Antibiotic Use In Dentistry

Introduction
Pharmacology of the
Antibiotics
 The anti-infective drugs
 Anti-infective agents are drugs that are designed to act selectively
on foreign organisms that have invaded and infected the body
Anti-infective drugs - range from
 Antibacterials
 Antifungals
 Antiprotozoals
 Antihelminthics
 Antivirals
 Antimycobacterial
 General Mechanisms of Action of anti-
infective agents

The mechanisms are:

 Inhibition the biosynthesis of bacterial cell WALL
 Inhibition of protein synthesis
 Some change the cell membrane permeability
 Some inhibit DNA synthesis
 Examples

CELL WALL penicillin,

INHIBITORS cephalosporin,
vancomycin
PROTEIN SYNTHESIS Macrolides,
INHIBITORS aminogylcosides
CELL WALL Ketoconazole
Permeability
DNA SYNTHESIS Quinolones
INHIBITORS
 Spectrum of Activity of Anti-infectives

 Narrow spectrum: Narrow spectrum anti-infectives affect only

a few bacterial types, the early penicillin drugs are examples.

 Broad-spectrum, affect many bacteria, Meropenem is an

example.
 Because narrow-spectrum antibiotics are selective, they are
more active against single organisms than the broad-
spectrum antibiotics.

 Spectrum of Activity of Anti-infectives
 Anti-infectives that interfere with the ability of the cell to
reproduce/replicate without killing them are called
BACTERIOSTATIC drugs. Tetracycline is an example.
 Antibiotics that can aggressively cause bacterial death are
called BACTERICIDAL.
 These properties (-cidal and –static) can also depend on the
antibiotic concentration in the blood. (e.g. Erythromycin and
Clindamycin may be bactericidal at higher blood levels)


 Spectrum of Activity of Anti-infectives

 Bacteriostatic
Erythromycin, tetracyclines, clindamycin, and
sulfonamides

 Bactericidal
- Penicillins, Cephalosphorins, Metronidazole,
Aminoglycosides, Vancomycin.
 Factors That Determine the Likehood Of a microorganism
Causing an Infection:

1. Virulence of the microorganism

2. Number of the microorganisms present
3. Resistance of the host
4. Existence of comorbid condition
Common Adverse Reactions to Anti-infective
Therapy

The most common adverse effects are due

to the direct action of the drugs in the
following organ system- Neuro, nephro
and GI system
Common Adverse Reactions to Anti-infective
Therapy

1. Nephrotoxicity
– Antibiotics that are metabolized and excreted in the
kidney most frequently cause kidney damage.
Common Adverse Reactions to Anti-infective
Therapy

2. Gastro-intestinal toxicity
 Direct toxic effect to the cells of the GI
tract can cause nausea, vomiting,
stomach pain and diarrhea.
 Some drugs are toxic to liver cells and
can cause hepatitis or liver failure.
Common Adverse Reactions to Anti-infective
Therapy

3. CNS toxicity
 When drugs can pass through the brain
barrier and accumulate in the nervous
tissues, they can interfere with neuronal
function..
Common Adverse Reactions to Anti-infective
Therapy

4. Hypersensitivity
 Most protein antibiotics can induce the
body’s immune system to produce
allergic responses.

 Drugs are considered foreign

substances and when taken by the
individual, it encounters the body’s
immune cells.
Common Adverse Reactions to Anti-infective
Therapy

5. Super-infections
 Opportunistic infections that develop
during the course of antibiotic therapy
are called SUPERINFECTIONS.
 β-lactam antibiotics
 Antibiotics containing β-lactam ring
 Classification (based on structure)
– Penicillins
– Cephalosporins
– Carbapenems
– Monobactams
Beta-lactamase inhibitors

17
 The PENICILLINS
Narrow spectrum penicillins
– Penicillin G
– Penicillin V
Broad Spectrum Penicillins (aminopenicillin)
– Amoxicillin
– Ampicillin
– Bacampicillin
Penicillinase-resistant Penicillin (anti-staphyloccocal penicillins)
– Cloxacillin
– Nafcillin
– Methicillin
– Dicloxacillin
– Oxacillin
Extended-Spectrum penicillins (Anti-pseudomonal penicillins)
– Carbenicillin
– Mezlocillin
– Piperacillin
– Ticacillin
-lactamase inhibitors
– Clavulanic acid
– Sulbactam
– Tazobactam
 Penicillins : Classification
Group 1: Benzyl penicillin
Pen G
Group 2: Orally absorbed penicillin
Pen V
Group 3: Staphylococcal penicillinase-resistant penicillins
Cloxacillin
Group 4: Extended or broad-spectrum penicillins
Aminopenicillins
Amidopenicillins
Group 5: Antipseudomonal penicillins
Carboxypenicillins
Ureidopenicillins
Group 6: -lactamase resistant penicillins

22
 Penicillin : Spectrum of Activity
Gram-positive Gram-negative Beta-lactamase Pseudomonas

Group 1 + 2 ++++ + Sensitive -

Pen G, Pen V

Group 3 +++ + Resistant -

Antistaph Pen S. aureus

Group 4 ++++ ++ Sensitive -

Aminopenicillins

Group 4 ++ +++ Sensitive -

Amidopenicillins

Group 5 ++++ ++ Sensitive +

Antipseudomonas

23
 Penicillin
The action of Penicillins
 The penicillin and penicillinase-resistant
penicillins produce BACTERICIDAL effects by
interfering with the ability of susceptible bacteria
to biosynthesize the framework of the cell wall.
 To be maximally effective, inhibitors of cell wall
synthesis require actively proliferating
microorganisms; they have little or no effect on
bacteria that are not growing and dividing.
 Penicillin
 Penicillins inhibit bacterial growth by interfering with the
transpeptidation reaction of bacterial cell wall synthesis.
The cell wall is a rigid outer layer that completely
surrounds the cytoplasmic membrane, maintains cell
integrity, and prevents cell lysis from high osmotic
pressure.
 The cell wall is composed of a complex, cross-linked
polymer of polysaccharides and peptides known as
peptidoglycan. The polysaccharide contains alternating
amino sugars, N-acetylglucosamine and N-acetylmuramic
acid. A five-amino-acid peptide is linked to the N-
acetylmuramic acid sugar. This peptide terminates in d-
alanyl-d-alanine.
 Penicillin-binding protein (PBP, an enzyme) removes the terminal
alanine in the process of forming a cross-link with a nearby peptide.
Cross-links give the cell wall its rigidity. Beta-lactam antibiotics,
structural analogs of the natural d-Ala-d-Ala substrate, covalently
bind to the active site of PBPs. This binding inhibits the
transpeptidation reaction and halts peptidoglycan synthesis, and the
cell dies. The exact mechanism of cell death is not completely
understood, but autolysins are involved in addition to the disruption of
cross-linking of the cell wall. -lactam antibiotics kill bacterial cells
only when they are actively growing and synthesizing cell walls.

