Professional Documents
Culture Documents
Manassery, Mukkam
ANTIBIOTICS
IN
DENTISTRY
Presented By:
Niyas Ummer
1st Year PG
Department of Oral Medicine and Radiology
Overview
Introduction
Terminology
History
Classification
General Considerations
o Routes of administration
o Choice of agent
o Combined use
o Problems with use
o Prophylactic use
o Failure
Recent Advances
Misuse
Conclusion
References
Introduction to Antibiotics
Terminologies Used
Antibiotics: Substances produced by microorganisms, which selectively suppress the
growth of or kill other microorganisms at very low concentrations. The term
"antibacterial" is derived from Greek anti - "against and baktria, "staff, cane". The
term "antibiotic" derived from anti and bios, "life".
Chemotherapy: Treatment of systemic infections with specific drugs that selectively
suppress the infecting microorganism without significantly affecting the host
Antimicrobial Agent: Synthetic as well as naturally obtained drugs that attenuate
microorganisms
History of Antibiotics
Milestones in History
Chenopodium
Chaulmoogra
Classification of Antibiotics
Domagk
Diaminopyridines
Trimethoprim, Pyrimethamine
Quinolones
-lactam
Tetracyclines
Oxytetracycline, Doxycycline
Nitrobenzene derivative
Chloramphenicol
Aminoglycosides
Macrolide
Lincosamide
Lincomycin, Clindamycin
Glycopeptide
Vancomycin, Teicoplanin
Oxazolidinone
Linezolid
Polypeptide
Nitrofuran derivatives
Nitrofurantoin, Furazolidone
Nitroimidazoles
Metronidazole, Tinidazole
Polyene
Azote derivatives
Others
Antifungal
Antiviral
Antiprotozoa
l
Anthelmintic
Narrowspectrum
Broad-spectrum
Tetracyclines, Chloramphenicol
Primarily
bactericidal
Bacteria
Actinomycete
s
Renal Failure
Dose reduction in
mild failure
Dose reduction in
moderate-severe
failure
Drugs to be avoided
Cephalothin, Talampicillin,
Nalidixic acid, Tetracyclines, Nitrofurantoin (except
doxycycline)
Liver Disease
Dose reduction
Drugs to be
avoided
d) Local Factors:
o Pus and secretions decrease the efficacy of sulfonamides and
aminoglycosides
o Necrotic material or foreign body makes eradication impossible
o Haematomas foster bacterial growth
o Lowering of pH at the site of infection reduces activity of macrolides
and aminoglycosides
o Anaerobic environment in the centre of an abscess impairs bacterial
transport processes which concentrate aminoglycosides in the cell
o Penetration barriers hamper the access to the site of infection
o Some drugs like trimethoprim and fluoroquinolones attain high
concentration due to ion trapping
e) Drug Allergy:
o If a drug has caused allergic reaction, it has to be avoided in that
patient.
o -lactams, sulfonamides, fluoroquinolones, nitrofurantoin frequently
cause allergy.
f) Impaired Host Defense:
o Pyogenic infections are common in neutropenic patients.
o Infections by low grade pathogens and intracellular organisms occur if
cell-mediated immunity is impaired.
o In a patient with normal host defense, a bacteriostatic AMA may
achieve cure.
Description
Adequate human studies are lacking, but animal studies have failed
to demonstrate a risk to the foetus amoxicillin
or,
Adequate studies in pregnant women have failed to demonstrate a
risk to the foetus, but animal studies have shown an adverse effect on
the foetus
Organism-related Factors
a) Initial Empirical Therapy:
Identification of the microorganism and antimicrobial sensitivity testing are
time consuming, expensive & impractical. Sometimes, it is not possible to obtain
appropriate samples of infected material. Furthermore, well defined site and features
of the infection enable organisms causing such infections to be reliably deduced. SO
empirical therapy is usually carried out. In addition, most dental infections are acute
in nature, hence treatment cannot be delayed.
