nonsurgical antibiotics 1 and 2 Flashcards by Luke Lloyd

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

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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

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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

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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

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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

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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

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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

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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

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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

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Azithromycin and Clarithromycin belonging to the _ class are more recent antibiotics being used

macrolides

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MOA of Penicillins (amoxicillin)

inhibiting the transpeptidase that catalyzes the final step in cell wall biosynthesis, the cross-linking of peptidoglycan

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MOA of

cycloserine
vancomycin, telchoplanin
bacitracin
cephalosporins
monobactams
carbapenems

inhibit or fuck with cell wall

like penicillins

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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

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MOA site ribosomes - common target
2 different subunits
50S
30S

50S - macrolides - azithromyocin - erythromycin - (clindmycin)

30S - tetracycline - doxycycline

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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

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bactericidal agent means

kills bacteria - preferred

metronidazole - outright kills - DNA replication

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bacteriostatic agent means

slows bacterial growth

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narrow spectrum agent means effective against _

specific families of bacteria (preferred, spares gut microbiota.

example - metronidazole, DNA replication -

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broad spectrum agent means effective against _

a wide range of clinically important bacteria

examples - tetracycline and Macrolides(azithromycin)

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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

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Amoxicillin has
_ spectrum
penetration
good activity against gram

broad spectrum
enhanced tissue penetration (compared to penicillin)
good against gram negatives

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what is Augmentin

amoxicillin combined with a beta-lactamase inhibitor

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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