The bacterium will have a weakened cell wall, will swell, and
then burst from the osmotic pressure within the cell.
 The penicillins are among the most widely effective
antibiotics and also the least toxic drugs known, but
increased resistance has limited their use.
 Resistance to penicillins and other β-lactams is due to one
of four general mechanisms:
 (1) inactivation of antibiotic by β-lactamase,
 (2) modification of target PBPs,
 (3) impaired penetration of drug to target PBPs (Gram–ve),
 and (4) antibiotic efflux.
 β-lactamase production is the most common mechanism of
resistance.
 Some β-lactamases are relatively narrow in substrate
specificity, preferring penicillins to cephalosporins.
 Other β-lactamases, eg, AmpC β-lactamase produced by
Pseudomonas aeruginosa and Enterobacter sp and
extended-spectrum β-lactamases (ESBLs) in
Enterobacteriaceae, hydrolyze both cephalosporins and
penicillins.
 Carbapenems are highly resistant to hydrolysis by
penicillinases
 and cephalosporinases, but they are hydrolyzed by
metallo-β-lactamases and carbapenemases.
 Penicillins : drug resistance
 Major mechanism – production of Beta-lactamases
– Penicillinases
– Cephalosporinases
– Carbapenem-hydrolyzing enzymes
 MRSA – Methicillin resistance S. aureus (Altered target PBPs are the basis of methicillin
resistance)
– MRSA – important health problem
– Order of resistance development of Staphylococci
 Non-resistant Staph sensitive to Pen G
 Resistant Staph resistant to Pen G sensitive to Methicillin
 MRSA resistant to Pen G resistant to Methicillin
32
 Penicillins : Pharmocokinetics
 Penicillins – Organic acid
 Penicillins 2 forms
– Acid-labile - Pen G parenteral route
– Acid-stable - Pen V oral route

 PK parameters in general
– Low Vd
– Short Half-life
– Distribute mostly in extracellular water
– Move hardly across biological membranes

 Excreted mostly via kidneys

33
 Absorption of most oral penicillins (amoxicillin being an exception) is impaired by
food, and the drugs should be administered at least 1–2 hours before or after a meal.
 Intravenous administration of penicillin G is preferred to the intramuscular route
because of irritation and local pain from intramuscular injection of large doses.

• Nafcillin
For penicillins that are
is primarily cleared cleared
by biliary by the
excretion. kidney, the dose must be
Oxacillin,
adjusted and
 dicloxacillin, according
cloxacillin to
are renal function,
eliminated withkidney
by both the approximately one-
and biliary excretion,
and no dosage
fourth adjustment is
to one-third required
the for these
normal dosedrugs in patients
being in renal failure.
administered if
Because clearance of penicillin sis less efficient in the newborn, doses adjusted for
creatinine clearance is 11ml/min or less
weight alone result in higher systemic concentrations for longer periods than in the
adult.
 Penicillin
Therapeutic Indications of
penicillin:
 The penicillins are indicated for
the treatment of streptococcal
infections
 Syphilis
 Tetanus
 Adverse Effects of Penicillins
 GI system effects- the major adverse
effects of penicillin therapy involve the
GIT.
 Nausea, vomiting, diarrhea, abdominal
pain, glossitis, stomatitis, gastritis, sore
mouth and furry tongue.
 The reason for some of these effects
(superinfection) is associated with the
loss of bacterial flora.
 Adverse Effects of Penicillins
 Hypersensitivity reactions- rashes,
pruritus, fever and urticaria
 These indicate mild allergic reaction.
Wheezing and diarrhea may also occur.
 Anaphylaxis can also happen leading to
shock or death. It occurs in 5-11% of
those receiving penicillins.
 Pain and inflammation on injection sites
 Adverse reactions of penicillin
 Nephritis:
 Neurotoxicity: The penicillins are irritating
to neuronal tissue, and they can provoke
seizures if injected intrathecally or if very
high blood levels are reached. Epileptic
patients are, particularly at risk.

 Penicillins : Clinical Uses
 Commonly used Penicillins
– Benzyl Penicillin
 Pen G, Pen V
– Extended-spectrum Penicillins
 Ampicillin, Amoxicillin
– Penicillins + -lactamase inhibitors
 Group 3 and Group 5
– Used for specific case of infection
– Group 3 Anti-Staph
– Group 5 Anti-Pseudomonas
39
 Penicillins and aminoglycosides: The antibacterial effects of
the β-lactam antibiotics are synergistic with the
aminoglycosides.
 Because cell wall synthesis inhibitors alter the permeability of
bacterial cells, these drugs can facilitate the entry of other
antibiotics (such as aminoglycosides) that might not ordinarily
gain access to intracellular target sites.
 This can result in enhanced antimicrobial activity.
 [Note: Although the combination of a penicillin plus an
aminoglycoside is used clinically, these drug types should
never be placed in the same infusion fluid, because on
prolonged contact, the positively charged aminoglycosides
form an inactive complex with the negatively charged
penicillins.]
Routes of administration:
Ticarcillin, carbenicillin, piperacillin, and the
combinations of ampicillin with sulbactam, ticarcillin with
clavulanic acid must be administered intravenously (IV)
or intramuscularly (IM).
Penicillin V, amoxicillin, amoxicillin combined with
clavulanic acid, and the indanyl ester of carbenicillin (for
treatment of urinary tract infections) are available only as
oral preparations.
Others are effective by the oral, IV, or IM routes.
Depot forms: Procaine penicillin G and benzathine
penicillin G are administered IM and serve as depot
forms. They are slowly absorbed into the circulation and
persist at low levels over a long time period.
 Distribution
 The β-lactam antibiotics distribute well
throughout the body.
 The penicillins cross the placental barrier,
but none has been shown to be teratogenic.
 However, penetration into certain sites, such
as bone or cerebrospinal fluid (CSF), is
insufficient for therapy unless these sites
are inflamed
 Excretion
 The primary route of excretion is through the
organic acid (tubular) secretory system of
the kidney as well as by glomerular filtration.
 Patients with impaired renal function must
have dosage regimens adjusted.
 The penicillins are also excreted into breast
milk.
 Cephalosporins
Introduction
 Effective in the treatment of strains of bacteria
affected by penicillins and some strains resistant to
penicillins
 Classification: Divided into first-, second-, third-,
and fourth-generation drugs
 Cephalosporins
 First generation Cephalosporins
– Cefazolin (Ancef) – MSSA, Surgical Prophylaxis
– Cephalexin