b) Identification of Causative Organism:
Type of bacteria (aerobic/anaerobic) and their specific identification is
necessary for proper management of the condition. Most odontogenic infections
Drug Factors
a) Spectrum of Activity:
For definitive therapy, a narrow-spectrum drug which selectively affects the
concerned organism is preferred. For empirical therapy, often a broad-spectrum drug
has to be used to cover all likely pathogens.
b) Type of Activity:
Acute infections resolve faster with a cidal drug and reduces the number of
bacteria at the site of infection. For patients with impaired host defence, lifethreatening infections, infections at less accessible sites (SABE) or when carrier state
is possible (typhoid), a bactericidal drug is preferred.
c) Sensitivity of the Organism:
On the basis of MIC values (if available) and consideration of postantibiotic
effect
d) Relative Toxicity:
Less toxic antibiotic is preferred
e) Pharmacokinetic Profile:
Antibiotic has to be present at the site of infection in sufficient concentration
for an adequate length of time. Aminoglycosides and fluoroquinolones produce
concentration-dependent inhibition, where the inhibitory effect depends on the ratio
of peak concentration to the MIC. -lactams, glycopeptides and macrolides produce
time-dependent inhibition where the antimicrobial action depends on the length of
time the concentration remains above MIC. Drug which penetrates better and attains
higher concentration at the site of infection is more effective.
f) Route of Administration:
Less severe infections warrant the use of oral antibiotic. Serious infections
require parenteral antibiotics.
g) Evidence of Clinical Efficacy:
Relative value of different AMAs in treating an infection is decided on the
basis of comparative clinical trials. Optimum dosage regimens and duration of
treatment are also determined on the basis of such trials. Reliable clinical trial data, if
available, is the final guide for choice of the antibiotic.
h) Cost:
Less expensive drugs are to be preferred
Routes of Administration
Antibiotic Combinations
More than one AMAs are frequently used concurrently to treat infections.
Objectives:
i.
ii.
iii.
iv.
v.
Prophylactic Use
Antibiotic prophylaxis with dental procedures is reasonable only for patients
with cardiac conditions associated with the highest risk of adverse outcomes from
endocarditis.
2. Hypersensitivity
Reactions that range from rashes to anaphylactic shock, that are unpredictable
and unrelated to dose. Practically all AMAs are capable of causing hypersensitivity.
More common culprits include penicillins, cephalosporins, sulfonamides,
fluoroquinolones.
3. Drug Resistance
Penicillin G
Penicillin V
Methicillin
lactamase inhibitors
Clavulanic acid
Aminopenicillins: Ampicillin
Carboxypenicillin: Carbenicillin
Ureidopenicillin: Piperacillin
a) Penicillin G
Antibacterial Spectrum:
Streptococci, pneumococci, N. gonorrhoea, clostridia, M. TB, spirochaetes,
actinomyces israeli, B. anthracis
Mechanism of Action:
Interfere with the synthesis of bacterial cell wall
Adverse Effects:
Local irritancy and direct toxicity
Hypersensitivity reactions
Super infections
Jarisch-Herxhemier reactions
Uses:
i.
Dental infections: periodontal abscess, periapical abscess, pulpitis
ii.
Medicinal uses: Gonorrhoea, syphilis, tetanus
Preparations and Dose:
Sodium penicillin G inj.:
Procaine penicillin G inj.:
Fortified procaine penicillin G inj.:
Benzathine penicillin G:
Contraindications:
Allergies
Poor renal function
Drug Interactions:
Oral contraceptives
Pregnancy category: B
Trade Names: PENCIP, PENTIDS, SODICILLIN
b) Ampicillin
Antibacterial Spectrum:
E. coli, proteus, salmonella, shigella and many Gram positive organisms like cocci,
bacilli etc.
Mechanism of Action:
Interfere with the synthesis of bacterial cell wall
Adverse Effects:
Diarrhoea
Rashes
Drug Interactions:
Oral contraceptives
Uses:
i.
