Prescription of antibiotics in odontostomatology

Prescription of antibiotics in odontostomatology

1. Introduction

• The prescription of drug treatment is a medico-legal act, the selection criteria and methods of action must be known by the dentist before its execution. 
• Antibiotic therapy represents a large part of prescriptions in dentistry.
• Antibiotic therapy should be given in addition to a local etiological procedure. 
• The correct indication must be given before any prescription, at an effective and sufficient dose, because excessive prescriptions are often the source of unfortunate resistance.

2. Definition

An antibiotic is an organic chemical substance of natural or synthetic origin that inhibits or kills pathogenic bacteria at low concentrations and has selective toxicity.

Antibiotics (ATB) are molecules with the following properties: 

• To inhibit bacteria and they are said to be bactericidal or 
• to limit the spread of bacteria and they are said to be bacteriostatic. 

The same antibiotic can be bacteriostatic at a low dose and bactericidal at a higher dose.

• ATBs differ from each other in their physical, chemical, pharmacological properties, antibacterial spectra and mechanisms of action.
• Dentists use 05 families of ATB representing approximately 50% of their prescription.

There are two main categories of antibiotic therapy: prophylactic antibiotic therapy and curative antibiotic therapy.

• Prophylactic antibiotic therapy (antibiotic prophylaxis) : aims to prevent the occurrence of postoperative infection, both locally and remotely. 

• It is not yet very well codified. 
• Although its use is mainly associated with certain cardiac pathologies (bacterial endocarditis), it remains true that several other medical situations may justify its use, the prevention of local postoperative infection in oral and perio-implant surgery constitutes the main indication.

• Curative antibiotic therapy : aims to shorten the clinical event in situations of documented or undocumented bacterial infection in accordance with therapeutic recommendations (AFSSAPS: 2001 and 2011).
• In practice, there are two types of curative antibiotic therapy: 

• probabilistic antibiotic therapy and 
• documented antibiotic therapy (bacteriological support).     

3. Characteristics of antibiotics
4. Activity spectrum

• The spectrum of activity of an ATB is defined as the sensitivity of germs to this anti-infective agent.
• ATBs are distinguished 

• broad spectrum (Tetracyclines),
•  medium spectrum (Penicillins), 
• narrow spectrum (Polymyxin) and
•  with a specific spectrum (Isoniazids only active on Koch’s Bacillus).
• It is therefore very important to take a sample and send it to the bacteriology laboratory in order to identify the germ responsible and determine its sensitivity to various antibiotics (antibiogram)

2. Mechanism of action

There are many of them and we can distinguish 4 main types of ATB activity on germs.

1. Action on the bacterial wall by inhibition of enzymes (transpeptidase, peptidoglycan synthetase) which allow the synthesis of mucopeptides of the bacterial wall. Ex: β lactams, Vancomycin…

b) Disruption of the permeability of the cytoplasmic membrane by alteration of its lipoprotein structure. Ex: Polymyxin, Bacitracin.

c) Modification of protein synthesis at all levels from RNA replication, transcription, translation with transfer RNA to regulation (macrolides, synergistins, streptomycin, tetracycline, chloramphenicol).

d) Action on nuclear DNA.

Prescription of antibiotics in odontostomatology

Prescription of antibiotics in odontostomatology

3. Pharmacokinetics

Antibacterial activity is of interest to the practitioner to the extent that it is exerted at concentrations achievable in the body.

• When the Minimum Inhibitory Concentration (MIC) of ATB on the germ is clearly lower than the average serum levels that can be obtained, the germ is susceptible.
• If the MIC is higher, the germ is resistant.
• Finally, when the MIC and the serum concentration achieved by a high dosage are of the same order, we speak of intermediate sensitivity.

Other factors come into play such as:

•  Diffusion of ATBs in tissues (at the level of the infectious focus).
•  The route of administration to achieve the appropriate mean serum concentration.
•  The digestive barrier…

To measure the activity of antibiotics, an antibiogram is carried out.

There are 3 clinical categories of strains: 

• Sensitive ones (those for which the probability of therapeutic success is high) 
•  Resistant (those for which there is a high probability of therapeutic failure regardless of the type of treatment) 
•  Intermediates (those for which therapeutic success is unpredictable)

To treat an infection, it is necessary to obtain at the site of infection a sufficient concentration for a sufficient time of an antibiotic active against the bacteria responsible.

4. Resistance to ATB

Different types of resistance exist:

Resistance may be natural if the bacteria does not belong to the spectrum of action of ATB. 

Resistance can also be acquired , we can distinguish several cases:  

a) Chromosomal resistance resulting from a mutation.

b) Extrachromosomal resistances: 

Their genetic support is a plasmid (DNA molecule distinct from the chromosome, optional for the definition of the species and conferring additional properties concerning metabolism, pathogenic power or resistance to one or more ATB). 