 Second generation Cephalosporins

– Cefoxitin
– Cefotetan
 Cephalosporins
 Third generation Cephalosporins
– Ceftriaxone – meningitis, pneumonnia,
gonorrhae
– Ceftazidime – Pseudomonas, Pyelonephritis
 Fourth generation Cephalosporins
– Cefepime – Similar to the 3rdgen. compounds,
but more resistant to hydrolysis by some β-
lactamases.
 Fifth-generation cephalosporins
 The 5th-generation cephalosporins ceftaroline
and ceftobiprole are active against
• Methicillin-resistant S. aureus (MRSA)
• Penicillin-resistant streptococci
• Ampicillin-susceptible and -lactamase–producing Enterococcus
faecalis
 Their activity against other gram-positive cocci and gram-
negative bacilli is similar to that of 3rd-generation
cephalosporins.
 The 5th-generation cephalosporins are not active
against Pseudomonas species.
z
 Cephalosporins: Actions

 Exert bactericidal effect

– Have a -lactam ring
 Targets the bacterial cell wall, making it
defective and unstable
 Cephalosporins: Uses
 Used to treat infections caused by bacteria
– Respiratory
– Ear
– Bone/joint
– Genitourinary tract infections
 Used during peri-operative period
 PHARMACOKINETICS
 Excretion is via the kidney and dose
adjustments must be made for impaired
renal function.
 Cephalosporins: Adverse Reactions
 Gastrointestinal reactions
– Nausea; vomiting; diarrhea
 Administration route reactions
– Intramuscularly; intravenously
 Cephalosporins: Adverse Reactions
(continue)
 Other body system reactions
– Headache; dizziness; malaise; heartburn; fever;
nephrotoxicity; hypersensitivity; aplastic anemia;
toxic epidermal necrolysis

 Allergy: Approximately 10% of people allergic

to penicillin are also allergic to cephalosporins
 In contrast, the incidence of allergic
reactions to cephalosporins is one to two
percent in patients not allergic to penicillin
 Cephalosporins: Contraindications and
Precautions
 Contraindicated in patients allergic to
cephalosporins or penicillins
 Used cautiously in patients with:
– Renal disease; hepatic impairment; bleeding
disorder
 Cephalosporins: Interactions
Drug Common use Effect of
interaction

Aminoglycosides Anti-infective Increased risk

for
(Gentamicin) nephrotoxicity
Oral Blood thinner Increased
anticoagulants risk for
bleeding
(Coumadin)
 Promoting an optimal response to therapy
– Oral administration: Question patient regarding
allergy to cephalosporins or penicillins
– shake oral suspensions
– Administer around the clock
– Administer orally at least 1 hour before or 2
hours after meals
– If patient experiences GI upset: Administer with
food
 Promoting an optimal response to therapy (cont’d)
 People with phenylketonuria need to be
aware that the oral suspension Cefzil
(cefprozil) contains phenylalanine
 Interferes with urine test results – diabetic
patients
 CARBAPENEMS
 IMIPENEM

 Meropenem

 Ertapenem
 ANTIBACTERIAL SPECTRUM
 Broadest antimicrobial spectrum of any
lactam antibiotic.

 Effective for Organisms resistant to

other types of antibiotics.
 MECHANISM OF ACTION
 Similar to other lactams.

 Resistant to hydrolysis by lactamases.

 PHARMACOKINETICS
Not absorbed orally; usually given IV.
Predominantly excreted by the kidneys.
Hydrolyzed by a renal tubular enzyme
(dehydropeptidase) so given combined with
cilastatin. This enzyme forms an inactive metabolite
that is potentially nephrotoxic. Compounding the
imipenem with cilastatin protects the parent drug and,
thus, prevents the formation of the toxic metabolite.
This allows the drug to be used in the treatment of
urinary tract infections.
 Lactamase inhibitors
 β-Lactamase inhibitors, such as clavulanic acid,
sulbactam, and tazobactam, contain a β-lactam ring
but, by themselves, do not have significant
antibacterial activity.
 Instead, they bind to and inactivate β--lactamases,
thereby protecting the antibiotics that are normally
substrates for these enzymes. The β--lactamase
inhibitors are therefore formulated in combination
with β--lactamase sensitive antibiotics.
 Vancomycin
 has become increasingly important because of its
effectiveness against multiple drug-resistant
organisms, such as MRSA and enterococci
 Vancomycin inhibits synthesis of bacterial cell wall
 Vancomycin is used in individuals with prosthetic
heart valves
 Vancomycin acts synergistically with the
aminoglycosides, and this combination can be
used in the treatment of enterococcal endocarditis
 vancomycin
 Side effects are a serious problem with
vancomycin and include fever, chills, and/or
phlebitis at the infusion site.
 Flushing and shock results from histamine
release associated with a rapid infusion.
 If an infusion-related reaction occurs, slow the
infusion rate to administer vancomycin over 2
hours, increase the dilution volume, or pretreat
with an antihistamine 1 hour prior to
administration. Additionally, reactions can be
treated with antihistamines and steroids.
 Dose-related hearing loss has occurred in
patients with renal failure who accumulate the
drug.
 Ototoxicity and nephrotoxicity are more
common when vancomycin is administered
with another drug (for example, an
aminoglycoside) that can also produce these
effects.
 It is not absorbed orally
 Protein synthesis inhibitors
 A number of antibiotics exert their antimicrobial effects
by targeting the bacterial ribosome, which has
components that differ structurally from those of the
mammalian cytoplasmic ribosome.
 the bacterial ribosome is smaller (70S) than the
mammalian ribosome (80S) and is composed of 50S
and 30S subunits (as compared to 60S and 40S
subunits).
 The mammalian mitochondrial ribosome,
however, more closely resembles the
bacterial ribosome.
 Thus, although drugs that interact with the
bacterial target usually spare the host cells,
high levels of drugs such as
chloramphenicol or the tetracyclines may
cause toxic effects as a result of interaction
with the host mitochondrial ribosomes.
 Tetracyclines
 As inexpensive, broad-spectrum, bacteriostatic
antibiotics, tetracyclines are effective against
gram-positive and gram-negative bacteria as
well as against organisms other than bacteria.
 Widespread resistance to tetracyclines limits
their clinical use.
 Tetracyclines are classified as:

1.Short-acting: This includes

oxytetracycline

2. Intermediate acting: This includes

demeclocycline and methacycline
(semisynthetic)
3. Long-acting, e.g., doxycycline and minocycline
which are semisynthetic derivatives

 The almost complete absorption and slow excretion of

doxycycline and minocycline allow for once-daily
dosing
 A newly approved tetracycline analog, tigecycline, Is a
semisynthetic derivative of minocycline
 MOA:
 Tetracyclines bind reversibly to the 30S subunit of
the bacterial ribosome, blocking the binding of
aminoacyl-tRNA to the acceptor site on the
mRNA-ribosome complex
 This prevents the addition of amino acids to the
growing peptide, with subsequent inhibition of
protein synthesis

Minocycline is usually the most active followed by doxycycline

•tetracycline-resistant strains may remain susceptible to doxycycline
or minocycline
 Absorption: Tetracyclines are adequately but
incompletely absorbed after oral ingestion.
 However, taking these drugs concomitantly with
dairy foods in the diet decreases absorption due to
the formation of nonabsorbable chelates of the
tetracyclines with calcium ions.
 Nonabsorbable chelates are also formed with other
divalent and trivalent cations (for example, those
found in magnesium and aluminum antacids and in
iron preparations).
tetracyclines
 Pharmacokinetics, contd.
 Tetracyclines cross the placenta to reach the fetus and are also excreted in milk. As a result of
chelation with calcium, tetracyclines are bound to—and damage—growing bones and teeth
 Tetracyclines are excreted mainly in urine and bile; Small % of the these drugs are excreted in
feces. Some of the drug excreted in bile is reabsorbed from the intestine (enterohepatic
circulation) and contributes to the maintenance of serum levels.
 Doxycycline, in contrast to other tetracyclines, is eliminated by nonrenal mechanisms (excreted in
feces), does not accumulate significantly in renal failure, and requires no dosage adjustment,
making it the tetracycline of choice for use in the setting of renal insufficiency
 Minocycline is recovered from urine and
feces in significantly lower amounts than are
the other tetracyclines, and it appears to be
metabolized to a considerable extent. Its
renal clearance is low. The drug persists in
the body long after its administration is
stopped, possibly due to retention in fatty
tissues.
 Side Effects
 Gastric discomfort: nausea, vomiting, and diarrhea.
Tetracyclines are given with food to minimize these effects
 Effects on calcified tissues: Deposition in the bone and primary
dentition occurs during calcification in growing children. This
causes discoloration and hypoplasia of the teeth and a temporary
stunting of growth.
 Hepatotoxicity:
 Phototoxicity: skin reactions and dermatitis on exposure to the
sun
 Pseudotumor cerebri: Benign, intracranial hypertension
characterized by headache and blurred vision may occur rarely in
adults.
 Superinfections
• Minocycline (the only one) causes vestibular
toxicity characterized by vertigo, dizziness,
ataxia, nausea, and vomiting
• Renal toxicity: Renal failure may be aggravated.
Outdated tetracyclines cause a syndrome like
Fanconi’s syndrome with vomiting, polyuria,
proteinuria, glycosuria and acidosis due to the
metabolites of outdated tetracyclines
 Aminoglycosides
 Aminoglycoside antibiotics had been the mainstay for
the treatment of serious infections due to aerobic gram-
negative bacilli.
 However, because their use is associated with serious
toxicities, they have been replaced to some extent by
safer antibiotics, such as the third- and fourth-generation
cephalosporins, the fluoroquinolones, and the
carbapenems.
 aminoglycosides are bactericidal. The exact mechanism
of their lethality is unknown because other antibiotics
that affect protein synthesis are generally bacteriostatic.
 The group includes streptomycin,
neomycin, kanamycin, amikacin,
gentamicin, tobramycin and others
Bacterial killing is concentration-dependent:
 The higher the concentration, the greater is the rate at
which bacteria are killed
A post-antibiotic effect (residual bactericidal activity
persisting after the serum concentration has fallen below
the MIC) is characteristic of such antibiotics; the duration of
this effect also is concentration-dependent
These properties probably account for the efficacy of once-
daily dosing regimens
 Administration: The highly polar, polycationic structure of
the aminoglycosides prevents adequate absorption after
oral administration.
 Therefore, aminoglycosides (except neomycin must be
given parenterally to achieve adequate serum levels.
[Note: The severe nephrotoxicity associated with
neomycin precludes parenteral administration.
 once-daily dosing with the aminoglycosides can be
employed; this results in fewer toxicities.
 The exceptions are pregnancy, neonatal infections, and
bacterial endocarditis, in which these agents are
administered in divided doses 8 hours apart.
 The dose that is administered is calculated based on lean
body mass because these drugs do not distribute into fat.]
 Fate: Metabolism of the aminoglycosides
does not occur in the host.
 They are rapidly excreted into the urine,
predominantly by glomerular filtration.
 Accumulation occurs in patients with renal
failure and requires dose modification.
 It is important to monitor plasma levels of
gentamicin, tobramycin, and amikacin to
avoid concentrations that cause dose-
related toxicities
 Patient factors, such as old age, previous
exposure to aminoglycosides, and liver and
kidney disease, tend to predispose patients
to adverse reactions.
Adverse effects
Ototoxicity
Deafness may be irreversible and has been known to affect fetuses in utero.
Patients simultaneously receiving another ototoxic drug, such as cisplatin or
the loop diuretics, furosemide, bumetanide, or ethacrynic acid, are
particularly at risk.
Vertigo and loss of balance may also occur because these drugs affect the
vestibular apparatus.
Nephrotoxicity
ranging from mild, reversible renal impairment to severe, acute tubular
necrosis, which can be irreversible.
other nephrotoxic antimicrobial agents (vancomycin, amphotericin) can
potentiate nephrotoxicity and should be avoided
 They produce a curare-like effect with neuromuscular blocking effect that
results in respiratory paralysis. The mechanism responsible is a decrease in
both the release of ACh from prejunctional nerve endings and the sensitivity
of the postsynaptic site
 Patients with myasthenia gravis are particularly at risk
 This paralysis is usually reversible by calcium gluconate or neostigmine
 In combination with a cell wall-active agent, such as penicillin
or vancomycin, an aminoglycoside produces a synergistic
bactericidal effect in vitro against enterococci, streptococci and
staphylococci
The aminoglycosides synergize with β-lactam antibiotics
because of the latter's action on cell wall synthesis, which
enhances diffusion of the aminoglycosides into the bacterium


