13. Antibiotics Flashcards
• Antibiotic: Any chemical which at ____ attainable blood levels, inhibits the growth of or kills pathogenic microorganisms
○ Usually are from natural sources
○ Don’t want to injure kill the patient/host
• People that make serendipitous discoveries typically due something with the mistake
○ Seen with the discovery of penicillin
therapeutically
• ____: Actively kills the pathogen
○ Are preferred since they depend less on the host ____
○ Advantages of bactericidal over bacteriostatic antibiotics:
§ More ____ –> work better
§ Less dependent on host ____
• ____: Prevents further growth of pathogen
bacteriocidal immune response efficacious mechanisms bacteriostatic
Antibiotic Groupings
• Depending on the antibiotic and bacteria the effects of the antibiotic can be either bactericidal or bacteriostatic
○ Also depends on ____
Bacteriostatic: • \_\_\_\_ • Macrolides: ○ Erythromycin ○ Clarithromycin ○ Azithromycin • \_\_\_\_ • Sulfonamides
Bactericidal: • \_\_\_\_ • Cephalosporins • \_\_\_\_ ○ Good for strict anaerobes or infections that are facultative anaerobes ○ Typically given with a Penicillin –> makes it easier for metronidazole to penetrate the cell wall ○ Metronidazole then can fragment \_\_\_\_ • Quinolones –> Ciprofloxacin • \_\_\_\_
Rules for combining multiple antibiotics:
1. \_\_\_\_ Effect: Static + Static (1 + 1=2 ) 2. \_\_\_\_ Effect: Cidal + Cidal (1 + 1 > 2) 3. \_\_\_\_ Effect: Static + Cidal (1 + 1 < 2) • Odontogenic Infections: Require two different \_\_\_\_ antibiotics with different mechanisms
dose
tetracyclines
clindamycin
penicillin
metronidazole
bacterial DNA
aminoglycosides
additive
synergistic
antagnoistic
bactericidal
• Selective Toxicity: The antibiotics should be harmful to the pathogens but ____ to the host
○ No drug is completely innocuous to everyone, all drugs have potential ____
innocuous
side effects
Selective Toxicity
1. Cell Membrane Synthesis Inhibitors (____)
○ Bactericidal mechanism that targets ____ only found in bacterial membranes!
§ Will be given as a rinse or paste –> very polar so little gets absorbed into the blood
1. ____
2. Amphotericin B: Given via ____ only when there are life threatening fungal infections (HIV patients!)
§ Has some potential to be toxic to the liver
3. ____: Will target cell membranes if it gets into the blood
§ Targets ergosterol which is similar to cholesterol –> drug might accidentally target human cells that contain cholesterol
2. Protein Synthesis Inhibitors 30S (Lower level of selective toxicity) (\_\_\_\_) ○ Bacteriostatic 1. Aminoglycosides: Large polar molecules that are given via IV during life-threatening Gram \_\_\_\_ infections § Have a low \_\_\_\_ –> Can damage kidneys and cause ringing of the ears □ Typically prescribed or given in a hospital § 3D structures resembles curare –> can block \_\_\_\_ receptors due to structure! 2. \_\_\_\_
bacteriocidal ergosterol nystatin IV vancomycin
bacteriostatic
negative
therapeutic index
nicotininc M cholinergic
tetracyclines
- Protein Synthesis Inhibitors 50S (Lower level of selective toxicity) (____)
○ Bacteriostatic
1. ____
2. Clindamycin: Preferred over Erythromycin since it’s good against ____ infections (PA lesions/abscesses) and better at targeting ____- DNA Synthesis Inhibitors (____ )
- ____ : Fragments DNA
§ Typically given with Penicillin where the Penicillin allows it to penetrate the cell walls
§ Good against strict anaerobes, but not ____ anaerobes - Quinolones: Inhibit DNA ____ that are used to ease super-coiling, thus preventing the uncoiling of DNA
§ Good against facultative anaerobes, but not ____ anaerobes (opposite of Metronidazole) - ____: Given to fight TB or leprosy and is a CYP3A4 inducer (will degrade drugs like Warfarin or oral contraceptives as a result –> can get pregnant)
- Sulfonamides: Inhibits the synthesis of ____ from PABA (Para amino benzoic acid) and are used in the treatment of UTIs and opportunistic infections in AIDs patients
§ Most oral bacteria are ____ to Sulfonamides
§ Bacteria make Folic Acid, humans must consume it –> ____ Toxicity
§ If given a local ____ –> can increase the [Sulfonamides] as a byproduct
