ANTIMICROBIAL DRUGS :

CLINICAL APPLICATION IN ORAL

MEDICINE

~
Caroline Shiboski, DDS., PhD.,
Professor in Oral Medicine

ANTIMICROBIAL DRUGS: CLINICAL APPLICATION

Outline
Pharmacologic management of
oral fungal infections

Candidiasis

oral viral infections

Herpes simplex infections
Varicella-Zoster infections
Major aphthous stomatitis
Necrotizing ulcerative periodontitis
Shiboski 2014

SUPERFICIAL FUNGAL INFECTIONS

OF THE ORAL CAVITY

Shiboski 2014

FUNGAL DISEASES
Oral Candidiasis: Pathogenesis
Overgrowth of Candida (predominantly C. Albicans)
Predisposing factors:
HIV / AIDS and immunosuppressive drug regimens
Immunologic immaturity of infancy
Endocrine disturbances (diabetes; pregnancy; steroid tx)
Antibiotic therapy
Cancer chemotherapy and radiation therapy
Removable dentures
Xerostomia
Shiboski 2014

FUNGAL DISEASES
Oral Candidiasis : Clinical presentations

Pseudomembranous candidiasis
Erythematous candidiasis
Angular cheilitis

Shiboski 2014

FUNGAL DISEASES
Pseudomembranous Candidiasis
White spots or plaques anywhere in the mouth
May be wiped off with gauze
Patient may report burning
Diagnosis usually made upon clinical examination

Shiboski 2014

Shiboski 2014

Note: white plaques do not always wipe off (a form

sometimes called hyperplastic candidiasis)
Shiboski 2014

FUNGAL DISEASES
Erythematous Candidiasis
Patchy erythema usually located on palate and
dorsum of tongue
Occasionally on buccal mucosa
Patient may report burning
Usually clinical diagnosis or after response to
antifungal therapy
Differential diagnosis: toothpaste-induced
irritation
Shiboski 2014

Erythematous candidiasis in a 6 year-old kidney

transplant recipient
Shiboski 2014

Denture-induced erythematous candidiasis

Erythematous candidiasis or median

rhomboid glossitis
Shiboski 2014

FUNGAL DISEASES
Angular Cheilitis

Red fissures
(cracks) or
linear ulcers
located at the
commissures
of the mouth

Shiboski 2014

Angular cheilitis often occurs with intra-oral

candidiasis
Shiboski 2014

FUNGAL DISEASES
Oral Candidiasis: Differential diagnosis
History plays a major role in the differential
diagnosis
Chief complaint may include burning, metallic/
altered taste
Medical history will alert the clinician on
predisposing factors

Shiboski 2014

FUNGAL DISEASES
Oral Candidiasis: Differential diagnosis
Clinically, oral candidiasis may resemble many
white or red lesions, but history helps rule out
other conditions
White or red lesions that may resemble oral
candidiasis: toothpaste-associated sloughing,
frictional keratosis (cheek chewing), mucosal
burns, WSN, lichen planus

Shiboski 2014

FUNGAL DISEASES
Oral Candidiasis Management

Antifungal to treat oral candidiasis may be either

topical or systemic drugs
Treatment duration: 10-14 days
Usually well tolerated, but systemic azoles may
potentiate the effect of certain drugs (e.g.,
coumadin; cyclosporine; hypoglycemic agents)

Shiboski 2014

Oral Candidiasis Management:

Topical antifungals (adult dosages); 2-week course
Clotrimazole troche [Mycelex] 10 mg: 1 troche to dissolve
by mouth 5x/d
Miconazole buccal tablet [Oravig] 50 mg: place one tablet
on gingiva qd for slow release
Nystatin vaginal tablet [Nilstat] 100,000 U: 1 tablet to
dissolve by mouth 3-4x/d
Ketoconazole cream [Nizoral] 2% (to treat angular cheilitis):
apply tid to corners of mouth
Nystatin/triamcinolone cream [Mycolog II] 100,000 U/g:
apply tid to corners of mouth
Nystatin powder (for oral use) 100,000U/g (to treat dentureassociated candidiasis): apply to dentures tid

Oral Candidiasis Management:

Systemic antifungals (adult dosages)

Fluconazole tablets [Diflucan] 100 mg: 1 tab/

d for 10-14 days
Ketoconazole tablets [Nizoral] 200 mg: 2 tabs
the first day then 1 tab/d for 10-14 days
Voriconazole and amphotericin B may be
used to treat fluconazole-resistant esophageal
candidiasis
Shiboski 2014

Erythematous candidiasis After a 10-day course of

topical antifungal
Shiboski 2014

Erythematous
Candidiasis

Shiboski 2014

After antifungal
treatment

Erythematous
Candidiasis
Shiboski 2014

After antifungal treatment

Oral Candidiasis Management:

Treatment considerations for angular cheilitis

Topical antifungal ointment or cream (e.g.,

nystatin; nizoral) + intra-oral topical
treatment (e.g., clotrimazole troches)
If ulcers + oozing remains despite
antifungal treatment, consider secondary
bacterial infection at commissures: may be
managed with mupirocin [bactroban]

