ANTIBIOTICS IN PEDIATRICS

Presented by:Dr. pawan sinsinwar

Guided by:Dr. kumar raghav

Dr. shefali chaturvediDr. tarun sethi

Antibiotics Act By Inhibition Of Protein

Synthesis•Tetracycline•Chloramphenicol•Aminoglycosides•Macrolides

TETRACYCLINES

From Actinomycetes

The tetracycline's still available in lndia for clinical use are: Tetracycline Oxytetracycline Demeclocycline Doxycycline Minocycline

Mechanism Of Action

1- Aminoglycosides2- Tetracycline3- Chloremphenicol4- Erythromycin

Broad-spectrum antibiotic

Promiscuous and often indiscriminate use has gradually narrowed the field of their usefulness.

1. Cocci 2. Most gram-positive bacilli 3. Gram-negative bacilli 4. Spirochetes, T. Pallidum 5. All rickettsiae (typhus, etc.) And chlamydiae are highly

sensitive. 6. Mycoplasma and actinomyces are moderately sensitive. 7. Entamoeba histolytica and plasmodia are inhibited at

high concentrations.

Antimicrobial Spectrum

The older tetracycline's are incompletely absorbed from GIT; absorption is better if taken in empty stomach.

Doxycycline and minocycline are completely absorbed irrespective of food.

Tetracycline's have chelating property-form insoluble and unabsorbable complexes with calcium and other metals.

Milk, iron preparations,nonsystemic antacids and sucralfate reduce their absorption.

Pharmacokinetics

They are concentrated in liver, spleen and bind to the connective tissue in bone and teeth.

Intracellularly, they bind to mitochondria.

Minocycline accumulates in body fat.

Most tetracycline's are primarily excreted in urine by glomerular filtration;

Doxycycline is an exception to this.

They are secreted in milk in amounts sufficient to affect the suckling infant.

1. Tetracycline: ACHROMYCIN, HOSTACYCLINE,RESTECLIN 250, 500 mg cap, 3% skin oint, 1% ear/eye drops and oint.

2. Oxytetracycline: TERRAMYCIN 250, 500 mg cap, 50 mg/ml in 10 ml vials inj;3% skin oint, 1% eye/ear drop and oint.

Preparations

3.Demeclocycline (Demethylchlortetracycline) LEDERMYCIN 150, 300 mg cap/tab.

4.Doxycycline: TETRADOX, BIODOXI, DOXT,NOVADOX 100 mg cap

5.Minocycline: CYANOMYCIN 50, 100 mg caps

Although tetracycline's are broad-spectrum antibiotics, they should be employed only for those infections for which a more selective and less toxic AMA is not available.

Clinical use declined due to fluoroquinolones and other efficacious AMAs.

Uses

The nature and sensitivity of the infecting organism cannot be reasonably guessed

Initial treatment of mixed infections

1. Empirical Therapy

(A) Venereal Diseases

(B) Atypical Pneumonia

(C) Cholera

(D) Brucellosis

(E) Plague

(F) Relapsing Fever

(G) Rickettsial Infections

2. Tetracyclines Are The First Choice

To Penicillin/Ampicillin To Ceftriaxone To Azithromycin For Pneumonia To Ceftriaxone/Azithromycin For Chancroid. To Streptomycin For Tularemia.

3. Tetracycline's Are Second Choice Drugs

(A) Urinary Tract Infections (B) Community Acquired pneumonia (C) Amoebiasis (D) As Adjuvant To Quinine Or Sulfadoxine (E) Acne Vulgaris (F) Chronic Obstructive Lung Disease

4. Other Situations In Which Tetracyclines May Be Used

Acute orofacial infections Chronic adult periodontitis Localized juvenile periodontitis Subgingivally

Dental use

Adverse Effects

Esophageal ulceration especially with doxycycline.

Intramuscular injection of tetracycline's are very painful; thrombophlebitis of the injected vein can occur, especially on repeated use

IRRITATIVE EFFECTS

1. Liver damage Fatty infiltration of liver and jaundice occur Pregnant women; can precipitate acute hepatic

necrosis which may be fatal.

