Anti-infectives therapy in

the dental setting Dr.Firoozed Samim

DMD, Msc, FRCDC, DIP:
Sep 19,2020 ABOMP
Disclosure of Potential conflict
of interest
• No conflict of interest; no remuneration
from any companies

• No financial interests of any nature in a

business, corporation/ pharmaceutical
company

• All of the patients have given consent for

the use of their image
Outline

• Introduction and Review of Cases

• Antibiotics
• Antiviral agents
• Antifungal Drugs
• Antibiotic Prophylaxis
Objectives

• To be able to prescribe appropriate anti-

The image part with relationship ID rId2 was
not found in the file. infective for your patient

• To identify anti-infective mechanism of

actions and their side effects
 • 19-year-old female
• CC: intraoral swelling between tooth 1.5 and 1.6 with pus
discharge
Case 1 • What do you do next?
• What are the treatment options? Would you prescribe AB?
More information

• Patient is Healthy
• No systemic involvement or
constitutional symptoms

• Incision and drainage

• Gray area of prescribing or not
prescribing AB
 The image part with relationship ID rId2 was
not found in the file.

Prescribing
Principle
• 3 indications for the use in dental practice
1. Treatment of acute or chronic infections of odontogenic
and non-odontogenic origins
2. Prophylactic treatment to prevent focal infection in
patients at risk
3. Prevention of local infection and systemic spread among
patients undergoing surgical oral or dental treatment
AB therapy

Advantages 😃 Disadvantages 😒
• Reduce numbers of bacteria in • Adverse effects such as
both periodontal and non • allergic or anaphylactic reactions
periodontal sites such as tonsils • superinfections of opportunistic bacteria
and tongue • development of resistant bacteria
• upset stomach
• nausea
• Treatment of several sites at the • Vomiting
same time
• Patient compliance
• Low cost
• interactions with other medications
General • Remove the cause of the infection is the
most important of all

Guidelines • I&D
• Med Hx and presents of the constitutional
symptoms
• Antibiotics are really an adjunctive therapy
Evaluate your • Severity of Infection
• Patients host defenses
patient • Treating the infection surgically (I&D)

carefully • Treating with antibiotics if necessary

 Case 2

• Emergency: 27-year old patient

• painful tooth #16 ; need extraction:
might be complicated
• no swelling , no trismus or increase in
temperature or constitutional symptoms
• Otherwise healthy
• Would you administer antibiotics to him
following an extraction,
• WHY ?
Principal Considerations in Antibacterial therapy

1. Establish a clear indication for AB therapy

• The patient presents with malaise, fever, chills, trismus, rapid
The image part with relationship ID rId2 was
respiration, swelling, lymphadenopathy, or hypotension
not found in the file.

• The signs and symptoms of infection escalated rapidly (within

24–48 hours)

• Oral soft tissue swelling appears to be spreading into adjacent

anatomical spaces and affects breathing and swallowing
Principal Considerations in Antibacterial therapy

• 2. Determine the patient’s health status:

The image part with relationship ID rId2 was
not found in the file.
• Systemic considerations (heart disease, total joint
replacement, neutropenia, splenectomy, diabetes mellitus,
end-stage renal disease, organ transplant, HIV infection,
hepatic dysfunction, pregnancy, and immune status)

• History of adverse drug events /allergy

• Potential drug-drug interactions

 Principal Considerations in Antibacterial therapy

3. Select an appropriate antibacterial agent with a narrow

spectrum and low toxicity:
The image part with relationship ID rId3 was not found in the
o Immune status of the patient
file.

• Bactericidal versus bacteriostatic antibacterial agent

• Empirical therapy (correlate to most likely organisms

associated with odontogenic infections)

• Focused therapy (correlate to culture and susceptibility tests)

(can’t always wait for results of bacterial assessment before
initiating treatment – could take up to 48hr.)
Principal Considerations in Antibacterial therapy

4. Establish dosage regimen, duration of therapy, and route of

administration:
• Consider the seriousness of the illness
• Consider potential compliance issues
• narrow spectrum cause less alteration in normal microflora
• Narrow spectrum: effective mainly against gram +ve or gram –ve
microorganisms, but not both
• Broad spectrum: inhibit both gram+ve& gram–ve and frequently other
microorganisms
 Principal Considerations in Antibacterial therapy

5. Follow-up in 48 to 72 hours;

• note that patients initially presenting with signs of impending airway

compromise, marked trismus (<25 mm), or dehydration (e.g., marked malaise,
disorientation, tachycardia) should be admitted to the hospital for urgent or
emergency care.

• Determine efficacy
a. Inadequate bacteriological information
b. Administration of suboptimal doses of the antibacterial agent
c. Inadequate debridement
d. Ability of the drug to reach the site of infection

• Monitor patient for adverse drug effects; level of conciseness , temperature

 Principal Considerations in Antibacterial therapy

5. Follow-up in 48 to 72 hours;

o Telephone follow-up is not reliable

o In general ANTIBIOTICS are prescribed for 7 days or until 3 days after symptoms
have resolved

o Give the patient very clear instructions

o Written instructions are always best

o Review instructions with the patient

Case 3
• 32-year old with left mandibular swelling
• X-ray

• How do you treat this patient?

Conditions
• Reversible pulpitis
• Irreversible pulpitis : would
you prescribe AB?
• Apical periodontitis
• Periodontitis
• Pericoronitis
• Cellulitis and abscess
 AB selection

Host-specific pharmacologic
factors factors
AB selection

Host factors pharmacologic factors

• Microbiology of odontogenic infections; • Spectrum of antibiotics ( sensitivity of
Most dental infection by gram +ve aerobes micro-organiam) ; narrow spectrum
and gram +ve & -ve anaerobes, generally
susceptible to penicillin • pharmacokinetics (serum concentrations
needed to kill bacteria or the time necessary to maintain
• history of allergic responses or intolerance adequate serum levels
• previous antibiotic therapy • tissue distribution of
• age antimicrobials (because abscess cavities
are avascular)
• pregnancy status
• immune system status • cost of antibiotics
• adverse reactions and
interaction
 Bacteriostatic Versus
Bactericidal Antibiotics

• Bacteriostatic: prevent the

growth of bacteria such as
• Tetracycline
• Clindamycin

• bactericidal antibiotics:
actually kill the bacteria,
less depend on the host
immune system
• Penicillin
• metronidazole
Basic Principals

• Hit hard, fast and early.

• Use the right drug.
• Use the right dose.
• Use the correct dosing schedule
• Use for the correct duration.
Short course antibiotic prescriptions ( drug
characteristics)

• Rapid onset of action

• Bactericidal activity
The image part with relationship ID rId2 was
• Inability to induce resistant mutants
not found in the file.
• Ease of penetration into tissues
• Activity against non-dividing bacteria not normal flora
• Unaffected by adverse infection conditions
• Administration at an optimal dose (effect at low
concentration)
• Given at an optimal dosing regimen ( long enough)
MECHANISMS OF ACTION
MOA
inhibition of cell wall β-lactam antibiotics and Penicillins, vancomycin
synthesis glycopeptides. cephalosporins
alteration of cell by displacing Ca2+ and Mg++ from Nystatin, {Amphotericin B}
membrane integrity membrane lipid phosphate group {Isoniazid}
inhibition of ribosomal either the 30S or 50S ribosomal subunit. 50 s: Macrolides ;erythromycin,
protein synthesis clindamycin,
30 S: tetracyclines, aminoglycosides
suppression of By inhibition of DNA gyrase and ciprofloxin (quinolones)
deoxyribonucleic acid topoisomerase IV, inhibition of DNA- Metronidazole
(DNA) synthesis dependent RNA polymerase, and damage to Fluoroquinolones
DNA
inhibition of folic acid inhibit sequential steps in the bacterial Sulfonamides and trimethoprim
synthesis (antimetabolic) synthesis of folic acid essential for one-
carbon transfers in nucleic acid synthesis
Medical management of
odontogenic infections
• The routine use of antibacterial agents for the
management of odontogenic infections has
not been shown to be effective.

• Most of these infections can be resolved

satisfactorily through debridement (primary
dental care) to reduce the microbial load.
Microbiology of Odontogenic Infection

• Odontogenic infections are characterized as a combination of

aerobic(cellulitis) and anaerobic bacteria ( abscess) or facultative (
mixed infection).

