Antibiotics in Endodntics FINAL

Yousra alkhairallah 2010

Antibiotic Use in Endodontics

Prepared by: Yousra AlkhairallahR1 Saudi Board in Endodontics


History

Antibiotics are chemical substances produced by microorganisms which have the capacity in dilute solutions to inhibit the growth of bacteria or to destroy bacteria and other microorganisms.

The word “ antibiotic” came from the Ancient Greek : ἀντί – anti, "against", and βίος – bios, "life")


History

Originally known as antiobiosis, they were first

described in 1877 in bacteria when Louis Pasteur

and Robert Koch observed that an airborne bacillus

could inhibit the growth of Bacillus anthracis

They weren’t called antibiotics Until 1942 by

Selman Waksman an American microbiologis


History

Prontosil, the first commercially available antibacterial

antibiotic was developed in Germany

Fleming's accidental discovery and isolation of penicillin in

September 1928 marks the start of modern antibiotics

Prior to this, most wartime deaths were due to bacterial

infections of wounds, rather than from the wounds

themselves


History


History

1890 W.D. Miller, the father of oral microbiology, was

the first investigator to associate the presence of

bacteria with pulpal disease

A classic study published in 1965 by Kakehashi et al

proved that bacteria caused pulpal and periradicular

disease


Microbiology

As long as the pulp is vital, it is a sterile tissue as any connective tissue elsewhere in the body

Infection occurs only after pulp necrosis

No single species will be discovered to be the “major” endodontic pathogen

The composition of the microbiota varies depending on the types of infection and periradicular lesions

Siqueira 2002


Microbiology

Primary root canal infectionCaused by microorganisms colonizing the necrotic pulp tissue

The involved microbiota usually shifts

depending on the time of infection.

Moreover, it has been strongly suggested

that the microbiota can differ according to

the type of periradicular diseases

Whereas a wide range of microbial species is associated with chronic periradicular lesions, a more restricted group of species is associated with symptomatic periradicular diseases such as acute apical periodontitis and acute periradicular abscess

Baumgartner 1986Sundqvist 1987Sjogren 1988Oliveira 2000Siqueira 2001

In general, primary infections are mixed and predominated by anaerobic bacteria. Predominant species usually belong to the genera Bacteroides, Porphyromonas, Prevotella, Fusobacterium, Treponema, Peptostreptococcus, Eubacterium, and Campylobacter.

Facultative or microaerophilic streptococci are also commonly found in primary infections

Siqueira 2002


Microbiology

Secondary root canal infection

Caused by microorganisms that were not present in the primary infection and have penetrated the root canal system during treatment, between appointments, or after the conclusion of the endodontic treatment

If the penetrating microorganisms are successful in surviving and colonizing the root canal system, a secondary infection is established

Siqueira 1997


Microbiology

Persistent root canal infection

Microorganisms that in some way resisted the intracanal procedures of disinfection cause persistent intraradicular infections

Causative microorganisms were members either of the primary infection or of a secondary infection

The microbiota associated with persistent secondary infections is usually composed of a single species or at least by a lower number of species when compared with primary infections

Gram-positive bacteria are the predominant bacteria

Sire´n 1997Molander 1998Sundqvist 1998Peciuliene 2000


Microbiology

Extraradicular infection

May be primary, secondary, or persistent.

The most common form of extraradicular infection is the acute periradicular abscess

The source of extraradicular infections is usually the intraradicular infection. A few oral microorganisms have the ability to overcome host defense mechanisms and thereby induce an extraradicular infection

Actinomyces species and Propionibacterium

propionicus, may be implicated in

extraradicular infections

Nair 1984Happonen 1986Sjogren 1988Iwu 1990

Microbiology

Siquiera 2002

Classification of Antibiotics

Inhibitors of Cell Wall Synthesis

Inhibitors of Nucleic Acid Synthesis and

Function

Protein Synthesis Inhibitors

Others:VancomycineBacitracin

ß-lactam antibiotics

Monobactams

Carbapenems Cephalosporins

Penicillins

Tetracyclines

MacrolidesClindamycine

Chloramphenicole

Quinolones

ErythromycineAzithromycineClarithromycine

Natural:Penicillin GPenicillin V

Antistaph:Methicillin

Extended spectrum:AmoxicillinAmpicillin

DoxycyclineMinocyclineTetracycline

Ciproflaxicine

Cephalexine

Metronidazole

Flagyl



Pinicillin VK

Penicillin VK is bactericidal against gram-positive cocci and the major pathogens of mixed anaerobic infections

Adv:

Narrow spectrum

Defuses into most body parts including oral tissues soon after dosing

Adverse effects: Allergy Oral candiasis Mild diarrhea Nausea



AmoxicillinExtended spectrum penicillin

Antibacterial spectrum similar to that of penicillin G, but are more effective against gram-negative bacilli

AB prophylaxis

Bacterial Resistance?

