Dental Antibiotic Pharmacology Flashcards
what are the normal flora of the mouth
- viridans group streptococci
- other strep spps
- lactobacillus
- actinomyces spps
- preveotella spps
what is the main gram negative in the mouth
prevotella spps
describe gram positive organisms
- bulk of oral bacteria
- primarily cocci or irregular shape (pleomorphic)
- oxygen tolerance varies from facultative anaerobes to strict anaerobes
- cell wall has thick peptidoglycan layer
are bacteria in the mouth more gram negative or gram positive
gram positive
what are the 3 important genera of gram positive oral bacteria
- actinomyces
- lactobacillus
- streptococcus
what type of bacteria is actinomyces and where is it found in the mouth
- facultative anaerobe
- periodontal pockets, dental plaques, on carious teeth
what type of bacteria is lactobacillus and what does it do
-facultative anaerobe
- produce lactic acid, role in dentine caries rather than enamel caries
what type of bacteria is streptococcus and what does it do in the mouth
- faculatative anaerobic cocci
- produce lactic acid some implicated in caries
oral streptococci are referred to as:
viridians streptococci
what does strep mutans do
- acidogenic (acid producing) and aciduric (acid tolerant) species
- highly associated with caries
- bacterial communities collected from dentin carious lesions contain notorious acidogenic and aciduric species including S mutans, Scardovia wiggsiae, parascardovia denticolens, and lactobacillus salivarius
what does strep mitis and S sanuinis do
- first oral organisms detected in newborn infants
- commensals
- peroxigenic (produce hydrogen peroxide) inhibits the growth of S mutans and porphyromonas gingivalis and other oral pathogens
describe gram negative organisms
- many gram negative bacteria found in the mouth, especially in established subgingival plaque
- range of oxygen tolerance but most important strict or facultative anaerobes
- some fermentative, produce acids which other organisms use acids as an energy source, others produce enzymes which break down tissue
- cell wall different to gram positive with a thin peptidoglycan layer, has B-lactamase which breaks down penicillin, also has LPS/endotoxin
what are the gram negatives in the oral cavity and what are they associated with
- porphyromonas: P.gingivalis major periodontal pathogen
- prevotella: P. intermedia a periodontal pathogen
- fusobacterium: F. nucleatum periodontal pathogen
- actinobacillus/aggregatibacter: A.actinomycetemcomitans associated with aggressive periodontisis
- treponema: group important in acute periodontal conditions - ANUG
- neisseria
- veillonella
what does bacteriostatic mean
arrests growth of organisms
bacteriostatic must have:
active immune system
what does bactericidal do
kill the organism
what is the MOA of bactericidal antibiotics
- cell wall inhibitors: beta lactams, penicillins, cephalosporins
- inhibit DNA: fluoroquinolones, metronidazole
which agents are better for patients with immunosuppression and severe disease
bactericidal
what is the MOA of bacteriostatic ABs
- protein synthesis inhibitors: macrolides, clindamycin, doxycyline
describe concentration dependent ABs
- higher peak concentration
- more extensive/faster kill-> greater killing
- maximize peak concentration (higher doses)
what is the post antibiotic effect
bacterial suppression after antibiotic concentrations fall below MIC
describe time dependent ABs
the more time above the MIC, more inhibition
- maximize duration of exposure above MIC
- concentrations need to be reinforced leading to more dosing
- more exposure -> more killing
what ABs are concentration dependent
fluoroquinolones and metronidazole
what are the the time dependent killing drugs
- No PAE: beta lactams
- Some PAE: clindamycin, azithromycin, tetracyclines
what is the usual dose range of cephalexin
250-1,000mg every 6 hours or 500mg every 12 hours
what type of drug is cephalexin, what is its half life and excretion
- time dependent: works best the longer concentrations stay above MIC
- half life: about 1 hour for adults
- excretion: urine 80-100% as unchanged drug in 6-8 hours
what does the excretion time of cephalexin suggest
4-6 hours of subtherapeutic blood concentrations with Q12 hour dosing
what is the cephalexin prescription for cellulitis
500mg 4 times daily
what is the cephalexin prescription for cystitis
500mg twice daily
what is the usual dosage range for amoxicillin for immediate release or extended release
- immediate release: oral 500mg to 1g every 8-12 hours