• Most common organisms responsible for odontogenic infections are

1. viridans streptococci (Streptococcus oralis, S. sanguis, and S. mitis)
2. Actinomyces
3. Peptostreptococcus The image part with relationship ID rId2
was not found in the file.
4. Fusobacterium
5. pigmented and non- pigmented Prevotella
6. Gemella, Porphyromonas, Bacteroides, and Veillonella.
Odontogenic infections

• Obtain your culture before you perform your incision

The image part with relationship ID rId2 was
and drainage
not found in the file.
• cultures should be taken for any patient who is
medically compromised
• culture all serious infections

• Penicillin is always your first choice unless there is an

allergy
 Penicillin is always your first choice unless
there is an allergy
General information For dental use
• 300 mg q6h X 7 days; May use a
loading dose of 600mg
• penicillin V (potassium) ( APO-
PENVK or PEN VEE K ) • If Severe infection
• 300 or 600mg q6h for 5-10/d 600mg. q6h x7 days
• Supplied as 300 mg. tabs • Caution elderly or frail patient
• Max: 3000mg/day use 300mg
• Compliance problem
Amoxicillin 500 mg q8h
Note

The image part with relationship ID

rId2 was not found in the file.
• Clear instruction
• Remember to include ” to take until all finished
Second choice : Amoxicillin
General information
• Broad-spectrum
• APO-AMOXI, NOVAMOX
• 500mg. q8h X 7-10 days
• supplied as 250 or 500 mg. caps
• Max: 4000 mg/d
• AVOID penicillin Allergy
Dentistry
• 500mg q8h x 7 days
for resistant infections:
• amoxicillin/clavulanic acid (
CLAVULIN )
250/125 mg. q8h or
• 500/125 q12h X 7-10 days
• if more severe:
500/125 q8h or 875/125 q12h
The image part with relationship ID rId2
was not found in the file.
Ab of choice for
odontogenic infection
• If no significant improvement in 48-72
hours

The image part with relationship ID rId2

was not found in the file.
• Refer patient to the hospital
• Consider adding an additional
antibiotic - metronidazole
• Do not stop penicillin or amoxicillin
but consider adding Metronidazole
No significant improvement after 48-72 h
Add metronidazole to penicillin or amoxicillin
General Dentistry
• Metronidazole • (Note: if added to Amoxicillin,
• 250 mg. q6h X 7 days the prescription would be q8h)
• supplied as 250mg. Tabs • often used in combination with
amoxicillin in mixed infections
• good for the management of
chronic infections with obligate
anaerobic bacteria
 First Choice if allergic to Penicillin;
Clindamycin

• clindamycin 150-300mg.
The image part with relationship ID rId2 was
not found in the file.
• supplied as 150 or 300 mg. caps.
• q6h X 7 days
• May be prescribed for 10 days, and the dose may
vary from 150-450 mg.
• Serious infections with bone involvement –
clindamycin
• Osteomyelitis – referral to hospital based OMFS
Other Macrolides

• Reserved for patients with an allergy to Penicillin and with a

relatively mild infection
The image part with relationship ID rId3 was
not found in the file.
• azithromycin (ZITHROMAX)
• 500 mg. (single dose) day 1; then 250 mg. qd x 4days
• (supplied as 250 mg. tablets)

• clarithromycin (BIAXIN)
• 250-500 mg. bid X 7 days
• (supplied as 250 mg. Tabs)
Case 4

• 24-year-old patient an abscess involving teeth

36 and 37
2 years ago before RCT
• RCT 2 years ago
• Mild discomfort since then
• Acute exacerbation of the chronic condition
presented as severe pain with localized
swelling

Recent radiograph
Culture
Actinomycosis
Actinomycosis

• Oral penicillin V (2 to 4 g per day, divided into four daily doses)

• Oral amoxicillin (1.5 to 3 g per day, divided into three or four daily
doses)
• In cases where copathogens are suspected, oral amoxicillin-clavulanate
• For 5- to 6-week course of penicillin; patients with deep-seated
infections may require up to 12 months.
• Refer to oral and maxillofacial surgeon
Case 5

• Extraction of impacted 45
• CC: “painful site of extraction+ swelling after a week
• Two weeks later, swelling and pain still persist +
numbness ; AB prescribed ( amoxicillin) + analgesics (
ibuprofen) for 3 weeks
• One month later, severe still pain at the area ; dentist
change the AB to clindamycin
• What is the most likely diagnosis? Why the pain still
persist?
Red flags in this case

• Persistent pain for more than a week

• Prescribing too much AB without knowing what the problem was

Osteomyelitis
• Surgical intervention to
1) resolve the source of infection,
2) establish drainage,
3) removal of obviously infected bone
4) obtain bacteriologic samples for culture and antibiotic sensitivity testing.
5)While waiting on the bacteriologic evaluation, antibiotics are administered
empirically, usually penicillin with metronidazole or clindamycin usually for 10-
14 days at least
 • 20-year-old female
• CC: “extremely painful gums” + chills for
the past two days.
• her temperature at 102 °F.
• Clinical examination: punched-out
interdental papillae, gingival bleeding,
abundant plaque, and a fetid odor.
• What is the most likely diagnosis?
• How would you treat this patient?
• Would you use systemic medications for
treatment?
• Describe potential and typical adverse
effects of your prescription(s).

Case 6
Case 6
• Diagnosis: acute necrotizing ulcerative gingivitis (ANUG).
• The patient’s chills and temperature indicate that she has signs of a
systemic infection, most likely due to the spread of the oral infection.
• You do two things at the first appointment:
• (1) debridement
• (2) prescribe amoxicillin 500 mg t.i.d. for 7 to 10 days.
• Although ANUG should be treated by local debridement, you reason
that the antibacterial drug is needed to reduce the systemic
involvement. Amoxicillin is an extended-spectrum penicillin.
Case 6
• When you begin debridement, the patient may complain of pain. As a
result you may use mild ultrasonic scaling to remove some of the
supragingival plaque in the first appointment.
• Give patient instructions on good oral hygiene, proper diet, and, if the
patient is a smoker, to enter a smoking cessation program.
• You instruct the patient to call in three days to check on progress. You
find that the patient is much better in three days and then schedule a
second appointment to complete the scaling and removal of plaque.
Case 6
• Adverse effects of amoxicillin or other penicillins include
• allergies that can range from mild to anaphylactic reactions.
• Amoxicillin is an extended-spectrum antibiotic. This could lead to a
superinfection if given for several days.
• Amoxicillin is usually well tolerated.
• You might add metronidazole 250 mg as well
PERIODONTITIS

• Antibiotics may be used as adjunctive therapy in certain

forms of periodontal disease, especially the aggressive
forms
• NEVER USED WITHOUT OTHER TREATMENTS – SCALING
AND ROOT PLANING
• Best prescribed by the periodontist
• May be used in patients with periodontitis that DO NOT
responded to conventional therapies
• ANTIBIOTICS are always considered as an adjunct and
NEVER replace scaling and root planing
Aggressive periodontitis in adults

• No best antibiotic ; the microflora associated with

periodontitis varies significantly from patient to
patient
• Culture and sensitivity is strongly recommended
• When (C&S) is not available, the choice of antibiotic
is based on the patient’s history and presentation
Sampling from the
pocket

1- remove Supragingival plaque

2- insert an endodontic paper point
isubgingivally into the deepest pockets
3- Place endodontic point in reduced
transfer fluid or a sterile transfer tube and
sent to the laboratory
Antimicrobial treatment for periodontitis

• There are 2 approaches for the treatment of

this chronic infection:

• Systemic antimicrobials
• Sub-antimicrobial dose doxycycline
• Local antimicrobial delivery [e.g. Arestin,
Atridox])
Local treatment

• Limited to a minimum number of sites; local delivery immediately

following debridement :
• Doxycycline GEL Subgingival Gel 44 mg/unit
• Indication for Subgingival doxycycline gel; treatment of chronic adult
periodontitis for gain in clinical attachment, reduction in probing depth,
and reduction in bleeding on probing.
• Minocycline Subgingival Controlled-release microspheres 1 mg/cartridge
• Subgingival minocycline controlled-release microspheres are indicated as
an adjunct to scaling and root planing procedures to decrease pocket
depth in adult patients with chronic periodontitis
Common Antibiotic
Regimens Used to
Treat Periodontal
Diseases
Periodontitis

• Amoxicillin 500mg. q8h X 7 days

• or
amoxicillin/clavulanic acid
• 500/125mg. q8h X 7 days
(possibly a better option than amoxicillin alone)
• Caution: older adults re: risk of adverse effects
Severe Periodontitis

• Extremely aggressive disease:

Metronidazole 250mg. q8h X 7 days added to
Amoxicillin

• Useful in some cases

Clindamycin 300mg. q6h X 8 days
 Periodontitis –suspect
A.actinomycetemcomitans

• Doxycycline 100-200 mg. qd X 21 days

 • Advantages;
1. targeted mixed infections
2. increases synergic effects
3. Reduction the dose needed

• Disadvantages
Combination 1.
2.
Augmentation of adverse effects
Interaction;

therapy o Antibiotics that are bacteriostatic (e.g.,

tetracycline) generally require rapidly
dividing microorganisms to be effective.
They do not function well if a bactericidal
antibiotic (e.g., amoxicillin) is given
concurrently.
o When both types of drugs are required,
they are best given serially rather than in
combination.
 • First choice for LAP refractory to
tetracycline and debridement
• Suppression of A.
actinomycetemcomitans, P.gingivalis
Metronidazole and P.intermedia
• Also used for refractory chronic
+ Amoxicillin periodontitis and periimplantitis
• Metronidazole + Amoxicillin: 250 mg
TID/8 days for each antibiotic .
 • Second choice for LAP /Refractory
periodontitis when no response to
Amoxicillin and metronidazole
• metronidazole targets obligate
anaerobes, and ciprofloxacin targets
Metronidazole facultative anaerobes

and • Powerful combination for mixed

infection
Ciprofloxacin • Only for adult; contraindication in
children
• Metronidazole + Ciprofloxacin: 500
mg BID/8 days . For each antibiotic
Summaries of the combinations
Condition
Aggressive periodontitis
Chronic periodontitis
Periodontitis as a manifestation of
systemic disease
NUG/P
Periodontal abscess
Treatment
1 choice; metronidazole and Amoxicillin
2 choice; metronidazole and cipro
3 choice metronidazole 250-500 mg TID/7 d and Spiramycin (250-500
mg TID for 14 days
Metro
1 choice: Amoxicillin
2 choice: Azithromycin ( first choice of allergic to penicillin)
3e choice: Clindamycin
Aggressive periodontitis in children
older than 8 years old