Plasmids are passed on to daughter cells, they replicate like the chromosome.      

• This acquired resistance can appear gradually (penicillin) or suddenly (streptomycin).
• It can be reversible or irreversible.
• It can be extended to one or more ATBs (cross resistance generally appearing between ATBs of close structures).

5. ATB association and interaction

– We combine 2 or 3 ATBs to have a maximum effect, so we are looking for a synergy or at worst an addition (the problem: antagonism). Ex: spiramycin + metronidazole.

– The combination of 2 ATBs with bactericidal action can have an additive or synergistic effect.

– Bacteriostatic ATBs are never synergistic and can neutralize the action of bactericidal ATBs (antagonism).

– ATBs associated with other drugs can give potentiating or antagonistic effects with very significant consequences (vigilance in polymedicated patients).

6. Criteria for choosing an ATB

The choice of an ATB is made based on certain criteria including:

• Bacteriological criteria:

• Affirm bacterial infection.
• Identify the probable germ: the prescriber must know the bacterial ecology (oral flora + 300 species listed), the epidemiology and carry out a good examination (to obtain the correct diagnosis).
• Physiological criteria:

• Reach the site of infection.

• Pharmacological criteria:

• Reach this site with sufficient concentration (which defines the dose and route of administration).

• Know the half-life and elimination route of the drug.   

• Individual criteria or terrain:
  • Healthy subject or carrier of chronic illness.
  • Child.
  • Elderly people.
  • Pregnant woman…etc. 
• Economic criteria: cost of the drug.

Prescription of antibiotics in odontostomatology

Rules of prescription

1- Knowledge and mastery of the pharmacology of prescribed substances

2- Good choice of ATB depending on the proven infection (degree of severity), the patient’s medical condition (medical and surgical history, current treatments and possible allergies) and their age.

3- First-line monotherapy is the rule (blind probabilistic ATBpie)

4- It is imperative to obey 3 essential rules: 

* Hit the mark (choice of molecule: sensitive responsible germ). (Antibiogram = ideal 🡨🡪 opportunity to exploit).

* Sufficient (doses appropriate to the pathology and diffusion to the infected site).

* For a long time (for a sufficient duration, any antibiotic therapy must last at least 7 days).

Noticed :

•  Any antibiotic therapy must last at least 7 days.
•  It can be extended if necessary.
•  72 hours after initiation of an ATBpie, evaluate the treatment: no improvement 🡪 failure 🡨🡪 change ATB family or reconsider the diagnosis.
•  For equal efficacy and tolerance, choose the least expensive ATB
•  Mode of administration is modulated by the guarantee of treatment  compliance .

7. Routes of administration 

1/ General antibiotic therapy: oral or parenteral route (+++)

2/ Local antibiotic therapy: 2 methods

• Immediate release  : local curative antibiotic therapy is justified for certain endodontic treatments (necrotic teeth).

• Dental pastes containing Metronidazole: Grinazole® and Imizine® at 10%.
• Sponges containing Framycetin sulfate and a corticosteroid: Arthrisone®, Cortiscan®, Framycetin, Streptomixin, Pulpomixin®.
• Sponges containing metronidazole: Métrogène® at 4.5 mg
• Sponges: polymixinB sulfate + tyrothricin = Néocônes®

NB : Local antibiotic therapy (immediate release) is not recommended because the action is too short and may cause resistance.

• Controlled release : only cyclines can be effective in the treatment of periodontitis, currently we find: 

* Metronidazole 25% in cartridge: Elyzol®

* Minocycline : parocline® 2%

* Tetracycline : actisite®

 * Doxycycline : atridox®

NB : These substances used in irrigation are only effective as an adjuvant to mechanical procedures: descaling; surfacing, etc.

8. Classification of ATBs

ATBs can be classified according to several criteria:

•  Chemical classification: according to their molecular and chemical structure. 
•  According to their broad, medium and narrow spectrum of action. 
•  According to their mechanism of action and point of impact: bacterial wall, cytoplasmic membrane, protein synthesis, etc.
• According to ATB families

Main antibiotic families used in dentistry

Antibiotic Family	Active Ingredients
Beta-Lactams	AmpicillinPivampicillin AmoxicillinAmoxicillin / Clavulanic Acid
Cephalosporins 1st generation 2nd generation 3rd generation	CephalexinCefoxitinCefixime (Oroken)Cefotaxime (Claforan)
Cyclines	TetracyclineDoxycyclineMinocycline
Macrolides	Spiramycin ErythromycinJosamycinAzithromycin

Antibiotic Families	Active Ingredients
Lincosamide	Clindamycin
Fluoroquinolone	Ciprofloxacin
Nitro-5 imidazole	Metronidazole

4. Antibiotic families
   1. β-lactams :

• Bactericidal ATBs including penicillins (G,M,A); cephalosporins, β-lactamase inhibitors (eg: clavulanic acid).
• Action on the bacterial wall.    
• Present an allergic risk: increased 🡨🡪 careful questioning is required.   

