2. Outline
• History
• Role of bacteria
• Mechanism of action of antibiotics
• Classification of antibiotics
• Bacterial resistance
• Misconceptions about antibiotics
• Principles of antibiotics prescription
• Results of our survey
3. The term “antibiotic” is used for chemicals that
are produced either by microorganisms or
produced by chemical synthesis that kills or
inhibits microorganisms and cures infection.
• The noun “antibiotic” was first used in 1942 by
Dr. Selman A. Waksman, soil microbiologist.
the accidental discovery of antibiotics
10. • Bacteriostatic: Inhibits bacteria from reproducing but
doesn’t otherwise kill them.
• Bactericidal: actively kills bacteria.
• In reality there is not a sharp distinction between the
two, as categorization depends upon drug
concentration and bacterial species.
Bacteriostatic vs Bactricidal
antibiotic
14. beta-lactam antibiotics
• β-lactam antibiotics contain a β-lactam ring in
their molecular structures.
• Humans have no cell wall (no peptioglycan),
so this is a good selective target for the
antibiotic.
16. Penicillin
Bactericidal
•Penicillins are unique in their lack of toxicity.
• if the patient is not allergic, there is no maximum
dose of penicillin and no side effects from
overdosage
Penicillin G: ( natural penicillin) active against Gram-
positive organisms that do not produce beta-lactamases,
and some anaerobes (I V use)
17. Penicllin
natural Penicillin
1st G(pen G)
Benzylpenicillin
benzathine penicillin
( I M) long acting
Procaine
penicillin
Semi synthnsitic
(Pen v)
Oral use
phenoxymethylpenicillin
Semi synthnsitic
Aminopenicillins
2nd G(pen A) Ampicillin
Amoxicillin
Penicillinase-stable penicillins
3rd G(pen M)
Anti-staphylococcal penicillins
Oxacillin
Methicillin
Dicloxacillin
Carboxypenicillins
(pen C)
Anti-psuedomonal penicillins
Ticarcillin
Ureidopenicillins
4th G(pen U)
Anti-psuedomonal penicillins
Piperacillin
18.
19. Penicillin
• Penicillin is the drug of choice in treating odontogenic
infections due to its effectiveness in polymicrobial infections
• as it is affective aganist gram positive aerobes and intraoral
anaerobes,
20. Penicillin
• about 10 percent of the population will give a
history of allergic reactions to penicillin.
• Patients allergic to penicillin are treated with
clindamycin 300 mg which is the ideal drug of
choice and followed by azithromycin and
metronidazole-spiramycin
21. • To achieve a steady serum level with penicillin
VK(ospen), it should be administered every four
to six hours
• Loading dose of 1,000 mg of penicillin should be
orally administered, followed by 500 mg every
four to six hours for five to seven days
22. Amoxicillin
• Amoxicillin is an analogue of penicillin that is rapidly
absorbed and has a longer half-life.
• give higher and more sustained serum levels than penicillin
VK.
• amoxicillin is often used for antibiotic prophylaxis of patients
that are medically compromised
• The usual oral dosage for amoxicillin is 1,000 mg loading dose
followed by 500 mg every eight hours for five to seven days.
Amoxicillin
Amoxil
Emox
23. beta-lactamase enzymes
All beta-lactams are subject to inactivation by
bacterial-produced enzymes called
beta lactamases: as
Penicillinases
Cephalosporinases
ß-lactamases hydrolyze the ß-lactam ring. The rate of
this hydrolysis depends on the rate on entry of the drug
and the level of ß-lactamase
activity.
24. Co-Drugs (Beta-lactam + penicillinase inhibitor)
• Some penicillins are combined with beta-lactamase
inhibitors, which themselves are beta lactams that
can inactivate beta-lactamases enzyme
25. • These enzymatic inhibitors have weak or poor
antibacterial activity alone, but have a strong affinity for
β- lactamases:
Ticarcillin + clavulanic acid
26. Augmentin
• The combination of amoxicillin with clavulanate is the
most effective antibiotic combination
• The usual oral dosage is 1,000 mg loading dose followed
by 500-600 mg every eight hours for five to seven days
27. cephalospornis
Broad spectrum group.