1. tetracycline HCl ; 250 mg. q6h X 2 weeks

- some patients fail to respond due to organism’s resistance
- not recommended child < 8 due to the effects on developing teeth

2. metronidazole ( FLAGYL )
• 250mg. q6h X 10 days
alone, but better used in combination with:
• Amoxicillin 375mg. q6h X 10 days
doxycycline hyclate (PERIOSTAT)

• Collagenase Inhibitor for Periodontal Use (Doxycycline

inhibits MMP, metalloproteinase inhibitor)
• adjunct to scaling and root planing to promote attachment
level gain and to reduce pocket depth in patients with adult
periodontitis.
• PERIOSTAT 20 mg twice daily as an adjunct following scaling
and root planing may be administered for up to 9 months.
• Safety beyond 12 months and efficacy beyond 9 months have
not been established.
 Refractory Periodontitis

• 3. Metronidazole 500mg. q8h X 8days

 Duration of AB therapy
• A common antibiotic course for
orofacial infection is 7 to 10 days.
• No difference with 5 days or 7
days when appropriate surgical
intervention is in place
Antibiotic strategies
• For localized infection:

Pharmacology in Dentistry
Dr. Peter Nkansah University
• Amoxicillin 875 mg bid for 5-7 days of Toronto October 21, 2016
• Clindamycin 300 mg tid for 5-7 days
• Azithromycin Z-Pak #1 as directed
• Doxycycline 100 mg bid for 5-7 days
•
Antibiotic strategies
For spreading infection:
• Augmentin 875 mg bid for 7-10 days
• Clindamycin 300 mg tid for 7-10 days
Pharmacology in Dentistry
Dr. Peter Nkansah University
of Toronto October 21, 2016

• Azithromycin Z-Pak #1 as directed

• Add metronidazole (Flagyl) 500 mg tid if necessary
Successful treatment of an infection
Outcomes and consequences of AB use
Positive outcomes
• Successful treatment of an
infection
• Decreased spread of an infection
in a community
Negative outcomes
• Development of resistant
bacteria
• Promotion of harmful bacterial
overgrowth
• Increased frequency of
development of systemic disease
and conditions
Reason for failure

• Wrong drug or dose

• Bacterial resistance
• Host defences depressed
• Poor compliance
Pericoronitis

if fever and LAD , then AB

B-Lactam • Penicillin
• Cephalosporins
Antibiotics • Carbapenems
• Monobactams
• Vancomycin
 • Bactericidal
• Inhibition of the cell wall synthesis

PENICILLINS • Resistance: Bacteria produce enzymes

that are capable of destroying penicillins
; B- lactamases
• Most commonly produced by Gram –
ve bacteria
• Chemicals have been developed to
inhibit these enzymes:
• 1. clavulanic acid
• 2. tazobactam
• 3. Sulbactam
Penicillin-beta- • ampicillin + sulbactam = Unasyn
• amoxicillin + clavulanic acid = Augmentin
lactamase inhibitor • ticarcillin + clavulanic acid = Timentin
combination drugs • piperacillin + tazobactam = Zosyn
Spectrum of • Penicillin G (IV) and Penicillin V (oral):
• non-B-lactamase producing aerobic
Activity bacteria
• oral anaerobes
• Ampicillin (IV) & Amoxicillin (oral) have an
added amino group:
• additional bacteria including gram
positive enterococcus and listeria, gram
negative bacilli such as E. coli, B-
lactamase negative H. influenzae
Penicillin • Penicillin is the first choice for odontogenic
infections

• G (+) cocci and rods, spirochetes and

anaerobes
Adverse Drug • As mammalian cells do not have a cell wall
the toxicity profile is very low