Why you don’t give people esters anymore like Procaine (Novocain
- ____ : Fragments DNA
- DNA Synthesis Inhibitors (____ )
bacteriostatic
erythromycin
bone
anaerobes
bacteriocidal metronidazole facultative gyrase/topoisomerase strict rifampin folic acid resistant selective anesthetic
Rifampin & Oral Contraceptives
• Breakthrough \_\_\_\_ –> Ovulation • 38/51 women on concomitant oral contraceptive therapy experience breakthrough bleeds • 68/88 women on concomitant oral contraceptive therapy experience breakthrough bleeds and resulted in 5 pregnancies • 76% of all alleged antibiotic/oral contraceptive interactions involve Rifampin • When taken off of Rifampin for a month –> oral contraceptive blood levels double ○ Confirmed with 99% significance
YAY
bleeds
- Rifampin is involved in many drug reactions and can decrease the blood levels of many drugs
- ____: Anticholinesterase used to treat Parkinson’s Disease
- *= drugs used in dentistry
tacrine
Antibiotic & Oral Contraceptive Controversy
• Rifampin reduces oral contraceptive blood levels via enzyme \_\_\_\_ • Reports with all other antibiotics are \_\_\_\_ (should be studied) • NEVER scientifically documented for \_\_\_\_ antibiotics • Normal oral contraceptive failure rates are between 1-3% ○ 4-8% failure rate for teens in the US due to non-compliance –> must miss a couple of pills
inducer
anecdotal
dental
• Estrogen and Progestin doses in oral contraceptives have been decreasing over the years
○ Estrogen + Smoking –> increased risk of thrombus formation since Estrogen inhibits ____
§ Increased risk of pulmonary embolism and stroke
• If you’ve been on oral contraceptives for 8+ years there has been shown to be a 20-30% increased risk of acquiring ____
anti-thrombin III
breast cancer
• 60-70% of oral surgeons will prescribe antibiotics before, during, or after impacted ____ molar extraction
○ People aren’t really at high risk for dangerous infections, the infections can be controlled and treated rather easily
third
Enterohepatic Recirculation Theory
• EE: Ethylene estradiol in oral contraceptives ○ Oral contraceptives target the Pituitary and Hypothalamus • Believed that \_\_\_\_ or \_\_\_\_ is added to EE inactivating the molecules ○ Believed normal \_\_\_\_ will cleave the Glucuronic Acid or Sulfate allowing EE to dissolve into the blood to the Pituitary or Hypothalamus ○ Once on antibiotics the normal flora is \_\_\_\_ resulting in improper removal of Glucuronic Acid or Sulfate from EE –> vulnerable to pregnancy
glucuronidation
sulfate
flora
inhibited
• ____ are prescribed at a much higher rate than anticonvulsants
○ Meaning the number of pregnancies while on ____ is rather alarming
antibiotics
anticonvulsants
• Doxycycline is a major drug that Periodontists use that is ____ spectrum
○ No change in ____ & progestin blood levels before or after taking Doxycycline
• Low N however (low amount of people tested)
○ Medically and legally must tell them about the very low chance of them becoming pregnant
○ Still take oral contraceptives and use condoms
§ Include this in the chart to prevent yourself from getting sued
broad
estrogen
• Tetracycline is ____ spectrum
○ Slight drop in oral contraceptive blood levels after one day but they rise again
• Broad spectrum antibiotics are more likely to eliminate the normal ____
• Low N however (low amount of people tested)
○ Medically and legally must tell them about the very low chance of them becoming pregnant
○ Still take oral contraceptives and use condoms
§ Include this in the chart to prevent yourself from getting sued
broad
flora
• Ampicillin is similar to amoxicillin
○ Amoxicillin has better ____ stability and less likely to be degraded by stomach acid
○ 6-7% decrease in oral contraceptive blood levels
• Low N however (low amount of people tested)
○ Medically and legally must tell them about the very low chance of them becoming pregnant
○ Still take oral contraceptives and use condoms
§ Include this in the chart to prevent yourself from getting sued
acid
• Metronidazole showed essentially no difference in ____ blood levels
• Low N however (low amount of people tested)
○ Medically and legally must tell them about the very low chance of them becoming pregnant