Amoxiciliin +Calvulanic Acid beta-Iactamase-stable antibiotics



FIRST GENERATION CEPHALOSPORINSInclude cefadroxil (Duricets®), cephalexin (Keflex®), and cephradine (Velosel®)

Most active against gram-positive cocci, but are not very active against many anaerobes

Active against gram-positive staphylococci and streptococci, but not enterococci.

Active against many gram-negative aerobic bacilli

Cephalexin (Keflex®):The first generation cephalosporin often used to treat odontogenic Infections

indicated as alternatives in early infections because they are effective in killing the aerobes

AP Prophylaxis Allergy to Penicillins

Adverse effects: diarrhea in 1% to 10% of patients



SECOND GENERATION CEPHALOSPORINSBetter activity against some of the anaerobes including some Bacteroides, Peptoeoccus, and Peptostreptococcus species

Cefaclor (Ceclo®) and cefuroxime (Ceftin®) have been used to treat early stage infections

The advantage of twice-a-day dosing



VancomycinesEffective against multiple drug resistant organisms such as methicillin-resistant staph

Restrict its use to treat serious infections caused by gram-positive bacteria and life threatening infections

AB prophylaxis (IV)

Adverse reactions: fever, chills, red man syndrome, shock, Dose-related hearing loss



Bacitracin

Active against a wide variety of gram-positve organisms

Potential nephrotoxicity


Inhibitors of Protein Synthesis

TETRACYCLINES Broad spectrum

Bacteriostatic

The treatment of choice in infections caused by Mycoplasma pneumonia,Spirochetes,gram-positive bacilli, gram-negative bacilli,gram-negative enteric rods.they are also effective against Chlamydia, Rickettsia, and Brucella species

Adverse effects:

Gastric discomfort

Effects on calcified tissues

Fatal hepatotoxicity

Phototoxicity

Vestibular problems

Pseudotumor cerebri

Superinfections

Contraindications:

Renally-impaired patients

Pregnant or breast-feeding women

Children under 8 years of age



MACROLIDESErythromycine:

Antihacterial spectrum of the erythromycin family is similar to penicillin VK

Narrow spectrum antibiotics

Was considered highly effective antibiotics for treating odontogenic infections, especially in penicillin allergy

Erythromycin is no longer very useful because of resistant pathogens

Harde 1997

Resistance develops rapidly to macrolides and there may be cross-resistance between erythromycin and newer macrolides

Montgommery1998



Clarithromycin :Shows good activity against many gram-positive and gram-negative aerobic and anaerobic organisms

Active against methicillin-sensitive S. aureus and most streptococcus species S. aureus strains resistant to erythromycin are resistant to clarithromycin

Azrithromycin :Similar to erythromycin in effectiveness against anaerobic gram-positive cocci and Bacteroides sp. Azithromycine is active against staphylococci, including S. aureus and S. epidermidis, as well as streptococci, such as S. pyogenes and S. pneumoniae. excellent activity against H. influenzae.

Both azithromycin and clarithromycin are presently recommended as alternatives in the prophylactic regimen for prevention of bacterial endocarditis.

MACROLIDES



ClindamycinBacteriostatic, but elicit bactericidal effects at higher concentrations

Antibacterial spectrum: Anaerobic bacteria, such as Bacteroides fragilis Nonenterococcal gram-positive cocci

Not effective against mycoplasma or gram-negative aerobes

Its small molecular weight enables it to more readily enter bacterial cytoplasm and to penetrate bone

Adverse effects Abdominal pain, nausea, vomiting, and diarrhea

Hypersensitivity reactions are rare

Pseudomembranous colitis characterized by severe diarrhea, abdominal cramps, and excretion of blood or mucus in the stools