reactions • Allergic reactions (said to occur in 10-12 % of

the population)
• Anaphylaxis reactions
• Rashes
• Nausea &Vomiting
• Diarrhea
• Others:
• Seizures with high blood concentrations
• C. difficile Pseudomembranous Colitis
(PMC)
Doses • Pen VK 300 mg QID (7-10 days)
• Amoxil 500 mg TID (7-10 days)
• Augmentin { Amoxil 500 mg &
Clavulanate 125 mg} BID
Penicillin V; (APO-PEN VK, NOVOPEN-VK)
indication and use : • Most commonly used in Dentistry
• Fist line of treatment for most odontogenic infections
• Narrow spectrum
• Mainly active against gram+ve bacteria, inc. strep & staph, and some
gram-ve cocci
Metabolism: • Well absorbed from the GI tract; resists acid degradation
• Widely distributed to tissues, will cross the placenta and enter breast milk
• Minimal metabolism by the liver, excreted by the kidney
Adverse effects • Hypersensitivity reaction in approx. 5% of population, with risk of
anaphylaxis which could be fatal
• Diarrhea, nausea, vomiting, epigastric distress
Interaction • Administration with tetracyclines or macrolide antibiotics will reduce the
antimicrobial effects of the penicillin
• probenecid (gout)will decrease the renal excretion and increase the serum
levels of penicillin
• probenecid may be used with penicillin for this purpose
Dosage • Dose Range: 300-600mg. q6h for 7-10 days
Supplied: 300mg • Sample Rx. Rx: penicillin V 300mg
tabs disp: 56 tabs
• sig: 4 tabs stat, then 2 tabs q6h take until all finished
amoxicillin ( pregnancy category B)
indication and • Broader spectrum than penicillin, more active against gram-ve cocci & bacilli
use : • Used as prophylaxis for prevention of infective endocarditis
• Used for more serious odontogenic infections or need for a broader spectrum
• May be first choice in dentistry for the immunocompromised
• Dosing scheduling and ability to be taken with food allow for better patient compliance
Metabolism: Diffuses into most body tissues and fluids; penetration in CNS is poor, Rapidly absorbed
METAB: Liver. Excretion: urine
Adverse • Similar to penicillin ; Diarrhea, nausea, vomiting
effects • Pseudomembranous colitis ( C. difficile) with high doses
• Caution: reduce dose in patients with renal insufficiency
• May cause seizures at high doses
Interaction • May potentiate the anticoagulant effect of warfarin ( decreased metabolism therefore INR may increase
• Concurrent use with allopurinol (gout) may increase the risk of development of a rash
• May decrease the effectiveness of oral hypoglycemics; cause hyperglucosemia
• Methotrexate: Possible methotrexate toxicity (decreased excretion)
• Probenecid will increase the plasma levels of amoxicillin because of a decreased renal clearance
Dosage Dose Range:250-500mg. q8h for 7-10 days ; Use lower dose range for an elderly patient
Supplied: 250 SampleRx: Rx. amoxicillin 500mg. Caps
and 500mg Disp: 21 capsules
capsules Sig:Take1capsq8hX7days.
NO REPEAT – see patient for a follow-up before prescribing more
amoxicillin/clavulanic acid; (AMOXI-CLAV, APO-AMOXICLAV, CLAVULIN) , Augmentin Pregnancy category B
indication and • A combination of 2 drugs with similar pharmacokinetic characteristics
use : • clavulanic acid extends the spectrum of the amoxicillin by inhibiting bacterial ℬ- lactamase activity
• clavulanic acid has no antibacterial activity
• Infection of lower respiratory, pneumonia, UTI
Metabolism: Diffuses into most body tissues and fluids; penetration in CNS is poor, Rapidly absorbed
METAB: Liver. Excretion: urine ( does reduction in renal ompairment)
Adverse effects • Oral candidiasis
• CNS; Agitation; anxiety; behavioral changes; confusion; convulsions; dizziness; fatigue; headache;
insomnia; reversible hyperactivity.
• GI: Diarrhea; nausea (3%); vomiting (1%); pseudomembranous colitis; rectal bleeding.
• MISC: Hyperthermia; superinfection.
Interaction Anticoagulants, oral: Increased anticoagulant effect (decreased metabolism)
● Avoid concurrent use or monitor INR.
Contraceptives, oral: Possible decrease in effectiveness of contraceptive (mechanism un- known)
● Advise patient to use additional form of birth control.
Dosage Do250-500mg. q8h x 7-10 days 250mg q8h or 500mg. Q12h
250/125mg. More severe: 500mg. q8h or 875mg, q12h
,500/125mg. Sample Rx: Rx: amoxicillin/clavulanic acid 250/125mg. Caps
,875/125mg. Disp: 22 caps
amoxicillin/clavul Sig: 2 caps stat, then 1 cap q8h until all finished NO REPEAT
anic acid capsules
Cephalosporins; cephalexin ( APO-CEPHALEX ), cefaclor ( CECLOR ),cefixime ( SUPRAX) ,cefuroxime (CEFTIN)
indication and • Semi-synthetic compounds, have a b-lactam ring
use : • Classified according to their generation
• May be used as a substitute for penicillin
• Limited use in dentistry; for prophylaxis for prosthetic hips joint replacement in selected patients
• May be considered when an oro-antral fistula has been created
• Active against many gram +ve cocci and some gram-ve bacteria;
• 3rd generation includes gram -ve anaerobes
Metabolism: Diffuses into most body tissues and fluids; penetration in CNS is poor, Rapidly absorbed
METAB: Liver. Excretion: urine ( does reduction in renal impairment)
Adverse effects • Hypersensitivity reaction Cross-reactivity with penicillin – Avoid if a true penicillin allergy
• Pseudomembranous colitis ( C. diff.) and oral candidiasis
• Diarrhea, vomiting
• Caution in patients with kidney disease, or gastritis
Interaction • probenecid increases the blood levels (decreased renal excretion of cephalexin)
• Use with loop diuretics may increase the risk of renal toxicity; such as Bumetanide, Ethacrynic acid
(EDECRIN), Furosemide (LASIX) , Torsemide (DEMADEX)
Dosage Dose Range ( cephalexin ):
250 & 500 mg. 250-500 mg. q6h x 7days
Capsules
Cephalosporins can cause tongue discolorations, glossitis and taste disturbances)
Tetracyclines ( Contraindicated for pregnants; cause teeth and bone discoloration
indication and • Antibiotics with a fused four ring structure
use : 30 S • bacteriostatic- inhibit bacterial protein; synthesis at the level of the 30s ribosome
inhibitor • Used systemically or locally for periodontitis, NUG, NUP & periodontal abscesses
• Gram-positive and Gram-negative organisms
Metabolism: Incomplete absorption by Gi tract, excellent distribution
METAB: Liver. Excretion: both urine and feces ( be careful in patient with renal impairment)
Adverse effects • Hypersensitivity reaction
• Black hairy tongue
• Diarrhea, dizziness, headache
• Pseudomembranous colitis
Interaction • Antacids: Decreased oral tetracycline effect (decreased absorption)
• Antiseptics, mercurial (contact lens cleansing solutions): Conjunctivitis (mechanism un- known)
• Atovaquone: Decreased atovaquone effect (decreased metabolism)
• Bismuth subsalicylate: Decreased tetracycline effect (decreased absorption)
• Digoxin: Possible digoxin toxicity (decreased metabolism)
• Iron: Decreased tetracycline effect (decreased absorption) ● Administer 3 hr apart.
• Risperidone: Possible decreased risperidone effect (mechanism unknown) ● Monitor clinical status.
• Zinc: Decreased tetracycline effect (decreased absorption) ● Avoid concurrent use.
Dosage Dose Range
250 mg. Cap/tab 250-500 mg. q6h x 7days
doxycycline ( VIBRAMYCIN, APO-DOXY, DOXYCIN) , Contraindicated during pregnancy ( Cat. D)
indication and • Active against some gram+ve and gram-ve
use : • bacteria associated with periodontal disease
• PERIOSTAT 20mg or ATRIDOX 40mg used orally/subgingival as an adjunct to debridement for chronic
adult periodontitis
Metabolism: Well absorb,
METAB: Liver. Excretion: excreted by the kidneys ( be careful in patient with renal and liver impairment)
Adverse effects • Diarrhea, nausea, vomiting
• Opportunistic fungal infections- candidiasis ; oral/ vaginal , black hairy tongue
• Photosensitivity
• Oral lichenoid (mucositis) reactions
• Not for children under 8, renal disease and SLE or breast feeding
Interaction • Increases anticoagulation effect of warfarin
• Reduces the efficacy of penicillins and cephalosporins: should not be used together
• Methotrexate: Possible methotrexate toxicity (mechanism unknown)
• Barbiturates, carbemazepine, phenytoin, rifampin, theophylline;decrease the activity of doxycycline
• Binds with Calcium, Iron and Magnesium; forms insoluble , non-absorbable chelates with
tetracyclines, and to a lesser extent, with doxycycline ; Do not take with Foods containing calcium
especially antacids (OTC)
Dosage ;100mg. 200mg. ( single dose ) 1st day, then 100mg. qd x 4-6 days
caps or tabs
Minocycline ; pregnancy category D, contraindicated in pregnancy
indication and • May be used to treat NUG and AA- induced periodontitis
use : • May be used as an adjunct to debridement in adult periodontitis
• Distributes to the gingival crevicular fluid
Metabolism: • High lipid solubility, readily penetrates cerebrospinal fluid, and displays a good penetration of saliva,
brain, eye, and prostate.
• METAB: Liver. Excretion: excreted in urine( be careful in patient with renal and liver failure )
Adverse effects • Opportunistic fungal infections - Candidiasis
• Photosensitivity, vestibular toxicity (vertigo) and Nephrotoxic:
• Nausea, diarrhea, abdominal pain
• Hepatotoxic: avoid use in patients with Liver disease
• May induce a blood dyscrasia = hemolytic anemia, thrombocytopenia
• Contraindicated in children under 8 years old
• tooth discoloration; oral cavity discoloration (e.g., tongue, lips, gingivae); brown-black microscopic
discoloration of the thyroid gland
Interaction • Decreased absorption with antacids, milk or other calcium & aluminum containing products
• Contraindicated with isotretinoin (ACCUTANE),– increased risk of hepatotoxicity
• Reduced efficacy of penicillins & cephalosporins: do not prescribe concurrently
• Enhanced anticoagulation effect of warfarin
Dosage ; 50 or 200mg. single dose 1st day, then 100mg. bid x 2weeks ( for periodontal disease)
100mg. Caps
Erythromycin (base, estolate, stearate, lactobionate ); Erythromycin estolate is contraindicated during pregnancy
indication • May be used to treat NUG and AA- induced periodontitis
and use : • May be used as an adjunct to debridement in adult periodontitis
• Distributes to the gingival crevicular fluid
Metabolism: • liver by the hepatic enzyme CYP3A4; Exc: bile
Adverse Nausea, vomiting, diarrhea
effects • Cholestatic jaundice (associated with estolate forms)
• Hepatotoxic- caution in liver disease
• May put patient at risk for the development of antibiotic-resistant microbes
• May result in increased QT interval therefore Increased risk of cardiac arrhythmias/worsening of an existing
arrythmia
Interaction • A potent inhibitor of CYP3A4
• May therefore increase the blood levels of other drugs the patient is taking to toxic levels ;theophylline,
carbemazepine, warfarin, cyclosporin, digoxin
• Antagonistic to clindamycin & lincomycin
• void grapefruit juice ; Grapefruit juice inhibits CYP450 ; Blood serum concentration of erythromycin
increase
• Midazolam or triazolam: Increased midazolam or triazolam toxicity (decreased metabolism)
Dosage ; Dose Range: 250 or 500mg. q6h x 7 days
Base Base ( 250, 333& 500 mg)
Estolate: 500mg tabs, 250mg. Caps and Stearate; film-coated tabs, 250 or 500mg.
clarithromycin ( BIAXIN, APO-CLARITHROMYCIN) ; do not use in pregnancy
indication • upper resp. tract infections, inc. strep pharyngitis, sinusitis and soft tissue infections
and use : • Maybe used for prophylaxis of infective endocarditis
• Spectrum includes gram+ve aerobic bacteria, inc. staph, aureus, group A strep and gram- ve aerobic
bacteria, such as H. influenzae
Metabolism: • liver by the hepatic enzyme CYP3A4 ; Exc: bile ( do not use in hepatic or renal failure)
Adverse • May cause bad taste , Stomatitis, glossitis
effects • Candidiasis
• Pseudomembranous colitis ( C. diff)
• Caution in severe liver or renal impairment
Interaction • A potent inhibitor of CYP3A4
• May lead to increased serum levels of carbemazepine, digoxin, theophylline, colchicine
• May increase the anticoagulant effects of warfarin
• QT prolongation and torsades-de-pointes with certain antiarrhythmics
• Risk of increased CNS depression with triazolam & alprazolam
• Risk of rhabdomyolysis with atorvastatin ( LIPITOR)
Dosage ; 250-500mg. bid x 7-10 days
250 & ( may give up to 14 days )
500mg.
Tablets
Azithromycin (• ( ZITHROMAX , APO-AZITHROMYCIN) ; category B pregnancy
indication • An azalide macrolide , Used for URT (upper respiratory tract) infections and skin/soft tissue infections
and use : • Alternative choice for the prophylaxis of infective endocarditis
• May be considered in some cases of periodontitis and periodontal abscesses
• Active against wide range of microorganisms
• Unique pharmacokinetic profile
• Tissue drug levels are higher than serum levels include saliva, bone and gingiva
Metabolism: Rapidly absorbed , Exc. Bile
Adverse • Hypersensitivity ( angioedema, anaphylactic)Caution with liver disease
effects • Pseudomembranous colitis (C. difficile) , Nausea, abdominal pain
• Taste disturbances , Stomatitis , Candidiasis, tongue discoloration
• Prolonged QT interval ; increased risk of arrhythmias
• polymorphic VT in patients with a long QT interval. It is characterized by rapid, irregular QRS complexes,
which appear to be twisting around the ECG baseline
Interaction • Digitoxin: Possible digitoxin toxicity (mechanism unknown)
• Nelfinavir: Possible increased azithromycin toxicity (inhibition of P-glycoprotein)
• Theophylline: Possible theophylline toxicity (decreased metabolism)
Dosage ; Dose Range: 500mg. as a single dose on the first day, then 250mg. qd for 1-4 days
250mg.,500 In certain cases, may be given as 500mg. q12h
mg. & Z-PAC for sinusitis – blister pack
600mg. Tabs
Metronidazole ; ( FLAGYL, NOVONIDAZOLE ) ; pregnancy category B
indication • A nitroimidazole
and use : • Bactericidal ; Inhibits nucleic acid synthesis by disrupting the DNA of microbial cells
• Broad spectrum, effective against gram+ve & gram-ve anerobes
• effective in treating infections in bone and oral infections such as acute pericoronitis, NUG and abscesses
• Used to treat C. difficile colitis
Metabolism: Well absorbed , Metronidazole appears in cerebrospinal fluid, saliva, and breast milk in concentra- tions
similar to those found in plasma. Exc; urine and feces (causion in hepatic failure patient and elderly)
Adverse • Nausea, Furry tongue; glossitis; stomatitis.
effects • Taste alteration; Metallic taste
• Dizziness, headache
• Large doses may cause seizures
Interaction • Avoid alcohol: disulfiram-like reaction ((inhibition of intermediary metabolism of alcohol)
• Increases the anticoagulant effects of warfarin
• Lithium toxicity ( possible phenytoin, carbamazepine and tacrolimus toxicity)
• Concurrent administration with cimetadine may decrease the metabolism of metronidazole
• An inhibitor of cytochrome P450
Dosage ; Dose Range: 250-500mg. q8h x 7 days
250mg.,500 Sample Rx: Metronidazole (Flagyl), 500-mg tablets
mg. Disp: 20 tablets
Sig: Take 1 tablet 4 times a day until all tablets are taken. (Q6h)
clindamycin ; Pregnancy category C
indication • DALACIN-C
and use : • A lincosamide
• Usually bacteriostatic
• Bactericidal in high concentrations
• Broad spectrum, indicated for the management of dental infections that have progressed to bone
• Alternative to penicillin in infective endocarditis prophylaxis for patients allergic to penicillin
Metabolism: Rapidly absorbed ( no need for dose adjustment in renal or hepatic impairment)
Adverse • GI upset ; Pseudomembranous colitis ( C. diff ) contraindicated in patients with pre-existing diarrhea
effects Neutropenia; leukopenia; agranulocytosis; thrombocytopenic purpura.
Interaction • Reduces the response to Vitamin K therapy
• May decrease the effect of cyclosporin
• Enhanced neuromuscular blockade produced by neuromuscular blocking agents such as pancuronium
Dosage ; Dose Range: 150-450mg. q6h x 7 days
150 & Sample Rx; Clindamycin, 300-mg tabs
300mg. Disp. 29 tabs
Caps Sig. Take 2 tabs stat, then 1 tab qid until all are taken
Tetracycline Staining
Clindamycin
Clindamycin
• Binds irreversibly to a site on the 50S subunit of the bacterial
ribosome, thus inhibiting the translocation steps of protein
synthesis
• Bacteriostatic
• Effective against:
1. Gram positives
2. anaerobes
3. Several oral pathogens
Indication and side effects
• Skin and soft tissue infections such as diabetic skin ulcer infections
• Oral infections
• Aspiration pneumonia