Mechanisms of Antibiotic Resistance
 Resistance mechanisms:
1. Inactivation of the drug by microbial enzymes such as phosphotransferases, adenyltransferases and
acetyltransferases
 Any of these enzymes has its own aminoglycoside specificity; therefore, cross-resistance is not an invariable
rule
 Amikacin is less vulnerable to these enzymes than are the other antibiotics of this group

2. Failure of the antibiotic to penetrate intracellularly: Decrease in the active transport of the drug
3. Altering the 30S ribosome binding site of the drug  Low affinity of the drug for the bacterial
ribosome
 Any organism resistant to one aminoglycoside is not resistant to others
 Macrolides
 Erythromycin was the first of these drugs to find clinical
application, both as a drug of first choice and as an
alternative to penicillin in individuals who are allergic to β-
lactam antibiotics.
 The newer members of this family, clarithromycin and
azithromycin, have some features in common with, and
others that improve on, erythromycin.
 Telithromycin is the first ketolide antimicrobial agent that has
been approved and is now in clinical use.
 Ketolides and macrolides have very similar antimicrobial
coverage. However, the ketolides are active against many
macrolide resistant gram-positive strains
 Mechanism of action
 The macrolides bind irreversibly to a site on the 50S
subunit of the bacterial ribosome, thus inhibiting the
translocation steps of protein synthesis
 Generally considered to be bacteriostatic, they may be
bactericidal at a higher dose
 Erythromycin: This drug is effective against many of the
same organisms as penicillin G. therefore, it is used in
patients who are allergic to penicillins.
 Penicillin is the drug of choice for the prophylaxis of
recurrences of rheumatic fever. Erythromycin is an effective
alternative for individuals who are allergic to penicillin
 Because it is inactivated by gastric acid, the drug is administered with enteric
coating that dissolves in the duodenum, or as an ester (Clarithromycin,
azithromycin, and telithromycin are stable to stomach acid and are readily
absorbed)
 Food, which increases gastric acidity, may delay absorption erythromycin
(and azithromycin but can increase that of clarithromycin)

 Azithromycin's unique pharmacokinetic properties include extensive tissue

distribution and high drug concentrations within cells, resulting in much greater
concentrations of drugs in tissue compared to simultaneous serum concentrations
 The drug is slowly released from tissues (tissue half-life of 2–4 days) to
produce an elimination half-life approaching 3 days. These unique properties
permit once-daily dosing and shortening of the duration of treatment in many
cases
Drug interaction:
 Erythromycin and telithromycin are
extensively metabolized and are known to
inhibit the oxidation of a number of drugs
through their interaction with the cytochrome
P450 system .
Interference with the metabolism of drugs such
as theophylline and carbamazepine has been
reported for clarithromycin
No interactions have been reported for
azithromycin.
Excretion:
Erythromycin and azithromycin are primarily
concentrated and excreted in in the bile


In contrast, clarithromycin and its metabolites are
eliminated by the kidney as well as the liver, and it is
recommended that the dosage of this drug be adjusted
in patients with compromised renal function.
 Macrolides
Side Effects:
Epigastric distress: This side effect is common and
can lead to poor patient compliance for erythromycin.
Cholestatic jaundice:
Ototoxicity: Transient deafness has been
associated with erythromycin, especially at high
dosages.
Patients with hepatic dysfunction should be treated
cautiously with erythromycin, Telithromycin, or
azithromycin because these drugs accumulate in the
liver.
 Resistance mechanisms:
 Resistance to macrolides usually results from one of the following
mechanisms:
1. The inability of the organism to take up the antibiotic or the presence of
an efflux pump, both of which limit the amount of intracellular drug
2. Ribosomal protection by inducible or constitutive production of
methylase enzymes which modify the ribosomal target and decrease
drug binding
 This results in decreased affinity of the 50S ribosomal subunit for the
antibiotic
3. Macrolide hydrolysis by esterases
4. Chromosomal mutations that alter 50S ribosomal protein

 Because the mechanisms producing resistance to erythromycin affect

macrolides, cross-resistance among them is complete
 Contraindications:
 Patients with hepatic dysfunction should be treated cautiously with erythromycin,
telithromycin, or azithromycin because these drugs accumulate in the liver. Similar
situation with patients who are renally compromised regarding Clarithromycin.

 Telithromycin has the potential to prolong the QTc interval in some patients.
Therefore, it should be avoided in patients with congenital prolongation of
the QTc interval and in those patients with proarrhythmic conditions
 Inhibitors of bacterial protein synthesis
Clindamycin

 Clindamycin is a chlorine-substituted derivative of

lincomycin, an antibiotic produced by Streptomyces
lincolnensis

 Clindamycin mode of action:

 Clindamycin, like erythromycin, binds to the ribosomal tunnel and interferes with
protein synthesis.
 The binding site for clindamycin on the 50S subunit of the bacterial ribosome is
identical with that for erythromycin
 Clindamycin is employed primarily in the treatment of infections
caused by anaerobic bacteria, such as Bacteroides fragilis.
 However, it is also significantly active against nonenterococcal,
gram-positive cocci.
 Some strains of streptococci that are macrolide-resistant remain
susceptible to clindamycin, Resistance to clindamycin generally
confers cross-resistance to macrolides
 Clindamycin is well absorbed by the oral route.
 Penetration into bone occurs even in the absence of
inflammation.
 Clindamycin undergoes extensive oxidative metabolism to
inactive products. The drug is excreted into the bile or urine by
glomerular filtration
Adverse effects
In addition to skin rashes, the most serious
adverse effect is potentially fatal
pseudomembranous colitis caused by overgrowth
of C. difficile, which elaborates necrotizing toxins.
Oral administration of either metronidazole or
vancomycin is usually effective in controlling this
serious problem.
[Note: Vancomycin should be reserved for a
condition that does not respond to metronidazole
Impaired liver function (with or without jaundice)
It can inhibit neuromuscular transmission and may
potentiate the effect of a neuromuscular blocking agent
administered concurrently
 Quinolones
 they inhibit the replication of bacterial DNA by interfering
with the action of DNA gyrase (topoisomerase II) and
topoisomerase IV during bacterial growth and
reproduction.
 [Note: Topoisomerases are enzymes that change the
configuration or topology of DNA by a nicking, pass-
through, and resealing mechanism. They do not change
the DNA's primary sequence1
 Binding of the quinolone to both the enzyme and the DNA
forms a ternary complex that inhibits the resealing step,
and can cause cell death by inducing cleavage of the DNA.
 All the fluoroquinolones are bactericidal.
 In general, they are effective against gram-
negative organisms such as the
Enterobacteriaceae, Pseudomonas species,
Haemophilus influenzae, Moraxella catarrhalis
 The newer agents (for example, levofloxacin
and moxifloxacin) also have good activity
against some gram-positive organisms .
 Moxifloxacin has activity against many
anaerobes.
 Ingestion of the fluoroquinolones with
sucralfate, antacids containing aluminum or
magnesium, or dietary supplements
containing iron or zinc can interfere with the
absorption of these antibacterial drugs.
 Calcium and other divalent cations have also
been shown to interfere with the absorption of
these agents.
 The fluoroquinolones with the longest half-
lives (levofloxacin and moxifloxacin) permit
once-daily dosing.
 All the fluoroquinolones distribute well into
all tissues and body fluids.
 Levels are high in bone
 They are excreted by the renal route.
 quinolones
 Gastrointestinal
 Central nervous system problems: headache and
dizziness Thus, patients with CNS disorders, such as
epilepsy, should be treated cautiously with these drugs.
[Note: Ciprofloxacin interferes in the metabolism of
theophylline and may evoke seizures.]
 Phototoxicity: Patients taking fluoroquinolones are
advised to avoid excessive sunlight and to apply
sunscreens.
 However, the latter may not protect completely. Thus, it
is advisable that the drug should be discontinued at the
first sign of phototoxicity.
 3
 Connective tissue problems:
Fluoroquinolones should be avoided in
pregnancy, in nursing mothers, and in children
under 18 years of age, because articular
cartilage erosion (arthropathy) occurs in
immature experimental animals.
In adults, fluoroquinolones can infrequently cause
ruptured tendons.
 Moxifloxacin may prolong the QTc interval and,
thus, should not be used in patients who are
predisposed to arrhythmias or are taking
antiarrhythmic medications.
 CONTRAINDICATIONS
AMINOGLYCOSIDES contraindicated in
1. allergies to aminoglycosides
2. renal failure
3. hepatic disease
4. pre-existing hearing loss
5. myasthenia gravis
6. Parkinson’s
7. pregnancy and lactation.
 Macrolides contraindicated in
1. the presence of known allergy to any
macrolide, because cross-sensitivity
occurs
2. Caution should be used in patients with
hepatic dysfunction that could alter the
metabolism of the drug
3. in lactating women because of drug
excretion in breast milk
4. in pregnant women because potential
adverse effects on the developing fetus
 tetracyclines

1. not recommended for use in pregnancy

and lactation because the drug can affect
the bones and teeth, causing permanent
discoloration and sometimes arrest of
growth.

2. Tetracyclines are also avoided in children

less than 8 (eight) years of age because of
the potential damage to the bones and
permanent discoloration of the teeth.
3. Avoided in renal failure only doxycycline.
 Quinonlones Contraindicated in
1. Pregnancy and lactation

2. These agents are found to cause

significant damage to the cartilages such
that they are given cautiously to growing
children and adolescents less than 18
years of age
Sulfonamides These agents are contraindicated to
1. patients with known allergy to sulfa drugs,
sulfonylureas and thiazide diuretics because they
share similar structures.
2. It is not recommended for use in pregnancy
because it can cross the placenta and cause birth
defects and kernicterus.
3. Lactating women who take these drugs will
excrete them in the breast milk potentially
causing kernicterus, diarrhea and rash in the
newborn.
In Summary….
 Antibiotic Choice
 Narrow Spectrum?
 Extended/Broad Spectrum?
 Gram positive
 Gram negative
 mixed
 Anaerobes? Consider if the infection is
present > 3days or if no improvement.
 Broad Spectrum Antibiotics
 Affects both Gram + and Gram – bacteria,
better for mixed infections.
 Examples: Amoxicillin, Ampicillin
 Narrow Spectrum Antibiotics
 Specific for the pathogen.
 Fewer disturbances of non-pathogenic
bacteria.
 Fewer side effects.
 Rapid response for sensitive organisms.
 Ex: Pen VK, Pen G, Erythromycin
 Principles of Antibiotic Therapy

 Therapeutic effectiveness
– Clinical indications
 Pharmcodynamics, pharmacokinetics
– Age and extent of infection
 Patient factors
 Age, allergies, compliance, pregnancy risk
 Patient function
– Renal, hepatic, immunosuppresion, route
applicability
 Cost
– Brand name, length of course, alternatives?
 Penicillin G administered parenterally or
penicillin V administered orally are currently
the antibiotics of choice for treatment of dental
infections of usual etiology.

 Infections caused by penicillinase-producing

staphylococci or those involving gram-
negative bacteria should be treated with a
penicillinase-resistant penicillin or an
ampicillin-like derivative, respectively.
 Erythromycin is a second-choice bacteriostatic
antibiotic, becoming first choice for treating
dental infections in patients allergic to penicillin.

 The cephalosporins, similar in action to

ampicillin-like penicillin derivatives, may be
used with caution in patients who have
exhibited delayed-type allergic reactions to
penicillin and when erythromycin cannot be
used. Their lack of advantage over other
agents, and their cost, precludes routine use
for usual dental infections.
 Clindamycin indicated for treatment of bone
infections and/or anaerobic infections refractory to
commonly used antibiotics.
 Tetracyclines are, at best, third-choice agents for
usual dental infections. However, they are useful
for cases of acute necrotizing ulcerative gingivitis
requiring systemic antibiotic therapy when
penicillin is precluded.
 Vancomycin and streptomycin are used
prophylactically for prevention of infective
endocarditis in patients with prosthetic heart
valves.
 Nystatin remains a first-choice agent for
treatment of oral candidal infections.
 Ketoconazole, an orally active systemic
antifungal agent, may be used for monilial
infections of the oral cavity refractory to
nystatin.
 Chemotherapy of viral infections is difficult
because lack of effective agents with
selective toxicity.
 Herpes infections of the oral cavity have
been treated--with limited success--with
idoxuridine.
 Acyclovir offers little clinical benefit for
herpes infections in usually healthy patients
but may be of value for treating such
infections in immunocompromised patients.
 All antimicrobial agents may cause adverse
reactions of varying degrees of severity.
 Most orally administered antibiotics may cause
gastrointestinal disturbances. Superinfections
occur with broad-spectrum antibiotics and a
severe form of superinfection, antibiotic-
associated colitis, has occurred with almost all
antibiotics.
 Allergic reactions of all degrees of severity can
occur with most antibiotics. The penicillins,
followed by the cephalosporins and tetracyclines,
are most frequently implicated in these reactions.
 Dental Infection

