seminar antibiotics

PRINCIPLES OF ANTIBIOTICS

Deepa V Post Graduate Student DSCDS,Bangalore

CONTENTS Definition History of Antibiotics Principles of antibiotics Problems with use of antibiotics Antibacterial Antifungal Antiviral Prophylactic antibiotics Antibiotics in oral surgery

ANTIBIOTICS

Definition Antibiotics are substances produced

by microorganisms, which suppress the growth of or kill other microorganisms at very low concentrations.

- (Essentials of Basic Medical Pharmacology, K.D.Tripathi, 5th edition.)

Antimicrobial Agent (AMA) It is the term used to designate synthetic as

well as naturally obtained drugs that attenuate microorganisms

History of Antibiotics Three phases

The period of empirical use.

Ehrlich’s phase of dyes and organometallic compounds (1980-1935).

Modern era of Chemotherapy.

Period of empirical use ‘Mouldy curd’ by Chinese on boils.

Chaulmoogra oil by Hindus in leprosy.

Chenopodium by Aztecs for intestinal worms.

Mercury by Paracelsus (16th century ) for syphilis

cinchona bark (17th century) for fevers.

Ehlrich’s Phase Later in the 19th century with the discovery of

microbes , that they are the causes of diseases, Ehrlich used dyes for staining and killing microorganisms .

Initially he tried methylene blue, tryptan red etc .

Later he developed the arsenicals – atoxyl (1906) for sleeping sickness and arsphenamine (1909) for syphilis.

He coined the termed chemotherapy, because he used drugs of known chemical structure.

Modern Era of Antibiotics Domagk in 1935 demonstrated the

therapeutic effect of prontonsil, a sulfonamide dye, in pyogenic infection.

Sulfapyridine was the first sufonamide to be marketed in 1938.

The phenomenon of antibiosis was demostrated by Pasteur in 1877; where growth of anthrax bacilli in urine was inhibited by airborne bacteria.

Fleming (1929),found a diffusible substance which was elaborated by penicillium mould which could destroy staphyllococcus on the culture plate and named this substance penicillin.

Chain and Florey followed this observation and used pencillin clinically in 1941.

In 1940’s Waksman and colleagues discovered Actinomycetes as source of antibiotics and discovered streptomycin in 1944.

Classification

Based on chemical structure

Sulfonamides and related drugs : Sulfones – Dapsone (DDS) Para amino salicylic acid (PAS)

Diaminopyrimidines Trimethoprim, pyrithamine

Quinolones Nalidixic acid, Norfloxacin, Ciprofloxacin etc

- lactam antibiotics Penicillins, cephalosporins, monobactams, carbapenems

Tetracyclines Oxytetracycline, Doxycycline etc

Nitrobenenzene Derivative Chloramphenicol

Aminoglycosides Streptomycin Gentamycin, Neomycin etc

Macrolide antibiotics Erythromycin, Roxithromycin, Azithromycin etc

Polypeptide antibiotics Polymyxin – B, colistin, Bacitracin, Tyrothricin

etc

Glycopeptides Vancomycin, Teicoplamin

Oxazolidinase Linezolid

Nitrofuran derivatives Nitrofurantoin, Furazolidine

Nitroimidazoles Metronidazole, Tinidazole

Polyene antibiotics Nystatin, Amphotericin – B, Hamycin

Azole derivatives Miconazole, clotrimazole, ketoconazole,

fluconazole

BASED ON THE MECHANISM OF ACTION

Inhibit cell wall synthesis

Cephalosporins, cycloserine, penicillin, vancomycin, Bacitracin.