○ Still take oral contraceptives and use condoms
§ Include this in the chart to prevent yourself from getting sued
oral contraceptive
• Spectrum: The range of pathogenic organisms against which an antibiotic is active
○ Broad vs narrow spectrum
• Principle: Use the ____ spectrum antibiotic directed against the specific pathogen
○ Want to use this especially when working with ____ infections
§ Penicillins and Amoxicillins are great
§ Mainly dealing with staph and some anaerobes
narrowest
odontogenic
Problems with Broader Spectrum Antibiotics • \_\_\_\_ complaints • \_\_\_\_ • Superinfections: ○ \_\_\_\_ overgrowths ○ \_\_\_\_ (C dificle) § Resistant to \_\_\_\_
GI diarrhea candida pseudomembranous colitis antibiotics
Penicillins I
• Mechanism –> Inhibition of ____ synthesis
○ ____ against actively growing cells
○ Most are inactivated by ____ (β-lactamase)
• Elimination –> Kidney remains unchanged
• Toxicity –> Low especially with ____ (narrow spectrum)
• Βeta-lactam ring:
○ Cleaved by:
§ Low ____
§ ____
cell wall bacteriocidal penicillinase penicillin V pH penicillinases
Penicillin Subclasses
• Narrow spectrum: ○ \_\_\_\_: Benzyl penicillin § First one discovered and \_\_\_\_ (destroyed by stomach acid) □ Given \_\_\_\_ as a result ○ \_\_\_\_: Phenoxy methyl penicillin § More acid stable and taken \_\_\_\_
• Broad spectrum: ○ \_\_\_\_ (Omnipen ®) ○ \_\_\_\_ (Trimox ®, Amoxil ®) § More superinfections than compared to Penicillin V which is narrow spectrum § Drug of choice for dentists replacing Penicillin V: □ Longer \_\_\_\_ than Penicillin V and given every 8 hours (taken 3 times a day) □ Used for infective \_\_\_\_ • Broadest spectrum: ○ \_\_\_\_ (Geopen ®) ○ \_\_\_\_ (Ticar ®) ○ Used for people who have suffered from burns to prevent \_\_\_\_ infections
• Penicillinase Resistant: ○ \_\_\_\_ (Staphcillin ®) § \_\_\_\_ is resistant to this ○ \_\_\_\_ (Bactocil ®) § Other "oxa" penicillins
penicillin G acid labile IM penicillin V orally
ampicillin amoxicillin half-life endocarditis carbencillin ticarcillin pseudomonas methicillin MRSA oxacillin
Narrow Spectrum Penicillins
• Penicillin G ○ Acid \_\_\_\_ –> resistant to corrosion via acid ○ Unpredictable oral absorption § Typically given \_\_\_\_ or IV ○ \_\_\_\_ or Benzathine suspensions –> Extended duration preparations (300K-600K U/mL) § Divide by 1,598 to get mg • Penicillin V (Pen VK ®) ○ Acid \_\_\_\_ ○ Better \_\_\_\_ absorption ○ Drug of choice for mild/moderate \_\_\_\_ infections
labile
IM
procaine
stabile
oral
odontogenic
Bacterial Susceptibility: Penicillin G and V
• Most important thing to do during dental infections is to remove the source of the infection • Gram positive bacteria: ○ \_\_\_\_ ○ Non-\_\_\_\_ producing Staphylococci § Typically in more immune resistant people • Gram negative cocci: ○ \_\_\_\_ • Some anaerobes: ○ \_\_\_\_ ○ Porphyromonas
streptococci
penicillinase
neisseria
fusobacterium
Dosing of Penicillin V
• Adult: ○ \_\_\_\_mg every 6 hours every 7-10 days ○ 1,000mg stat for more severe infections § Loading dose • Child ○ \_\_\_\_mg/lb ○ Every 6 hours for 7-10 days • Try to take it an hour or 2 \_\_\_\_ meals
500
3-6
after
Broad Spectrum Penicillins
• Medical indications: ○ \_\_\_\_ (Urinary Tract Infections) ○ URI (Upper Respiratory Tract Infections) ○ \_\_\_\_ infections • Less effective than Penicillin V against \_\_\_\_ ○ More effective than Penicillin V against \_\_\_\_ and bacilli • Ampicillin (Amcill ®, Omnipen ®): Erratic \_\_\_\_ absorption • Amoxicillin (Amoxil ®, Trimox ®): Well absorbed by the \_\_\_\_ ○ Drug of choice for infective endocarditis prophylaxis (2 grams) § Don't need to take as frequently as Penicillin V ○ Penicillin V is still the drug of choice for most \_\_\_\_ infections § Amoxicillin has more adverse drug reactions than Penicillin V because of its \_\_\_\_ spectrum ○ Neither Amoxicillin or Penicillin V are effective in infections harboring \_\_\_\_ producing pathogens
UT gonococcal gram positive cocci oral mouth odontogenic broader penicillinase
Extending the Spectrum of Amoxicillin