Chloramphenicole

Active against a wide range of gram-positive and gram-negative bacteria,but because of its toxicity, its use is restricted to life threatening infections in which there is no alternatives Antimicrobial activity:Excellent against Anaerobes

Adverse effects:

GI upset

Overgrowth of candida

Anemias: Hemolytic anemia

Gray baby syndrome

Interactions:

Inhibition of some of the hepatic mixed function

block the metabolism of such drugs as warfarin, phenytoin,

tolbutamide and chlorpropamide

Elevation their concentrations and potentiating their effects



Metronidazole

a broad spectrum against protozoa and anaerobic bacteria

Known for its strong antibacterial activity against anaerobic cocci as well as Gram-negative and Gram-positive bacilli

Readily permeates bacterial cell membranes and it then binds to DNA, disrupting its helical structure, which leads to rapid cell death

(Windley et al. 2005) Metronidazole had excellent activity against anaerobes but it had no activity against aerobes

Roche & Yoshimori (1997)


AB Prophylaxis


Antibiotic Prophylaxis

A life threatening disease with substantial

morbidity and mortality which affects indivisuals

with underlying structural cardiac defects who

develop bacteremia

Often as a result of

dental ,GI,genitourinary,respiratory or cardiac

invasive/surgical procedures

Infective Endocarditis (IE):

It’s a microbial infection of the endothelial surface

of the heart or heart valves that most often occurs

in proximity to congenital or acquired cardiac

defects



Manipulation of the oral tissues may be associated with

a transient bacteraemia

(Bender & Montgomery 1986)

Bacteraemia is usually eradicated by the reticulo-

endothelial system within a few minutes and poses no

threat to the healthy patient. However, some medically

compromised patients may be at risk from this transient

blood-borne infection, most notably infective

endocarditis (IE)

(Dajani et al. 1997)

Because of the high morbidity and mortality related to

IE, it has long been advised that AP is required before

dental procedures likely to induce bacteraemia

(Tomas Carmona et al. 2002)



Bacteremia associated with Endodontic treatment:

No bacteraemia was elicited if instrumentation was kept within the root canal

(Baumgartner et al. 1976)Detectable bacteraemia was found in only one of the 30 patients undergoing nonsurgical root canal treatment, with an incidence of 3.3% as opposed to 83.3% following flap retraction, 33.3% following periapical curettage and 100% following dental extraction

(Baumgartner et al. 1977)

In studies where more selective techniques for

culturing microorganisms were used, the incidence

of bacteraemia has been reported as up to 20% after

nonsurgical endodontic treatment, where

instrumentation was confined to the root canal

(Heimdahl et al. 1990)

A series of studies found no statistically significant

difference between the incidence of bacteraemia

following instrumentation within and outwith the root

canal

(Debelian et al. 1992, 1995, Debelian et al. 1996)

Bacteraemia was elicited in 31–54% of root canal

treatments

(Debelian et al. 1998)

Nonsurgical RCT might involve a detectable bacteraemia

(Jordan & Durso 2000)



Infective endocarditis and nonsurgicalendodontics

Up to 1953, no reported cases of IE traceable to root

canal therapy had been described

(Kolmer 1953)

In a review of 53 cases of IE following dental

procedures, seven were attributed to previous RCT. In

all cases, there was clear evidence of extracanal

instrumentation, mainly through the apical foramen

(Martin et al. 1997)

In a large case–control study three cases of IE were found

which were apparently attributed to root canal treatment

based on the premise that the infecting organism was

consistent with those inhabiting the root canal system and

also that the patient had had endodontic treatment in the

last 30 days

(Van der Meer et al. 1992)



Does the use of AP prevent EI ?(Van der Meer and colleagues 1992) published a study of

dental procedures in the Netherlands and the efficacy of

antibiotic prophylaxis to prevent IE in patients with native

or prosthetic cardiac valves. They concluded that dental or

other procedures probably caused only a small fraction of

cases of IE and that prophylaxis would prevent only a small

number of cases even if it were 100% effective

Same authors performed a 2-year case-control study.