Cause leakage from cell membranes Polypeptides – Polymyxins, colistin, Bacitracin Polyenes – Amphotericin B, Nystatin

Inhibit protein synthesis Tetracyclines, chloramphenicol, Erythromycin,

Clindamycin, Linezolid

Cause misleading of m-RNA code and affect permeability Aminoglycosides – Streptomycin,

Gentamycin etc

Inhibit DNA gyrase Fluroquinolones – Ciprofloxacin

Interfere with DNA function Rifampicin, Metronidazole

Interfere with DNA synthesis Idoxuridine, Acyclovir, Zidovudine

Interfere with intermediary metabolism Sulfonamides, sulfones,Trimethoprim,

Pyrimethamine, Ethambutol

Spectrum of activity

NARROW SPECTRUM PENCILLIN G STREPTOMYCIN

ERYTHROMYCIN

BROAD SPECTRUM: TETRACYCLINE CHLORAMPHENICOL CEPHALOSPORIN

Extended spectrum Semi synthetic Penicillins,

new cephalosporins, aminoglycoside

Based on type of organism against which the drug is primarily active against:

Anti bacterial- Penicillins, Aminoglycosides, erythromycin etc

Antiviral-Idoxuridine, Acyclovir, Amantadine, Zidovudine etc

Anti fungal - Griseofulvin, amphotericin B, ketoconazole etc

Antiprotozoal Chloroquine, pyrimethamine, metronidazole etc Antihelminthic Mebendazole, nicosamide, diethyl carbamazine etc

Type of action

Bactericidal Vancomycin Aminoglycosides Metronidazole Pencillin Cephalosporin Flouroqunolones Imipenem

Bacteriostatic[acts by inhibiting protein synthesis]

Clindamycin Clarithromycin Erythromycin Tetracycline Azithromycin Sulfa

BacteriocidalADVANTAGES1.Less reliance on host resistance2.Killing of bacteria by antibiotic itself3.Faster results4.Geater flexliblity with dosage

Source Fungi: penicillin, cephalosporin. Bacteria: polymyxin, bacitracin. Actinomycetes: aminoglycosides,

macrolides, tetracyclines chloramphenicol.

PRINCIPLES FOR CHOOSING ANTIBIOTICS

Identification of causative organismDetermination of antibiotics sensitivityUse of narrow spectrum antibiotics Least toxic antibioticsPatient drug historyUse of bactericidal rather than

bacteriostaticCost of antibioticsEncourage patient compliance

PRINCIPLES OF ANTIBIOTIC ADMINISTRATION

Proper dose Proper time interval Proper route of administration Consistency of route of administration Combination of antibiotic therapy

Rapidly progressive swelling Diffuse swelling Compromised host defenses Involvement of facial spaces Severe pericoronitis Osteomyelitis

Indications for use of antibiotics

Chronic well localized abscess

Minor vestibular abscess

Dry socket

Mild pericoronitis

Use of antibiotics is not necessary

Beta-Lactum Antibiotics

These are so called because they have beta lactum ring in their chemical structure.

The two major groups are penicillins and cepahalosporins.

Introduction

PENCILLIN

Penicillin was the first used clinically in 1941.

Penicillins constitute one of the major important group of antibiotics and presently the drug of choice for a large number of infectious diseases.

Originally it was obtained from the fungus penicillinium notatum, but the present source is a high yielding mutant of penicillinium chrysogenum

Mechanism of Actions of Penicillins and Cephalosporins

The cell walls of bacteria are essential for their normal growth and development.

Peptidoglycan is a component of cell wall. That provides rigid mechanical stability by its highly cross linked latticework structure.

The last step in the synthesis of peptidoglycan is inhibited by the beta lactum antibiotics and glycopeptide antibiotics such as vancomycin

Classification of Penicillins I. Natural penicillins

A. Penicillin G (benzyl penicillin)B. Procaine penicillin GC. Benzathine penicillin G

II. Acid resistant penicillinsA. Phenoxy methyl penicillin (penicillin V)B. Phenoxy ethyl penicillin (phenithicillin)

III. Penicillinase resistant penicillinsA. Acid labile - Methicillin,CloxacillinB. Acid resistant - Flucloxacillin

IV. Penicillins effective against Gram positive and some Gram negative organisms.

- Ampicillin, Amoxicillin

V. Extended spetrum penicillinsA.Carboxy penicillins

- Carbenicillin

B. Ureido penicillins -Pipericillin

VI. betalactamse inhibtiors

- -Clavulanic acid -Sulbactum

Antimicrobial activity.

