother during
pregnancy
Tetracycline can affect bones & teeth of
fetus , may develop fatal acute fatty necrosis
of liver pancreatitis & associated renal
39. Drug allergy
A antibiotics especially- B-lactum are
notorious or provoking allergic reaction
Sulfonamides trimethoprim nitrofurapterin
and erythromycin also has been associated
with hypersentitivity reaction especially
rash.
Antimicrobial agent like othe drugs can
caused drug fever
40. Therapy with combined
antimicrobial agent
Indication
Empirical therapy of severe infections in which a
cause is unknown
Treatment of polymicrobial infection
Enhancement of antibacterial activity in the
treatment of specific infection.
41. Disadvantage of combination of
antimicrobial agents
Risk of toxicity from two or more agent
The selection of multiple drug resistance
micro organism
Increased cost to the patient
45. Mechanism of action
Act by inhibiting cell walll synthesis in
bacteria. they prevent sythesis &
crosslinkage of peptidoglycans which is the
integral part of bacterial cell wall.
50. AMINOGLYCOSIDES
These are group of natural & semisynthetic
drugs having polybasic amino groups &
linked glycosidically to two or more amino
sugars.
51. Mechanism of action
The drugs combine with the bacterial
ribosomes & interfares with m-RNA
ribisomes combination which ultimately
prevents protien synthesis.
52. Absorbtion fate and excreation
It is excreted mainly by glomerular
filtration &asmall portion in bile
54. This group includes drug like
Streptomycine
Gentamycine
Kanamycine
55. Tetracycline
They are naphthalene derivatives
it’s nucleus is made up by the fusion of foci
partialy unsaturated cyclohexiane radius
and hence named tetracycline
56. Mechanism of action
Interfer with protein synthesis by blocking
the attachment of amino acyl transfer rna
to acceptor site on m-RNA ribosome
complex.
57. Absorption fate & excretion
Tetracycline form insoluble complexes
by chelation with calcium ,magnesium
& aluminium
Iron interferes with absorption
excreted mainly in urine
58. Spectrum
Includes both gram +ve & -ve orgamism
Dose –
orally-250-500mg TDS
Parantally- 1-2gms in two equal doses 12hrly
interval.
Newer drug are-
Doxycycline
Demeclocycline
Methacycline
Minocycline
lymecycline
59. Disadvantages
GI system
Diahrroea
Nausea
Vomiting
Suprinfection
Candida infectionis comman
Fetal hepatic disfuction
Azotemia may be agrevated to renal
impairment
Chelating effect in teeth & bone
60. Cephalosporins
1st generation
They are highly effective against gram +ve
but weaker against gram _ve bacteria
These are
cephalexim
Cephalethin
Cephaloridine
Cephradine
cefadroxil
61. Cephalexin
Only orally active first generation cephalosporin with
spectrum
Strptococcus
Staphylococci
Gonococci
Closridia
C. diptheria
Actinomyces
Klebshiella
Protease
Salmonella
shingella
62. Dose
Adult – 25mg to 1gm 6 to 8 hrly.
children – 25mg to 100mg/kg/day
63. Cefadroxil
A it is close congener of cephalexim& has
good tissue penetration
B can be given 12 hrly
C spectrum is same as cephalexim
Dose 0.5gm -1gm BD.
64. SECOND GENARATION
They are newer to first genaration.
They have more activity against gram –ve
organisms.
E.g. cefuroxime – it is higher activity
against penicilliase producing organisms
and all ampicillin resistant H-influenzae.
65. Other spectrum
More active against klebsiella, E-coli,
enterobacter, indole positive protiens.
Dose – a. 0.75 – 1.5 gms/ IM or IV/9 hrly
b.30- 100mg/kg/day.
Available as- supacef.
66. Third generation
These were developed in end of 1980’s.
They have augmentation activity against –ve
Endobactericeae.
They are resistant to β lactamase.