• Combine Amoxicillin with \_\_\_\_ and related compound sublactam to target penicillinase producing bacteria • On its own Clavulanic Acid lacks any effects ○ Resembles a \_\_\_\_ ring of Penicillins and are targeted instead of Amoxicillin § Clavulanic Acids are β-lactam inhibitors • Reserved for specialized instances (\_\_\_\_ infections) or when a culture and sensitivity dictates its use
clavulanic acid
beta-lactam
maxillary sinus
Broadest Spectrum Penicillins
• Medical indications: ○ Serious Gram Negative infections: § \_\_\_\_ –> seen in burn victims § Proteus § \_\_\_\_ fragilis infections possibly in bone • UTI and \_\_\_\_ infections • Inactivated by β-lactamases • Includes: ○ \_\_\_\_ ○ \_\_\_\_
pseudomonas bacteroides GI carbenicillin ticarcillin
Penicillinase Resistant Penicillins
• Sole indications: ○ Infections harboring penicillinase producing pathogens § \_\_\_\_ and some Gram Negative \_\_\_\_ • Less \_\_\_\_ than Penicillin V against Streptococci and other organisms typically found in odontogenic infections • \_\_\_\_ (Staphcillin ®): Poor oral absorption and nephrotoxic ○ Targets Staphylococcus • Oxa, Cloxa, Dicloxa, Floxa -\_\_\_\_ –> better \_\_\_\_ absorption ○ Bactocil ® –> target \_\_\_\_ ○ Prostaphlin ® –> targets \_\_\_\_
staphylococcus aureus bacilli active methicillin cillins oral bacteriodes staphylococcus
Staphylococcal Strain Resistance • ALL: ○ \_\_\_\_ § Including penicillinase resistant ○ Cephalosporins ○ \_\_\_\_ ○ Tetracyclines ○ \_\_\_\_ ○ Clindamycin
penicillins
aminoglycosides
erythromycin
Mechanisms of Resistance
Enzymes that destroy drugs
Done to ____
Decreased cell permeability or increased efflux
Done to ____
Altered antibiotic targets
Done to ____
Change in ribosomal ____ structure
penicillins
tetracyclines
erythromycin 50S
Mechanisms of Resistance Transfer • \_\_\_\_ mutation • Conjugation (“X” rated figure) • \_\_\_\_ • R-factors
sponataneous
plasmids
Penicillin Toxicity
Mild ____ disturbances, Candida overgrowths
____ > Penicillin V
Drug Allergy: Allergic to one, then allergic to ____
o Rash, hives, uticaria
o ____ Sickness
o Anaphylaxis
Incidence: up to 1:10 patients – ____
1:10,000 patients – ____
GI amoxicillin all serum mild anaphylaxis
Drug Allergy or Hypersensitivity
Requires \_\_\_\_ exposure (sensitizing dose) Independent of d\_\_\_\_ Antigen-Antibody Rxn > Mediator release A. \_\_\_\_ B. Complement C. \_\_\_\_ D. Leukotrienes E. \_\_\_\_ Skin/Bronchioles/Cardiovascular System
previous dose histamine heparin PAF, ECF
Pharmacological Interventions for Drug Allergy
Mild: Oral ____ receptor blocker (antihistamine) ____ (Benadryl®) 25 – 50 mg
Severe: ____ 1:1000 (1 mg/ml) Preloaded syringe 0.3 – 0.5 ml
IM, Subcutaneous, Sublingual
H1
diphenydramine
epinephrine
Epi receptor actions
A1: ____ skin, gut
B1: increased ____, increased ____
B2: ____, ____ internal organs and skeletal muscles
vasoconstriction HR contraction force bronchodilation vasodilation
Drug Toxicity
1. Can occur on 1st ____
2. Phenomenon is ____-related
3. Involves specific tissue ____
4. Symptoms appear in tissues harboring specific ____
Example: Pharmacologic activity of codeine
exposure
dose
receptors
receptors
Cephalosporins
Spectrum: ____, hits some penicillinase producing bugs
1st Generation: ____ (Keflex®), Cephradine (Velosef®)
2nd Generation: ____ (Duricef®), Cefaclor (Ceclor®)
3rd Generation: ____ (Cefobid®), Cefotaxime (Claforan®)
4th Generation: ____ (Maxipime®), Cefpirome ( Cefrom®)
Mechanism: ____ - ____
extended cephalexin cefadroxil cefoperazone cefepime
cell wall
bactericidal
Cephalosporins continued
Uses in dentistry: Occasionally when culture and sensitivity dictates their use. Do not use ____!
Prophylaxis of some joint replacement patients: ____ (Keflex®) or Cephradine (Velosef®) 2g
Toxicity: More GI and superinfections than ____ Approximately 10% cross allergenicity with ____
empirically
cephalexin
penicillin V
penicillins
Cephalosporin Spectrum Gram Positive \_\_\_\_ Streptococci \_\_\_\_ Clostridium
Gram Negative \_\_\_\_ Proteus \_\_\_\_ Neiserria \_\_\_\_
staphylococci
pneumococci
E. coli
klebsiella
bacteroides
Macrolide Antibiotics
Drugs: ____ (Eryc®, Ery-Tab®) Clarithromycin (Biaxin®) ____ atoms in macrocyclic lactam ring. Many ____ interactions.