Penicillin G (benzyl penicillin) and penicllin V (phenoxymethyl derivative ) are active against sensitive strains of gram +ve cocci.

Both are readily hydrolyzed by penicillinase and thus ineffective against most strains of S.aureus.

Natural Penicillin:Penicllin G and Penicllin V

USES Pneumococcal infections such as pneumococcal

pneumonia, pneumococcal meningitis. Streptococcal infections such as streptocaccal

pharyngitis ,streptococcal pneumonia, arthritis, meninigtis, endocarditis.

Infections with anaerobes. Staphylococcus infections. Meningococcal infections . Gonococcal infections. Syphilis . Actinomycosis . Diphtheria . Anthrax.

These are resistant to hydrolysis by staphylococcal penicillinase

Use should be restricted to treatment of infections caused by staphylococci

These are much less active against other penicillin sensitive microorganisms

Penicillinase Resistant Penicillins

These includes Ampicillin , Amoxicillin.

They are bactericidal for both gram positive and gram negative bacteria.

The Aminopenicillins

AMPICILLIN Stable in acid and well absorbed after

oral adminstration.

Peak concentrations 2hrs for oral dose and 1hr for I.M injections respectively.

Half life time is approximately 80 minutes.

AMOXICILLIN Is close congener of ampicillin and is a

penicillinase suceptible semisynthetic penicillin.

Stable in acid and designed for oral use , since it is more rapidly and completely absorbed from GIT than apmicillin.

Peak concentrations more compared to ampicillin and is achieved at 2 hrs after administration.

Upper respiratory infections –sinusitis, otiits media, acute excerbations of chronic bronchitis, epigottitis.

Urinary tract infections – caused by enterobacteriaceae.

Acute bacterial meningtitis.

Salmonella infections- high doses of ampicillin is found to be effective.

Therapeutic Uses for the Aminopenicillins

Antipseudomonal-Extended Spectrum P Carboxypenicillins,Ureidopenicillin

The carboxypenicillins, carbenicillin and ticarcillin are active against some isolates of pseudomonas aerugenosa and proteus species which are resistant to ampicillin and its congeners.

Ureidopenicillins, mezlocillin and piperacillin have superior activity against P.aeurogenosa compared to carboxypenicillins.

Both Carboxypenicillins and Ureidopenicillins are sensitive to beta lactamases.

ADVERSE EFFECTS

Hypersensitivity reactions. Most common adverse effects seen with

penicillins Penicillins are the most common agents for

the cause of drug allergy.

Manifestations of drug allergy includes Maculo papular rashes Urticarial rashes Fever Brochospasm Serum sickness Exfoliative dermatitis Anaphylaxis

Hypersensitivity reactions may occur with any dosage form of penicillin.

May occur in the absence of a previous known exposure to the drug.

Acute Anaphylactic reactions are the most important immediate danger concerned with use of penicillins

Anaphylactic reactions may occur at any age and most often followed by injection of penicillin.

Most dramatic instances includes sudden, severe hypotension, rapid death.

In other instances it is characterized by brochoconstriction with severe asthma, abdominal pain, nausea and vomiting , extreme weakness and fall in blood pressure, or diarrhea and purpuric skin eruptions

OTHER EFFECTS Toxic effects such as bone marrow

depression and hepatiits are also involved.

Defect in Hemostasis due to impaired platelet aggregation seen with administrations of penicllin G, carbenicillin, pipracillin, and ticarcillin.

Oral use of penicillins changes the composition of microflora by eliminating sensitive microorganisms and its reestablished once therapy is stopped.

CEPHALOSPORINS Are group of semisynthetic antibiotics

derived from cephalosporin-c obatained from a fungus cephalosporin acremonium.

Cephalosporins are bactericidal and inhibit cell wall synthesis in a manner similar to that of penicillins.

Mechanism of bacterial resistance to cephalosporins is similar to penicillins and most common is by hydrolysis of beta lactum ring by beta lactamase.