1. Penicillins 

• Natural penicillins: sensitive to penicillinases:

Peni V or Oracillin (Ospen®) (phenoxymethyl-penicillin)

Peni G (benzyl penicillin)

Extencillin –biclinocilin (benzyl penicillin salts)

• Semi-synthetic penicillins M: resistant to penicillinases: Oxacillin
• Extended spectrum penicillins: Ampicillin and Amoxicillin.

  Amoxicillin + Clavulanic Acid

•  They are the most used in first-line anti-infectious therapy.
• Bactericidal ATBs: action on the bacterial wall of gram + and gram negative bacteria. 
• β-lactams are time-dependent ATBs.
• In practice: β-lactams should be prescribed as frequently as possible: at least 3 doses per day.
• Their spectrum is described as “medium”. 
• These molecules can cause significant imbalances in the gastrointestinal flora (diarrhea and colitis).
• Plasma half-life = 1 hour (90 min for penicillins).
• Amoxicillin is the first-line ATB of choice whenever an ATBpie is required; if there is no contraindication (CI).
• Comments: Penicillins are prescribed for patients with hepatic insufficiency (even severe) without changing the dosage and regardless of the class (predominance of renal elimination and only 30% are metabolized by the liver).

Prescription of antibiotics in odontostomatology

2. β-Lactamase Inhibitors

• Some bacteria have acquired the ability to resist β-lactams by synthesizing β-lactamases which, through hydrolysis, degrade the β-lactam nucleus.
• The strategy for using β-lactamase inhibitors acting as suicide substrates consists of co-administering an antibacterial molecule with a β-lactamase inhibitor.
•  Clavulanic acid is one of the molecules that behaves like a decoy.
• Its pharmacokinetic properties are very close to those of Amoxicillin.
• It has good oral absorption allowing a serum peak in less than one hour.
• Side effects: gastrointestinal disorders, allergic reactions, promotes candida infections (imbalance of flora).

3. Cephalosporins  

• Are bactericidal and act by inhibiting the synthesis of the bacterial wall.
• Few indications in dentistry except for odontogenic sinusitis or if an antibiogram indicates it.
• Indicated for patients allergic to β-lactams.
• ^1st generation cephalosporins : Cephalexin

^2nd generation cephalosporins : Cefoxitin

^3rd generation cephalosporins : Cefixime (Oroken®), Cefotaxime (Claforan®)

2. Tetracyclines : bacteriostatic e.g.: Doxycycline: vibramycin®, oxytetracycline.

• We distinguish: 

^{* 1st} generation molecules : chlortetracycline, oxytetracycline, tetracycline.

* Second generation molecules obtained by semi-synthesis: doxycycline and minocycline: their action is more prolonged.

• In dentistry, the use of tetracyclines is reserved for very limited indications. These are mainly aggressive periodontitis in addition to local mechanical treatment. This indication is officially recognized only for doxycycline.
• Present the risk of dental dyschromia and photosensitivity.

3. Macrolides and related compounds : bacteriostatic

• Less allergenic eg: Erythromycin, Spiramycin, Josamycin.
• Good tolerance. 
• They nevertheless have drug interactions with many products including: ergot derivatives, carbamazepine, theophylline, bromocriptine, ciclosporin.
• The best-known macrolide: spiramycin combined or not with metronidazole (Orogyl®, Biorogyl® and other generics).
• The plasma half-life of macrolides varies depending on the molecules considered. It is 2 to 3 hours for erythromycin, 4 to 5 hours for josamycin, 7 to 8 hours for clarythromycin and more than 20 hours for azithromycin.
• The prescription rate can therefore vary from three doses per day for erythromycin or spiramycin to one dose per day for azithromycin.

* Related products : eg: Lincosamides (Lincocine®), Synergistines (Pristinamycin: Pyostacine®).             

4. Sulfonamides : Bacteriostatics e.g. Bactrim, salozopyrine, etc.

• Folate inhibitory molecules: sulfonamides. 
• Their prescription is very reduced in odontostomatology 
• Can cause allergic reactions (Stevens-Johnson or Lyell syndrome).

5. Phenicols : ex Chloramphenicol, Thiamphenicol.

• Not prescribed in odontostomatology.
• Possess a risk of bone marrow suppression and fatal accidents in newborns.

