antibiotics page Flashcards
Principles of effective antimicrobial chemotherapy:
a) The drug must reach the _.
b) The drug’s concentration at the site of action must be sufficient to inhibit microflora.
c) The duration of chemotherapy must be sufficient to allow the drug to act.
site of action
Routes for delivery of antimicrobial agents to the periodontal pocket and adjacent tissue ;
reach the site of action
attain adequate concentration
retained for adequate duration
Mouthrinses
each the site of action - poor
attain adequate concentration - good
retained for adequate duration - poor
Routes for delivery of antimicrobial agents to the periodontal pocket and adjacent tissue ;
reach the site of action
attain adequate concentration
retained for adequate duration
systemic antibiotic
each the site of action - good
attain adequate concentration - fair/good
retained for adequate duration - good
Routes for delivery of antimicrobial agents to the periodontal pocket and adjacent tissue ;
reach the site of action
attain adequate concentration
retained for adequate duration
local antibiotic
each the site of action - good (for pocket)
attain adequate concentration - good
retained for adequate duration - good
pathogens associated with periodontal breakdown
Localized aggressive periodontitis is associated with
Aggregatibacter actinomycetemcomitans (A. a.).
In addition, Porphyromonas gingivalis (P. g.) and Fusobacterium nucleatum are frequently associated.
pathogens associated with periodontal breakdown
Recurrent (“refractory”) chronic periodontitis is associated with
P. g., and Prevotella intermedia (P. i.). Tannerella forsythia, Fusobacterium, Campylobacter rectus and spirochetes (e.g., Treponema denticola) are also common isolates
The “red complex” associated with chronic periodontitis consists of
P. g, T. forsythia and T. denticola.
Scaling and root planing (SRP) usually eliminates many species of bacteria from the pocket. However, _, _ and _(and probably others) are difficult to eliminate by SRP alone because they have the ability to invade pocket epithelial cells. Moreover, they all possess potent endotoxins and release noxious proteases (e.g., collagenase).
A. a., P. g. and P. i.
Antibiotics are most useful in treating periodontal diseases in which _ and _ bacteria play a significant pathogenic role (e.g., localized aggressive periodontitis and recurrent periodontitis).
A. a. and P. g.
Systemic Antibiotics can be useful adjuncts in the treatment of aggressive periodontitis and chronic periodontitis. Several issues must be considered to use them effectively:
a) Antibiotics don’t always improve the treatment outcomes of mild-to-moderate _ periodontitis cases, since conventional mechanical therapy (SRP and oral hygiene) eliminates most disease-associated bacteria.
b) To be effective, antibiotics must be used in conjunction with SRP during _ therapy
c) Antibiotics are not effective in controlling _ plaque.
d) Antibiotic combinations often work best. Most single antibiotics can’t inhibit all the bacteria associated with different forms of periodontal disease at drug levels attainable in the periodontal pocket.
a. chronic
b. initial therapy
c. supragingival
Penicillins (PCNs) are bactericidal in vitro and reach effective levels in gingival fluid. However, PCN doesn’t inhibit all A. a. strains, and is inactivated in vivo by _ produced by certain subgingival bacteria.
Compared to PCN, _ has enhanced tissue penetration and enhanced activity against Gram-negative bacteria.
penicillins inactivated by β-lactamases
amoxicillin has higher tissue penetration, enhanced activity against gram negative
Augmentin, a combination of _ and _, is the most effective penicillin used in periodontal therapy.
amoxicillin and the β-lactamase inhibitor clavulanic acid
_ provides excellent bactericidal activity against strict anaerobes, but is less inhibitory towards facultative bacteria like A. a.
Metronidazole
Tetracycline (TCNs) and its derivatives doxycycline and minocycline are effective bacteriostatic agents against most periodontal pathogens, including A. a.
TCNs reach relatively _ in gingival fluid. In addition to their antimicrobial properties, TCNs inhibit _from a variety of cellular and tissue sources. Tetracyclines are taken up by _ and _
high concentrations (4 to 8 μg/mL) in GCF
inhibit collagenases - Collagenase mediates collagen breakdown in periodontitis, arthritis, and other inflammatory disorders.
taken up by oral epithelial cells and PMNs.
Fluoroquinolones (e.g., ciprofloxacin and ofloxacin) inhibit bacterial DNA gyrase and are among the most potent inhibitors of A. a. Ciprofloxacin is actively taken up by _ and _, so it can be used to treat infections by invasive bacteria (e.g., A. a.).