____ (Zithromax) ____ atoms in macrocyclic lactam ring. Far ____ drug interactions.
Mechanism of action: ____ ribosomes, ____
erythromycin
14
drug
azithromycin
15
less
50S
Erythromycin
Indications: ____, Legionairre’s, ____, Bordatella
Pen-V sensitive infections in penicillin-allergic individuals
*Generally less effective than ____ in odontogenic infections especially against odontogenic anaerobes.
Absorption: erratic, acid ____, many enteric-coated preparations
ADRS: High incidence of nuisance GI side effects
*Cytochrome P-450 (CYP-3A4, -1A2) ____
diptheria
mycoplasma
Pen-V
labile
inhibitor
Clarithromycin
- More rapid and complete absorption than ____
- Longer ____ than erythromycin
- Better ____ (GI) than erythromycin
- ____ prophylaxis (500 mg) in penicillin allergic individuals
- Cytochrome P-450 (CYP-3A4) ____
e-mycin T1/2 tolerated endocarditis inhibitor
Fexofenadine (Allegra ®) is non-sedative since it doesn’t get to the brain
Accumulation of Terfenadine is cardio-toxic –> ____
torsades de pointe
____: Used to treat GERD
Stimulation or peripheral cholinergic receptors increases stomach contractions and the rate at which food passes
[Cisapride] increase when taken with ____
Can increase the odds of Torsades de pointes however via QT Interval increase
Low variability with a small number of people –> effective
cisapride
clarithromycin
____: Too high of an accumulation can cause Torsades de Pointes
Works in treating tourettes
[] increases when on ____
primozide
clarithromycin
ALL of the drugs are either CYP3A4 or CYP1A2 substrates
____ is a non-sedating anti-histamine no longer on the market
____: Dopamine 2 agonist for treating Parkinson’s
Get ____ since stimulating dopamine receptors in the periphery opens up the vasculature
____: Anti-convulsant for trigeminal neuralgia
\_\_\_\_: De-methylated caffeine 4th line drug for asthma CNS and cardiac stimulant Blocks adenosine receptors –> normally are inhibitory transmitters Results in uncontested transmission
Ca2+ blockers treat hypertension
Too much cause hypotension
Warfarin with erythromycin and clarithromycin is NOT as bad compared when taken with ____ or ____
astemizole
bromocriptine
hypotension
carbamazepine
theophylline
fluconazole
metronidazole
____ : A sedative
Taken by kids orally due to the large therapeutic index
Can’t be titrated since it’s taken ____
Prolonged and over-sedation of kids
When kids are over-sedative they can lose their protective reflexes
Can restrict their own airway due to head ____
midazolam
orally
placement
Azithromycin (Zithromax®)
Indications: ____, LRIs, skin and soft tissue, occasionally ____ infections (periodontal abscesses)
Unique property: Actively taken up by ____ and delivered by them to the infected site. Concentrates in ____ with high levels found in saliva, bone and gingival tissues.
Long \_\_\_\_ ~ 68 hours; Dosed 500 mg day 1, 250 mg days 2-5. \_\_\_\_ prophylaxis (500 mg) in penicillin allergic patients.
Better tolerated than ____ and no ____ interactions.
Very expensive: 5-day Z-pack = $60 7-day Pen V = $5
URIs
oral
phagocytes
tissue
T1/2
endocarditis
erythromycin
CYP-450
Tetracycline HCl
Drugs: ____-Acting, Lower Potency
Tetracycline, ____ (Teramycin®)
250 mg – 500 mg q 6h
Longer-Acting, Higher Potency
____ (Vibramycin®), Minocycline (Minocin®) 50 mg –100 mg BID
PO Absorption: Chelate ____ and ____ cations
shorter
oxytetracycline
doxycycline
divalent
trivalent
Tetracyclines Continued
Spectrum: Very ____, gram +, gram -, gram – ____
____
Mechanisms of Action:
• ____ ribosome inhibitor –specifically inhibits binding of aminoacyl-tRNA synthetases to ribosomal receptor
•Non antimicrobial actions in periodontal disease:
•inhibit tissue ____ and metalloproteinases
•Enhance periodontal ____ and bone formation
Example: Low dose ____ therapy (Periostat®)
20 mg BID for up to one year
broad
anaerobes
bacteriostatic
30S
collagenases
reattachment
doxycycline
Tetracyclines Continued
Unique property: Concentrate in ____ after systemic administration.
gingival crevicular fluid
Tetracyclines Continued
Compared to penicillin V, tetracyclines produce:
1) A higher incidence of ____ problems (cramping, diarrhea)
2) A higher incidence of superinfections
a) ____ (Candida) overgrowths (oral, vaginal, GI) b) ____
Other ADRS: Permanently ____ Teeth (Children < 8 years)
Do not prescribe to ____ individuals!