Acute—Rapid growth
Chronic > 3 days
< 3 days

Pen VK 500mg q6h or Think Anaerobes

Amox 500mg q8h or Add Metronidazole 250-500mg
Cephalosporin To PCN, Amox, or Ceph

Allergic to PCN Clindamycin 300mg q8h

Clindamycin 300mg q8h or

Cephalosporin (check allergic Rxn) or
Azith or Clarithromycin
 The association amoxicillin-clavulanate was
the drug most frequently prescribed by
dentists during 2005.
 The use of antibiotics in dental practice is
characterized by empirical prescription
based on clinical and bacteriological
epidemiological factors, with the use of
broad spectrum antibiotics for short periods
of time, and the application of a very narrow
range of antibiotics.
 The simultaneous prescription of NSAIDs
can modify the bioavailability of the
antibiotic.
 In turn, an increased number of bacterial
strains resistant to conventional antibiotics
are found in the oral cavity.
 Pregnancy, kidney failure and liver failure
are situations requiring special caution on
the part of the clinician when indicating
antibiotic treatment.
 Antibiotic Strategies
Cardinal Rules:
1) Use the right drug.
2) Use the right dose.
3) Use the correct dosing schedule.
4) Correct duration.
 Hard and Fast
 Use a loading dose to rapidly achieve therapeutic
blood levels.
 Avoid combinations of bacteriostatic and
bacteriocidal drugs.
 Bacteriostatic
Erythromycin, tetracyclines,
clindamycin, chloramphenicol,
spectinomycin, sulfonamides
Erythromycin and Clindamycin may be
bactericidal at higher blood levels
 Common pathogens in oral cavity
the list of bacteria related with oral infections is
relatively long (cocci, bacilli, gram positive and gram
negative organisms, aerobes and anaerobes).
Necrotic pulp and apical abscesses
Obligate anaerobic bacteria
Gram negative rods
Prevotella & porphyomonas spp. (resistance)
Fusobacterium spp.
Campylobacter rectus
Gram positive rods
Eubacterium spp.
Actinomycetes spp.
Gram positive cocci
Peptostreptococcus spp.
Facultative anaerobic bacteria
Gram positive cocci
Strep and Entercoccus spp.
 Periodontal Diseases
Gingivitis
Fuso, strep, & actinomycetes
Adult periodontitis
Bacteroides, porphyomonas, peptostreptococcus
& prevotella
Acute necrotizing ulcerative gingivitis
Spirochetes, prevotella, fuso
Localized juvenile periodontitis
Actinobacillus
 Streptococcus mutans – causing dental caries ( most
common dental infection)
treatment of choice: local physical removal of microbial
plaque on a regular basis( good oral hygiene)
 Antibiotics are typically prescribed in dental
practice for some of the following purposes:
(a) as treatment for acute odontogenic
infections;
 (b) as treatment for non-odontogenic
infections;
 (c) as prophylaxis against focal infection in
patients at risk (endocarditis and joint
prostheses); and
 (d) as prophylaxis against local infection and
systemic spread in oral surgery.
 TREATMENT OF THE ACUTE
ODONTOGENIC INFECTION
 Despite the high incidence of odontogenic
infections, there are no uniform criteria
regarding the use of antibiotics to treat them.
 It is suggested that treatment should be
provided in ulcerative necrotizing gingivitis,
in periapical abscesses, in aggressive
periodontitis, and in severe infections of
the fascial layers and deep tissues of the
head and neck.
 They do not recommend antibiotic treatment
in chronic gingivitis or periodontal
abscesses (except in the presence of
dissemination).
 There is considerable agreement that the
beta-lactam derivatives are the antibiotics of
choice for these processes, provided there
are no allergies or intolerances. However,
there is less consensus regarding which
drug belonging this family should be
prescribed.
 While some authors consider the natural and
semisynthetic penicillins (amoxicillin) to be the
options of first choice, others prefer the
association amoxicillin-clavulanate, due to the
growing number of bacterial resistance, as well as
its broad spectrum, pharmacokinetic profile,
tolerance and dosing characteristics.

 As has been commented above, some authors

have proposed clindamycin as the drug of choice,
in view of its good absorption, low incidence of
bacterial resistances, and the high antibiotic
concentrations reached in bone.
 TREATMENT OF NON-
ODONTOGENIC INFECTIONS
 Non-odontogenic infections include specific
infections of the oral cavity (tuberculosis,
syphilis, leprosy), and nonspecific infections
of the mucosal membranes, muscles and
fascias, salivary glands and bone. Bone
infections are included here on the grounds
that many of them may be of dental origin.
 These processes require prolonged
treatments, and drug associations are used
that usually include clindamycin, due to its
capacity to reach high concentrations in
bone, and fluorquinolones (ciprofloxacin,
norfloxacin, moxifloxacin) – to extend the
bacterial spectrum to include gram
negative bacilli, gram positive aerobic
cocci and, in the case of third generation
fluorquinolones (moxifloxacin), anaerobes.
 It is recommended that empirical treatment
with betalactams associated to
fluorquinolones should be limited, since both
groups of antibiotics activate common
resistance mechanisms – thus favoring the
appearance of resistances in important
pathogens such as Pseudomona
aeruginosa and Acinetobacter spp
 The treatment of specific infections caused by
mycobacteria requires the use of antibiotics
for long periods of time (from 6 months to 2
years), and includes the administration of
dapsone (a sulfamide analog), clofazimine (a
dye with bactericidal action) and rifampicin for
leprosy, and associations of ethambutol,
isoniazid, rifampicin, pyrazinamide and
streptomycin for tuberculosis.
 The treatment of syphilis, caused by
Treponema pallidum, is based on the use of
penicillin G benzatine.
 Administration comprises 2.4 million IU in a
single intramuscular dose in the primary
period, three doses of 2.4 million IU via the
intramuscular route, spaced one week apart,
in the secondary period. In the tertiary
period a first treatment is provided with
intravenous penicillin G, followed by
penicillin G benzatine via the intramuscular
route once a week during 3 weeks, involving
a dose of 2.4 million IU each.
 PROPHYLAXIS OF FOCAL
INFECTION
 The use of antibiotics as prophylaxis for
focal infection is common practice, and has
been widely accepted in the dental
profession. The paradigm of this model of
treatment is the prevention of bacterial
endocarditis, indicated in risk patients in the
context of any invasive procedure within the
oral cavity.
 Prophylaxis for Gastrointestinal and
Genitourinary Procedures: (Gram-negative
procedures)
Parenteral: Ampicillin 2 g IV plus Gentamicin:
1.5 mg/kg IM or IV (not to exceed 80mg) 30 min
before procedure; followed by ampicillin 1 g IV 6
hr later