- XR: 775mg once daily
what is the amoxicillin prescription for periodontitis
oral- 500mg every 8 hours in combination with metronidazole for 7 to 14 days, used in addition to periodontal debridement
what is another acceptable dosage for amoxicillin
875mg po BID immediate release
what is the absorption of amoxicillin immediate and extended release
- immediate: rapid with or without food
- XR: rate of absorption is slower compared to immediate release formulations; food decreases the rate but not extent of absorption
what is the distribution of amoxicillin
- readily into the liver, lungs, prostate, muscle, middle ear effusions, maxillary sinus secretions, bone, gallbladder, bile and into ascitic and synovial fluids, poor CSF penetration
what is the protein binding of amoxicillin
20%
what is the half life elimination of amoxicillin
adults: immediate release: 61.3 minutes
- extended release: 90 minutees
what is the time to peak of amoxicillin
capsule, oral suspension: 1-2 hours; chewable tablet 1 hour; extended release: 3.1 hours
what is the excretion of amoxicillin
urine (60% as unchanged drug)
what are the downfalls of having an allergy to amoxicillin
- receive more vancomycin, clindamycin, and fluoroquinolones
- 63-158% higher cost of antibiotics
- increase length of hospitalization, average 0.59 more days
- increased drug resistant organisms
- 69% increased risk of MRSA infections
- 30.1% more VRE infections
- 26% increased risk of C. difficile infection
describe a side effect
- predictable, dose related, can affect anyone
what is an example of an overdose
hepatic failure (acetaminophen)
what is an example of a side effect
nephrotoxicity (with aminoglycosides); diarrhea (amoxicillin)
which is more common: an allergy or side effect
side effect
describe an allergy
- unpredictable (hypersensitivity reaction), not dose related, cannot affect anyone
- anaphylaxis or photoallergy
- antibody or T-cell stimulation
describe allergic-like or pseudo-allergic reactions and give examples
- resemble allergic reaction; NOT immune mediated
- vancomycin infusion reaction; morphine rash
what is the mechanism of the delayed onset benign cutaneous reaction
T-cell
what is the mechanism of acute onset benign cutaneous reaction
IgE
any non-SJS rash history to amoxicillin, re-exposed to amoxicillin ______ tolerate with no subsequent reactions
94-96%
what are the low risk penicillin allergy assessment symptoms
- non-hive rash
- itching
- hive rash
- diarrhea
- vomiting
- nausea
- runny nose
- cough
- family hx of allergy
what are the high risk symptoms for penicillin allergy
- lip/facial swelling
- difficulty breathing/wheezing
- skin peeling
- mouth blisters
- drop in BP
hives is _______ to avoid penicillin
not a reason
viral infections cause _____ of all cases of acute hives in children
more than 80%
what is the presentation of benign T-cell mediated cutaneous drug reactions
- delayed onset (greater than 6 hours after course begins)
- typically less pruritic than IgE mediated reactions
- each lesion lasts more than 24 hours
- fine desquamination with resolution over days to weeks
describe the presentation of IgE mediated cutaneous drug reactions
- onset minutes to hours into course
- significant pruritis
- raised off the skin
- each lesion lasts less than 24 hours
- fades without scarring
what is the presentation of severe T cell mediated or severe cutaneous reactions
- onset days to weeks into treatment course
- mucosal and/or organ involvement
- blistering and/or skin desquamination
- usually requires hospitalization
what are the low risk reaction symptoms and what is the action
- isolated reactions unlikely allergic (gastrointestinal symptoms, headaches)
- self limited rash
- remote (more than 10 years) non-severe reaction
- family history of Pcn allergy
- action: prescribe amoxicillin course or perform a direct amoxicillin challenge under observation
what are the medium risk symptoms and action
- reactions with IgE features but not anaphylaxis
-action: skin test plus amox challenge or graded challenge
what are the high risk symptoms and what is the action
- anaphylactic symptoms
- positive skin testing
- recurrent reactions
- reaction to multiple Beta lactam antibiotics
- action: skin test plus amoxicillin challenge
what is considered in the allergy assessment
- describe rxn: extent, where, itching, red, pain, duration, route administered
- timing of rxn: immediate (less than 4 hours), delayed (more than 24 hours)
- how long ago did rxn occur
- any treatment required?