Shiboski 2014

VIRAL DISEASES
Herpes simplex infections
Herpes simplex type 1
Primary herpes gingivo-stomatitis
Secondary herpes (oral and labialis)
Herpetic whitlow
Occasionally, genital herpes
Herpes simplex type 2
Genital herpes
Occasionally, oral herpes
Shiboski 2014

VIRAL DISEASES
Herpes simplex infection: Pathogenesis
Contact
with HSV

Host (seronegative)

PRIMARY DISEASE
Gingivo-stomatitis
or subclinical infection

Reactivation

SECONDARY DISEASE
Lip, palate, gingiva,
finger

Host (seropositive)
Latent virus
Shiboski 2014

Resolution

VIRAL DISEASES
Herpes simplex infections: Clinical features
Primary herpetic gingivostomatitis

Usually in children

Vesicular eruption precedes multiple ulcers which

can occur anywhere in the mouth (palate and
gingiva usually most severely affected)

Painful mouth and/or throat

Fever, arthralgia, malaise, headache, cervical

lymphadenopathy

Duration: 1 week to 10 days

Shiboski 2014

Primary HSV infection in a 8 year-old child

Shiboski 2014

Primary herpetic gingivo-stomatitis may affect both

intra-oral and peri-oral areas
Shiboski 2014

VIRAL DISEASES
Herpes simplex infections: Clinical features
Secondary or recurrent HSV infections
Reactivation of latent virus (latent in trigeminal
ganglion)
Short lived vesicular eruption on vermilion border or
hard palate
Map-like superficial ulcer
Duration: 1 week to 10 days

Shiboski 2014

Note the vesicle preceding the ulcer

SECONDARY HERPETIC INFECTION

Early vesicular
stage

Later ulcerative
stage

Recurrent HSV infection: vesicles rupture and are

replaced by small reddish ulcerations
Shiboski 2014

Recurrent HSV infection: small ulcers eventually

merge to form map-like ulcers
Shiboski 2014

Late stage recurrent

HSV infection: maplike ulcer(s)

Shiboski 2014

VIRAL DISEASES
Herpes simplex infections: Diagnosis
Primary herpetic gingivostomatitis
Diagnosis usually based on clinical features and
history
Can be confirmed by virus culture, but must be done
during early phase (before virus shedding completed),
also takes 2-4 days for results
Clinical features may resemble streptococcal
pharyngitis or erythema multiforme but history differs

Shiboski 2014

VIRAL DISEASES
Herpes simplex infections: Diagnosis
Secondary or recurrent HSV infections
Diagnosis usually based on clinical features and
history
Differential diagnosis: Herpes Zoster, trauma, contact
mucositis

Shiboski 2014

VIRAL DISEASES
Herpes simplex infections: Management
Timing

Must be initiated within 48 hrs of onset of symptoms

Acyclovir

200 mg, 5 x/d for 10 days (400-600 mg 5x/d in HIV+

patients)
In virus-infected cells, acyclovir is converted by virusinduced enzyme (thymidine kinase) to a form that
inhibits specifically viral DNA polymerase (not host cell
DNA polymerase)

Valacyclovir

1000 mg bid for 10 days (twice as expensive as acyclovir)

Shiboski 2014

VIRAL DISEASES
Herpes Zoster infections: Pathogenesis
Primary HZV infection: chickenpox
Reactivation of latent HZV: shingles or acute herpes
zoster

Occurs in immunosuppressed patients

Sensory nerve of head & neck often affected

Pain, paresthesia in prodromal stage

Unilateral maculo-papular rash, becomes vesicular,

then ulcerated
Post-herpetic neuralgia may occur

Shiboski 2014

VIRAL DISEASES
Herpes zoster: Diagnosis
Diagnosis based on history and clinical features
Differential diagnosis
HSV infection
Characteristics of oral herpes zoster versus HSV
infections
Similar mucosal eruption but longer duration, higher
intensity of prodromal symptoms, unilateral distribution
and abrupt ending at midline

Shiboski 2014

VIRAL DISEASES
Herpes zoster: Management
In patients > 50 years-old or if immunosuppressed,
treatment advised to prevent post herpetic neuralgia
Valacyclovir 1000 mg 3x/d for 7 -10 days
Or acyclovir 800 mg 5x/d for 7 -10 days

Shiboski 2014

IDIOPATHIC ORAL MUCOSAL CONDITIONS

THAT MAY REQUIRE ANTI-INFLAMMATORY
AND ANTI-MICROBIAL COMBINATION
THERAPY

IDIOPATHIC CONDITIONS
Aphthous ulcers: Pathogenesis
Most common type of ulcerative condition
Possible defect of cell-mediated immune response
Patients report a history of recurrent ulcers
Episodes may be aggravated by stress, diet
Deficiencies of vit B12, folic acid, and iron found in a
small percentage of cases
Two main forms: minor and major