CLASSIFICATION

Based on the chronological sequence of development , overall antibacterial spectrum as well as the potency, they classified as:

First generation Second generation

Third generation

Fourth generation

First Generation

ORAL PARENTRAL

Cephalothin Cefazolin

CephalexinCephlaradineCefadroxil

Second Generation

Oral

CefaclorCefuroxime axetil

Parentral

Cefuroxime Cefoxitin

Third Generation

Oral Parental

Cefotaxime Ceftizoxime Ceftriaxone Cefperazone

Cefexime Cefdinir Cefbuten

Fourth Generation

Parental Cefipime

Cefpirome

Adverse Effects Pain after IM injections.

Thrombophlebitis can occur with I.V injections.

Diarrhoea

Hypersensitivity reactions, rashes are more frequent manifestations

Uses I generation drugs – excellent for skin and

soft tissue infections .

The oral II generation drugs are used to treat respiratory tract infections.

The III geneartion drugs are used to treat serious infections caused by enterobacter, proteus, hemophilus species.

Cefotaxime used to treat meningitis .

Tetracyclines

Chloramphenicol

Macrolides

Also known as protein synthesis inhibitors.

Broad Spectrum Antibiotics

Primarily bacteriostatic.

Inhibits bacterial protein synthesis by binding to the 30 S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor site on the mRNA- ribosome complex.

As result peptide chain fails to grow.

The drug enters the gram –ve bacteria by passive diffusion through porin channels (doxycycline and minocycline) and by active transport by an energy dependent system which concentrates tetracyclines intracellularly.

Tetracyclines-Mechanism of Action

Bacterial Resistance Decreased accumulation of tetracycline:

as result of either decreased antibiotic influx or acquisition of an energy dependent efflux pathway.

Decreased access of tetracycline to the ribosome :because of presence of ribosome protection proteins.

Enzymatic inactivation of tetracyclines.

Uses Rickettsial infections.

Mycoplasma infections .

Chlamydiae infections.

STDs .

Acne.

Adverse Effects Irritative effects.

Epigastric pain, nausea, vomiting, and diarrhoea. I.M injections are painful. Thrombophlebitis of injected vein can occur.

Hepatic toxicity. Tetracycline can precipitate acute

hepatic necrosis in pregnant women. Renal toxicity

Phototoxicity.

Effects on Teeth and Bones.

Long or short time therapy with tetracyclines develops brown discoloration of teeth.

Discoloration is permanent.

Duration is less important than the quantity of antibiotic administered.

Pigmentation of the permanent dentition occurs when the drug is given at the ages of 2 months to 5years when the teeth are bieng calcified.

The deposition of drug in the teeth and bones is due to its chelating property and the formation of a tetracycline – calcium orthophospate complex.

Tetracyclines are edveloped in skeleton during gestation and throughout childhood which results in depression of bone growth.

Oxytetracycline. TERRAMYCIN- 250, 500 mg cap, 50 mg/ml in 10 ml

vials. 3% skin ointment , 1% eye /ear ointment.

Tetracycline. ACHROMYCIN, HOSTACYCLINE, RESTICLIN - 250, 500

mg cap. 3% skin oint, 1% eye/eardrops and oint.

Domeclocycline. (Di methyl chlor tetracycline) LEDEROMYCIN – 150, 300 mg cap /tab.

Doxycycline. TETRADOX,DOX T, NOVODOX, DOXY-DE, CEEDOX –

100 , 200 mg tabs.

Minoxycline. CYANOMYCIN – 50, 100 mg caps.

Preparation and Dosage

History and Source.

- Produced from streptomycin venezuelae an oraganism first isolated in 1947 from a soil sample collected in Venezuela.

- Now available synthetically.

Chemistry.

It is a unique among natural compounds and contains a nitrobenzene moiety which is responsible for microbial activity.

Chloramphenicol

Mechanism of Action.

Acts by interfering with synthesis of bacterial proteins by inhibiting 50 S ribosomal subunits.

Bacterial Resistance.

Is caused by a plasmid encoded acetyl transferase that inactivates the drug and leads to failing of binding of drug to the bacterial ribosome.

Uses Typhoid fever .