____
GI
monolilial
pseudomembranous colitis
stained
pregnant
photosensitivity
Local Delivery Systems for Periodontal Disease
Direct placement of agents into periodontal pockets:
a) increases ____ concentrations of antimicrobial
b) decreases ____ concentrations of antimicrobial
Example: Monolithic 25% tetracycline fiber (____®)
GCF levels > 1600 ug/ml at 24 hours
> 1200 ug/ml at 10 days Systemic blood levels non-detectable.
local
systemic
acticite
10% ____ in a biodegradable polymer that solidifies on contact with the GCF (____®)
“Flows where fibers and chips can’t go.”
GCF Levels: 1100 ug/ml at 24 hours 200 ug/ml at 7 days
0 ug/ml at 14 days MIC(90) for perio pathogens = 2-6 ug/ml
Only system approved for ____.
doxycycline hyclate
atridox
monotherapy
Biodegradable 2.5 mg chlorhexidine gluconate chip (____®)
Rapid Insertion: < 1 minute
GCF levels > 1000 ug/ml at 4 hours > 480 ug/ml at 72 hours
MIC for most perio pathogens < 2 ug/ml Non detectable ____ levels
No ____ visit (biodegradable)
periochip
systemic
return
Clindamycin
Mechanism of action: ____ ribosome, protein synthesis inhibitor.
Absorption: nearly 100% PO Actively transported into ____ and WBC providing high [ ] in abscesses and bone.
Clinical uses: Prophylactic ____ and ____ regimens (600 mg) in penicillin allergic individuals
Chronic/persistent ____ infections (osteomyelitis) ____ infections in penicillin allergic patients
____ infections that don’t respond to Penicillin V
Typical endodontic regimen: ____ mg stat, then 300 mg q 6h for 5-7 days
50S macrophages endocardititis joint bony odontogenic endodontic
600
Clindamycin Toxicity
• ____ (3-5% of patients)
• Diarrhea(10-20%ofpatients)
• Pseudomembranous colitis
– Occurs just as frequently with other ____ spectrum antibiotics (ampicillin, cephalosporins, tetracyclines)
– More commonly associated with parenteral ____ clindamycin formulation than oral clindamycin HCl salt
– ____ event in ambulatory dental patients
– Overgrowth of antibiotic-resistant Clostridium dificile that produces ____/cytotoxin-B
rash broad PO4 rare enterotoxin A
Predisposing Factors For C. Dificile Colitis Development
- ____, cephalosporin, broad spectrum ____, or quinolone antibiotic administration
- Previous antibiotic associated ____
- Diabetes
- ____age
- Use of H-2 blockers - ____ (Tagamet®), ranitidine (Zantac®), famotidine (Pepcid®) or proton pump inhibitors – ____ (Prilosec®), esomeprazole (Nexium®)
- ____ use
clindamycin penicillin diarrhea older cimetidine omeprazole diuretic
Treatment of Pseudomembranous Colitis
• ____ patient and restore electrolyte balance
• Antibiotic therapy
– ____ 500 mg q 6h for 10 days
– ____ 500 mg q 6h for 10 days
• ____ therapy (for diarrhea) is contraindicated
hydrate
vancomycin
metronidazole
narcotic
Metronidazole
Indications: ____, amebic infections, Giardia, and ____ bacterial infections
Mechanism of action: ____, parent molecule is reduced to ____ active metabolites by an anaerobic pathway
that disrupts bacterial ____
Dental uses: Highly effective against ____ bacteria associated with periodontal disease, endodontic infections and oral surgery infections. It is most often given with ____.
Dosing: 250 mg – 500 mg TID for 5 to 7 days.
____ delivery systems for periodontal disease are now available. 25% metronidazole gel (Elyzol Dental Gel®)
trichomonas
anaerobic
bactericidal
electronegative
DNA
anaerobic
penicillin V
local
Metronidazole Adverse
____ for teratogenicity
____ inhibits the enzyme
Effects Disulfiram (Antibuse®) effect:
____, flushing, palpitations, nausea, vomiting
Other ADRs – Sharp ____ taste, stomatitis, nausea, headache, rarely seizures/peripheral neuropathy, use in pregnancy controversial.
Other Potential Drug Interactions:
Inhibition (2C9) of ____ (Coumadin®) metabolism > ____
Decreased ____ (Eskalith®) clearance > Confusion, ataxia
Kidney damage
____ much bigger issue than metronidazole with lithium!!
category B
alcohol
headache metallic warfarin bleeding lithium
NSAIDs
Ciprofloxacin (fluroquinolones)
Drugs: ____ Ofloxacin (Floxin®) Levofloxacin (Levaquin®)
Uses: UTIs, ____s, Perio
Mechanism: DNA ____
inhibitor,
____
Spectrum: ____ gram negative Bacteria, but not strict anaerobes.