Classified as 1st – 2nd – 3rd – 4th & 5th generations.
• there is a possibility of cross allergy of cephalosporins
with penicillin.
• Cephalosporin have good bone penetration
28. From 1st to 4th
none have activity to MRSA
Cephalosp
ornis
1st generation
cephradine (Velosef )
Cefadroxil (duricef)
cephalexine (ceporex)
2nd
generation
Cefaclor
colorcef
3rd
generation
Cefotaxime (Cefotax)
Ceftriaxone
cefoperazone (cefobid)
4th
generation
cefepime
5th
generation
Ceftaroline
29. • Cephalosporins are usually not indicated for the
treatment of endodontic infections.
• 1st generation do not have activity against the anaerobes
usually involved in endodontic infections but provide a
broad spectrum against gram positive.
• 2nd generation have some efficacy for anaerobes
• dose 250-500mg/ 6 to 8 hours
30. Third generation cephalosporins
Ceftriaxone
• used to treat Bacteremia, Bacterial Endocarditis Prevention, Bone infection,
Bronchitis, Eye Conditions, Gastroenteritis, Joint Infection, Kidney Infections,
Meningitis, Pneumonia, Salmonella Gastroenteritis, Septicemia and Urinary
Tract Infection.
this medication is given by injection into a muscle or vein
31. • 4th generation
• Broadest spectrum of action ( unisef vial-expensive )
• Active against high level cephalosporinase enzyme
5th generationNew anti- MRSA Cephalosporins ,unlike
any other beta-lactam antibiotic
Broad spectrum; active against the common Gram-
negative bacteria. Some Gram-positive activity.
• Penicillins & cephalosporins are relatively free of drug
interactions
32.
33. Beta-lactam: carpapenems
• Slightly different structure than the
other ß-lactams, make the Penems
much more resistant to beta-
lactamase hydrolysis.
• Penem: Oral administration
• Primarily for respiratory tract
infections
Imipenem(Tienam®)
Meropenen(Meronem ®)
35. • Erythromycin is prescribed for patients allergic to
penicillin; however, it is not effective against anaerobic
bacteria.
• Erythromycin is no longer recommended for treatment
of endodontic infections because of poor spectrum of
activity and GIT upset. (30mg/Kg/Day)
Azithromycin and clarithromycin
are semi-synthetic derivatives of erythromycin that
have a broader spectrum of antibacterial activity and
improved tissue penetration
Erythromycin has been showed to elevate serum level of theophyline (used for broncial asthma )
36. • •For patient with true allergy to penicillin, the primary
alternative antibiotic recommendation has changed. It
is now azithromycin with a loading dose of 500 mg,
and then 250 mg for four additional days.
• Clindamycin now has a U.S. FDA black box warning for
Clostridioides difficile infection, which can be fatal.
Therefore, it is only indicated if the patient cannot take
azithromycin.
37. Azithromycin has shown enhanced activity against the
anaerobes involved in endodontic infection.
Food and heavy metals may inhibit the of absorption
azithromycin.
Single dose daily of 500mg on empty stomach
(10mg/kg/day)
38. •Clarithromycin metabolized by both the liver and the
kidney
•Caution is warranted, however, in patients with either
kidney or liver compromise because the half-life of the
drug is prolonged. (15mg/kg/day)
•Clarithromycin has greater antibacterial spectrum and
less GIT upset
39. serious interactions
•Macrolides interact with Cisapride (Propulsid®)
(increase gut motility ) fatal heart arrhythmias.
•Macrolides push theophylline (bronchodilator) to
toxic levels
•Macrolids Interact with other drugs that share the
same metabolic pathway in liver as non sedating
antihistaminic serious cardiac arrhythmia
41. Tetracycline
•Resistance is common which limits its use
•The most directly toxic antibiotic
•Not recommended for pregnant women and
children (less than 2-8 years old) because of the
precipitation in bones and teeth of the fetus
Tetracyclines have the broadest spectrum of all
antibiotics
Bacteriostatic to gm+ve and gm-ve.
