nonsurgical antibiotics 1 and 2 Flashcards
potential indications for use of systemic antibiotics
3 cases
aggressive periodontitis almost always stage 3/4(localized or generalized forms)
Periodontal abscess (if severe) - ○ Focal infection of swelling and pain, soft tissue Neutrophils
Infection can’t drain
If localized - we prob won’t prescribe antibiotics
If fever and generalized maliase, swollen lymohnodes - we use antibiotics
NUG (if severe) - disease caused by fusuo spirochete
○ Necrotic response - loss of interdental papilla and tissue
○ Can cause malaise, fever
Localized - clean it up no antibiotics
Generalized - might want to prescribe antibiotics
- Chronic Periodontitis ○ Pretty common ○ Typically progresses more slowly ○ We don't usually use antibiotics If initial nonsurgical therapy and give time to resolve and doesn't improve - and test postive for p. gingi and AA because those are tough bacteria to get rid of
when is it reasonable to consider use of antibiotics to treat chronic periodontitis
poor response to intial therapy and continued Aloss
patients with subg biofilm test postive for P. gingivalis or A.A.
sever cases with generalized deep pocket depths
Chronic with a lot of deep pockets and attachment loss
If we are considering using antibiotics we are doing it as part of the nonsurgical SRP not by itself
Rationale for use of antibiotics
some periodontal pathogens invade _, making them difficult to eliminate by SRP(mechanical)
invade soft tissue and dissapear from PMNs and fibroblasts
AA - LAP juvenile
P. gingivalis - chronic periodontitis
P. intermedia
in addition, it is difficult to access and remove biofilm from periodontal sites with deep probing depths or furcations
When dealing with very deep pockets - its tough to get all the way apical - beyond 5mm it’s tough
Furcations - more difficult to debrid
Dentin tubules - some are big enough for bacteria to get down into there and can’t get mechanically
Goal - to create a blank slate and to recolonize with healthy flora Antibiotics helpful eliminating disease associated
do we usually/rountinely treat chronic periodontitis with antibiotics?
no not routinely
SRP removes most subg bacteria from moderately deep sites and provide reasonable degree of pocket reduction and clinical attachment gain without antibiotics
we don’t usually treat chronic periodontitis with antibiotics because SRP is pretty good for moderately deep sites - reasonable degree of pocket reduction and clinical attachment gain without Rx
in conjunction with debridement, the _ and _ mechanisms are usually effective in coping with a bacterial challenge
innate and acquired host defense mechanisms
the small clinical benefit from using the antibiotic may not be worth the risks
~can cause gastroenteritis
~bacterial resistance
typical clinical outcomes of SRP - attachment gain and depth reduction
shallow 1-3mm
moderate 4-6
deep >6
shallow =-0.34mm (caused more loss) and PD reduction =0.03mm - so not too good with shallow pockets
moderate = +.55mm attachment gain, 1.29mm PD reduction
deep = 1.19mm clinical attachment gain and 2.19mm PD reduction
the deeper the pocket the better the outcome
Deeper the pocket the more attachment gain and reduction in pocket depths
systemic antiobiotics are potentially helpful in periodontal therapy if:
~they distribute to the _ and its _
~they reach inhibitory levels in the pocket
~their levels are maintained for an adequate duration
~they penetrate _and kill invasive bacteria
~they distribute to the pocket and its soft tissue wall
~they reach inhibitory levels in the pocket
~their levels are maintained for an adequate duration
~they penetrate host cells and kill invasive bacteria
junctional epi - permeable
First comes from gingival then JE then something else
bacteria in biofilm are somewhat resistant to antibiotics, so subg biofilm muct be disrupted by SRP prior to using antibiotics to treat periodontitis
Normally bacteria exist in biofilm
Biofilm is imperable to antibotics
Matrix - keeps antibiotic from diffusion into the film
In order to use antibiotic to kill bacteria in the biofilm we have to scale and root plane(remove cementum) and break the biofilm up so antibiotic can kill
general species of bacteria at different levels of the pocket/biofilm
suprag: G+ Cocci = G+rod > G- rods > motile rods
gingival margin: G+ rods = G- rods > Cocci
pocket plaque: G- rods = Motile rods > G+ species
as you move apically it changes to more G- rods and species - harmful endotoxin - LPS bacteria
Azithromycin and Clarithromycin belonging to the _ class are more recent antibiotics being used
macrolides
MOA of Penicillins (amoxicillin)
inhibiting the transpeptidase that catalyzes the final step in cell wall biosynthesis, the cross-linking of peptidoglycan
MOA of
- cycloserine
- vancomycin, telchoplanin
- bacitracin
- cephalosporins
- monobactams
- carbapenems
inhibit or fuck with cell wall
like penicillins
which antibiotics MOA site is DNA gyrase, an essential bacterial enzyme that catalyzes the ATP-dependent negative super-coiling of double-stranded closed-circular DNA. Gyrase belongs to a class of enzymes known as topoisomerases that are involved in the control of topological transitions of DNA.