Absorption: Inhibited by ____ and trivalent cations (like tetracyclines)
Dosing: 500 mg q 12h for 7 days
For mixed anaerobic infections combined with ____
ciprofloxacin
LRI
gyrase
bactericidal
facultative
divalent
metronidazole
Fluroquinolone Adverse Reactions
____, diarrhea, insomnia, ____ damage and rupture, ____ (like tetracyclines).
Inhibits biotransformation of ____ leading to arrhythmias and seizures.
(CYP-1A2 ____ - theophylline)
nausea
tendon
photosensitivity
methylxanthines
inhibition
Dangers of Indiscriminate Use
- Development of new ____ strains
- Development of ____
- Drug toxicity
- Drug ____ and allergy
- Potential for drug interactions
resistant
superinfections
sensitization
Therapeutic Index = ____
risk/benefit
Principles of Antibiotic Therapy
- Identify ____ ASAP
- Culture and sensitivity
- ____ spectrum possible
- Least toxic
- ____ if possible
First line drug = ____
pathogens
narrowest
bactericidal
penicillin V
Antibiotic Prophylaxis Controversy • Healthy dental surgery patients? [strike-through] • \_\_\_\_ surgical patients • At-risk patients for bacterial \_\_\_\_ • Patients with \_\_\_\_ implants
immunocompromised
endocarditis
orthopedic
Endocarditis: “The Myths”
- ____ procedures cause most of the cases.
- Incubation period can be up to ____ year.
- Many ____ clinical trials.
- Most physicians have a high ____ of endocarditis prophylaxis regimens.
dental
one
controlled
knowledge
Endocarditis: “The Facts”
- Dental procedures at most cause ____% of the cases.
- ____ sources, especially in at-risk. patients with poor oral hygiene > 90% of cases.
- Typical incubation period < ____ weeks.
- Never a ____ clinical trial.
- Generally compliance among ____ is less than dentists.
4 physiological 2 controlled physicians
Showing how there are procedures that don’t require antibiotics that still have a high chance of causing ____
bacteremias
Cardiac Conditions Associated With The Highest Risk of Adverse Outcome From Endocarditis for Which Prophylaxis Before Dental Procedures is Reasonable
• ____ or prosthetic material used for valve repair
• Previous infective ____
• Certain congenital heart diseases (CHDs)
– Unrepaired ____ including palliative shunts and conduits
– Completely repaired ____ defect with prosthetic material or device whether placed via open surgery or catheter during the first ____months after the procedure
– Repaired CHD with residual defects ____ to the site of prosthetic patch or device (which inhibits endothelialization)
• Cardiac transplantation recipients who develop
____
prosthetic cardiac valve endocarditis cyanotic CHD six adjacent cardiac valvulopathy
Prophylaxis not recommended for:
• All other \_\_\_\_ diseases • Beyond \_\_\_\_ months of a successful CHD repair • \_\_\_\_ and atrial septal defects • All forms of \_\_\_\_ valve prolapse • Aortic calcified \_\_\_\_ • And as in past: – Implanted \_\_\_\_ and defibrillators – \_\_\_\_ surgery patients – \_\_\_\_ patients w/o valvulopathy – \_\_\_\_ or innocent murmurs
congenital heart 6 ventricular mitral stenosis pacemakers CABG cardiac transplant functional
Dental Procedures for Which Endocarditis Prophylaxis is Reasonable in At-Risk Patients
Prophylaxis Not Recommended
• ____ restorative procedures w/o wedge and/or matrix placement
• Local ____ injections through non-infected tissue
• Dental ____
• ____ bracket placement
• Placement or adjustment of removable appliances
• ____ treatments
• Impressions
• Shedding of ____ teeth
• Bleeding from injury to ____ or oral ____
Prophylaxis Recommended Ø \_\_\_\_ Ø Apicoectomies Ø \_\_\_\_ therapy Ø Rubber dam clamp placement Ø \_\_\_\_ surgery Ø Scaling and root planing, periodontal probing, sub-gingival restorative, supra-gingival preps with wedge/matrix placement Ø \_\_\_\_ Ø Placement of local delivery systems Ø \_\_\_\_ injections Ø Placement or removal of orthodontic bands
supra-gingival anesthetic radiographs orthodontic fluoride primary lips mucosa
extractions root canal periodontal biopsies intraligamental
Main talking points to patients regarding new guidelines
- Infective endocarditis is much more likely to result from frequent exposure to random ____ (brushing, flossing, chewing) than from bacteremias caused by dental procedures.
- ____ may prevent an exceeding small number of cases of IE, if any, in people undergoing dental procedures.
- The ____ of antibiotic-associated adverse events may exceed the benefit , if any, from prophylaxis regimens.