These are-
Cefotaxamine
Ceffizoxime
Ceftriaxone
Moxalactum
ceftazidium
67. Cefotoxamine
Potent action on gram-ve as well as gram+ve
It is not so active against anaerobic like bact.
Fragillis, Staphylococcous aureus, Pseudomonas
aerugemosa.
It is very important drug in teratment of
meningitis, hospital acquired diseases septicaemia
and infection in immuno compromised pt.
Dose –
A.1-2gms/Imor IV/6- 12hrly
50-100mg/kg/day
69. Ceftizaxone
Long acing cephalosporin
One daily dose is good enough and it has good
CSF penetration
Dose
Adult - 1-2gms/IM or IV /day
Child- 75-100mg/kg/day
70. Ceftazidime
Most prominent feature is high activity againt
pseudomonas.
It is used in febrile pt including pt with burns.
It is less effective to staphylococcus aureus.
Dose
Adult-0.5-2gms/IM or IV/ every 8 hours
Child- 30mg/ kg/day
71. Forth generation
cephalosporine
E.g. cefepime(maxipime) and cefpirome
It is new cephalosporine with properties like those of
3rd generation cephalosporine but more resistance to
some beta-lactumase.
It is active against streptococci and methyciline
sensetive staphylococci but not against methyciline
resistance staphylococci.
72. Spectrum
It’s main use is in serious gram –ve infection (H-
influenza, Neisseria- gonorrhoae and Neissera
meningities) including infection of CNS inti which it
has exelent penetration.
Half life is of 2hrs.
Dose -2gm I.V. every 12hrs
73. Fifth generation
cephalosporine
Ceftobiprole has been described as "fifth
generation",though acceptance for this terminology is
not universal.
Ceftobiprole (and the soluble prodrug medocaril) are
on the FDA fast-track. Ceftobiprole has powerful
antipseudomonal characteristics and appears to be
less susceptible to development of resistance.
74. These cephems have progressed far enough to be
named, but have not been assigned to a particular
generation.
Cefaclomezine
Cefaloram
Cefaparol
Cefcanel
Cefedrolor
Cefempidone
Cefetrizole
Cefivitril
76. Adverse effect
Pain after injection.
Diarrhoea due disturbance in Gut ecology
Hypersensitivity reaction- anaphylaxis,
angiodema, asthma, urticaria.
Nephrotoxicity
Neutropenia or thrombocytopenia
Hyperprothombinemia
A flase +ve cmbs test may occur in as many
as 60%of pt or cephalathin therapy.
77. Macrolides
They are antibiotics having a macrocyclic
lactone ring with attached sugars
They are bacteriostatic drug
78. Erythromycin
Used as aternative in penicillin sensitive
individuals
CONTRAINDICATIONS
Hypersensiivity
Liver dieases- ester salt is avoided
Available as –tablet & syrup
Dose ADULT- 250-500mgQID
CHILDREN-30-50mg kg/day
in form of divided doses.
80. Azithromycin
This new azalide longer of erytromicin has
an expanded spectrum, hyper…,
Pharmacokinetics, better tolerability and
drugs interation profile however it is not
effective against erythromycin resistant
bacteria.
82. Contraindications
Hypersensitivity
Hepatic impairment
DOSE- ADULT-500mg OD for 3days OR 500mg OD on
days one followed by 250mg OD for 4 days.
CHILDREN- 10mg/kg/ day for 3 days OR
10mg/kg/day followed by 5mg/kg/day OD for 5day.
ONSET OF ACTION- one to two hrs
85. Mode of action
In anarobic micro-organisms metronidazole
is converted into an active form by
reduction of it’s nitro group.
This binds to DNA and prevents formation
of nuclic acid.
86. Absoption fate and excretion
The drug is well absorbed after oral or
rectal administration.