PMNs and epithelial cells
tetracycline and ciprofloxacin(fluoroquinolone) reaches higher concentrations in gingival fluid than in serum. However, _ is less active against anaerobic bacteria.
ciprofloxacin less effective
Clindamycin is a potent inhibitor of many _ species, but is less effective against A. a.
strict anaerobes
_ is a macrolide that is not very useful for treating periodontitis, since it doesn’t reach effective concentrations in gingival fluid and has weak activity toward A. a. and Fusobacterium
Erythromycin
Azithromycin and clarithromycin are macrolides that have better tissue distribution and longer half-lives than their parent compound, erythromycin. Both have good activity against A. a., P. g., Provotella species, fusobacteria and other anaerobic and facultative pathogens. Both compounds reach steady-state concentrations that are much higher in _ and _ than in _.
Both appear to reach higher concentrations in inflamed gingiva than in healthy gingiva. Both penetrate PMNs and oral epithelial cells, so they are capable of killing invasive bacteria like A. a. and P. g. Azithromycin appears to produce anti-inflammatory effects in gingiva, reducing levels of _, _, and _ in gingival crevicular fluid.
gingival tissue and gingival crevicular fluid than in serum.
IL-1β, IL-8 and TNF-α
There are three potential approaches to deciding which antibiotic to use:
a) Use an empirical approach based on _ demonstrating that specific antibiotics are effective in treating specific forms of periodontal disease.In situations that warrant using antibiotics, most clinicians initially use an empirical approach to select the antibiotic regimen.
b) Use a molecular technique to identify specific DNA sequences associated with periodontal pathogens, then prescribe an antibiotic regimen known to inhibit the pathogens.Molecular assays for identifying common periodontal pathogens are available and are relatively inexpensive, BUT they don’t provide any information about antibiotic _.
c) _ isolated bacteria to identify them and determine their antibiotic susceptibility patterns. Problem: culturing periodontal bacteria is slow and very expensive, and there are only a few specialized microbiological labs in the US that can culture periodontal bacteria and determine their antibiotic susceptibility.
a. based on clinical studies
b. antibiotic susceptibility
c. Culture bacteria to determine susceptibility
Antibiotic regimens for treating Aggressive Periodontitis and Severe Chronic Periodontitis
Amoxicillin (500 mg TID) and metronidazole (250 mg TID) combined for 8 days. This is one of the most widely used regimens.
b) [alternative for patients allergic to Amoxicillin] Azithromycin (500 mg dose on the first day, then 250 mg per day for the next 4 days). Patient compliance is good with this one-dose-per-day regimen.
c) [alternative for patients allergic to Amoxicillin] Metronidazole (500 mg TID for 7 days).
Adverse side effects associated with systemic antibiotics
a) Drug resistance may be induced (e.g., by transfer of DNA _).
b) Some antibiotics (e.g. TCN, amoxicillin, and other PCNs) have the potential to inhibit _.
c) Antibiotics may induce microbial overgrowth (e.g., TCN-induced Candida infection).
d) Possibility of hypersensitivity or toxicity. PCNs can induce anaphylaxis or serum sickness. TCNs can cause nausea, vomiting, diarrhea and photosensitivity. Metronidazole can induce nausea, vomiting, diarrhea, neutropenia, headache and depression.
a. β-lactamase
b. oral contraceptives
_delivery of antibiotics: Advantages a) Higher concentrations of TCN (600 μg/mL) can be attained at a local site.
b) Effective concentrations can be maintained for long periods of time (10 days).
c) Effective drug levels can be established at sites that are difficult to reach by other means
.d) Systemic effects of the antibiotic are minimized. Thus, antimicrobial agents not suitable for systemic administration may be used.
Local
As a chemotherapeutic approach for treating periodontitis, local delivery has several disadvantages: a) It appears to be less effective than systemic antibiotics in suppressing bacteria that _
b) In contrast to systemic antibiotics, local controlled delivery cannot eliminate pathogenic bacteria from the entire oral cavity. Thus, re-infection may occur more readily. c) Placement and removal of local delivery device can be time consuming (10 minutes/tooth)
a. invade periodontal tissues
b.
local delivery will not replace existing treatment modalities. However, it may prove to be a useful adjunct in treating_ sites that have not responded well to traditional periodontal therapy. Each practitioner must determine whether these products have the potential to provide meaningful benefits to the individual patient.
localized recurrent