Quinolones
MOA site ribosomes - common target
2 different subunits
50S
30S
50S - macrolides - azithromyocin - erythromycin - (clindmycin)
30S - tetracycline - doxycycline
mechanism of action metronidazole
DNA replication
Metronidazole is of the nitroimidazole class. It inhibits nucleic acid synthesis by disrupting the DNA of microbial cells.[1] This function only occurs when metronidazole is partially reduced, and because this reduction usually happens only in anaerobic bacteria and protozoans, it has relatively little effect upon human cells or aerobic bacteria
bactericidal agent means
kills bacteria - preferred
metronidazole - outright kills - DNA replication
bacteriostatic agent means
slows bacterial growth
narrow spectrum agent means effective against _
specific families of bacteria (preferred, spares gut microbiota.
example - metronidazole, DNA replication -
broad spectrum agent means effective against _
a wide range of clinically important bacteria
examples - tetracycline and Macrolides(azithromycin)
Penicillins
bactericidal or bacteriostatic
inactivated by _
How does it act against AA
penetration?
bactericidal
inactivated by beta-lactamases
Don’t inhibit all strains of AA but most strains are inhibited
don’t penetrate epithelial cells very well
Induce resistance - bacteria make beta-lactamases - need this for bacteria activity
Absorbed reasonably well
Are not actively taken up by cells
They diffuse into cells
Pencillin b - narrow specrutm
Amoxicillion - broad spectrum
Good against gram negative
Amoxicillin has
_ spectrum
penetration
good activity against gram
broad spectrum
enhanced tissue penetration (compared to penicillin)
good against gram negatives
what is Augmentin
amoxicillin combined with a beta-lactamase inhibitor
Metronidazole
bactericidal or bacteriostatic
narrow or broad spectrum
how does it act against AA
bactericidal agent
narrow-spectrum- active against strict/obligate anaerobes
activity against facultative bugs like AA is less potent
inexpensive, usually well tolerated
Tetracyclines (minocycline and doxycycline)
bactericidal or bacteriostatic
narrow or broad spectrum
MOA?
bacteriostatic (slows growth) against most periodontal pathogens
broad spectrum
protein synthesis inhibitors. They inhibit the initiation of translation in variety of ways by binding to the 30S ribosomal subunit, which is made up of 16S rRNA and 21 proteins.
Show up in high concentrations in gingival crevices/fluid and pockets than you can find in blood serum/plasma -
actively accumulated by oral epithelial cells, gingival fibroblasts and PMNs
tetracyclines (minocycline and doxycycline)
Inhibit collagenase - which mediates collagen breakdown in periodontitis
tetracyclines (minocycline and doxycycline)
Fluoroquinolones (ciprofloxacin)
bactericidal or bacteriostatic
narrow or broad spectrum
how do they act against AA and Pg
GCF/blood levels?
MOA?
bactericidal - kills
broad spectrum
extremely active against AA, less active against anaerobic bactertia like Pg
reach higher levels in GCF than in blood
penetrate epithelial cells and phagocytes and can kill invasive bacteria
It is active against both Gram-positive and Gram-negative bacteria. It functions by inhibiting DNA gyrase, and a type II topoisomerase, topoisomerase IV, necessary to separate bacterial DNA, thereby inhibiting cell division
antibiotic most active against AA
Fluoroquinolones (ciprofloxacin)
MOA- DNA gyrase cell division
not used often
not the most active against Pg
Clindamycin
bactericidal or bacteriostatic
how do they act against AA and Pg
potent bacteriostatic activity against strict anaerobes
less effective against facultative pathogens like AA
primarily bacteriostatic effect. It is a bacterial protein synthesis inhibitor by inhibiting ribosomal translocation,[50] in a similar way to macrolides. It does so by binding to the 50S rRNA of the large bacterial ribosome subunit,
clindamycin
penetrates bone
can occasionally induce ulcerative colitis
used as an alternative antimicrobial agent in penicillin-allergic patients
clindamycin
not so much for aggressive periodontitis
reach high concentrations in tissue
have good activity against AA, Pg, and many other gram negative anaerobes
penetrates epithelial cells and kills invasive bacteria - also taken up by PMNs and fibroblasts
Macrolides(azithromycin and clarithomycin)
broad spectrum - risk for resistance
against 50S ribosome
antibiotic that produce anti-inflammatory effects
simple regimen (one dose per day)
expensive
Macrolides(azithromycin and clarithomycin)
Study about Macrolides
oral epi cells, phagocytes and gingival fibroblasts take up and concentrate azithromycin and clarithromycin
azithromycin:
48ug/ml inside epi
8ug/ml inside phagocytes
10ug/ml inside fibroblasts
clarithromycin:
6.6ug/ml inside epi
31ug/ml inside phagocytes
76ug/ml inside fibroblasts
Each of these cells that take up the antibiotics
They can act like a reservoir
Improves the bioavailabity over a long period of time
azithromycin levels are higher in _ than in _