2. Kidney damage In the presence of existing kidney disease. Except doxycycline, accumulate and enhance

renal failure. A reversible fancony syndrome llke condition is

produced by outdated tetracyclines

3. Phototoxicity

Dose Related Toxicity

4. Teeth and bones

Brown discoloration, ill-formed teeth, more susceptible to caries.

Tetracyclines have chelating property Calcium-tetracycline chelate gets deposited in

developing teeth and bone. Given from midpregnancy to 5 months of extra

uterine life, deciduous teeth are affected. 3 months and 6 years of age affect the crown

of permanent anterior dentition. Late pregnancy or childhood, temporary

suppression of bone growth. Deformities and reduction in height are a

possibility with prolonged use.

First, the ‘extrinsic theory’ (Berger et al. , 1989), Tetracycline attaches to the glycoproteins in acquired pellicles. This in turn etches the enamel, and demineralization/

remineralization cycles occur. It oxidizes on exposure to air or as a result of bacterial activity,

and so causes degradation of the aromatic ring, forming insoluble black quinone.

The second is the ‘intrinsic theory’ (Bowles and Bokmeyer, 1997; Bowles, 1998),

Where the tetracycline bound to plasma proteins is deposited in collagen rich tissues, such as teeth.

This complex oxidizes slowly over time with exposure to light. This deposition in teeth occurs solely within the dentin matrix as secondary and reparative dentin is formed

Mechanism of tetracycline staining

5. Antianabolic effect Reduce protein synthesis and have an overall catabolic

effect. They induce negative nitrogen balance and can

increase blood urea.

6. Increased intracranial pressure Noted in some infants.

7. Diabetes insipidus Demeclocycline antagonizes ADH action and reduces

urine concentrating ability of the kidney.

8. Vestibular toxicity Minocycline has produced ataxia, vertigo and

nystagmus, which subside when the drug is discontinued.

Resistance to tetracycline develops slowly in a graded manner.

Tetracycline concentrating mechanism becomes less efficient or the bacteria acquire capacity to pump it out.

Plasmid mediated synthesis of a 'protection‘ protein which protects the ribosomal binding site from tetracycline.

Resistance

Infrequent with tetracycline's.

Skin rashes, urticaria, glossitis, pruritus ani and vulvae, even exfoliative dermatitis have been reported.

Angioedema and anaphylaxis are extremely rare.

Hypersensitivity

The tetracycline should be discontinued at the first sign of superinfection and appropriate therapy instituted.

Doxycycline and minocycline are less liable to cause diarrhoea, because only small amounts reach the lower bowel

Superinfection

1. Not be used during pregnancy, lactation and in children.

2. Avoided in patients on diuretics: blood urea may rise in such patients.

3. Used cautiously in renal or hepatic insufficiency.

4. Never be used beyond their expiry date.

5. Do not mix injectable tetracycline's with penicillin-inactivation occurs.

6. Do not inject tetracycline's intrathecally.

Precautions

CHLORAMPHENICOL

Chemical structure

Mechanism Of Action

1- Aminoglycosides2- Tetracycline3- Chloremphenicol4- Erythromycin

Antimicrobial spectrum

Completely absorbed after oral administration,

Bound to plasma protein (approximately 60%) and widely distributed in body.

Crosses the blood-brain and placental barrier and shows its presence in csf, bile and milk.

It is conjugated with glucuronic acid in liver and excreted in urine.

Small amount is excreted in urine in unchanged form.

Pharmacokinetics

Because of Bone Marrow Toxicity its use is restricted to

the treatment of infection caused by S. Typhi And

Paratyphi

Other - H. Influenzae Meningitis, Urinary Tract

Infections, Anaerobic Infections Caused By Bacteroides Fragilis

And Locally In Eye And External Ear Infections.