It is elimanated urine, partly unchanged &
party metabolized
91. Indication for antibiotic used
n Systemic indications
i Congnital or acquired heart
a. Rheumatic heart disease
b. Valvular diseases
c. Pt with ventricular defects
2. Severe kidney diseaes
a. chronic glumerulonephritis
b. pt undergoing dialysis
92. 3. Active leukemia, agranulocytosis, aplasia ,
anemia
4. Metabolic disturbances – diabetes
5. Pt on chemotherapeutic drugs
6. Pt with vascular graft
93. B. Maxillo- facial trauma
1.Hard tissue trauma-the consensus is that
antibiotic convert should be used for any
mandibular or maxillar fracture compented
into mouth or paranasal sinus through mouth.
2.Soft tissue trauma
3.Orthognathic & recontructive maxillo- facial
surgery.
4.Odontogenig infection
5.Pericoronities
6.Osteomylitis
94. contraindication
Minor chronic localised abscess.
Well localised vesibular abscess .
Localised ostitis
For sterilizing root canal
Pt with mild pericoronitis, minor gingival
oedema & mild pain which do not required
antibiotcs
95. Prophylactic antibiotic therapy
Standard recommendation
A cephalosporin cefadroxil preferred
1preoperatively 500 mg orally 1hr before surgery
2 post operatively 250 mg orally 6hr after initial
dose
or
Clindamycin in penicillin allergic pt
1 pre operatively 300 mg orally 1 hr before surgery
2 post operatively 150 mg orally 6hr after initial
dose
96. Principles of antibiotic
prophylaxis
1 antimicrobial agent t is chosen on basis of
most likely micro organisum to cause
infection
2 an antibiotic loading dose should be
employed
3 antibiotic should present in sufficient
concentration in blood and targate tissue
prior to dissemination of offending micro
organisum
97. 4 antibiotics should be continued only as
long as microbial contamination from
operative site persist
5 patient benefits from prophylaxis should
out high risk of antibiotic included allergy ,
toxicity , superinfection.
98. Dental procedure that require
endocardititis prophylaxis
Tooth extraction
Periodontal suergery
Subgingival dental prophylaxis
Endodontic surgery
Incision & Drainage of infection
99. do not require endocardiatis
prophylaxis
Supragingival prophylaxis
Restorative tooth preparation
Placement of orthodontic appliances
Conserative endodontic theraphy
100. REASONS FOR ANTIBIOTIC
FAILURE
INAPPROPIATE choice of antibiotics
Too low blood concentration
Poor penetration to infected site
Limited or decreased vascularity
Impaired host defence
Unfavourable local factors
101. Increased plasma protein binding
Antibiotic antagonism
Slow microbial growth
Antibiotic resistant organisms
Patient failure to take antibiotics
Failure to eradicate sorce of infection
102. Myths &misconception in
antibiotic th erapy
Myth- antibiotics cure pt
1 except in immunocompramised pt
antibiotics are not curative but rather
function to provide time for normal host
defence initially overwhelmed by micro
organisum to gain and control &eventually
eliminate the in fectious process
103. 2 .Antibiotics
are substitute for surgical
drainage - never are antibiotics a
substituted for eradication of the source of
infection ( extraction, incision, drainage )
unless the infection is too diffuse
(pericoronitis)
104. 3 culture and sensitivity test are required -
orofacial infection are characteristically
acute in nature, polymicrobial in cause,
short in duration with proper treatment.
These infection require immediate
attention and a dealy of 18 to 36 hrs for
result of culture & sensitivity tests prior to
initiation of antibiotics therapy is usually
not appropriate because the microbial
cause Is commly such that common
antibiotics are effective, incision &drainage
are relatively easy.
105. Myth – antibiotics incresed
host defence to infection
The followoing condition appear valid at present
1 antibiotic that can peenetrate into the
mammelion cell (tetracycline , eryt hromycin) are
more likely to affect host defence than those that
can not (beta lactum)
2 tetracycline may supress white cell chemotaxis
where as betta lactum do not
3 most antibiotics (except tetracycline) do not
depress phagocytosis
Tnb lymphocyte transformation may be depressed
by trtracyclines
106. Multiple antibiotics are
superior to as single antibiotics.