because cells sequester the antibiotic
more than 2 weeks
higher in GCF than in blood
_ antibiotic induces a decrease in GCF IL-8 and TNF content
anti-inflammatory effect
Azithromycin
can be used to treat respiratory infections
bottoms out at day 4
and then goes back up to normal levels
_ helps eliminate invasive AA infection from cultured oral epi cells
azithromycin
common features of tetracyclines, ciprofloxacin, azithromycin and clarithromycin
levels in GCF are often higher than levels in blood
drugs are actively accumulated by PMNs, gingival fibroblasts and oral epithelium
can potentially kill bacteria that have invaded/entered host cells
Macrolides
bactericidal or bacteriostatic
bacteriostatic - slows growth
which antibiotic
[GCF] - 3-4 1/2life in serum - 1-2hrs AA - okay 0.4-1ug/ml Pg - good <0.016ug/ml Tf- okay 0.38
amoxicillin - bactericidal
which antibiotic
[GCF] - 8-10 high 1/2life in serum - 6-12 AA - 64-96ug/ml - bad Pg - good <0.016ug/ml Tf - good 0.005
metronidazole - bactericidal
which antibiotic
[GCF] - 2-8 1/2life in serum - 12-22 AA - 1ug/ml - okay Pg - good 0.047ug/ml Tf - good 0.38ug/ml
doxycycline - bacteriostatic
which antibiotic
[GCF] - 3-10 1/2life in serum - 40-68 AA - 0.87-4 ug/ml - good/okay Pg - good 0.09-0.5ug/ml Tf - okay 0.5-1ug/ml
azithromycin bacteriostatic
approaches for deciding which antibiotic to use
_-based on data from randomized clinical trials, this is the usual approach - 98% of the time
-educated guess
empirical approach
~ID pathogens at the site with a molecular technique, then prescribe an antibiotic that will presumably inhibit them
~culture isolated bacteria to ID them and determine their susceptibility to antibiotics
advantages of _ tests
plaque and saliva specimens are east to collect
sample collection is non-invasive
tests are specific for AA,Pg,Pi,Tf,Td,Fnuc
more sensitive than other methods
test requires DNA, not live bacteria
molecular tests
Disadvantage - no info about bacteria suspectibility
advantages of _ tests
reflects viable bacteria in the pocket
can assess the predominance of a particular pathogen
can grow and study unusual bacteria
can determine antibiotic susceptibility
bacterial culturing
disadvantage - not many labs do this testing
Fastidious - spirochetes - don’t want to leave - so that will be dead and gone and impossible to detect
time consuming, costly
transport to lab problems (have to keep alive)
difficult to grow some organisms (spirochetes)
accuracy dependent on good sampling technique
not very sensitive
how to best use microbiological tests?
complete initial periodontial therapy before testing
assess the response
-if not good, sample the deepest pockets and test for presence of pathogens with a molecular test
prescribe an antimicrobial regime that is active against the pathogens ID’d by the test
empirical regimen for aggressive periodontitis or severe chronic periodontitis
Toxcity it relatively low - and is good against all of the pathogens
amoxicillin (500mg TID) combined with metronidazole (250mg TID) for 8 days
Two bactericidal agents
TID-3x per day
this regimen has been examined in numerous clinical trials
if we don’t treat aggressive perio or severe chronic peri with amoxicillin (500mg TID) combined with metronidazole (250mg TID) for 8 days
we use _ as second option
_ as 3rd option
Second Azithromycin -Once a day - easy on patient compliance - 500mg starting dose then 240mg per day for for days
3rd - allergic to pencillin - metronidazole 500mg TID for 7 days
Narrow spectrum antibiotic - lower potential to induce bacterial resistance than the other regimes
Looking at a different type of infection
Odontogenic infections - penicillin B
Periodontal - the combo of amoxicillin and metronidazole
At sites with initial PD >6, SRP alone provides a mean of CAL gain of ~_mm and mean PD reduction of ~_mm
Combine with AMX+MET - even more attachment gain 3.1mm
SRP alone provides a mean of CAL gain of ~1.19mm and mean PD reduction of ~2.19mm
systemic antibiotics are not consistently beneficial unless the biofilm is disrupted by SRP
SRP should be completed in a short period of time like _
when to start antibiotics?
less than one week
start antibiotics the day SRP is completed
Little evidence that giving antibiotics at the time of surgery produces a huge benefit
frequent adverse effects of _
rashes, allergy, diarrhea
penicillins
frequent adverse effects of _
nausea, diarrhea, dental staining
tetracyclines
frequent adverse effects of _
nausea, diarrhea, altered taste(metallic), antabuse effect(malaise when alcohol is consumed)
metronidazole
frequent adverse effects of _
diarrhea, nausea, cholestatic jaundice (rare), cardiac arrhythmia (rare)
azithromycin
local delivery or systemic delivery of antibiotics
case specific but local is less effective at eradicating invasive bacteria
site adjacent may still have bacteria and get recurrent infection
bacteria in subg biofilm are resistance to antibiotics, so antibiotics shold only be prescribed after _
after SRP