• Side effects and ADRS:

1. Skin rushes
2. Diarrhea
3. Hepatotoxicity (rare)
4. Often implicated as cause of PMC
Treatment of PMC

• Stop all antibiotics

• Keep the patient hydrated
• Refer to a physician

• Prescribe:
• Vancomycin 500 mg po qid for 2 days (if severe)
• Vancomycin 125 mg po qid for 10-14 days
• Metronidazole 500 mg po tid for 7-14 days
Dosage of Macrolids
• Dosage:
• Erythromycin IV, Oral 250mg qid (7-10 days)
• Clarithromycin 250-500mg po bid (7-10 days)
• Azithromycin IV, or oral 500mg stat then 250mg qd for 4 days ( good
choice if your patient is allergic to penicillin and you can not give
them clindamycin)
Adverse drug reaction
• Gastrointestinal :Nausea, vomiting, diarrhea, dyspepsia
• Cholestatic hepatitis - rare
• ototoxicity (high dose erythro)
• Allergy
Drug interaction
• Drug Interactions
• Erythromycin and Clarithromycin – are inhibitors of cytochrome p450
system in the liver; may increase concentrations of:
METRONIDAZOLE

• Bactericidal
• Effective against Bacteroides species,
esp. in periodontal infections and
abscess
• IV, oral dose: 250-500mg bid to tid
• FDA category B (However, small number
of reports raised suspicion of teratogenic
effect)---USE CAUTIOUSLY
 • The use of metronidazole during
Metronidazole lactation is controversial
• Excreted into breast milk in relatively
and lactating high amounts Concern expressed
of adverse effects in nursing infants
mother • THM: USE CAUTIOUSLY
Metronidazole
• PK
• Oral absorption is 80-85%
• Metabolized in the liver
• Half life is 8 hrs
Metronidazole: therapeutic use
• Anaerobic infections
• Vaginal infections
• Used with other antibiotics for H.pylori
• Other protozoal infections
• ANUG, oral abscesses
Metronidazole: adverse drug reaction

• GI (N&V, abdominal cramps)

• An unpleasant Metallic taste
• Dizziness and vertigo
What about • Disulfiram-like reactions
• Metronidazole contain a moiety
alcohol and that is structurally related to
Metronidazole? disulfiram and may inhibit
aldehyde dehydrogenase, thereby
leading to accumulation of
acetaldehyde
• Tell your pt to avoid alcohol while
taking these medications and for 2-
3 days after discounting the drug
Inhibition of folic acid synthesis

• Enzymes requiring folate-derived cofactors are essential for the

synthesis of purines and pyrimidines (precursors of RNA and DNA)
and other compounds necessary for cellular growth and replication
• Therefore, in the absence of folate, cells cannot grow or divide
• The sulfonamides (sulfa drugs) are a family of antibiotics that inhibit
the synthesis of folate.
• Trimethoprim, second type of folate antagonist
SULFONAMIDES
• Bacteriostatic
• Used in combination with Trimethoprim
• Broad range activity against gram-positive and gram-negative
bacteria; used primarily in urinary tract and Nocardia infections.
• Oral absorption is excellent 95%
• Half life is 9-10 hrs
Adverse drug reaction of SULFONAMIDES
• Crystalluria
• Hypersensitivity
• Hemolytic Anemia
• Hepatitis
Case
• 27-year-old Caucasian patient
• Chief Complaint:“My gums bleed when I brush my teeth.”
• Non-smoker
• no systemic medical conditions
• allergic to penicillin
• Her sister, who is 32 years old, has a similar gum condition
• brushes twice a day and flosses three or four times in a week
• Probing depths are in the range of 1 to 8 mm. The deeper (>6 mm) probing
depths are confined to maxillary incisors and first molars
• Oral hygiene is optimal. Radiographically, vertical defect is noted mesial to all
first molars
CASE-BASED QUESTIONS
Would you need to prescribe AB? Can you prescribe a combination of
amoxicillin and metronidazole for this patient while performing scaling
and root planing?
• A. Yes
• B. No
Q-2
• Answer: B
Explanation: This patient is allergic to penicillin, and because
amoxicillin is a derivative of penicillin, it should not be given to a
penicillin-allergic patient. In such cases, metronidazole can be given
alone or combined with other antibiotics, such as ciprofloxacin.
 Adverse reactions to AB
Adverse reaction
Allergies
Antibiotic Resistance
Superinfection
pseudomembranous colitis (PMC)
Nephrotoxicity
Ototoxicity
Antibiotic-Induced Photosensitivity,
Photoallergy, and Phototoxicity
Long QT Interval Syndrome
Unwanted pregnancy (Antibiotics and
Oral Contraceptives
Most common cause
penicillins
Tetracycline
An example of superinfection in the mouth is the growth of Candida albicans
as a result of treatment with an antibiotic, especially one with a broad or
extended spectrum or metronidazole.
amoxicillin, followed by third-generation cephalosporins and clindamycin
aminoglycoside and peptide antibiotic
Aminoglycosides and peptide antibiotics
sulfonamides, tetracyclines, and fluoroquinolones.
fluoroquinolones (gatifloxacin, levofloxa- cin, moxifloxacin, sparfloxacin),
macrolides (erythromycin, clarithro- mycin), and clindamycin.
rifampin
Decision tree for the selection of antibiotic therapy
Antiviral
medications
OROLABIAL HERPETIC INFECTIONS
• Represent the most common viral infection.
• HSV-1 and HSV-2
• Transmitted via direct contact with contaminated secretions from an
infected individual
• Incubation period of 2-20 days
• HSV-1 is predominantly associated with orolabial disease
• HSV-2 is predominantly associated with genital disease
• Asymptomatic or mild.
Oral Herpes Simplex:

• Acyclovir 400mg TID

• Valacyclovir 1000mg BID
• Famciclovir 250mg TID
Adverse effects

• Nausea and vomiting ,diarrhea

• Neurotoxicity (1-5% of patients) (headache, tremor,
• behavioral changes, delirium, seizures, coma)
• Nephrotoxicity (high doses)

• neutropenia, thrombocytopenia (gancyclovir)

Case
• A 22-year-old man presented to our clinic with inflamed,
erosive, and painful gingiva for 4 days. He had a cold and
cephalosporins were taken before the onset of oral lesions.
• Past Medical History: None.
Allergy: None.
Physical Examination:
Generalized inflamed and swollen gingiva was detected,
with vesicles and ulcers distributed in clusters on the palate
and palatal gingival mucosa
Diagnosis
• Primary herpetic gingivostomatitis
• Treatment should focus on early intervention with antiviral agents
and relieving symptoms, preventing secondary infection, and
supporting general health.
• Supportive therapy includes forced fluids, protein, vitamin (C and B
12)and mineral food supplements, and rest.