Therapeutic Uses

Adverse Effects

Aminoglycosides

Bactericidal Antibiotics Various Streptomyces Species

Chemical structure

Act By Inhibiting Protein Synthesis Of Bacteria By Directly Combining With Ribosomes.

Other Aminoglycosides Bind To Additional Sites On 50s Subunit As Well As To 30s-50s Interface.

Mechanism of action

Mechanism Of Action

1- Aminoglycosides2- Tetracycline3- Chloremphenicol4- Erythromycin

Poorly absorbed after oral administration,

More active in alkaline ph

Excreted unchanged by glomerular filtration accumulation occurs in renal impairment.

Pharmacokinetics

All Aminoglycosides produce cochlear and vestibular damage (Ototoxicity) And Nephrotoxicity.

Reduce the acetylcholine release from motor nerve endings and cause neuromuscular blockade.

Adverse effects

STREPTOMYCIN

Used In All Tuberculosis Along With Antitubercular Drugs.

Other Indications: Tularemia, Plague, Brucellosis, Bacterial Endocarditis, Enterococcal Endocarditis.

Used concomitantly with Penicillin G for synergistic effect in the treatment of Enterococcal Endocarditis when other antibiotics are ineffective or contraindicated

Pain At Injection Site

Ototoxicity

Nephrotoxicity

Skin Rash

FeverExfoliative Dermatitis

Eosinophilia

Anaphylaxis Rarely

Optic Nerve Dysfunction

Adverse effects

AMIKACIN

From Streptomyces

Kanamyceticus.

Active Against Pseudomonas

Severe Ototoxicity And Nephrotoxicity

Replaced By Other

Aminoglycosides

Occasionally Used In

Multidrug Resistant Cases Of

Tuberculosis.

Kanamycin

From Streptomyces

Fradiae

Effective Against Most

Gram Negative

Bacilli And Some Gram

Positive Cocci.

High Ototoxicity

And Nephrotoxicity

,

Not Systemically Used Locally Skin And Eye

Infections.

Neomycin

Sulfonamides

Derivatives Of Sulfanilamide (P-

aminobenzene Sulfonamide)

First Antimicrobial Agents Effective Against Pyogenic

Bacterial Infections

Chemical structure

Sulfanilamide exhibits a structural similarity to para-amino benzoic acid (PABA).

WOODS AND FIELDS proposed theory that sulfonamides, inhibit bacterial FOLATE SYNTHETASE so folic acid is not formed which is needed for a number of metabolic reactions.

Causes FOLIC ACID deficiency and ultimately cause injury to the bacterial cell.

Mechanism of action

Bacteriostatic Antibacterial Activity Against Gram

Positive And Gram Negative Organisms ,

Certain Species Of Chlamydia

Infections Such As: Streptococci,

Staphylococci, Pneumococci, Gonococci,

Meningococci,.

Haemophilus Influenzae, Granulomatis, Vibrio

Comma, Vibrio Cholerae, E. Coli, Pasteurella Pestis,

Shigella

Antimicrobial spectrum

rapidly and completely

absorbed from GIT mainly in small

intestine

Binding with plasma proteins

differ considerably

among different groups.

The highly plasma protein

bound sulfonamides have longer

action.

Pharmacokinetics

I. Urinary Tract Infection

Ii. Acute Bacillary Dysentery Iii. Ulcerative Colitis

Iv. Streptococcal Pharyngitis, And

Tonsillitis.

V. Trachoma And Inclusion

Conjunctivitis:Vi. Chancroid

Vii. Meningococcal Meningitis.

Viii. Chloroquine Resistant Malaria Ix. Toxoplasmosis

X. Burns

Therapeutic uses

Adverse reactions

Allergic Symptoms Drug Fever, Skin Rash, Urticaria, Eosinophilia,

Photosensitization Reactions, Serum Sickness Like Syndrome.

Stevens- Johnson Syndrome And Exfoliative Dermatitis Are Also Common

With Longer Acting Agents Uncommon Allergic Reactions Acute Toxic Hepatitis, Toxic Nephrosis And

Acute Haemolytic Anaemia.