- Maintenance of optimal ____ and hygiene may reduce the incidence of bacteremia from daily activities and is more important than ____ for a dental procedure to reduce the risk of IE.
bacteremias prophylaxis risk oral health prophylactic
1997/2007 Endocarditis Prophylaxis Regimens
Standard: ____ 2 grams (50 mg/kg Peds)
Penicillin Allergic: ____ 600 mg (20 mg/kg Peds)
____ or Clarithromycin 500 mg (15 mg/kg Peds)
____ or Cefadroxil 2 grams‡ (50 mg/kg Peds)
*All regimens ____ hour before procedure
‡ Cephalosporins should not be used in individuals with a history of ____, angioedema or ____ to penicillins.
amoxicillin
clindamycin
azithromycin
cephalexin
one
anaphylaxis
urticaria
Additional Endocarditis Tidbits
“If the dosage of antibiotic is inadvertently not administered before the procedure, the dosage may be administered up to ____ hours after the procedure.”
Another concern that dentists have expressed involves patients who require prophylaxis but are already taking antibiotics for another condition. In these cases, the recommendations for infective endocarditis recommend that the dentist select an antibiotic from a different ____ than the one the patient is already taking.
For example, if the patient is taking amoxicillin, the dentist should select ____, azithromycin or ____ for prophylaxis.
two
class
clindamycin
clarithromycin
1997 ADA/AAOS Advisory Statement
“Antibiotic prophylaxis is not indicated for dental patients with ____, plates, and screws, nor is it routinely indicated for most dental patients with total ____ replacements.
However, it is advisable to consider pre-medication in a small number of patients who may be at potential risk of ____ total joint infection.”
pins
joint
hematogenous
Patients at Increased Risk of Hematogenous Total Joint Infection
•Immunocompromised/immunosuppressed patients
– ____
– Systemic lupus erythematosus
– ____ dependent diabetes
– Disease, drug or radiation induced immunosupression
– ____
– Malnourished
• Other patients
– First ____ years following joint replacement
– Previous joint____
rheumatoid arthritis insulin hemophilia 2 infections
February 2009 AAOS Information Statement
Given the potential adverse outcomes and cost of treating an infected joint replacement, the AAOS recommends that clinicians consider antibiotic prophylaxis for all total joint replacement patients prior to any ____ procedure that may cause bacteremia. This is particularly important for those patients with one or more of the following risk factors. Same as previous slide but add ____, megaprostheses and ____ infection and delete within ____ years of surgery.
invasive
malignancy
HIV
2
July 2009 JADA Editorial by Michael Glick
Contrary to other practice guidelines that have recognized the harm in using antibiotics when not absolutely necessary, these new recommendations could result in an increased use of ____ for patients, the vast majority of whom are not in need of prophylactic coverage.
In the case of the new 2009 AAOS recommendations, it will be hard to argue that the benefit to the individual patient outweighs the harm to the public. Using clinical guidelines that cannot be scientifically supported will tarnish our professional integrity and diminish the public’s trust in our profession.
antibiotics
2012 Joint ADA/AAOS Statements
The Guideline Recommendations:
1. The practitioner might consider discontinuing the practice of routinely prescribing prophylactic antibiotics for patients with hip and knee prosthetic joint implants undergoing dental procedures. Strength of Recommendation: ____
A Limited Recommendation means the quality of the supporting evidence that exists is ____, or that well-conducted studies show little clear advantage to one approach versus another.
Practitioners should be cautious in deciding whether to follow a recommendation classified as Limited, and should exercise judgment and be alert to emerging publications that report evidence. Patient preference should have a substantial influencing role.
limited
unconvincing
2012 Joint ADA/AAOS Statements
- We are unable to recommend for or against the use of topical oral antimicrobials in patients with prosthetic joint implants or other orthopaedic implants undergoing dental procedures.
Strength of Recommendation: ____
An Inconclusive Recommendation means that there is a lack of ____ evidence resulting in an unclear balance between benefits and potential harm.
Practitioners should feel little constraint in deciding whether to follow a recommendation labeled as Inconclusive and should exercise judgment and be alert to future publications that clarify existing evidence for determining balance of benefits versus potential harm. Patient preference should have a substantial influencing role.
inconclusive
compelling
2012 Joint ADA/AAOS Statements
3. In the absence of reliable evidence linking poor oral health to prosthetic joint infection, it is the opinion of the work group that patients with prosthetic joint implants or other orthopaedic implants maintain appropriate oral hygiene.
Strength of Recommendation: ____
A Consensus Recommendation means that expert opinion supports the guideline recommendation even though there is no available empirical evidence that meets the inclusion criteria.
consensus
Joint Prophylaxis Regimens
Not Allergic to Penicillin:
____ 2 grams
or ____ 2 grams
or ____ 2 grams
Allergic to Penicillin: ____ 600 mg
- All regimens taken ____ hour before the procedure
cephalexin cephradine amoxicillin clindamycin one