Bacterial meningitis .

Rickettsial diseases- as an alternative to Tetracyclines in case of allergic reactions.

Adverse Effects Hematological toxicity. Hypersensitivity Reactions. Local Irritant Effects

Preparation and Dose Dosage -250, 500 mg cap 6 hrly. Children 25, 50 mg

/kg/ day.

CHLOROMYCETIN, ENTEROMYCETIN, PARXIN – 250, 500 cap, 1% eye oint, 0.5 %eye drops, 5% ear drops, 1% appli caps.

Chloramphenicol palmitate CHLOROMYCETIN PALMITATE– 125 mg/ ml oral susp.

Chloramphenicol succinate CHLOROMYCETEIN SUCCINATE, KEMICETINE - 1 gm/

vial inj.

VAMYCTETIN - 0.4% eye drops, 250 mg opticaps, LYKACETIN 1% skin cream, 10 % Otic solution.

Macrolides These are antibiotics having a large

lactone ring attached with one or more deoxy sugars. Hence the name macrolides.

Includes Erythromycin, Clarithromycin and Azithromycin.

Erythromycin was discovered in 1952 and obtained from streptomyces erythreus.

Clarithromycin and Azithromycin are semisynthetic derivatives of erythromycin.

Mechanism of Action They are bacteriostatic agents that inhibit

protein synthesis by binding reversibly to 50s ribosomal subunits of sensitive microorganisms.

Erythromycin appears to inhibit the translocation step where in a newly synthesized peptidyl tRNA molecule moves from the acceptor site on the ribosome to the peptidyl site.

Alternatively, macrolides may bind and cause a conformational change that terminates protein synthesis by indirectly interfering with tranpeptidases and translocation.

Uses Mycoplasma pneumoniae infections Diptheria Pertussis Streptococcal infections Staphylococcal infections Helicobactor pylori infection Tetanus Syphilis As prohylactic use in penicillin allergic patients in

treating rheumatic fevr , prevention of bacterail endocarditis

Adverse Effects Serious adverse effects are uncommon.

Allergic reactions include fever, eosinophilia, urticaria, dermatitis, and lymphadenopathy.

Transient auditory impairment is a potential complication associated with erythromycin in larger doses.

Preparation and Dose Erythromycin

250 – 500 mg , 6 hrly ( max 4 gm /day), children 30/60 mg/ kg / day .

Erythromycin base ERYSAFE 250 mg tabs, EROMED 333 mg tab , 125

/5ml susp.

Erythromycin stearate ALTHROCIN 250, 500 mg tab, 125mg kid tab,

125mg/5ml susp.and 250 mg / 5ml dry syrup, 100mg / ml ped drops.

Erythromycin ethyl succinate ERYTHROCIN 100mg/ ml drops, 125 mg/ 5ml syrup.

Gery ointment 30 % ointment for topical application in treating

boils, carbuncles, skin infections.

Clarithromycin – 250 mg BD for 7 days ; severe cases 500mg BD upto 14 days CLARIBID 250, 500 mg tab, 250 mg / 5ml dry

syrup. CLARIMAC 250, 500 mg tabs.

Azithromycin – 500 mg once daily ( children above 6 months 10 mg/kg ) for 3 days . AZITHRAL 250 , 500 mg cap and 250 mg per 5

ml dry surup, 500mg inj.

Roxithromycin

Semisynthetic , long acting stable macrolide.

More potent.

Good absorption, tissue penetration, better tolerability .

Newer Macrolide

Metronidazole

Metronidazole is an antibiotic that acts on anaerobes.

Indications; Trichomonal vaginitis surgical and gynaecological sepsis pseudomembranous colitis Anaerobic bacterial infections Entamoeba histolytica infections Ulcerative gimgivitis

Side-effects: nausea, vomiting and gastrointestinal disturbances drowsiness headaches rashes leucopenia darkens urine peripheral neuropathy with prolonged treatment dizziness

metronidazole and alcohol;A disulfiram like reaction occurs when consuming

alcohol and the patient may complain of symptoms such as facial flushing, throbbing headache and palpitations.