Renal Irritation And May Precipitate Renal Colic. Crystalluria, Haematuria And Albuminuria Can

Occur May Lead To Oliguria And Anuria.

Hematopoietic Toxicity Agranulocytosis, Thrombocytopenia And Rarely Aplastic

Anaemia Patients With G-6- Pd Deficiency,Cause Intravascular

Haemolysis.

The Other CNS Effects Include Depression, Confusion, Tinnitus,

Fatigue Etc.

Trimethoprim

Therapeutic usesInfection caused by salmonella typhi, klebsiella, enterobacter,pneumocystis carinii etc

And many other sulfonamide resistant strains of s. Aureus,strep. Pyogenes, shigella, e. Coli, h. Influenzae, meningococci and gonococci etc.

Effective as a second line agent in penicillin allergic patients where newer antibiotics are contraindicated or can’t be used.

UT IAcute

Cystitis

Bacterial Diarrhoea And

Dysentery.

Respiratory Tract Infection - Chronic

Bronchitis And Otitis Media Etc.

Typhoid.Nosocomial Infections

Chancroid

Sexually Transmitted

Diseases

Prophylaxis And Treatment HIV

Associated Infections

Prophylaxis - Organ

Transplantation

Patients Receiving

Immunosuppressants

The common indications are:

Quinolones

Quinolone Block bacterial DNA synthesis by inhibiting bacterial Topoisomerase II (DNA Gyrase)

and Topoisomerase IV

Inhibition of DNA gyrase prevents the relaxation of positively

supercoiled DNA that is required for normal transcription and

replication.

Mechanism of action

It is 4-QUINOLONE derivative effective against gram negative bacteria mainly E. Coli and Shigella.

Acts by inhibiting bacterial DNA GYRASE.

Used as urinary antiseptic and in diarrhea caused By E. Coli, Shigella,salmonella.

The side effects are GIT upset, Headache, Drowsiness, Vertigo, Visual Disturbances and on prolonged use can produce parkinsonism like symptoms.

In Individuals with G-6-PD deficiency can cause haemolysis.

Nalidixic acid

Quinolone AMAs having one or more fluorine substitutions, relatively broad spectrum of action and effective against gram positive And gram negative organisms.

They are highly effective against E. Coli, Klebsiella, Proteus Mirabilis, Shigella, Salmonella Species, H. Ducreyi Etc.

Fluoroquinolones

The presence of a 6-fluoro and 7- piperazine substitution greatly enhances their antimicrobial efficacy as compared to nalidixic acid.

The fluorine atom is responsible for increased potency against gram negative organisms and broadens the spectrum of their activity including gram positive organism.

Mechanism of action

After oral administration, well absorbed with the bioavailability Of 80 to 95 % and distributed widely in body fluids and tissues.

The fluoroquinolones are excreted mainly by tubular secretion and by glomerular filtration.

Pharmacokinetics

UTI

Dental UseNot indicated in acute

orofacial infectionsCiprofloxacin may be

used in rapidly progressive or

refractory periodontitis

Bacterial gastroente

ritis.

Typhoid fever.

Septicemia.

Otitis media.

Acute pneumonia

Ocular infections

Therapeutic uses

Fluoroquinolones are well tolerated.

Tendinitis is rarely reported in adults. Because of cartilage damage in children it must be used under close supervision.

Phototoxicity Reported With Pefloxacin, Lomefloxacin, Sparfloxacin And Ofloxacin.

Adverse effects

Most potent first generation fluoroquinolone,

Aerobic gram negative bacilli.

Higher concentration in the urine than plasma.

Produces rapid and complete clinical relief in nosocomial bronchopneumonia

Used prior to cardiac surgery and has attained levels higher than mics for at least 8 hours.

Ciprofloxacin

It is more potent than ciprofloxacin for gram positive organisms.

It also inhibits Mycobacterium tuberculosis and mycobacterium leprae and used as alternative in multidrug resistant therapeutic regimens.