Among patients for whom prophylaxis was

recommended, 5 of 20 cases of IE occurred despite

receiving antibiotic prophylaxis. The authors concluded

that prophylaxis was not effective

(Van der Meer and colleagues 1992)

Huge number of prophylaxis doses would be necessary to

prevent a very low number of IE cases(Duval 2006)



IE is much more likely to result from frequent exposure to random bacteremias associated with daily activities than from bacteremia caused by a dental, GI tract, or GU tract procedure

Prophylaxis may prevent an exceedingly small number of cases of IE, if any, in individuals who undergo a dental, GI tract, or GU tract procedure

The risk of antibiotic-associated adverse events exceeds the benefit, if any, from prophylactic antibiotic therapy

Maintenance of optimal oral health and hygiene may reduce the incidence of bacteremia from daily activities and is more important than prophylactic antibiotics for a dental procedure to reduce the risk of IE




Patients who have taken prophylactic antibiotics routinely

in the past but no longer need them include people with:

Mitral valve prolapse

Rheumatic heart disease

Bicuspid valve disease

Calcified aortic stenosis

Congenital heart conditions such as ventricular septal

defect, atrial septal defect and hypertrophic cardiomyopathy




Regimen Agent Situation Adults: 2.0 g; children 50 mg/kg,

orally 1 h before procedure Amoxicillin Standard general prophylaxis

Adults: 2.0 g IM or IV; children 50 mg/kg IM or IV within 30 min

before procedure

Ampicillin Unable to take oral medications

Adults: 600 mg; children 20 mg/kgorally 1 h before procedure Clindamycin Patient is allergic to

penicillin Adults: 2 g; children 50 mg/kgorally 1 h before procedure Cefadroxil or

cephalexin Adults: 500 mg; children 15 mg/kg

orally 1 h before procedure Azithromycin or clarithromycin

Adults: 600 mg; children 20 mg/kgIV within 30 minutes before

procedure

Clindamycin Allergic to penicillin and unable to take oral

medicationsAdults: 1.0 g; children 25 mg/kg IM

or IV within 30 min before procedure

Cefazolin


Clinical Scenarios



During RCT, you discovered that your patient (who needs AP) has not taken the prescribed antibiotic prophylaxis ?

Antibiotics should be administered as soon as possible

Drug can be effective if it is given up to2 hours after bacteremia begins



Patient who is already receiving antibiotics ?

Another possibility is the use of second-choice

antibiotics

In patients with periodontal diseases being

treated with tetracycline treatment should be

stopped for a minimum of 3 or 4 days before

giving the prophylactic regimen with amoxicillin



Waiting for 9 to 14 days between prophylactic

cover periods

Patients who requires multiple dental treatment sessions?


AB for treatment of Odontogenic Infections


ADA Recommendations

An infection must be persistent or systemic to justify the

need for antibiotics: i.e. fever, swelling,

lymphadenopathy, trismus, or malaise in a healthy

patient. Antibiotics are also more likely to be needed in

an immunocompromised patient or a patient in poor

health. The decision to prescribe antibiotics should not be

influenced by patient demand, expectation of referring

dentists, “just in case” situations, or because it is the day

before a weekend or holiday. These reasons constitute

inappropriate use of antibiotics


treatment of Odontogenic Infections

The decision to use an antimicrobial/antibiotic agent in managing an odontogenic infection is based on several factors

The clinician must first diagnose the cause of the infection and determine the appropriate dental treatment that may include multiple modalities, including initiation of endodontic therapy and pulpectomy, odontectomy, or surgical or mechanical disruption of the infectious environment

Antibiotic therapy should be used as an adjunct to dental treatment and never used alone as the first line of care



Determinant Factors as to whether conjunctive

antibiotic therapy is indicated :

Host defense mechanisms

Severity of the infection

Magnitude of the extension of the infection

Expected pathogen



The choice of an antibiotic should be based on

knowledge of the usual causative microbe (Empiric

prescription)



Which AB to prescribe?Penicillin is the gold standard in treating dental infections

Aerobic and anaerobic microorganisms are susceptible to penicillin

(Owens and Schuman 1993)

Pen VK is the obvious choice over Pen G because of the greater oral absorption by Pen VK

It’s bactericidal and active against replicating bacteria often encountered in odontogenic infections

(Smith and Reynard1992)

Penicillin VK is the first choice for treatement of odontogenic infections

(Wynn 2002)



Resistance?!Natural resistance to the penicillins :

In organisms that either lack a peptidoglycan cell

wall (e.g, Mycoplasma) or that have cell walls that

are impermeable to the drugs

Acquired resistance to the penicillins

1. ß-lactamase activity: This family of enzymes hydrolyzes the cyclic amide bond of the ß-lactam ring, which results in loss of bactericidal activity 2. Decreased permeability to drug: Decreased penetration of the antibiotic through the outer cell membrane prevents the drug from reaching the target penicillin-binding proteins (PBPs)