It is often assume that antbiotic combination are
superior to single antibiotic such as not
commonly the case.
The primary clilical indication for antibiotic
conbination therapy is severe infection in which
ofending organism is unknown and major
conciquences may ensue if antibiotic therapy is
not instituted immediatey before culture and
sensetivity test are available.
107. Antibiotic prophylaxis usually
effective
It is commonly assume that antibiotics
administered prior to invasive surgical
procedure remain post operative infection.
The reality based on laboratoru studies is
that antibiotic prophalaxis is only some
time effective.
108. Bacteriocidal agents are always
superior to bacteriostatic agent
Bacteriocidal antimicrobials are
required in pt with impaier host
defenses (nutropenia, meningitis) but
bacteriostatic agent are uaually
satisfactory, if host defence against
infection are adequqte.
109. Antimicrobials are effective in
chronic infectious disease
Antimicrobials are never been
successful in the eradication of a
chronic infection because the prolong
exposure of micro-organism to
chemical leads to eventual dominance
of drug resistance organism
110. Antibiotics are safe and non
toxic
Most antimicrobials are among safest drug
yet all are associated with allergy, ecological
damage to human and microbial
environment.
111. Infection require a complete
course of therapy
There is no such things as predetermine complete
course of antibiotic therapy.
The only guide for determining the effectiveness of
antibiotic therapy and hence duration of treatment is
related to clinical improvement of pt.
112. Misconceptions
Prolong therapy destroy resistant micro-organism.
Prolong therapy is necessary for rebound infection
that recur as organism is suppresed but not
eliminated (orofacial infections do not rebound if
the sourse of infection is properly eliminated)
Antibiotic doseges and duration of therapy can be
extra polated from one infection to another
115. INTRODUCTION:
Infections and their consequences are a considerable
problem inorthopedic surgery.
Despite systemic prophylaxis, infection rates after
orthopedic surgery are above1%.
Antibiotic loaded PMMA bone cements have been
shown to enhance the efficiency of intravenous
prophylactic treatments for total hipreplacement1.
However, less than 10% of the load is released during
the first 5-10 days ofimplantation2: the remaining
antibiotic is released at low levels over many months3
and could select antibiotic-resistant strains2.
116. Methods
A commercial bone substitute composed of 70%
Hydroxyapatite and 30% β- Tricalcium Phosphate4
containing 125 mg of Gentamicin (ATLANTIK Genta,
Medical Biomat, France) was used in this study.
The release rate of Gentamicin from the bone
substitute was investigated after implantation in the
femoral condyle of 5 sheep. In order to investigate the
local and systemic Gentamicin concentrations,
synovial fluids and blood samples were assessed by
immunoassay over a 5 day period.
117. There were differences in local Gentamicin
concentrations between individuals but for all
animals, the local Gentamicin concentrations
measured during the first 8 hours were higher than
the minimal bactericidal concentration of the
majority of the germs responsible for infections in
orthopedic surgery, i.e. 6-12 μg/ml. After 48 hours, the
concentration in blood and synovial fluids was less
than 0.5 μg/ml.
118. The mean Gentamicin concentration peak obtained in
blood was 4.2 μg/ml and then mean local Gentamicin
concentration obtained in synovial fluids during the
first 8 hours was305 μg/ml
The Gentamicin amount remaining in the implant
explanted at day 8 was less than 0.003% of the initial
amount
120. It is a fact that selection of multi-drug-resistant
bacteria has occurred throughout history.
Unfortunately, however, drug-resistant bacteria have
been met with antibiotics that are nothing more than
recapitulations of earlier drugs. There has been an
urgent need for new avenues of therapeutic
treatment, and a new era of prophalytic (preventative)
treatment has begun. Here the most plausible
approaches are described:
bacterial interference
123. One way is to inoculate hosts
with nonpathogenic bacteria.
Bacterial interference, also known as bacteriotherapy,
is the practice of deliberately inoculating hosts with
nonpathogenic (commensal) bacteria to prevent
infection by pathogenic strains. To establish an
infection and propagate disease, pathogenic bacteria
must find nutrients and attachment sites (adhesion
receptors).