42. • Adult dose: tablets 2 to 4 doses.
Usually 250 to 500 mg
• Tetracyclines are rarely the drug of choice for facial and
dental infections
43. Quinolones
•Gram-negative and Gram-positive coverage
•Fluoroquinones are indicated for bone and
joint infections
Quinolones
1st generation
Nalidixic
acid
Floroquinolones
Ciprofloxacin
(Ciprofluxacin)
Levofloxacin
(Tavanic )
Norfloxacin
(Noracin)
Moxifloxacin
Rapid bactericidal activity
45. • Ciprofloxacin is a quinilone antibiotic that is not
effective against anaerobic bacteria usually found
in endodontic infections.
• It may be indicated with a persistent infection
46. •Fluoroquinolones are not effective against
microbes commonly seen in endodontic
infections.
•Their use in dentistry should probably be
limited to cases in which culture and
sensitivity results prove their indication.
47. • Ciprofloxacin is one of the common drugs used
for endodontic infections
• The effective action against oral anaerobes, gram
positive aerobics (Staph.aureus, Enterobacter
species and Pseudomonas) demands the need of
ciprofloxacin for endodontic infections
• Distributed in all tissue specially bone infection
48.
49. Lincosamides
Bacteriostatic
Their spectrum of activity is limited to Gram-
positive cocci and some anaerobes.
(large molecules that cannot pass through the porins)
Lincosamides
Clindamycin
(Dalacin c)
(clindam)
oraly
Lincomycin
(Lincocin)
parenterally
50. Clindamycin
• Clindamycin remains the second drug of choice
next to penicillin in treating odontogenic
infections specially for Patients who are allergic
to penicillin
• effective against 75% of cultivable
endodontic pathogens
Skucaite N, Peciuliene V, Vitkauskiene A, Machiulskiene V. Susceptibility of endodontic pathogens to antibiotics in patients
with symptomatic apical periodontitis. J Endod 2010;36:1611-6.
51. • Recommended dosage for infections
of endodontic origin is 600 mg as a
loading dose followed by 300 mg
every 6 hours,
• Not impaired by concomitant food
consumption
• Reaching peak plasma levels in 1 hour
Clindamycin
52. • Clindamycin is well distributed throughout most body
tissues and reaches a concentration in bone
approximating that of plasma.
• so bone infection and anaerobic infections are managed
by clindamycin or lincomycin
Rapidly and completely absorbed
53. Pseudomembranous colitis
A life-threatening condition in which large patches
of gut slough epithelium because of toxins from
overgrowth of the nonsusceptible organism
Clostridium difficile.
This serious condition requires hospital
management with intravenous fluids and
antibiotics specific for the causative Clostridium.
54. The first signs of this disease (i.e. diarrhea with
fever, abdominal pain, mucus and blood in the
stool)
Pseudomembranous colitis
55. Clostridium difficile was responsible for almost half a
million infections and was associated with
approximately 29,000 deaths in 2011
Pseudomembranous colitis
clindamycin, amoxicillin, cephalosporins are commonly
associated with C. difficile infection, whereas macrolides and
metronidazole are less commonly
56. • Due to its adverse side effects the routine use of
clindamycin is not advised
• pseudomembranouscolitis
• Sweet’s syndrome
• neutropenia
• One of the more common side effects of antibiotic
therapy is diarrhea, which results from the antibiotic
disrupting the normal balance of intestinal flora
57. Patients with a history of penicillin allergy and severe
gastrointestinal reactions to clindamycin require
alternative antibiotics such as macrolides or
quinolones
58. Aminoglycosids
(Bactericidal)
Gentamicin (garamycin - most nephrotoxic),Tobarmycin (most
safe), Amikacin (most ototoxic)
•Most commonly used for serious infections caused by aerobic gram
negative rods
•Not sued as monotherapy for gram positive infections but sometimes
used in combination with a beta lactam or vancomycin especially for
endocarditis.