It is also used in the treatment of chronic bronchitis and other ENT infections.

Ofloxacin

It is the levoisomer of ofloxacin and having better activity than ciprofloxacin and ofloxacin against s. Pneumoniae.

It is also used in chronic bronchitis, sinusitis, pyelonephritis, and other related infections of soft tissues.

Due to high oral bioavailability, patient can be shifted from Iv to oral therapy.

It can be administered just once a day regimen as an alternate to other fluoroquinolones in the treatment of respiratory infections.

Levofloxacin

It is less potent than ciprofloxacin

Primarily used in genitourinary tract infections.

It is not useful in respiratory and systemic infections due to gram positive cocci.

Norfloxacin

It is Difluorinated quinolone effective against gram positive bacteria, anaerobes and mycobacteria.

It is used in the treatment of pneumonia, chronic bronchitis, sinusitis etc.

Sparfloxacin

Macrolide antibiotics

Macrolides, as their name indicates are characterized by a large or macrocyclic lactone ring with attached sugar residue

First macrocyclic antibiotic From streptomyces erythreus.

Widely used antibiotic both in children as well as in adults.

It acts by binding with 50s ribosomal subunit of bacteria and inhibit protein synthesis.

Narrow spectrum, low concentration are bacteriostatic, however high concentrations are bactericidal.

Erythromycin

Mechanism Of Action

1- Aminoglycosides2- Tetracycline3- Chloremphenicol4- Erythromycin

The spectrum of activity also depends on the concentration of drug. It is more active in alkaline medium.

Effective against gram positive and few gram negative organisms

Also effective against penicillin resistant staphylococci, mycoplasma, campylobacter, legionella, gardnerella vaginalis are also highly sensitive.

Substitute to penicillin in allergic patients for upper respiratory tract infections, prophylaxis of rheumatic fever.

Atypical pneumonia due to mycoplasma pneumoniae,and whooping cough.

Wound and burn infections and severe impetigo not responding to topical antibiotics.

Therapeutic uses

Dental uses

Acute Orofacial Infection- Erythromycin

Acute Periapical Abscesses- Azithromycin

IE Prophylaxis

Gastrointestinal side effects like nausea, epigastric pain are common. Diarrhoea occurs occasionally.

Skin rashes, hypersensitivity reaction, hepatotoxicity Oral candidiasis, thrombophlebitis and fever have been reported.

Adverse effects

Azithromycin is an azalide antibiotic, a sub-class of the macrolides.

Azithromycin differs chemically from erythromycin in that a methyl substituted nitrogen atom is incorporated into the lactone ring.

oral administration, rapidly absorbed and widely distributed throughout the body.

Rapid distribution into tissues and high concentration within cells result in significantly higher azithromycin concentration is tissues than in plasma or serum.

Azithromycin

1. Lower respiratory tract infections:

2. Ear, nose and throat infections like tonsillitis, sinusitis, otitis media and pharyngitis.

3. Skin infections

Therapeutic uses

Adverse reactions include vomiting, dyspepsia, flatulence, jaundice, palpitations, chest pain. Allergic reactions include rash, photosensitivity and angioedema.

CNS side effects are headache, dizziness, vertigo and fatigue.

Adverse effect

Nitroimidazoles are imidazole heterocyclic compounds with a nitro group that have been used to combat anaerobic bacterial and parasitic infection .

Nitroimidazoles:

Anaerobic cocciAnaerobic gram –ve bacilli including bacteroidsAnaerobic spore-forming gram +ve bacilliAerobic and Facultative anaerobic bacteria

Metronidazole :

After entering the micro-organisms by

diffusion , its nitro group is reduced to

intermediate compounds which cause

cytotoxicity probably by damaging DNA.

