O-Med: Antibiotic Therapies (lecture 3)

• ¡Passage from the birth canal
• ¡Nursing
• ¡Interaction with the adult family members

• - role is unclear
• - Potentially prevents colonization of the non-indigenous bacteria

> 300

- Same microbial density as large intestine 10^11/g wet tissue weight

few days after newborn: strep.

after tooth eruption: s. mutans & s.sanguis, actinomyces, bacteroides, fusobacterium

after puberty: spirochetes

• 1. selective toxicity
• 2.Consider agent’s activity & concentration
• 3. Use drug dosing & schedule with respect to in-vitro MIC

- Use bactericidal agents over bacteriostatic

- If using combination tx:

• - Bacteriostatic + bacteriostatic: additive effect (1+1=2)
• - Bacteriostatic + bacteriocidal: antagonism (1+1<1)
• - Bacteriocidal + bacteriocidal: synergism (1+1>2)

- Whenever possible, determine the sensitivity of pathogen

¡Concentration-dependent drugs – the more you increase the dose, the higher the killing rate nDoses used achieve peak plasma levels that are 8-10x the in-vitro MIC - Metronidazole and quinolones

¡Time-dependent drugs – once concentration threshold has been reached increasing drug concentration will not increase the killing rate nDoses used achieve plasma levels that are 4-5x the in-vitro MIC - Penicillins & cephalosporins - to ensure threshold has been reached use a loading dose

• Correct diagnosis of the infection
• Choice of most specific and effective drug (antibiotic spectrum)
• Adverse effects (allergy Hx, & toxicity)
• Cost  
• Bacterial resistance

- Use an agent with a spectrum appropriate for the type of infection

- Employ high doses for a short duration

- Use the oral route

- Use dosing intervals appropriate for drug half-life

- Determine the duration of therapy by the remission of disease + 48 hrs

- Consider host factors; adjust for renal and hepatic diseases

1.Odontogenic infections involve a mix of g+, g-, facultative anaerobes.

Strict anaerobes are found in:

• ~ 60% of pulp necrosis (non-intact teeth)
• ~ 90% of pulp necrosis (intact teeth)

involves g+ and g- organisms;

g- anaerobes (Porphyromonas & Bacteroides) predominate as pockets deepen

Staph. aureus and epidermis are the most common causes

may be due to S. aureus or any commensal organism

mix of superficial anaerobic infections

• Bacteriocidal antibiotics
• Include penicillins and cephalosporins
• Good diffusion in organic fluids, infected tissues
• All cleared through the renal system
• Most cross the placenta; excreted in breast milk
• Resistance is an issue
• Hypersensitivity, GI disturbance, anemia, renal damage

• penicillins
• - broad spectrum
• - narrow spectrum

cephalosporins

• - Amoxicillin
• - ampicillin
• - carbenicillin
• - ticarcillin
• - mezlocillin
• - piperacillin

• 1. Beta lactamase sensitive:
• - Penicillin G (benzylpenicillin)
• - Penicillin V (phenoxymethyl penicillin)

• 2. Beta lactamase resistant/inhibitor:
• - Cloaxacillin, oxacillin, methicillin, clavulanic acid

- First through 5th generations: cefazolin, cefriaxone…


- broad – similar to broad spectrum penicillins plus pseudomonas & Klebsiella

- used for: Hospital-acquired pneumonia & GI infections

- tetracyclines, clindamycin and macrolides

- Mostly bacteriostatic (except clindamycin)

- Some have poor tissue concentration (esp erythromycin)

- Excreted via kidney and hepatic bile

- Teracyclines bind to Ca; inhibited by anti-acids & dairy, not used in pregnancy

- All secreted in breast milk

• Side effects:
• - Can cause GI symptoms (esp erythromycin)
• - Over growth of Clostridium difficile w/ clindamycin
• - Candida superinfection w/ tetracyclines (oral, vaginal)

• 1. tetracyclines
• - Short acting: tetracycline
• - Long acting: doxycycline and minocycline