59. Aminoglycosides are positively charged molecules which
means they rapidly enter bacteria (negatively charged)
•Cocentration-dependent killing is a pharmacodynamic
characteristic of aminoglycosides that contributes to the
clinical success of its regimens;
•the higher the level of aminoglycoside, the greater the
bactercidal.
60. •Inhibit cell wall synthesis at a site
different than the beta-lactams
• All are bactericidal
•All used for Gram-positive infections.
• (No Gram-negative activity)
•Good diffusion in all tissues
Glycopeptides
Vancomycin
MRSA (Methicillin Resistant Staph. aureus)
61. Metronidazole
• Metronidazole is a synthetic antimicrobial agent
• most effective against obligate anaerobes
• lacks activity against aerobes and facultative anaerobes.
Bactericidal
62. Metronidazole shares properties with a drug used to
help alcoholics avoid alcohol by inducing violent vomiting
{disulfiram (Antabuse®)}.
So patients taking metronidazole should avoid alcohol
Side effects include
•an unpleasant metallic taste
• brown discoloration of the urine.
These effects are dose related.
63. • Metronidazol demonstrated the greatest amount of
bacterial resistance and is only effective against
anaerobes.
• Therefore, it should not be used alone for the
treatment of endodontic infections
64. • Metronidazole may be used in combination with
penicillin or clindamycin.
• If a patient’s symptoms worsen within 48-72 hours after
initial treatment, metronidazole may be added to the
original Antibiotic
• Dose is 1,000 mg loading dose followed by 500 mg every
8 hours for five to seven days
69. Bacterial Resistance to Antibiotics
• Antibiotic resistance is not a new problem.
Resistant disease strains began emerging not long
after the discovery of antibiotics more than 70
years ago.
70. microbial resistance to antibiotics
in bacterial Infections that are caused by antibiotic-
resistant microorganisms are not only difficult to
treat, but also prolong treatment duration and
result in higher mortality rates and greater
treatment costs.
71. approximately 30% of severe dento-alveolar
infections have strains resistant to penicillin-like
drugs
Kim MK, Chuang SK, August M. Antibiotic Resistance in Severe Orofacial Infections. J Oral
Maxillofac Surg 2016.
73. Antibiotic prophylaxis
Antibiotic prophylaxis is the administration of
antibiotics to patients without evidence of infection
to prevent bacterial colonization and reduce
subsequent postoperative complications.
74. Antibiotic prophylaxis is employed for
3 main reasons:
•1- to prevent surgical infections or their
postoperative sequela
•2-to prevent metastatic bacteremias
•3- as “drugs of fear”
75. Bacteremia & dental procedures
• A study reported by Roberts et al. (1997) on 13 operative
procedures used routinely in pediatric dentistry as to
whether they caused bacteremia.
76. A randomized clinical trial compared giving 256 patients
undergoing endodontic surgery either preoperative 600 mg
tablet of clindamycin or placebo . The results were that four
patients in the placebo group and two in the clindamycin
group developed postoperative infection, and this difference
was not statistically significant.
81. Limitations of current topical or systemic
antimicrobial treatment strategies to manage
infectious diseases
Nanotechnology in Endodontics Anil Kishen and Annie Shrestha
82. Myth 1: Antibiotics cure patients
Except in patients with a compromised immune
system, antibiotics are not curative,
• but instead function to assist in the re-
establishment of the proper balance between the
host’s defenses and the invasive agent.
• Antibiotics do not cure patients; patients cure
themselves
83. Myth #2: Antibiotics are substitutes
for intervention
• Very seldom are antibiotics an appropriate
substitute for removal of the source of the
infection (extraction, endodontic treatment,
incision and drainage, periodontal scaling)
84. Myth #3: The most important decision
is which antibiotic to use.
• To avoid the adverse effects of needless
antibiotics on patients and the environment.
• the most important initial decision is not which
antibiotic to prescribe but whether to use one or
not.