what symptoms are not true allergies of penicillin and what do you give instead
- family history of penicillin allergy, GI symptoms, headache, yeast infection
- comfortable giving any penicillin
what symptoms are likely not a type 1 allergy and what do you give instead
- hive and non-hive rash reports (not SJS-like)
- may give amoxicillin, especially with distant history and non- immediate onset benign skin reactions
what is the risk of using amoxicillin
- no risk if the reaction is GI, headache, yeast infection, family history
- any non-SJS rash history to amoxicillin, re-exposed to amoxicillin 93-94% tolerate with no subsequent reactions
what oral antibiotic has the highest fatal, serious, and overall ADR rates
clindamycin
risk of clindamycin is ______ higher than amoxicillin
15 times higher
what has the lowest fatal, serious, and overall ADR rates
amoxicillin
outpatients with clindamycin antibiotic are ______ to develop C. difficile infection
5x more likely
when is the highest risk for c. difficile infection after clindamycin
first month after antibiotic exposure
risk for c.difficile infection remains elevated for how long
3 months after exposure
what can clindamycin cause
c. difficile infection
cross reactivity for cephalosporins with similar side chains is _____
higher
in cephalosporins without similar side chains to penicillin is considered _____ and ________
low risk and safe in patients with reported history or positive skin test
what are the cephalosporins that do not have similar side chains to penicillins
- oral: cefuroxime, cefdinir
- IV: cefazolin, ceftriaxone, cefepime
CDI is _____ in patients prescribed a PPI and antibiotic vs antibiotic alone
twice as high
exposure to PPI prior to initial CDI event _______ risk of recurrence
doubles
how can you prevent antibiotic issues
- limit spectrum
- limit duration
- limit combination
when would you consider recommending probiotics with the antibiotic
- 65 years and older
- recent hospitalization or nursing home
- weak immune system
- previous C. diff infection
- taking proton pump inhibitors
what are the history elements that favor low risk of penicillin hypersensitivity
- remote history of symptoms not suggestive of severe reaction more than 5-10 years ago
- delayed onset urticaria
- urticaria only, greater than 5-10 years ago
- self limited mild exanthem incompatible with allergy
- gastrointestinal symptoms only
- family history of penicillin allergy only
- avoidant from fear of allergy only
what percentage of penicillin allergy labels are acquired by age 3
75%
what are the consequences of a penicillin allergy label
- pressure prescribing of 2nd and 3rd line antimicrobials
- increased inappropriate antibiotic selection
- increased mortality risk during cancer and infection treatment
- delay the onset of appropriate antimicrobial therapy
- increase treatment failures/surgical infections
- associated increase in multidrug resistant infections
- longer lengths of stay
- higher healthcare costs
what are the best anti- infectives
beta lactams
what are the two main beta lactams
- penicillins
- cephalosporins
what are the penicillins that are beta lactams
- penicillin
- amoxicillin/ampicillin
- dicolxacillin
- peperacillin
what are the cephalosporins that are beta lactams
- cephalexin
- cefuroxime
- cefaclor
- cefprozil
- cefdinir
what is the beta lactam MOA
binds and inhibits penicillin binding protein
- block cell wall synthesis causing walls to leak
- lower cell death threshold
- includes penicillins, cephalosporins, carbapenems
all beta lactams are:
bactericidal
beta lactams are the ___used and effective antibiotics with_____
most used; least toxicitiy
side chains in beta lactams account for:
acid stability, absorption, spectrum, susceptibility to beta lactamases
how are beta lactams absorbed in pregnant women
cross placenta and distributed in breast milk
how are beta lactams eliminated
high renal excretion
which penicillins are inhibited by beta lactamases
penicillin G
- penicillin K
- ampicillin
amoxicillin
what are the resistance mechanisms to beta lactams
- efflux pumps
- beta lactamases
- RNA modifcation
what are the beta lactamase inhibitors
- calvulante (paired with amoxicillin)
- sulbactam (paired with amoxicillin)
- tazobactam (paired with piperacillin)
what is the MOA of beta lactamase inhibitors
- irreversibly bonds with beta lactamase
- ties up all beta lactamase
- allows the antibiotic to persist and extends activity to beta lactamase producing pathogens
beta lactamase inhibitors extends more coverage:
more gram negatives, anaerobes and staph
augmentin =
more gram negatives, anaerobes and staff
what is augmentin usually prescribed for with augmentin
dental infections with abscess or failed amoxicillin
what are b-lactams
- group of antibiotics
- have beta lactam ring as part of their structure
what is b-lactamase
- enzyme released by bacteria
- disables the bea-lactam ring thus the antibiotic is ineffective
what is beta lactamase inhibitor
- compound added to b-lactam antibiotic
- disables the beta lactamase thus antibiotic is effective again
what is the amoxicillin dose for adults and peds
- adult: 500mg PO Q8 hours
- pediatric: 20-40 mg/kg/day divided Q8 hours or 25-45 mg/kg/day divided Q12 hours
what is the dose for augmentin
adult:500mg PO Q8 hours or 875mg PO Q12 hours
- peds: 20-40 mg/kg/day divided by Q8 hours
or 25-45 mg/kg/day divided Q12 hours
is diarrhea associated more with augmentin, amoxicillin or penicillin
augmentin
what is the rate of diarrhea with augmentin
25%