3. Altered penicillin binding proteins: Modified PBPs have a lower affinity for ß-Iactam antibiotics, requiring clinically unattainable concentrations of the drug to effect binding and inhibition of bacterial growth. This mechanism may explain methicillin-resistant staphylococci, although it does not explain its resistance to non-Iactam antibiotics like erythromycin to which they are also refractory



If a patient with an early stage odontogenic infection

does not respond to penicillin VK within 24-36 hours,

it is evidence of the presence of resistant bacteria

Bacterial resistance to the penicillins is

predominantly achieved through the production of

beta-lactamase

A switch to beta-Iactamase-stable antibiotics should

be made

Clindamycin or Amoxicillin/clavulanic acid (Augmentine)



Resistance may also be due to alteration of

penicillin-binding proteins

Drugs which combine a beta-Iactam antibiotic with a

beta-Iactamase inhibitor, such as

amoxicillin/clavulanic acid (Augmentine®), may no

longer be more effective than the penicillin VK alone

Clindamycin

Resistance may also be due to alteration of penicillin-binding proteins. Consequently, drugs which combine a beta-Iactam antibiotic with a beta-Iactamase inhibitor, such as amoxicillin/clavulanic acid (Auqrnentine®), may no longer be more effective than the penicillin VK alone. In these situations, clindamycin is the recommended altemate antibiotic. Evidence suggests Ihat empirical use of penicillin VK' as the first-line drug in treating



Empirical use of penicillin VK' as the first-line drug in treating early odontogenic infections is still the best way to ensure the minimal production of resistant bacteria to other classes of antibiotics, since any overuse of clindamycin or amoxicillin/clavulanic acid (Augmentin®) is minimized in these situations. There is concern that overuse of clindamycin could contribute to development of clindamycin- resistant pathogens

Wynn 2002



In late odontogenic infections:

Clindamycin, because of its relatively broad spectrum of

activity and resistance to beta-Iactamase degradation, is an

attractive first-line therapy in the treatment of these

infections

In these infections, anaerobic bacteria usually predominate

Another alternative is to add a second drug to the penicillin

(eg, metronidazole [Flagyl®]). Consequently, for those

infections not responding to treatment with penicillin, the

addition of a second drug (eg, metronidazole), not a beta-

Iactam or macrolide, is likely to be more effective. Bacterial

resistance to metronidazole is very rare

Metronidazole should rarely be used as a single agent

Metronidazole is not effective against gram-positive

aerobic cocci and most Actinomyces, Lactobacillus, and

Proprionibacterium species



SEVERE INFECTIONSIn patients hospitalized for severe odontogenic infections,

I.V antibiotics are indicated and clindamycin is the clear

empiric antibiotic of choice. Alternative antibiotics include

an I.V combination of penicillin and metronidazole or I.V.

ampicillin-sulbactam (Unasyn®). Clindamycin, I.V.

cephalosporins (if penicillin allergy is not the

anaphylactoid type), and ciprofloxacin have been used in

patients allergic to penicillins


Type of infection Antibiotic of choice Dose

Early (first 3 days of symptoms)

Penicillin VK (Veetids®)Clindamycin (Cleocin®)

Cephalexin (Keflex®)

500 mg qid150 mg qid500 mg qid

No improvement in 24-36 hours

Penicillin allergy

ß-lactamase-stable AB:Clindamycin

Amoxicillin/clavulanic acid

Clindamycin (Cleocin®)Cephalexin (Keflex®)

Clarithromycin (Biaxin®)

150 mg qid500 mg q8h

150 mg qid500 mg qid

Two 500 tablets once/day

Late ( > 3 days)

Penicillin allergy

Clindmycin (Cleocin®)Penicillin VK+Metronidazole

Clindamycin (Cleocin®)

150 mg qid500 mg q8h

150 mg qid



Pinicillin VK X Amoxicillin

Antibiotic Use by Members of the AmericanAssociation of Endodontists in the Year 2000:

Report of a National SurveyYingling 2002



Analysis of Analgesic and Antibiotic Preference for Endodontic Management in KSA:

Sample size: 342 Endodontists (19.8%) = 129 nSBARD (16.1%) = 105 nAGD (13.4) = 88 nGP (50.7%) = 331 n