85. Myth #4: Antibiotics increase the
host’s defense to infection
• Antibiotics that can penetrate into the cell
as(erythromycin, tetracycline, clindamycin and
metronidazole) are more likely to affect the host
defenses than those that cannot( nonpenetrating
agents as beta-lactams)
• Tetracyclines may suppress white cell chemotaxis;
• T- and B-lymphocyte transformation may be depressed
by tetracyclines
• Most antibiotics (except tetracycline) do not depress
phagocytosis;
86. Myth #5: Multiple antibiotics are
superior to a single antibiotic
• The combined antibiotic therapy results in a
greater selective pressure on the microbial
population to develop drug resistance.
• The broader the antibacterial spectrum of the
antimicrobials used, the greater the number
of drug-resistant microorganisms that develop,
(superinfection).
87. • Narrow spectrum antibiotics should be
considered the first choice as it produces less
alterations in the GIT flora.
88. Myth #6: Bactericidal agents are always superior
to bacteriostatic agents
• Bactericidal agents are required for patients with
impaired host defenses. However, bacteriostatic
agents are usually satisfactory when unimpaired
host’s defenses.
• Post-antibiotic effects are more reliable with
bacteriostatic agents (erythromycin, clindamycin)
than with bactericidal agents (beta-lacatam)
Post antibiotic effects (PAEs): persistent suppression of bacterial growth after previous
exposure to antibiotics. (pharmacodynamic)
91. Myth #7: Bacterial infections require a
“complete course” of antibiotic therapy.
• There is no such thing as a “complete course” of
antibiotic therapy. The only guide for determining
the effectiveness of antibiotic therapy, and the
duration of treatment, is the clinical improvement
of the patient.
92. • Orofacial infections do not “rebound” if the source
of the infection is properly eradicated.
• Most orofacial infections persist for two to seven
days, and often less.
Systemic administration of the appropriate
antibiotic dosage is usually for five to seven
days.
93. Myth #8: Antibiotic dosages, dosing intervals and
duration of therapy are established for most infections
• After more than 80 years of antibiotic usage, the
proper dosages, dosing intervals and duration of
therapy are unknown for most specific infections.
• Infectious diseases are associated with a high
number of variables that affect treatment
outcome
94. principles of antibiotic dosing
• The major factor in the clinical success of most
antimicrobial agents is the height of the serum
concentration of the drug and the resulting
amount in the infected tissue
95. Principle 1
The shorter the duration of therapy
the lower the risk to the patient for the
development of antibiotic-induced toxicity
and/or allergy
and a reduced risk of developing resistant
microorganisms
96. Principle 2
The goal of antibiotic dosing is to achieve drug levels in
the infected tissue equal to or exceeding the minimal
inhibitory concentration of the target organism
Minimal
inhibitory
concentration
(MICs)
the lowest
concentration of an
antimicrobial that will
inhibit the growth of a
microorganism after
overnight incubation
97. • Serum levels of antibiotics do not necessarily reflect
those in tissues. Blood concentrations of the antibiotic
should exceed the MIC by a factor of two to eight times
in order to offset the tissue barriers that restrict access
of the drug to the infected site.
• MIC x 4 = dosage to obtain peak achievable
concentration
98. • for beta-lactams, glycopeptides, macrolides,
and clindamycin, prolonged exposure at
concentrations greater than the MIC is the
important variable (time-dependent killing);
(constant level above the MIC)
• while increasing the level to higher multiples of
the MIC does not increase the rate of kill.
99. The higher the level of aminoglycoside,
fluoroquinolones and metronidazole
above the MIC
the greater the rate
of kill
( concentration dependent killing )
100. Principle 3
If you have a drug with a long half
life, you can achieve a target
steady state level more quickly by
using a loading dose
101. loading dose
• an initial dose that is higher than the maintenance
dose
•A loading dose of two times the
maintenance dose is recommended for
acute orofacial infections,
• which better achieves the goal of rapid,
high blood levels
102. Half-life of the drug
This is the time required for the concentration or
amount of drug in the body to be reduced by one-
half
half-life depends on how quickly the drug is
eliminated from the plasma
The removal of a drug from the plasma is known as
clearance and the distribution of the drug in body
tissues is known as the volume of distribution
103. Impairment of renal or hepatic function may
cause prolongation of the serum half-life and
accumulation of drug if the dosage or dosing
interval is not altered accordingly.