Urinary tract infection
ii.
Respiratory tract infection
iii.
Meningitis, gonorrhoea
iv.
v.
Contraindications:
Allergies
Poor renal function
Dosage:
0.5-2g oral/I.M/I.V every 6 hrs for adults
25-50 mg/kg/day for children
Trade Names: AMPISYN, AMPILIN, AMPI-500, ALFACILLIN, AMPICILLIN
c) Amoxicillin
Similar to ampicillin in all aspects except:
Oral absorption is better
Incidence of diarrhea
It is less active against Shigella and H. influenzae
Dosage:
250-500mg TDS given for 5 days
Uses:
Choice of drug for prophylaxis of local wound infection as well as distant infection
following dental surgery
Trade Names: MOX, AMOX, AMOXIL, AMOXIPEN, AUGMENTIN (Amoxicillin
and clavulanic acid)
d) Methicillin
MRSA (methicillin resistant staph. aureus) are organisms resistant to methicillin.
Drug of choice: vancomycin/linezolid. Ciprofloxacin can also be used
2. CEPHALOSPORINS
Mechanism of Action:
Interfere with the synthesis of bacterial cell wall
Classification:
a) First Generation:
Effective against gram positive cocci, including penicillinase
producing staph, most anaerobes and community acquired infections
caused by E.coli, Proteus and klebsiella
Examples are: Cefalexin, Cefadroxil
b) Second Generation:
Show increased antibacterial activity
Cefmandole has markedly increased activity. But it has less activity
against strep.
Cefactor, increased activity against H.influenzae
c) Third Generation:
Ceftriaxone shows high efficacy in bacterial meningitis, multi
resistant typhoid fever, complicated urinary tract infections,
abdominal sepsis and septicemias
Examples are: Cefpodoxime proxetil, cefoperazone
d) Fourth Generation:
Examples are: Cefepime, cefpirome
Dosage: 250-1000 mg q 6 h x 7-10 days
Uses:
i.
Dental infections
ii.
General medical uses like meningitis, typhoid etc
Adverse Effects:
Pain after I.M injection
Diarrhoea
Hypersensitivity reactions
Nephrotoxicity
Bleeding
Neutropenia and thrombocytopenia
Contraindications:
Allergies
Poor renal function
Drug Interactions: Probenecid
Pregnancy Category: B
3. TETRACYCLINES
Antibacterial Spectrum:
Cocci: N. gonorrhoea and N. menigitidis
Bacilli: Clostridia and anaerobic bacilli, H. ducreyi
Some spirochetes, mycoplasma, actinomyces
Mechanism of Action:
Enteric fever
H. influenzae meningitis
Anaerobic reactions
Intraocular infections
Adverse Effects:
Bone marrow depression
Hypersensitivity reactions
Irritative effects
Superinfections
Gray baby syndrome
Dosage: Daily dose not to exceed 23 g; duration of therapy to be < 2 weeks, total
dose in a course < 28 g
Contraindications:
Pregnancy
Drug Interactions:
Inhibits metabolism of tolbutamide, chlorpropamide, warfarin,
cyclophosphamide and phenytoin
Phenobarbitone, phenytoin, rifampin enhance metabolism
Antagonize the cidal action of -lactams/aminoglycosides on certain bacteria
Pregnancy category: D
5. AMINOGLYCOSIDES
Antibacterial Spectrum:
Gram negative bacilli, H.ducreyi, yersinia pestis, gram positive cocci, enterococci
Mechanism of Action:
Inhibit protein synthesis
Uses:
i.
ii.
iii.
iv.
v.
vi.
Tuberculosis
Plaque
Tularemia
Brucellosis
Enterococcal infections
Subacute bacterial infections
Adverse Effects:
Ototoxicity
Nephrotoxicity
Neuromuscular blockade
Allergy
Superinfection
Mechanism of Action:
Act by inhibiting protein synthesis by binding to the bind to the 23S rRNA of 50S
ribosomal subunits
Uses:
i.