A patient taking metronidazole orally should abstain from drinking alcohol while taking metronidazole and for 48 hours after stopping it.

Dose;

Anaerobic infections (usually treated for 7 days) Orally , either 800mg initially then 400mg 8-

hourly or 500mg 8-hourly By rectum, 1g 8-hourly for 3 days, then 1g

every 12 hours

• Child: -any route, 7.5mg/kg 8-hourly

Acute ulcerative gingivitis: -Orally, 200-250 mg 8-hourly for 3 days

• Child:

--1-3 years 50 mg 8-hourly for 3 days

-3-7 years 100 mg twice daily -7-10 years 100 mg 8-hourly

Acute dental infections: -Orally, 200 mg 8-hourly for 7 days

FLAGYL, METROGYL, METRON, 400 mg tab, 200 mg /100 ml susp. 500 mg/ 100 ml I.V Infusion.

PROPHALAXIS Antibiotic prophylaxis is recommended for the

following:

High-risk category ;

Prosthetic cardiac valves, including bioprosthetic and homograft valves 

Previous bacterial endocarditis 

Complex cyanotic congenital heart disease (e.g., single ventricle states, transposition of the great arteries, tetralogy of Fallot) 

Surgically constructed systemic pulmonary shunts or

conduits

Moderate-risk category:

Most other congenital cardiac malformations

Acquired valvar dysfunction (eg, rheumatic heart disease) 

Hypertrophic cardiomyopathy 

Mitral valve prolapse with valvular regurgitation

Low/negligible risk category:

Surgical repair of atrial septal defect, ventricular septal defect

Previous coronary artery bypass graft surgery 

Mitral valve prolapse without valvar regurgitation  

Previous rheumatic fever without valvar dysfunction

Cardiac pacemakers (intravascular and epicardial) and implanted defibrillators

ANTIBIOTICS IN ORAL & MAXILLOFACIAL SURGERY

Earlier penicillin was the drug of choice, especially for infections above the diaphragm.

Susceptibility of the anaerobic isolates were least to erythromycin.

Chloramphenicol: against anaerobic infections

Clindamycin against periodontal pathogens. (anaerobic G-ve).

cefotaxime: aerobes and facultative anerobes.

Metronidazole: good and cheap drug effective against anaerobic periodontal pathogens.

The antibiotics in oral surgery are mainly used for two purposes.

1. Antibiotic prophylaxis to prevent infections.

2. Antibiotics in treatment of infections.

The prophylactic antibiotics a) Reducing the number of bacteria in the surgical wound

b) Enhancing the host defenses so as to prevent the bacteria that inevitably enter the wound from causing clinically evident infection.

Risk of infection Wound contamination Age of patient Nature of underlying disease Presence of necrotic tissue and a

decreased blood supply.

Classification of surgical wounds CLASS-1: clean surgical wounds infection rate

is 2%.

CLASS-2: clean contaminated surgical wounds communication with oral cavity

Class -3: contaminated surgical wounds, fresh

traumatic injuries involving oral cavity. 20-30% infection chances.

Class -4: dirty wounds , may be of traumatic origin and contain devitalized tissues.

Selection of antibiotic must be effective against the bacteria that are

most likely to cause infection following surgical procedure.

Streptococci, Aerobic gram+ve cocci and aerobic gram –ve rods are commonly contaminating organisms of wounds in oral and maxillofacial surgery. The infections by anaerobic bacteria are also considered. When the skin is involved, the presence of staphylococcus aureus and epidermidis also considered.

least toxic agent. bactericidal, nonallergic, and capable of

achieving therapeutic tissue concentrations and have a long half-life so that redosing generally not required during the procedure.

Proper administration of antibioticspreoperative prophylactic -given twice the

usual therapeutic dose for an antibiotic to maximally effective.

Correct time of administration –for the drug to be maximally effective

Intravenously/ intramuscularly 30 minute before the placement of incision at twice the therapeutic dose

Use the shortest effective antibioticAntibiotics that have little or no toxicity like

Penicillin, and cephalosporins are used

For transcutaneous procedures a first generation cephalosporins - cefazolin, -effective against most staphylococci.