Dose: 200,400 mg TDS

Mechanism of action

INDICATIONAmoebiasisAnaerobic

bacterial inf.Ulcerative Gingivitis

CONTRAINDICATION

In neurological

diseasesChronic

AlcoholismFirst

trimester of pregnancy

ADVERSE EFFECT

Anorexia, Nausea

Abdominal cramps

Metallic tasteHeadache ,

GlossitisRashes,

DizzinessSeizures,

Thrombophelbitis

Clinical Application

Non-indicated Cases for Antibiotic Prescription:

Acute Periapical Infection

Dry Socket Acute Pulpitis Chronic Marginal

Gingivitis Chronic Periodontitis

Indications for the Use of Antibiotics in Dentistry:

Oral infection accompanied by elevated body temperature,

Evidence of systemic spread, Facial cellulitis and/or

dysphagia. Periodontal abscess Acute nercotizing ulcerative

gingivitis Sinusitis Pericoronitis

Dental Procedures Requiring Antibiotic Coverage (2007

Guidelines) All dental procedures that involve manipulation

of gingival tissue or the periapical region of teeth or perforation of the oral mucosa

Suture removal

Extractions

Periodontal procedures (scaling, root planing, probing, surgery, recall maintenance)

Dental Procedures Requiring Antibiotic Coverage (2007 Guidelines)

Implant placement and reimplantation of avulsed teeth

Placement of orthodontic bands

Bacteremia is anticipated following invasive dental procedures

Infective endocarditis is an uncommon but life-threatening complication resulting from bacteremia

AAPD GUIDELINES 2012 ON ANTIBIOTIC PROPHYLAXIS

1. Prosthetic cardiac valve or prosthetic material used for cardiac valve repair

2. Previous IE

3. Congenital heart diseasea. Unrepaired cyanotic CHDb. Completely repaired defect with prosthetic material for 6months

after procedurec. Repaird CHD with residual defects

4. Cardiac transplant pts who develop cardiac valvulopathy

WHICH PATIENTS?

WHICH PROCEDURES? All dental procedures that involve

manipulation of gingival tissue

WHICH PROCEDURES DO NOT? LA through non-infected tissue, X-rays, Placement of removable prosthodontic or orthodontic

appliances, Placement of brackets, Shedding of deciduous teeth, Bleeding from trauma to the lips or oral mucosa

ABLE TO TAKE ORAL MEDS?-Amoxicillin 50mg/kg

UNABLE TO TAKE ORAL MEDS?-Ampicillin or Cefazolin 50mg/kg IV/IM

ALLERGIC TO PCN, ORAL?-Clindamycin 20mg/kg or Azithromycin/Clarithromycin 15mg/kg

ALLERGIC TO PCN, NON-ORAL?-Clindamycin 20mg/kg IV/IM

Weight Age % of adult dose

3 Newborn 11

4 2 month 13

6 3 month 18

8 6 month 22

10 1 yr 25

12 2 35

15 3 39

20 5 45

25 7 52

30 9 57

35 11 64

40 12 71

50 14 82

60 16 91

CONCLUSION: The role of antibiotics in odontogenic infections is of

paramount importance and one that cannot and

should not be neglected.

The fact that the microbial flora responsible for

odontogenic infections is a limited one only

emphasizes the need for proper antibiotic selection

and administration.

Too often in the look out for curing the infection, we

as dental practitioners tend to adopt a ‘shotgun

approach’ and prescribe unnecessary antibiotics.

1. St. Joseph Literature Review Some good stuff to know about kids‘ teeth.Wednesday, October 31, 2012 AAPD GUIDELINES ON ANTIBIOTICS Resident: Elliot Chiu

2. Laurence L. Brunton ,John S.Lazo ,Keith L. Parker; Goodman and Gilman’s The pharmacological basis of therapeutics; 11th edi,McGraw Hill,2006

3. KD Tripathi :Essentials of medical pharmacology; Jaypee brothers, 5th edi,2004

4. Naresh Kumar khanna; Principles of pharmacology for dental students, CBS publishers, 3rd edi,2010

5. Antibiotic & antimicrobial use in dental practice 2nd ed. by Michael G. Newman.

6. Tetracycline induced tooth discoloration Venkateswarlu M1 and Naga Sailaja R2

REFERENCES