• Systemic antiviral medications appear to be more effective if

administered within the first 2 days of onset of symptoms.
Treatment
1. Topical anesthetics
Diphenhydramine (Children’s Benadryl) elix 12.5 mg/5 mL (OTC) 4 oz mixed with Kaopectate or Maalox (OTC) 4 oz (to make a
50% mixture by volume).
Disp: 8 oz.
Sig: Rinse with 1 tbs (5 mL) every 2 h and spit out.

2. SYSTEMIC ANTIVIRAL THERAPY

Rx: Acyclovir (Zovirax) caps 200 mg
Disp: 35 caps.
Sig: Take 2 caps three times daily for 7 days.
Or Rx: Valacyclovir (Valtrex) caplets 500 mg
Disp: 20 caplets. Tak e 2 caplets twice daily for 5 days.
Treatment
• 3. Systemic analgesics ; based on the severity of the pain
Rx
: Acetaminophen tablets 325 mg
Disp: 1 btl.
Sig: Take two tabs every 4 – 6 h when necessary for pain and fever.
Do not exceed 4 g per 24 h period.

Severe pain: Rx: Acetaminophen 300 mg with codeine 30 mg (Tylenol No. 3) Disp: 20 tabs.
Sig: take 1 or 2 tabs four times daily for pain
Anti-Viral therapy in the oral cavity
• Herpesviruses causes a variety of oral mucosal lesions
Antiviral medications
• Acyclovir (ZOVIRAX)
• Valcyclovir (VALTREX)
• Famcyclovir (FAMVIR)
• Docosanol (ABREVA)
• Acyclovir-corticosteroid (XERESE)
• Penciclovir (DENAVIR)
Acyclovir (Zovirax) ; use with caution in both Pregnant and breast-feeding ( category B)
indication • HSV 1 and 2 (ORAL AND GENITAL) both primary or recurrent and VZV Herpes zoster
and use : • Synthetic acyclic purine nucleoside analogue
• Inhibits viral DNA replication by inhibition of DNA polymerase
• Available forms; Acyclovir cream; Acyclovir ointment; Acyclovir tablets; Capsule, Acyclovir sodium injection
Metabolism: • Metabolize in liver
• eliminated primarily unchanged in the urine via active renal tubular secretion
• Topical application has minimal systemic absorption
Adverse Topical: Burning, stinging sensation of site (Costly)
effects Systemic:
• headache, nausea, GI disease
• Renal insufficiency or acute renal failure; may be associated with renal pain. (required dose adjustment in
patient with renal diseases)
Interaction • No clinically significant interaction
• Possible meperidine toxicity (decreased renal excretion)
• Zidovudine: Severe drowsiness and lethargy (mechanism unknown)
Dosage ; Acyclovir cream 5% (ZOVIRAX CREAM) for Recurrent Herpes Labialis ; Apply liberally to the affected area 4 to
Tab: 200 mg 6 times daily for up to 10 days.
Sample Rx: Acyclovir cream 5%
Suspension Disp: 5 gram tube
200mg/5ml Sig: Apply 4-6 times daily for 7-10 days
Acyclovir cream 5%
• Indications:
1. Recurrent Herpes Labialis
2. Not for recurrent intraoral HSV on
palate or gingiva
3. not recommended for application to
mucous membranes such as the
mouth or vagina.
4. Apply liberally to the affected area 4
to 6 times daily for up to 10 days.
 Acyclovir cream 5%
• Application/how to use :
a. Use a finger cot or rubber glove while applying
acyclovir cream, in order to prevent
autoinoculation of other body sites or
transmission of infection to other persons.

a. Therapy should be initiated as early as

possible following onset of signs and
symptoms

a. May reduce viral shedding and duration by a

few days
 Acyclovir cream 5%
• Side effects
• Burning, stinging sensation of site
• Costly
• Note: Acyclovir Ointment is less effective

• Sample Rx:
Acyclovir cream 5%
Disp: 5 gram tube
Sig: Apply 4-6 times daily for 7-10 days
Acyclovir tablets/suspension

• Tablets 200mg
• Suspension 200mg/5ml
• The treatment of initial episodes of genital
herpes. (Treatment of primary AHGS)
• The suppression of unusually frequent
recurrences of herpes genitalis (6 or more
episodes per year).
• The acute treatment of herpes zoster
(shingles) and varicella (chickenpox)
Acyclovir tablets/suspension
• Contraindications

1. Renal insufficiency or acute renal failure

2. Acyclovir is eliminated by renal clearance
3. dose must be reduced in patients with renal
impairment

Adverse effects: nausea/vomiting , GI

distress and headache
Treatment of Initial Infection of Herpes Genitalis or
Acute Herpetic Gingivostomatitis

• 200 mg (one 200 mg tablet or one teaspoonful

of suspension [5 mL])
• Every 4 hours
• 5 times daily for a total of 1 g daily for 10 days.

• Therapy should be initiated as early as possible

following onset of signs and symptoms.
Treatment of Herpes Zoster
• 800 mg of oral ZOVIRAX
• every 4 hours
• 5 times daily for 7 to 10 days.

• Treatment should be initiated within 72 hours of the

onset of lesions.

• In clinical trials, the greatest benefit occurred when

treatment was begun within 48 hours of the onset of
lesions.
Treatment of Chickenpox

• 20 mg/kg (not to exceed 800 mg) orally,

• 4 times daily for 5 days.

Therapy should be initiated within 24 hours of the

appearance of rash.
Valacyclovir (Valtrex) ; in pregnancy and nursing women use with caution (category B)
indication Treatment of HSV 1 and 2 both primary and recurrent as well as herpes zoster VZV (shingles).
and use : To reduce the risk of transmission of genital herpes with the use of suppressive therapy
Inhibit DNA polymerase and replication
Prodrug, ester of acyclovir; Converted to acyclovir during first pass intestinal or hepatic metabolism
Metabolism: • Converted to acyclovir , recovered in urine and feces
Adverse • Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome
effects • Acute Renal Failure (Renal insufficiency ), may be associated with renal pain
• The dosage of VALTREX should be reduced in patients with impaired renal function
• Central Nervous System Effects
• Headache, Nausea , GI distress
Interaction • No clinically significant interaction in general
• Ceftriaxone: Possible increased risk of renal toxicity (mechanism unknown) renal function.
• Meperidine: Meperidine toxicity (decreased renal excretion)
• Probenecid: Possible valacyclovir toxicity (decreased renal excretion)
• Theophylline: Possible theophylline toxicity (decreased metabolism)
• Zidovudine: Severe drowsiness and lethargy (mechanism unknown)
Dosage ;
Tab: 500 mg Therapy should be initiated as soon as possible after a diagnosis of herpes zoster, or at the first sign or
and 1000 symptoms of an outbreak of oral or genital herpes
mg
Herpes zoster (shingles)

• 1000 mg orally three times daily for 7 days.

• Treatment with VALTREX should be initiated

within 72 hours of the onset of rash.
Initial Episode of Genital Herpes
and Herpetic Gingivostomatitis
• An initial episode of genital herpes ; 1000 mg
orally twice daily for 10 days.
• HPG: 500 mg twice daily for 5 days
• Therapy was most effective when administered
within 48 hours of the onset of signs and
symptoms.
• There are no data on the effectiveness of
treatment with VALTREX when initiated more
than 72 hours after the onset of signs and
symptoms.
Recurrent Episodes of Recurrent Herpes
Labialis/Intraoral

• 500 mg orally twice daily for 3 days.