• 2. macrolides
• - Erythromycin
• - Semi-synthetic erythromycins: clarithromycin, azithromycin

3. Clindamycin

- broad spectrum

- most g+ and g- bacteria including many anaerobes (chlamydiae, rikettsia, spirochetes), even some protozoa¡

- used for: Acne, rosacea, intestinal infections, PID, UTI & spirochetal infections (syphilis, lyme disease, periodontitis)

- narrow spectrum

- streptococci, staphylococci, pneumococci and very specific for anaerobes (fusobacterium, bacteroides, porphyromonas, prevotella)

- used for: Anaerobic dental & periodontal infections, acne, infections of the soft tissues and respiratory tract

- narrow spectrum

– streptococci, staphylococci, mycobacteria (M. pneumonia) and some anaerobes (chlamydia, haemophilus, spirochetes)

- Skin infections, pharyngitis/tonsillitis/sinusitis, bronchitis, pneumonias, chlamydial infections

1. Metronidazole

2. Quinolones - Ciprofloxacin

- Spectrum: narrow, strict anaerobes        

- used for: trichomonal infections, brain & lung abscesses, periodontitis)

- Crosses placenta & is mutagenic

- Excretion: renal

- Interferes w/ anticoagulants, potentiates alcohol

- Chlamydial infections, hospital acquired pneumonias

- Crosses placenta & secreted in breast milk

- Excretion: renal

Odontogenic infections range from:

• - periapical abscesses
• - superficial and deep infections of orofacial spaces

• ¡Excessive extraoral swelling
• ¡Trismus
• ¡Dysphagia
• ¡Drooling
• ¡Voice changes
• ¡Infraorbital or periorbital swelling
• ¡Descending swelling to the neck & airway compromise
• ¡Deviation of the uvula, fever, chills, malaise
• ¡Potential for spread to facial spaces

- Target facultative cocci w/some anaerobes

- When no soft tissue involvement, chemomechanical debridement of root canals can be effective

- w/ soft tissue involvement, use systemic ABs (Because broad spectrum ABs alter the gut flora, have more side effects and select resistant strains, use narrow spectrum

- Penicillins V, clarithromycin; although extended spectrum, amoxicillin is also a good choice

- For facial spaces use surgical intervention & ABs against anaerobes (clindamycin, metronidazole) & Klebsiella(first generation cephalosporins)

• 1. Tetracyclines
• 2. Doxycycline
• 3. Metronidazole
• 4. Clindamycin

- Short –acting; drug conc. in GCF is 7x higher than serum

- Useful for aggressive tx of periodontitis in young pts, Juvenile periodontitis, rapidly advancing disease or those refractory to tx

- The greatest anti-collagenase activity

- Because it is long acting

- used as once daily low dose

- Narrow spectrum, effective for g- anaerobes

- used in tx of periodontitis in combination w/ conventional tx methods

- Can cause metallic taste, HA, vertigo and peripheral neuritis

- Narrow spectrum targeted to g- anaerobes,

- useful for disease refractory to tetracycline & metronidazole

- Very good at penetrating bone

- of major salivary glands is the most common cause

- Partial obstruction causes intermittent swelling at mealtime

- Full obstruction leads to infection & painful swelling of the affected gland

Patients with decreased salivary flow have an increased risk for sialadenitis

• Swelling is in:
• - submandibular triangle when it involves the submandibular glands
• - preauricular area when it involves the parotid glands.

Skin overlying the gland may be erythematous

Gland is tender to palpation

There may also be purulent discharge from the Stensen’s or Wharton’s duct

- Radiographic examination to rule out sialoliths

- Culture and sensitivity

In the absence of stones a lacrimal probe may be utilized to dilate the stricture or to relieve blockage

A broad-spectrum antibiotic such as tetracycline or Cephalexin may also be used

- An acute periodontal infection, involves a number of organisms including:

• - Fusobacterium nucleatum
• - Borrelia vincenti

DEBRIDEMENT!