The List of AB included: Amoxicillin,Augmentin,Penicillin, Cephalexin, Erythromycin, Metronidazole and Tetracycline

Results:

500 mg Amoxicillin was the first choice of AB for patients not allergic to penicillin,being used :

51.1 % endodontis72.7% SBARD75.6% AGDs59.8% GPs

H.Balto ,S.AlSubait,D.Hashim2008



Penicillin VK has been found to be effective against most

aerobic and anaerobic organisms present in orofacial

infections and since the 1940s, continues to be the drug

of choice in nonallergic, immunocompetent patients

It is a narrow spectrum antibiotic for infections caused by

aerobic Gram-negative cocci and anaerobes

It is bactericidal and has a 1% to 10% hypersensitivity rate



Amoxicillin, a penicillin derivative with a broader spectrum, is a good choice for immunocompromised patients

It is a good drug for orofacial infections because it is readily absorbed and can be taken with food

Longer half-life and more sustained serum levels

Its broad spectrum is more than is required for endodontic needs, and its use in a healthy individual may contribute to the global antibiotic resistance problem



In a randomised, operator-blind, comparative clinical trial,

the efficacy of co-amoxiclav (250 mg amoxycillin plus 125

mg clavulanic acid, eight-hourly) was compared to that of

penicillin V (250 mg phenoxymethylpenicillin, six-hourly)

in the treatment of acute dentoalveolar abscess.

Symptoms improved in all patients, however those

receiving amoxicillin/clavulanic acid recorded a

significantly greater decrease in pain during the second

and third days of the treatment. Only one patient

reported a significant adverse effect associated with drug

therapy, and this was in the penicillin group

Lewis 1993



Amoxicillin does not offer any advantage over penicillin VK for treatment of odontogenic infections

Less effective than penicillin VK for aerobic gram-positive cocci, and similar to penicillin for coverage of anaerobes

Although it does provide coverage against gram-negative enteric bacteria, this is not needed to treat odontogenic infections, except in immunosuppressed patients where these organisms may be present

If one adheres to the principles of using the most effective narrow spectrum antibiotic, amoxicillin should not be favored over penicillin VK


Clinical Scenarios



Patient is complaining of Severe Pain with necrotic pulp and acute apical abcess

I & D should performed without using antibiotics, which has no benefit as a supplement to appropriate local treatement

Walton 1997Mattthews 2003



Severe pain and the diagnosis of irreversible pulpitis with acute periapical periodontits

Definitive treatment in such a case is the removal of the

source of pain, that is; inflamed pulpal tissue and

adjustment of occlusion. A NSAID may be prescribed

when needed, but antibiotics are not indicated in this case

Walton & Torabinijad 2002Sutherland 2003

Administration of penicillin did not significantly reduce pain,

percussion pain, or the number of analgesics taken by

patients with untreated irreversible pulpitis

Nagle 2000

From the Cochrane Systemic Review by Keenan et al

2005,evidence that there was no sginificant differnece in

pain relief for patients with untreated irreversible pulpitits

who received antibiotics versus those who did not

Keenan 2005



If a patient presented with a localized swelling after completion of RCT

Cases with acceptable RCT that develop swelling after obturation should be incised and drained; such cases usually resolve without re-treatment

When swelling occurs, a cold compress or an ice bag should be applied on the face over the affected area; keeping it on for ten minutes and off for five, for several hours. This intraoral warming and extraoral chilling is usually effective in reieving post-endodontic swelling and discomfort

Stephen Cohen 2006



Hypochlorite accidents

It is advisable to prescribe AB because of the potential for spread of infection related to tissue destruction

Barrowman 2007



After Surgical endodontic treatment

The routine use of the prophylactic, or the therapeutic use

of antibiotics given to healthy patients undergoing surgical

endodontic is not necessary

Pallasch 1989Longman & Martin 1991

Longman 2000Igor 2003

Iqbal 2007



Tooth avulsion

A broad-spectrum antibiotic should be administered for 7 days to avoid bacterial proliferation in the area of the ongoing repair process and contribute to the prevention of inflammatory resorption