Dental infections: Periodontal, periapical abscess, necrotizing ulcerative
gingivitis, gingival cellulites
ii.
General medical uses: Pharyngitis, tonsillitis, rheumatic fever
Adverse Effects:
Gastrointestinal problems
Hypersensitivity
Reversible hearing impairment
Dosage:
Erythromycin: 250-500 mg 6 hourly (max.4g/day), children 30-60-mg/kg/day
Azithromycin: 500 mg once daily 1hr before or 2hrs after food for 3 days
Precautions:
Poor hepatic function
Drug Interactions:
Cytochrome P-450
Pregnancy category: B
7. METRONIDAZOLE
Antibacterial Spectrum:
Entamoeba histolytica, giardia lamblia, anaerobic bacteria, like clostridium,
spirochetes, peptococcus
Mechanism of Action:
Reduced intermediate interacts and breaks the bacterial or parasitic DNA
Adverse Effects:
Anorexia, nausea, metallic taste, abdominal cramps
Headache, dryness of mouth, rashes, and Glossitis (rare)
Thrombophlebitis of the injected vein
Uses:
i.
ii.
iii.
iv.
v.
Orodental infections
Drug of choice in acute necrotizing ulcerative gingivitis
Periodontitis, pericoronitis, acute apical infections, brain abscess
Drug of choice for all forms of anaerobic infections, acute dysentery, liver
abscess
Drug of choice for intestinal giardiasis and trichomonas vaginitis
Antibacterial Spectrum:
All organisms are susceptible except some strep, anaerobic cocci, mycobacterium
Mechanism of Action:
Bind to A subunit of DNA gyrase with high affinity and interfere with strand cutting
and resealing functions
Adverse Effects:
GIT: Nausea, vomiting, bad taste, anorexia
CNS: Dizziness, headache, restlessness, anxiety
Skin/hypersensitivity
Uses:
i.
ii.
iii.
iv.
Methamoglobinemia
Blood dyscarasis
Nausea, vomiting, stomatitis, headache and rashes
Neonatal hemolysis
Contraindications:
Pregnancy
Newer Antibiotics
i.
ii.
iii.
iv.
v.
vi.
Misuse in Dentistry
Treatment of Nonresponsive Infections:
Diseases caused by viruses are self-limited
Therapy of Fever of Unknown Origin:
Fever persisting for 2 or more weeks only 1/4th are due to infections
Require treatment with agents that are not used commonly for bacterial
infections, surgical drainage or prolonged courses of pathogen-specific
therapy
May mask an underlying infection, delay the diagnosis, and prevent
identification of the infectious pathogen
Noninfectious causes
Inappropriate Reliance on Chemotherapy Alone:
Drainage, debridement, and removal of foreign body
Misuse in Dentistry
Improper Dosage:
Dosing errors (wrong frequency of administration or use of either an
excessive or a subtherapeutic dose)
Excessive amounts can result in significant toxicities
Too low a dose may result in treatment failure or resistance
Lack of Adequate Bacteriological Information:
Bacterial cultures and Gram stains of infected material
Frequent use of drug combinations or drugs with the broadest spectra
Agents are selected more likely by habit than for specific indications
Dosages employed are routine rather than individualized
Conclusion
Antibiotic therapy is an art and a science. There are so many confounding
variables (such as suspected pathogen, ability to establish drainage, pharmacokinetic
properties of the drug, mechanism of action of the antibiotic, virulence of the
infection, the current health status of the host, and host defense mechanisms), that it
is not possible to make antibiotic therapy into a mechanistic technologic science.
The most important decision for the dental practitioner to make is not only
which antibiotic to use but whether to use one at all.
References
i.
ii.
iii.
iv.
v.
Online sources:
http://www.medclik.com
http://en.wikipedia.org/wiki/Antibacterial