6. Nitro 5 imidazoles : 

This family includes several molecules (Ornidazole, Tinidazole) including the most used in oral infectiology: 

• Metronidazole (Flagyl®) is a bactericidal antibiotic, inhibits the synthesis of nucleic acids.
• It is used for the treatment of infections caused by anaerobic bacteria as well as protozoa.
• In odontostomatology, it is almost always used in association.            
• Active nucleus: 5-nitroimidazole with various substitutions.

NB : Prescribing nitroimidazole to a patient taking antivitamin K may lead to an increase in the effect of the oral anticoagulant and the risk of bleeding by reducing its hepatic metabolism.

7. Other antibiotics:

Some ATBs are only mentioned for their interest in the prophylaxis of infective endocarditis or their local application.

1. Glycopeptides:

• Are reserved for hospital use
• Bactericides
• Teicoplanin (Targocid®) and Vancomycin used in the prophylaxis of bacterial endocarditis, in case of allergy to β-lactams for oral and dental surgical procedures under general anesthesia.
• Half-life = 40 to 70 hours
• Dosage: 400mg 1 hour before the procedure intravenously (not suitable for children).

2. Aminoglycosides: gentamicin (80 mg)

•  Bactericide
•  Half-life = 2 hours
•  Urinary elimination (caution in case of nephropathies)
•  Routes of administration: intramuscular (IM); intravenous (IV: infusion); local: in ointment and eye drops
•  Interest in dentistry: synergy with penicillins in severe spreading or stubborn infections
•  Contraindications: muscle relaxants (myasthenia), curarants, diuretics (hypertension). 
•  Are ototoxic.

Prescription of antibiotics in odontostomatology

8. ATB Local

The pharmaceutical industry regularly offers new ATB-based drugs for local application for endodontics (Grinazole®), periodontics (Elyzol®: metronidazole) or for surgery (Neocones®, etc.).

With the exception of ophthalmology, AFSSAPS 2011 issued unfavourable recommendations regarding local antibiotic therapy, which is in no way recommended for oral and dental infections. 

Prescription writing

• Writing a prescription is not a trivial act. This act is governed by strict rules and is mainly framed by three codes: 

• the Code of Ethics, 
• the Public Health Code and 
• the Social Security Code.

• The prescription must be written accurately and legibly for both the patient and the pharmacist.
• It must contain mandatory information.
• Information concerning the prescriber

The only indications that a practitioner is authorized to mention on his prescription sheets are:

• Their names, first names, professional postal and electronic addresses, telephone and fax numbers, consultation times.
• Its quality and its specialty;
•  Diplomas, titles and functions recognized by the National Council of the Order of Dental Surgeons (and Dentists);
• The prescription must also bear the practitioner’s signature .
• Please note that it is mandatory to enter the date on which the order is written .
• Patient information

• The beneficiary’s first and last name are essential. 
• Age, weight and height must be added if the person is a child under 15 or an elderly person.
• Information regarding the prescribed product

The following are mandatory:

• The name of the specialty (princeps or generic) or the international common name of the active ingredient (INN);
•  Dosage and dosage form ;
• The number of packaging units  : the packaging unit may be a box, a bottle, a tube, a blister, etc.
• The statement: sufficient quantity (QSP) for x days can be used to allow the pharmacist to dispense the appropriate number of units.
• Dosage : namely the number of units per dose, the number of doses per 24 hours with the time interval between two doses and the total duration of treatment. If it is a preparation, the detailed formula must be mentioned .
•  The instructions for use, i.e. the appropriate time to take it or the specifics of taking it (diluting with water, for example)
•  The number of prescription renewals if necessary.

Prescription of antibiotics in odontostomatology

Conclusion

• The prescription of antibiotics follows rules and takes into account the patient’s background and the possible risks of selection of resistant bacteria.
• A thorough knowledge of the different drug classes is an essential point in the success of the treatment .
• In many situations, in oral medicine, amoxicillin proves to be the antibiotic of choice; its antimicrobial spectrum particularly adapted to stomatological infections, as well as its high tolerance, make it a particularly interesting molecule. In cases where it is not possible to prescribe it, the choice must then be made on the other available molecules, of which the benefit/risk ratio for the patient to be treated must be assessed.

Prescription of antibiotics in odontostomatology

  Cracked teeth can be healed with modern techniques.
Gum disease can be prevented with proper brushing.
Dental implants integrate with the bone for a long-lasting solution.
Yellowed teeth can be brightened with professional whitening.
Dental X-rays reveal problems that are invisible to the naked eye.
Sensitive teeth benefit from specific toothpastes.
A diet low in sugar protects against cavities.
 

Prescription of antibiotics in odontostomatology