Sae-Lim, Wang , Trope 1998


Local Use of Antibiotics



The rationale for local application of antibiotics

Whilst, systemic antibiotics appear to be clinically effective as an adjunct in certain surgical and nonsurgical endodontic procedures, their administration is not without the potential risk of adverse systemic effects, such as allergic reactions, toxicity and the development of resistant strains of microbes. In addition, the systemic administration of antibiotics relies on patient compliance with the dosing regimens followed by absorption through the gastro-intestinal tract and distribution via the circulatory system to bring the drug to the infected site. Hence, the infected area requires a normal blood supply which is no longer the case for teeth with necrotic pulps and for teeth withoutpulp tissue. Therefore, local application of antibiotics within the RCS may be a more effective mode for delivering the drug

(Gilad et al. 1999)



The first reported local use of an antibiotic in endodontic

treatment was in 1951 when Grossman used a

polyantibiotic paste known as PBSC (penicillin, bacitracin,

streptomycin, and caprylate sodium). PBSC contained

penicillin to target gram-positive organisms, bacitracin for

penicillin-resistant strains, streptomycin for gram-negative

organisms, and caprylate sodium to target yeasts. These

compounds were all suspended in a silicone vehicle



Tetracyclines:

tetracyclines have been used to remove the smear layer from

instrumented root canal walls (Barkhordar et al. 1997,

Haznedaroglu & Ersev 2001), for irrigation of apical root-end

cavities during periapical surgical procedures (Barkhordar &

Russell 1998), and as intracanal medicaments (Molander

&Dahlen 2003)



Substantivity of Tetracyclines

Tetracyclines readily attach to dentine and are subsequently

released without losing their antibacterial activity. This

property creates a reservoir of active antibacterial agent,

which is then released from the dentine surface in a slow and

sustained manner

(Torabinejad et al. 2003)

Abbott et al. (1988) demonstrated that tetracyclines form a

strong reversible bond with the dental hard tissues and that

they exhibit slow release and diffusion through dentine over

an extended period of time up to at least 12 weeks

Khademi et al. (2006) compared the antibacterial

substantivity of 2% CHX, 100 mg mL)1 doxycycline–HCl and

2.6% NaOCl in bovine root dentine over five experimental

periods of 0, 7, 14, 21 and 28 days in vitro. Their findings

indicated that after 7 days, the NaOCl and doxycycline

groups had the lowest and the highest number of colony

forming units (CFU), respectively. However, after the longer

time periods, the CHX group had the lowest number of

CFU’s



BioPure (MTAD)

Introduced by Torabinejad & Johnson (2003)

Contains doxycycline (at a concentration of 3%), citric acid (4.25%) and a detergent, Polysorbate 80 (0.5%)



Several studies have evaluated the effectiveness of MTAD for the disinfection of root canals

MTAD is able to remove the smear layer (Torabinejad & Johnson 2003)

MTAD is effective against E. faecalis

(Shabahang & Torabinejad 2003)(Shabahang et al. 2003)

(Torabinejad et al. 2003b)



Shabahang et al. (2003) compared the antibacterial

efficacy of a combination of 1.3% NaOCl as a root

canal irrigant and MTAD as a final rinse with that of

5.25% NaOCl. Their findings showed that using

MTAD in addition to 1.3% NaOCl was more

effective at disinfecting root canals than using

5.25% NaOCl alone



In another study, Shabahang & Torabinejad (2003)

compared the antibacterial effects of MTAD with

those of NaOCl and EDTA by standard in vitro

microbiological techniques and reported that MTAD

was significantly more effective against E. faecalis



Kho & Baumgartner (2006) compared the antimicrobial efficacy against E faecalis of 1.3% NaOCl/MTAD with that of the combined alternate use of 5.25% NaOCl and 15% EDTA for root canal irrigation. Bacterial samples taken early in the canal cleaning process revealed growth in none of the 20 samples irrigated with the 5.25% NaOCl/15% EDTA combination but 8 of the 20 samples irrigated with 1.3% NaOCl/MTAD had bacterial growth. Further samples taken after additional canal enlargement revealed growth in none of 20 samples when 5.25% NaOCl/ 15% EDTA were used, but there was still growth in 10 of the 20 samples when 1.3% NaOCl/MTAD was used. This investigation showed consistent disinfection of infected root canals when a combination of 5.25% NaOCl and 15% EDTA was used. However, the combination of 1.3% NaOCl/ MTAD left nearly 50% of the canals contaminated with E. faecalis