Shiboski 2014

IDIOPATHIC CONDITIONS
Minor aphthous ulcers: Clinical features

Well circumscribed white-yellow round lesion with

red margin

Usually less than 5 mm in size

Affects non-keratinized oral mucosa

Moderate to severe pain

Heals without scarring within 7 to 10 days

IDIOPATHIC CONDITIONS
Minor aphthous ulcers: Management

Inquire about type of toothpaste used (SLScontaining toothpastes may aggravate condition)

Discontinue any SLS-containing toothpaste for 1

month, and replace with baking soda

Discontinue use of any mouthwash

Rx topical steroid compound (e.g., fluocinonide,

clobetasol mixed with orabase) to be applied tid as
soon as prodromal symptoms occur (may reduce
duration of ulcer by half)

Always instruct patient to RTC if ulcer not healed

after 2 weeks

IDIOPATHIC CONDITIONS
Minor aphthous ulcers: Management

Prescription for topical steroid compound:

Fluocinonide ointment 0.05% to be mixed 1/1 with
orabase B (disp 30g). Apply to ulcer(s) tid for at most 1
week
Clobetasol or halobetasol ointment may be used
similarly (higher potency)
Instruct patient to return if episode of non-healing ulcer
occurs (e.g., if no healing after 2-week use)

Alternative topical steroid (if multiple ulcers)

Dexamethasone elixir (or solution) 0.5mg per 5 mL
(disp 250mL) rinse with 5mL for 1 min then expectorate
tid

Shiboski 2014

IDIOPATHIC CONDITIONS
Major aphthous ulcers: Clinical features
Larger, more severe, less common than minor ulcers
10 to 30 mm in diameter
Extremely painful
Heals with scarring within weeks or even months (in
immunosuppressed patients)

Shiboski 2014

Major aphthous ulcer 3 months after

kidney transplantation
Shiboski 2014

MANAGEMENT OF MAJOR
APHTHOUS ULCERS
Antibacterial rinses to clear secondary bacterial
infection

Doxicyclin capsules (100 mg): dissolve in 1 Tbsp

water, then rinse for 1 minute + expectorate qid

Topical steroids:

Fluocinonide ointment 0.05% mixed 1/1 with orabase

B (apply tid) or

Clobetasol ointment 0.05% mixed 1/1 with orabase B

(apply tid)

NECROTIZING ULCERATIVE PERIODONTITIS

Clinical features
Sudden onset Periodontitis characterized by soft
tissue loss as a result of ulceration or necrosis
Exposure, destruction or sequestration of bone
may be seen, and the teeth may become loosened
Pain may be a prominent feature
Characterized by strong malodor associated with
abundance of anaerobic pathogens
Occurs predominantly in immunosuppressed
patients

NECROTIZING ULCERATIVE PERIODONTITIS

(Courtesy of Dr. Jim

Winkler)

Debridement and curetage with povidone-iodine irrigation

(Courtesy of Dr. Jim Winkler)

(Courtesy of Dr. Jim Winkler)

Patient immediately post-debridement.

Prescription of:
Chlorhexidine mouthwash 0.12%: rinse for 1 min 2x/d
Metronidazole 250 mg 4x/d for 7 days

Patient one week post debridement

(Courtesy of Dr. Jim Winkler)

CLINICAL CASES

CASE #1
Chief Complaint and History
55 year-old man referred by KTU for evaluation of
multiple oral ulcers. Very painful
5 days duration
Increasing severity
No tx attempted

CASE #1
Medical History and Social History
Kidney transplant 3 months ago
Lost kidney due to HBP
Meds: Prednisone 10mg/d; Cellcept; prograf;
septra; valcyte; lopressor; clonidine; INH as TB
prophylaxis

Differential diagnosis?

Major aphthous ulcer

1 week after tx initiation

(fluocinonide oint in
orabase +
tetracycline rinses
+ increased pred to 40mg/
d for 4 days)

3-week FU
What is happening
1) on the lower lip?
2) on the right lateral
border of the tongue?

Granulation tissue formation.

Could lead to a pyogenic
granuloma

Pseudomembranous
candidiasis secondary
to topical steroid tx

5-week FU

Clinical case #2
A 19 year-old woman presents to the OM clinic
complaining of a sore mouth and throat
What questions do you need to ask her before
you proceed with the oral examination?

Differential diagnosis?

Primary HSV infection

Clinical case #3
A 45 year-old man presents to OM clinic with a
chief complaint of white plaques spreading to
the entire mouth
What questions do you need to ask him before
you proceed with the oral examination?

Clinical case #3
HxPI:
He reports he had white plaques on each side
of the tongue for the past 9 months
3 weeks ago, the white plaques spread to the
entire mouth
He reports a metallic taste

Clinical case #3
Med Hx:
Good general health
No current meds
Had syphilis 6 years ago

Clinical case #3
Differential Diagnosis
Pseudomembranous candidiasis
Management?

Clinical case #4
CC: 85 year-old woman referred by PG endo for
evaluation of sudden-onset sore in the roof of
mouth. Extremely painful
HxPI: Sores appeared 4 days ago after RCT
completed
MedHx:

HBP; she reports getting cold sores on lip

Meds: Amlodipine; Fosamax