- Gentle local debridement (3% hydrogen peroxide)

- Systemic tx if there is evidence of deep or systemic involvement (gingival destruction, masticatory dysfunction and palpable lymph nodes)

- Use metronidazole in severe cases

1. Chlorohexidine gluconate 0.12% is a broad spectrum Bis-Biguanide that acts on bacterial and fungal cell membrane permeability

- Long term use: exogenous staining and calculus accumulation

2. Povidone Iodine 10% has bactericidal and virucidal activity

- Used for disinfection of wounds, burns, and tx of LGE

• How did patient find out?
• - Patient feels bad taste
• - Patient’s contacts react
• - Patient’s dentist notices

• Who refers?
• - 84% of patients came spontaneously
• - 7% were referred by their general practitioner
• - 5% referred by various specialists
• - 1% sent by their dentists

• Assess Pt’s Hx:
• - PMH, SHx, DHx, h/o oral malodor, diet

• PE
• - Head & neck structures, intraoral tissues

Breath analysis

• - Poor restorations
• - Poor oral hygiene practices
• - Malpositioned teeth
• - Impactions
• - Periodontal disease
• - Oral ulcers (Autoimmune disorders, Reactive lesions, Neoplasms)
• - Oral infections (Odontogenic bacterial infections, Recurrent viral infections, Fungal infections)
• - Xerostomia (aging, drug induced/cancer/systemic dz/taste alterations)

• nGastrointestinal diseases¡Esophageal reflux¡Pyloric stenosis¡Hiatal hernia¡Malabsorption¡CarcinomasnLiver/gallbladder diseasesnKidney diseases nDiabetes mellitusnHemorrhagic diseases¡Hematopoietic neoplasms
• nPulmonary Diseases¡Anaerobic infections¡Tuberculosis¡NeoplasmsnNose and Sinus Diseases¡Chronic sinusitis/post-nasal dripnTonsillitis¡TonsillolithsnPharyngitisnTrimethylaminuria

nTobacco historynAlcohol intakenIllicit substancesnPsychogenic factors¡Individuals’ variations in odor perception¡Depression, phobias, Obsessive/Compulsive Disorder, Body Dysmorphic Disease, psychotic disorders

nOdoriferous foods (transient)¡Garlic, onion, spices, herbsnOdorigenic foods¡High protein diets provide a continuous source of aminoacids for bacterial breakdown nSulfur containing aminoacids (cysteine, cystine, methionine) and other types of amino acids (tryptophan, ornithine, arginine) undergo putrefaction by gram negative bacteria producing sulfur containing volatiles

1. Evaluate Head & Neck (lymph nodes, nasal and paranasal sinuses

2. evaluate oral tissues (salivary flow, dentition)

3. Periodontium (AL, mobility, BOP, abcesses)

4. Oral mucosa (atrophy, desquamation, ulcers, necorsis, masses, pseudomembrane)

5. Oral Hygiene (plaque, gross debris, tongue coating)

Organoleptic tests:

• Examination of the expired air
• Wrist-Lick test
• Spoon test

1. Volatile Sulfur Compounds (VSCs) detection test (Halimeter)

- Measurement of VSCs in ppb in the air collected from the anterior mouth, posterior tongue and each of the nostrils

2. Gas chromatography

Identification and quantification of the specific VSCs in the headspace air sample

3. The electronic nose

Identification of the specific odorous bacterial species in the headspace air sample

1. Reduce the bacterial reservoir:

- Antibacterials (Cetylpyridium chloride, Benzethonium chloride, Chlorine dioxide)

Mechanical removal (tongue scraper)

2. Transform odorous gases into non volatile form (zinc salts)

3. Reduce levels of nutrients available for use by the bacteria (avoid high protein diets)

4. Restore to normal the salivary flow

• Are there any accompanying symptoms?
• (Cough, mildly productive cleansing of the throat, heavy coating on the posterior dorsal tongue, obstruction and congestion)

• If suspect chronic sinusitis refer for ENT evaluation
• Allergy vs obstruction
• Rhinoscopic examination w/ flexible endoscope
• Sinus series of radiographs & MRI
• Appropriate Tx (allergy vs obstruction)

Nasal irrigation