Therapy should be initiated at the earliest sign or

symptom of recurrence.
VALTREX can prevent lesion development when
taken at the first signs and symptoms of a genital
herpes recurrence.
Suppression of Herpes Labialis (Maybe used for
Erythema multiforme )

• 1000 mg orally once daily in patients with normal

immune function.
• The safety and efficacy of VALTREX 1000 mg once
daily beyond 1 year have not been established. In
patients with a history of 9 or fewer recurrences per
year, an alternative dose is 500 mg orally once daily.
• The safety and tolerability of VALTREX 500 mg once
daily have been established for up to 20 months
Cold Sores (Herpes Labialis)

• 2000 mg orally twice daily for 1 day (24-hour period).

• The second dose should be taken approximately 12
hours after the first dose, but not less than 6 hours
after the first dose.
• Therapy should be initiated at the earliest symptom
of a cold sore (e.g., tingling, itching, or burning).
• There are no data on the efficacy of treatment
initiated after the development of clinical signs of a
cold sore (e.g., papule, vesicle or ulcer).
famciclovir ( FAMVIR)
famciclovir ( FAMVIR) ; during pregnancy appears to be well tolerated (category B)
indication Inhibition of DNA polymerase
and use : Treatment of acute herpes zoster (shingles).
Treatment or suppression of recurrent episodes of genital herpes in immunocompetent adults.
Treatment of recurrent episodes of mucocutaneous herpes simplex infections in HIV-infected patients
Action effective when virus is replicating
Ester prodrug; converts to penciclovir during passage from GI tract to systemic circulation
Metabolism: • Metabolize in liver and Excrete in the urine
Adverse • headache ( inc. migraine)
effects • nausea
• diarrhea
Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required.
Interaction • no documented drug-drug interactions
Dosage ; VZV; 500 mg 3 times per day for 7 days. (initiated within 72 hours of the onset of the rash)
Tab: 500 mg Recurrent Genital Herpes Episodes (Recurrent herpes labialis); 125 mg twice a day for 5 days. Initiation of
and 250 and treatment is recommended during the prodromal period or as soon as possible at the first sign or symptom of
125 mg a recurrent episode (e.g. tingling, itching, burning, pain, or lesion).
Suppression of Recurrent Genital Herpes Episodes:250 mg twice daily for up to 1 year. (The safety and
efficacy of Famvir therapy beyond one year of treatment has not been established.
Herpes zoster and
famciclovir

• Early treatment of acute herpes zoster with oral

famciclovir resulted in decreased duration of post-
herpetic neuralgia.

• Those most likely to benefit are patients who

initiate treatment within 48 hours of onset of rash
or are greater than 50 years of age or those
patients with severe pain at the time of treatment
initiation.
docosanol 10% cream(ABREVA)

• Viral Entry Blocking Agent

• MOA: inhibition of fusion between the plasma membrane and the HSV
envelope.
• Blocks viral entry into the cell and subsequent viral replication.
• Indication: acute episodes of recurrent oral-facial herpes simplex (fever
blisters or cold sores) in adults.
• ABREVA shortens healing time and the duration of cold sore symptoms
including pain, burning, tingling and itching.
• ABREVA soothes on contact. ; “tingling” at application site
• INTERACTIONS ; no documented drug-drug interactions
docosanol 10% cream(ABREVA)

• Applied topically 5 times/day and continued until the lesion is

healed up to a maximum of 10 days.
• Begin treatment as soon as possible, preferably at the
prodrome or erythema stage.
• Treatment is most effective if applied at the first symptoms
(pain, itching, burning or tingling) or sign, (redness), prior to the
formation of a papule (bump) or a blister.
docosanol 10% cream(ABREVA)

• supplied as a 10% cream, needs to be applied to

affected area 5X per day
• wash hands immediately after application; apply with
a cotton tip applicator
• not for intraoral use
• Tubes and pumps of 2 grams
Acyclovir 5% hydrocortisone 1% (XERESE )

• Antiviral—Corticosteroid (acyclovir 5% and

hydrocortisone 1%) Topical Cream
• treatment of early signs and symptoms of
recurrent herpes labialis (cold sores) to reduce
the progression of cold sore episodes to
ulcerative lesions in immunocompetent adults
and adolescents (12 years of age and older).
• 5 gram tube
Acyclovir 5% hydrocortisone 1% (XERESE )

• combination of acyclovir and hydrocortisone

• Purpose: control viral replication and mitigate
the local inflammatory response to provide
improved efficacy in terms of fewer ulcerative
herpes labialis lesions.
• Ulcerative herpes labialis lesions are those
lesions which progress beyond the papule
stage
Acyclovir 5% hydrocortisone 1% (XERESE )

• should not be used in or near the eyes, inside

the mouth or nose, on the genitals, or rectal
area.
• It is not recommended for application to
mucous membrane.
• The possibility of clinically significant acyclovir
viral resistance exists with the use of XERESE
Acyclovir 5% hydrocortisone 1% (XERESE )

• A sufficient amount of the XERESE Topical Cream

should be applied each time to cover all the
lesions including the outer margin.
• Avoid unnecessary rubbing of the affected area to
avoid aggravating or transferring the infection.
• Wash your hands before and after the use of the
cream to avoid spreading the infection.
Acyclovir 5% hydrocortisone 1% (XERESE )

• applied topically to all the lesions 5 times per day

for 5 days.
• For adolescents 12 years of age and older, the
dosage is the same as in adults.
Penciclovir DENAVIR

• Inhibition of DNA polymerase

• For HSV ( recurrent herpes labials)
• Apply to the area every 2 hours for 4
days
• Discontinued at some point in Canada
Stepwise
guidelines for
recurrent herpes
labialis infection
in adult patients.
Topical Antiviral therapy
Antifungal
Case
• 69-year-old female came to your office for
reline of her denture
• When you remove the maxillary denture, on
the palate you notice white, raised patches
that easily wiped off
• You also notice the redness at the commissure
of the lips.
• What is your clinical diagnosis and how would
you treat this condition ?
Fungal infections
• Fungal diseases may take the form of
• superficial infections involving the skin or mucous membranes
• systemic (deep) infections involving various internal organs.

• Deep infections are treated with systemically administered drugs

• The superficial mycoses, primarily of dermatophytes and Candida

species, are generally managed with topical drugs.
 • Candidiasis is by far the most common oral
fungal infection
• C. albicans may be a component of the
normal oral microflora
Oral • At least three general factors may determine
Candidiasis whether clinical evidence of infection exists:
1. The immune status of the host
2. The oral mucosal environment
3. The strain of C. albicans
Clinical Forms of Oral
Candidiasis

• Candidiasis of the oral

mucosa may exhibit a
variety of clinical patterns
Antifungal medications
• Polyene Agents
• Nystatin
• Amphotericin B
• Imidazole Agents
• Clotrimazole
• Ketoconazole
• Triazoles
• Fluconazole
• Itraconazole
• Posaconazole
• Echinocandins
• caspofungin
• Other Antifungal Agents
• Iodoquinol
 • MOA: binding to ergosterol; a component of
the cell membrane
• This binding forms channels in the cell
membrane, altering its permeability and causing
leakage of Na+, K+, and H+ ions.
POLYENE • also bind to a lesser extent to cholesterol of
ANTIFUNGAL mammalian plasma membrane, which accounts
for most of the toxicity associated with their use.
DRUGS • Resistance to the polyenes is associated with a
replacement of ergosterol with other sterols in
the fungal plasma membrane.