104. azithromycin has a 40-hour half-life
The average half-life of clindamycin is about 3 hours
The half-life of metronidazole is in the 8- to 10-hour range
Half-lives of most tetracycline are about 10 hours, whereas
doxycycline’s half-life is 16 hours, allowing twice-daily dosing
Penicillins have a short half-life, limited to about 1 hour
105. • The shorter the serum half-life of the
drug, the shorter the dosing interval will
need to be in order to maintain
continuous therapeutic blood levels of
the drug
106. steady state of drug
• When the rate of drug input is equal to the
rate of drug elimination, steady state has been
achieved.
• parameters associated with steady state
Dose
Dose intervals
Clearance rate
107. • Steady-state blood levels of any drug are
usually achieved in a time equal to three to
five times the drug’s half-life.
• Amoxicillin has a half-life of one to one-and-
a-half hours. A steady-state blood level
would then be achieved in three to seven
hours
108. • An oral antibiotic should ideally be administered
at dosing intervals of three to four times its
serum half-life, particularly if steady-state blood
levels are desired
• as may be indicated with beta-lactams.
• the half-life of Pen-V is 0.75 hours.
• Higher blood levels of this antibiotic are obtained
with four-hour rather than six-hour dosing
intervals.
109. life-threatening infections
• for infections when
possible, intravenous administration is usually
preferred over intramuscular,
• not only for patient comfort but because the rate
of absorption from muscle may be erratic
depending upon local perfusion
110. Cavernous sinus thrombosis
• (CST) is the formation of a blood clot within the
cavernous sinus, a cavity at the base of the
brain which drains deoxygenated blood from
the brain back to the heart.
111. • CST most commonly results from spread of
infection from a nasal furuncle (50%), sphenoidal
or ethmoidal sinuses (30%) and dental infections
(10%).
• Staphylococcus aureus is the most common
infectious microbe, found in 70% of the cases.
Streptococcus is the second leading cause.
Cavernous sinus thrombosis
112. • symptoms include:
1. decrease of vision
2. exophthalmos (bulging eyes)
3. headaches
4. paralysis of the cranial nerves which course through the
cavernous sinus.
• This infection is life-threatening and requires immediate
treatment, which usually includes antibiotics and
sometimes surgical drainage.
Cavernous sinus thrombosis
113.
114. • Broad-spectrum intravenous antibiotics are
used until a definite pathogen is found.
• Nafcillin 1.5 g IV q4h
• Cefotaxime (Cefotax,3rd) 1.5 to 2 g IV q4h
• Metronidazole 15 mg/kg load followed by 7.5 mg/kg IV q6h
• Vancomycin 2.7 g/day to cover the CNS infection and potential (MRSA)
122. Results of survey conducted on
PhD students , Endodontic department , Ain Shams university , 2015
0
5
10
15
20
25
30
35
40
45
50
Amoxicillin Penicillin Augmentin cephalosporins Macrolids Clindamycin Metronidazole
First choice of Antibiotic
126. • The authors surveyed dentists in Canada and found
that confusion about prescribing antibiotics was
evident,
• and that inappropriate antibiotic use, such as improper
dosing, duration of therapy and prophylaxis are all
factors that may affect development of antibiotic
resistant microorganisms
127. The increase in the use of amoxicillin over penicillin may be due to
the ease of use and patience compliance since penicillin has to be
taken 4 times a day before meals while amoxicillin can be taken 3
128.
129.
130. The average duration of antibiotic therapy was 6.8 days
(86.1%) chose amoxicillin in patients with no medical
allergies , alone (44.3%) or associated with clavulanic acid
(41.8%).