Penicillin Allergy: Vancomycin 1 g IV infused

slowly over 1 hr plus Gentamycin 1.5 mg/kg IM
or IV ( not to exceed 80 mg) 1 hr before
procedure
 Antibiotic prophylaxis is NOT
recommended for dental patients
with plates, pins, or screws, nor is
it routinely recommended for
MOST dental patients with TOTAL
JOINT REPLACEMENTS.
 AAOS recommendations
 Prophylaxis recommended
– Total joint replacement within the last two years
AND:
 Compromised immune system OR
 Type 1 DM OR
 Previous prosthetic joint infections OR
 Malnourishment OR
 Hemophilia
PROPHYLAXIS OF LOCAL INFECTION
AND SYSTEMIC SPREAD
 Prophylaxis of local infection is taken to
comprise the administration of antibiotics on
a pre-, intra- or postoperative basis, to
prevent bacterial proliferation and
dissemination within and from the surgical
wound.
 prophylaxis in oral surgery in a healthy patient
was only recommended in the case of the
removal of impacted teeth, periapical surgery,
bone surgery, implant surgery, bone grafting and
surgery for benign tumors.
 In subjects with risk factors for local or
systemic infection - including oncological
patients, immune suppressed individuals,
patients with metabolic disorders such as
diabetes, and splenectomized patients,
prophylactic antibiotic coverage should be
provided before attempting any invasive
procedure.
 Antibiotics and pregnancy
 group B (i.e., warranting caution with treatment
during pregnancy) contains the following
antibiotics: azithromycin, cephalosporins,
erythromycin, metronidazole and penicillins with
or without beta-lactamase inhibitors.
 Group C in turn includes clarithromycin, the
fluorquinolones and the sulfa drugs (including
dapsone).
 group D contains the aminoglycosides and
tetracyclines
 ANTIBIOTIC USE IN RENAL FAILURE
 Many antibiotics are actively eliminated
through the kidneys.
 The presence of impaired renal function
requires reduction of the drug dose in order to
avoid excessively elevated plasma drug
concentrations that could lead to toxicity.
 dose adjustment can be carried out by
reducing the amount administered in each
dose or by increasing the interval between
doses (without modifying the amount of drug).
 ANTIBIOTICS AND LIVER DISEASE
 Some antibiotics are metabolized in the
liver, followed by elimination in bile.
 In patients with liver failure, the use of such
antibiotics should be restricted in order to
avoid toxicity secondary to overdose.
 Erythromycin, clindamycin, metronidazole
and anti-tuberculosis drugs are antibiotics
requiring dose adjustments when
administered to patients with liver failure.
 Regardless of the above considerations,
some antibiotics are potentially hepatotoxic.
As a result, and whenever possible, they
should be avoided in patients with some
active liver disorder. Specifically,
tetracyclines and anti-tuberculosis drugs
should be avoided
 Potentially Periodontopathic
Bacteria:
 Adult peiodontitis
- Bacteriodes gingivalis
- B. intermedius
- Fusobacterium nucleatum
- Veillonella parvula
- Actinomyces (naestundii, israelli, viscosus)

Localized Juvenile Periodontitis

- Actinobacillus actinomycetemcomitans
- Capnocytophaga sp.
 Streptococcus mutans – causing dental
caries ( most common dental infection)
treatment of choice: local physical removal
of microbial plaque on a regular basis( good
oral hygiene)
 Antimicrobial use in dentistry
Infection/Situation Drug of Choice Alternative drugs
Periodontal Disease
ANUG (Vincent) Penicillin V Metronidazole
Tetracycline

Abscess (perio) Penicillin V Erythromycin

Tetracycline
Periodontitis
Juvenile Tetracycline ----
Adult Tetracycline Metronidazole
Clindamycin
Oral Infections
Soft tissue (abscess, cellulitis, post Penicillin V Erythromycin, Cephalosporin, Clindamycin,
surgical pericornitis) Tetracycline
Osteomyelitis Penicillin V Cephalosporin, Clindamycin, Erythromycin

Penicillinase-producing staphylococci Cloxacillin Cephalosporin, Clindamycin

Mixed infection insensitive to penicillin
Aerobes Amoxicillin Cephalosporin, Sulfonamides,Tetracycline
Anaerobes Clindamycin Cephalosporin, Metronidazole,
Erythromycin, Tetracycline
Prophylactic for Infective endocarditis
Rheumatic heart Disease Penicillin V Erythromycin, (Cephalosporin)
prosthetic Heart valve Ampicillin +
gentamicin
I. Prophylaxis treatment For Infective Endocarditis:
Prophylaxis for dental, oral, upper respiratory tract or esophageal procedures: (Gram –
positive organisms)
Oral: Amoxycillin 2 g orally 1 hr before procedure; children 50mg/kg orally 1 hr before
procedure

Penicillin allergy: Clindamycin 600mg orally 1hr before procedure or Cephalexin 2 g

orally 1 hr before procedure

Parenteral: Ampicillin 2 g IM or IV 30 min before procedure

II. Prophylaxis for Gastrointestinal and Genitourinary Procedures:(Gram-negative

procedures)
Parenteral: Ampicillin 2 g IV plus Gentamicin 1.5 mg/kg IM or IV (not to exceed 80mg)
30 min before procedure; followed by ampicillin 1 g IV 6 hr later

Penicillin Allergy: Vancomycin 1 g IV infused slowly over 1 hr plus Gentamycin 1.5

mg/kg IM or IV ( not to exceed 80 mg) 1 hr before procedure
4. Hypersensitivity
 Most protein antibiotics can induce the
body’s immune system to produce
allergic responses.
 Drugs are considered foreign substances
and when taken by the individual, it
encounters the body’s immune cells.
5. Super-infections
 Opportunistic infections that develop
during the course of antibiotic therapy
are called SUPERINFECTIONS.