• Examples: Nystatin and Amphotericin B

Nystatin
Nystatin ; safe to use in pregnant and breastfeeding
indication • Topical treatment for oropharyngeal candidiasis ( drug of the choice)
and use : • Binds to fungal cell wall membrane, allowing leakage of cellular contents
• either fungistatic or fungicidal depending on the concentration of the drug , the pH of the surrounding
medium, and the nature of the infecting organism
• Forms: oral suspension (100,000 U) or lozenges (200,000 units per each)
• Ointment or cream for angular cheilitis or denture stomatitis
• Well-tolerated
Metabolism: Poorly absorbed from the skin, mucous membranes, or gastrointestinal tract
After swallowing, the bulk of the administered dose appears unchanged in the feces.
Adverse Mild and transient gastrointestinal disturbances such as nausea, vomiting, and diarrhea
effects The major complaint associated with nystatin is its bitter, foul taste.
Interaction • None known
Dosage ; oral suspension:100,000 units per ml. 5 ml q.i.d. X 10 -14days ( swish / swallow)
Pastilles or lozenges; One or two pastilles (200,000-400,000 units) dissolved slowly in the mouth 4 to 5 times
daily for 10 to 14 days
Nystatin cream (NYADERM or RATIO-NYSTATIN) 100,000u. Per gram, 30g. Tube
Sample Rx:
Nystatin oral susp. 100,000u./ml.
Disp. 200ml.
Sig. 5ml qid S&S and keep for as long as possible x 10 -14 days
Amphotericin
B
Amphotericin B ; IV form with caution in pregnant and better to do not use in breastfeeding
indication • either fungistatic or fungicidal activity depending on the concentration of the drug, the pH, and the fungus
and use : involved
• broad spectrum of antifungal activity
• Binds to fungal cell wall membrane, allowing leakage of cellular contents
• IV infusion for deep fungal infection
• Topically as a 3% cream, ointment, or lotion is useful in the treatment of superficial Candida infections
Metabolism: • Not absorbed from the skin or mucous membranes and is poorly absorbed from the gastrointestinal tract
• Bind in plasma to lipoproteins and in tissue to cholesterol containing membranes
• slowly excreted by the kidney
Adverse Topical or oral suspensions: mild GI disturbances if swallowed
effects IV: most toxic anti- fungal in current use ; nephrotoxicity, Hypochromic normocytic anemia
hypotension and delirium along with fever, nausea, vomiting, abdominal pain, anorexia, headache, and
thrombophlebitis.
Interaction • Topical or oral suspensions; Not known for topical ,
• IV: maybe increase toxic effect of cyclosporine and digoxin
Dosage ; oral suspension for oral candidiasis :1 mL (100 mg) rinse and hold in the mouth for as long as possible, q.i.d.,
p.c., and h.s. for 2 weeks
Not available anymore in oral suspension form
 • Imidazoles and triazoles
• The azoles inhibit the enzyme involved in
the synthesis of fungal ergosterol
• The triazoles has lower toxicity and fewer
AZOLE drug–drug interactions compare to
imidazoles
ANTIFUNGAL • Imidazole Agents Clotrimazole and
DRUGS Ketoconazole
• Triazoles ; Fluconazole , Itraconazole ,
Posaconazole
Clotrimazole
Clotrimazole (Mycelex ); safe for pregnancy and breastfeeding
indication • imidazole antifungal drug used for various mucosal and cutaneous infections
and use : • fungistatic
• oropharyngeal candidiasis
• highly effective and is the drug of choice for the treatment of oral candidiasis in patients with AIDS
• 1% cream or lotion For cutaneous candidiasis and dermatophytosis
• Clotrimazole cream is also effective treatment for angular cheilitis, because this drug has anti- bacterial and
antifungal properties.
Metabolism: • Poorly absorbed by GI tract
• It is metabolized in the liver and eliminated in the feces along with the unabsorbed drug.
Adverse • more pleasant taste compared with nystatin
effects • Oral burning, altered taste, and xerostomia.
• Occasionally, minor gastrointestinal upset may follow oral ingestion of the drug.
• Mild elevations of liver enzymes; in 15% of patients
• Periodic assessment of liver function in patients with hepatic impairment
• Nausea, vomiting
Interaction No significant drug interactions
Dosage ; Dissolve 1 troche (10 mg) slowly in the mouth, 5 times daily for 10 to 14 days
10 mg
troche
Ketoconazole
Ketoconazole (Nizoral ); contraindicated safe for pregnancy (teratogen) and breastfeeding ( excreted in milk)
indication Imidazole antifungal agent ; Disrupts the fungal cell wall
and use : Treatment of systemic and life-threating fungal infections and severe resistant mucocutaneous candidiasis

Metabolism: metabolized by CYP3A4

Absorption from the GI tract is pH dependent
Partially metabolized by the liver, excreted in feces via biliary excretion
Adverse • Serious hepatotoxicity ; Monitoring of liver function
effects • Serum testosterone is lowered
• Nausea, vomiting
• Anaphylaxis
• prolong the QT interval. Hypertension, orthostatic hypotension and peripheral edema
Interaction • Serious and/or life-threatening interactions with erythromycin (macrolids)
• Metabolism of cyclosporine, tacrolimus, methylprednisolone (corticosteroids), Benzodiazepine (midazolam,
triazolam), coumarin-like drugs, lipid lowering agents phenytoin, and rifampin may be altered
• Avoid alcohol
• Drugs which increase gastric pH, including antacids and proton pump inhibitors decrease the absorption of
ketoconazole
Dosage ; Sample Rx:
Oral tab 200 Ketoconazole 200mg. Tabs.
mg 14tabs
1 tab. qd x 2 weeks
Fluconazole
Fluconazole (DIFLUCAN ) ; safe for pregnancy (teratogen) and breastfeeding ( excreted in milk)
indication A triazole antifungal agent; Inhibits the synthesis of fungal sterols,a necessary component of the fungal cell
and use : wall
Indicated for the treatment of serious fungal infections, including oropharyngeal and esophageal candidiasis
and systemic candidiasis
Fungistatic: maybe fungicidal at higher concentrations
Metabolism: • Well absorbed ( not required acidic environment), widely distributed , long half-life
• Over 80% excreted unchanged by the kidneys
Adverse • Hepatotoxicity (fatal in some patients); rare
effects • Exfoliative skin disorders, including Erythema multiforme -Stevens-Johnson syndrome
• Toxicity may occur in patients with renal failure
• Headache, nausea, vomiting, abdominal pain, diarrhea
Interaction • Enhances the anticoagulation effect of warfarin
• Increases the hypoglycemic effects of tolbutamide & glyburide
• Interact with rifampin, theophylline, rifabutin, and tacrolimus
• phenytoin toxicity- avoid concurrent use
• cyclosporine: renal toxicity-avoid concurrent use
Dosage ; For very serious systemic infections may give up to 400mg. qd Supplied as 50,100,150 & 200mg. Tablets
100mg. qd For oral candidiasis: two tablets (200 mg) on day 1 and then one tablet (100 mg) daily for 1 to 2 weeks
for 7- 14 Sample Rx:
days Rx: Fluconazole 100mg. Tablets. disp: 7 tabs
Sig: 1 tab po qd until all finished
Antifungals for the Treatment of Oral
Candidiasis based on e-cps canada

https://www-e-therapeutics-ca.proxy3.library.mcgill.ca/search
Angular cheilits

• Clotrimazole: betamethasone diproprionate

cream (LOTRIDERM CREAM)

• Topical Antifungal and Corticosteroid Agent

• Lortriderm cream
Disp: 15 gram tube
Sig: Thin coat BID x 2 weeks.
Angular cheilits

• Clotrimazole 1% Canesten® Topical

cream is available OTC 15 & 30 gram
tubes

• Clotrimaderm 2% vaginal cream 25

gr tube
 VIADERM
KC, 0.1%+,
CREAM
triamcinolone acetonide—neomycin sulfate—nystatin—
gramicidin
Case
• 69-year-old female came to your office for
reline of her denture
• When you remove the maxillary denture, on
the palate you notice white, raised patches
that easily wiped off
• You also notice the redness at the commissure
of the lips.
• What is your clinical diagnosis and how would
you treat this condition ?
Diagnosis
• Oral candidiasis +. Angular cheilitis

• Denture hygiene + Nystatin ointment 100, 000 U to apply inside the

denture
• Nystatin oral susp. 100,000u./ml.
Disp. 200ml.
Sig. 5ml qid S&S and keep for as long as possible x 10 -14 days
• Angular cheilitis : Lortriderm cream
Disp: 15 gram tube
Sig: Thin coat BID x 2 weeks
The interaction between Antibiotics and OC:

• Antibiotics that interfere with this flora may reduce the blood levels of
estrogens and decrease the efficacy of oral contraceptives
Antibiotics during pregnancy and lactation

• In pregnancy drug treatment presents a special concern due to the

threat of potential teratogenic effects of drug and changes in the
physiology
AB for pregnant women: Penicillin

• FDA--- B
• Safe in all trimesters
• No teratogenic
• Amoxicillin and cephalosporins also considered safe to use during
pregnancy
• Amoxicillin and cephalosporins also considered safe to use during
breastfeeding
• No increase risk of malformations with amoxicillin-clavulanic acid (Clavulin)
in several studies
Metronidazole
• Used for periodontal conditions
• FDA category B
• Small number of reports raised suspicion of teratogenic effect

• USE CAUTIOUSLY
Lactating mother and Metronidazole

• The use of metronidazole during lactation is controversial

• Excreted into breast milk in relatively high amounts

• Concern expressed of adverse effects in nursing infants

• THM: USE CAUTIOUSLY

What about Chlorhexidine rinse?

• FDA Category B
SAFE TO USE FOR
• PREGNANAT WOMEN
• SAFE TO USE FOR Lactating mother
Antifungals • Nystatin- FDA Category B
• Ketoconazole- FDA Category C (use
and Pregnancy cautiously)
• Fluconazole- FDA Category C (use cautiously)
Antibiotics during pregnancy
Geriatric Patients

• ADVERSE DRUG REACTIONS

• DRUG-DRUG INTERACTIONS

• WHY in the Elderly?

• Complex drug therapies
• PK changes
• Cognitive problems
• Co-morbidity
Geriatric Patients

• There are no specific changes in the therapeutic use and dose of anti-infectives in our elderly healthy
pts.
• However, doses may need to be reduced because of decreased lean body mass, especially older women
• ADRs
• Also, there are number of potential drug interactions that may lead to modification of the anti-infective
that we select.
Examples

• Cephalothin can cause nephrotoxicity at high doses

• Erythromycin can cause ototoxicity if impaired renal function is
present.
• Clindamycin can increase the incidence of GI problems such as
diarrhea and colitis.
• Clarithromycin (and Clindamycin) may interact with digoxin (this Anti-
infective may decreases the clearance of digoxin from the body)
• Metronidazole and Ciprofloxacin will increase the anticoagulant effect
of Warfarin by decreasing its hepatic metabolism.
Antimicrobial-induced adverse drug reactions in
elderly patients.
Antimicrobial-induced drug interactions in elderly
patients.