Davis et al. (2007) investigated the antimicrobial action of

Dermacyn (broad sperctrum superoxideised water), MTAD,

2% CHX and 5.25% NaOCl against E. faecalis using a zone

of inhibition test. MTAD showed significantly larger zones

of inhibition than 5.25% NaOCl, 2% CHX and Dermacyn



Substantivity of MTAD

The substantivity of MTAD was significantly greater than CHX and NaOCl

Mohammadi & Shahriari (2008)



Tetraclean

a mixture of an antibiotic, an acid and a detergent. However, the concentration of the antibiotic, doxycycline and the type of detergent differ from those of MTAD

(Giardino et al. 2006)

Tetraclean caused a high degree of biofilm disaggregation when compared with MTAD

(Giardino et al. 2007)



Ledermix paste

Ledermix is a glucocorticosteroid-antibiotic compound that was developed by Schroeder & Triadan in 1960.

The primary interest in developing Ledermix paste was based on the use of corticosteroids to control pain and inflammation associated with pulp and periapical diseases

The sole reason for adding the antibiotic component to Ledermix was to compensate for what was perceived at the time to be a possible corticoid-induced reduction in the host immune response

Today, Ledermix paste remains a combination of the same

tetracycline antibiotic, demeclocycline–HCl (at a

concentration of 3.2%), and a corticosteroid,

triamcinolone acetonide (concentration 1%), in a

polyethylene glycol base



Ledermix paste is capable of diffusing through dentinal

tubules and cementum to reach the periradicular and

periapical tissues

(Abbott 1990)

Ledermix paste prevented experimentally induced external

inflammatory root resorption in vivo

Pierce et al. (1988)



Periodontal ligament inflammation and inflammatory root

resorption were markedly inhibited by both the calcium

hydroxideand corticosteroid-antibiotic pastes relative to

untreated controls. Replacement resorption was the

lowest in the corticosteroid-antibiotic group, and

significantly more normal periodontal ligament was

present in this group than in the calcium hydroxide and

control groups

Thong et al. (2001)



Ledermix paste-treated roots had statistically significantly

more healing and less resorption than the roots treated

with Ca(OH)2

Bryson et al. (2002)



Ehrmann et al. (2003) investigated the relationship of

postoperative pain associated with three different

treatment regimes for infected teeth with acute apical

periodontitis after complete biomechanical debridement

of the root canal system in patients presenting for

emergency relief of pain. They reported that the patients

with teeth dressed with Ledermix paste had less pain

than that experienced by patients who had teeth dressed

with calcium hydroxide or no dressing at all



Ledermix:

Effective in preventing infalmmatory resorption in avulsed teeth

Pain management



Clindamycin Molander & Dahlen (2003)

investigated the effect of clindamycin on root canal infections and apical periodontitis when placed as an intracanal dressing. Clindamycin offered no advantage over conventional root canal dressings, such as calcium hydroxide

Lin et al. (2003)

compared the antibacterial effect of clindamycin and tetracycline Clindamycin significantly reduced the amount of viable



Metronidazole

Siqueira & de Uzeda (1997)

Metronidazole was more effective than calcium hydroxide/CPMC

Hoelscher et al. (2006) evaluated the antimicrobial effects against E. faecalis of five antibiotics (amoxicillin, penicillin, clindamycin, metronidazole and doxycycline) when added to Kerr Pulp Canal Sealer EWT in vitro. They found that all of these antibiotics except metronidazole could enhance the antimicrobial efficacy of the sealer



Local AB Treatment for Avulsed Teeth:

Topical doxycycline application significantly increased the chances of successful pulp revascularization

Cvek et al 1990

The beneficial effect of soaking a tooth in doxycycline has also been confirmed by

Yanpiset & Trope (2000)


Conclusion

Prophylactic antibiotics are usually only indicated in

medically compromised patients; an exception would

be in the re-implantation of an avulsed tooth

The treatment of acute and chronic infections of

endodontic origin is primarily by operative intervention.

The therapeutic use of antibiotics is thus as an adjunct

to mechanical treatment


Conclusion

The use of topical anti-microbial agents has declined

and requires further research and evaluation

The potential benefits of antibiotic administration should

therefore outweigh the possible disadvantages

associated with their use. A dentist who prescribes an

antibiotic for a questionable indication may be seen as

placing a patient at risk from potential adverse effects of

drugs

Antibiotics in Endodntics FINAL

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