Patient if has non-anaphylactic reactions to penicillin, a first generation cephalosporin indicated.

patients who had an anaphylactoid reaction to penicillin, clindamycin is often recommended as the third choice.

Specific application of antibiotic use in Oral and Maxillofacial surgery

Dentoalveolar surgery

Prophylactic antibiotics are indicated in following scenario:

1. Involvement of maxillary sinus or nasal cavity, 2. Host defense mechanism is compromised, 3. Patient who have received organ transplants

may be on long-term immunosuppressive therapy

4. patients receiving chemotherapy for cancer -preventive antibiotic coverage.

5. uncontrolled diabetes mellitus

Impacted third molar surgery The infections after third molar removal

are relatively uncommon

The postoperative infections include alveolar osteitis and facial space infections. In these conditions however, antibiotics are given postoperatively.

Preoperatively does not cause significant reduction in problems. In these cases it should be given before surgery and for 3 to 5 days after surgery to provide an adequate period of coverage.

Orthognathic surgery Orthognathic surgery performed via an

extra oral approach is considered a clean procedure and prophylactic antibiotic should not be necessary unless communication with the mouth is anticipated

Intraoral procedures and surgeries that involve maxillary sinus and nasal passage are clean contaminated wounds and short-term antibiotics have been shown to reduce the postoperative infection rates

Maxillofacial fractures

In patients with compound fractures of the facial skeleton antibiotics are necessary to prevent infection at fracture sites

Patients with traumatic injuries that involve the oral mucosa, gingiva/ tongue do not require prophylactic antibiotics because such wounds, although contaminated, generally heal without infections.

Guidelines for administration

Administer immediatelyAdminister IVDose of drug should be doubled

than normalDiscontinue antibiotics at the end

surgery unless persistent contamination

Choose antibiotic depending on the basis of potential infectious organism.

Indications for prophylaxis in trauma

When wound enters joint space or when associated with open fracture

Heavy contamination Debridement is inadequate/ delayed Burns Prone for clostridial infection

BURNS During 1st week wound is usually colonized B hemolytic streptococci staph aureus & aerobic g –ve enteric flora

colonize. Ps. Aeruginosa, clostridia also become evident.

Choice of antibiotic must be on considerations regarding infectious organism, pattern of sensitivity, status of pt.

1% silver sulfadiazine has been used as topical antibacterial

Major head and neck surgery

Transoral preprosthetic surgery craniofacial surgery tumor surgery with clean contaminated have

been demonstrated that the use of short-term peri-operative antibiotics demonstrated to be effective in preventing postoperative wound infections.

IMPLANT SURGERYAlthough incidence of infection

seems to be low when most surgeons have used antibiotics regimen.

Studies showed that infectious complications were reduced to almost by 50% with pre operative & post operative and also with intaoperative use of chlorhexidine mouthwash.

Antibiotic in head and neck infections

The infections can be 1. odontogenic 2. the sinus infections3. osteomyelitis 4. fungal infections. Odontogenic infections are the most

commonly occurring infectious process

Principles of managing odontogenic infections

1. Determine severity of infection2. Evaluate the host defenses noting any

disease states/ medications, which could adversely affect the host.

3. Drainage4. Prescribing antibiotics of proper dosage

regimen and duration of therapy.5. Consider culturing and susceptibility

testing in case of treatment failure

The increase in penicillin resistance and failure of penicillin therapy:

Clindamycin as the emperic antibiotic of choice.

A loading dose of 600mg may be administered approximately 1 hour before the surgical therapy begins, followed by 300mg every 6hours for the duration of infection.

Penicillin V remains the antibiotic of choice for out patient odontogenic infections.

A loading dose of Penicillin V 2gm approximately 1 hour before the beginning of surgical therapy followed by 500mg every 6 hours prescribed.

If within 48 hours the patient is not responding to penicillin, one could consider adding Metronidazole. It is prescribed in a 500mg dose every 8 hours.