.
124. Infection by pathogenic bacteria is prevented by
commensal bacteria, which compete with pathogenic
bacteria for nutrients and adhesion receptors or spur
attack through secretion of antimicrobial compounds
125. This treatment has had promising results in infections
of the gut, urogenital tract, and wound sites. The
major advantage of using bacteria in a positive way to
benefit health, known as “probiotic” usage, is that
infection is avoided without stimulating the host’s
immune system and decreases selection for antibiotic
resistance. Understanding how bacterial species
compete, an essential criterion for research, has been
known for at least 20 years but its practical
application has yet to be realized.
127. Bacteriophages (commonly called “phages”) are
viruses that infect bacteria and were recognized as
early as 1896 as natural killers of bacteria.
Bacteriophages take over the host’s protein-making
machinery, directing the host bacteria to make viral
proteins of their own. Therapeutically, bacteriophages
were used as a prophylaxis against cholera, typhoid
fever, and dysentery from the 1920s to the early 1940s.
128. The practice was abruptly stopped when synthetic
antibiotics were introduced after World War II. Now
that there is a plethora of multi-drug-resistant
bacteria, bacteriophage therapy once again has
become of keen interest.
129. Pathogens may be targeted
through manipulation of
phage DNA.
Bacteriophage therapy is quite attractive for the
following reasons:
phage particles are narrow spectrum agents, which
means they posses an inherent mechanism to not
only infect bacteria but specific strains
130. Other pathogens may be targeted through
manipulation of phage DNA
exponential growth and natural mutational ability
make bacteriophages great candidates for thwarting
bacterial resistance.
Development of bacterial vaccines has become an
increasingly popular idea with the advent of complete
genomic sequencing and the understanding of
virulence regulatory mechanisms.
132. Bacterial genomics allows scientists to scan an entire
bacterial genome for specific sequences that may be
used to stimulate a protective immune response
against specific bacterial strains. This approach
expedites the drug discovery process and, more
importantly, provides a more rational, target-based
approach.
The best targets are essential bacterial genes that are
common to many species of bacteria, which code for
proteins with the ability to gain accesses through lipid
membranes, and possess no homology to human
genes.
133. Regulatory genes that control virulence protein
production are excellent vaccine candidates for
priming the human immune system or inhibiting
virulence production.
Bacterial genomics can also detect conserved
sequences from bacterial species and strains
worldwide. This technology will inevitably yield
superior clinical vaccine candidates.
135. These diverse peptides are natural compounds that
posses both hydrophobic and hydrophilic
characteristics, which means portions of the molecule
are water avoiding or water loving. Cationic peptides
are found throughout nature in the immune systems
of bacteria, plants, invertebrates, and vertebrates
136. Other Peptides are synthetic,
and are engineered to kill
bacterial cells.
These peptides are not the usual synthetic drugs
encountered in pharmaceutical drug design; however,
they do exhibit antibacterial effects. Cationic peptides
have several mechanisms of action, all of which
involve interaction with the bacterial cell membrane
leading to cell death. From a therapeutic standpoint,
these proteins have great promise, as they have
coevolved with commensal bacteria yet have
maintained the ability to target pathogenic bacteria.
137. Other peptides are synthetic,
or engineered, to kill bacterial
cells.
Unlike cationic peptides, cyclic D,L-a-peptides are
synthetic and amphipathic (molecules having both
water loving and water hating characteristics) cell
membrane disruptors. As the name implies these
peptides are cyclic in nature and are composed of
alternating D and L amino acids. Cyclic D,L-a-
peptides are engineered to target gram-positive and
negative membranes (not mammalian cell
membranes).
138. In contrast to any other known class of peptides,
these peptides can self-assemble into flat ring shaped
conformations forming structures known as
nanotubes, which specifically target and puncture
bacterial cell membranes resulting in rapid cell death