Sinus infections If the incidence of strept. pneumonia is

more than 30%, amoxicillin and clavulinic acid/

second-generation cephalosporin is prescribed for 2 weeks.

Recent studies show that penicillin/ amoxicillin alone is as effective as other broad spectrum and expensive antibiotics.

Osteomyelitis of the jaws Odontogenic pathogens. Actinomyces are another prominent pathogen

in chronic osteomyelitis. Recommended regimen: 1st choice: PENCILLIN AQUEOUS PEN-2 mu IV every 4th hrly OXACILLIN- 1gm IV every 4th hrlyAfter 48-72 hrs, PEN V 500mg 4hrly + CLOX

250mg 4hrly orally for 2- 4 wks

2nd choice: CLINDAMYCIN 300- 600mg 6 hrly po 3rd choice: CEFAZOLIN/ CEPHALEXIN 500mg 6 – 8 hourly 4th choice: ERYTHROMYCIN 2g 6 hourly iv then 500mg

every 6 hrly orally. The dose & duration of AMA dependent on

severity of infection & response

Recently systems that deliver a high concentration of antibiotic locally at the site of osteomyelitis have been developed

These system employs usually gentamicin which is then implanted

Factors affecting selection of antibiotic

Common pathogen FACULTATIVE STREPTOCOCCI (3%) AND ORAL

ANAEROBES [PEPTOSTREPTOCOCCI AND MEMBERS OF THE GENERA PREVOTELA AND PORPHYROMONAS (25%) PREDOMINATES.]

Penicillin sensitive streptococci predominate during the first 3 days of clinical symptoms and the more resistant gm-ve and +ve obligate anaerobes appear in significant number there after.

The fluoroquinolones have become the antibiotic of choice for the infections caused by Eikenella corrodens .

Allergy/intolerance/ adverse drug reactions

The history of allergy obtained from the patient/ from the patients family

The choice of clindamycin, metronidazole/ newer antibiotics should be considered

The newer B-lactam antibiotics, the monobactams and carbepenems, have much less frequent cross sensitivity with the penicillin group.

Immune system compromise

Whenever possible in immune compromised patients, a bactericidal rather than bacteriostatic antibiotic

In head and neck infections B-lymphocytes is largely responsible for combating extra cellular

bacterial pathogen

Tissue distribution of antibiotics

Best penetrates abscess cavity - CLINDAMYCIN -33% of serum level

accumulate in bone -- TETRACYCLINE'S, CLINDAMYCIN, and FLUOROQUINOLONES.

CSF penetration/ the ability of bacteria to cross blood brain barrier CNS infections

Penicillin G in high doses reaches 5% to 10% of the serum concentration in the cSF when meninges are inflamed

the addition of metronidazole (30%- 100% penetration), ampicillin (13%- 14%penetration) is more efficacious than using penicillin G alone.

Antibiotics in pregnancy penicillin’s, cephalosporins, erythromycin, and

clindamycin cross the placenta have therapeutic effects on the fetus as well as the mother and are not associated with congenital defects

Amino glycosides fetal toxicity and nephrotoxicity.

Tetracycline if given after 5 months of gestation -permanent discoloration of fetal teeth, maternal liver toxicity, & congenital defects

Sulfonamides when administered in 3rd trimester /close to delivery persists in blood for 2 to 3 days after birth and are associated with jaundice, hemolytic anemia, and kernicterus in new born.

Adjuvant therapy Mouth wash Rexidine BetadineMultivitamin tabletsIncision & drainage in case of abcess

References

ESSENTIALS OF MEDICAL PHARMACOLOGY- TRIPATHI 5 EDITION

GOODMAN AND GILMAN-PHARMACOLOGICAL BASIS OF THERAPEUTICS

ORAL & MAXILLOFACIAL TRAUMA- VOL. 1 & 2 R J FONSECA, R V WALKER, N J BETTS, H D BARBER ORAL AND MAXILLOFACIAL INFECTIONS RICHARD G

TOPAZIAN-4TH EDITION TEXTBOOK OF OMFS- NEELIMA A MALIK

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