Antibiotics used in dentistry

							DEFINATION
 Antibiotics are chemical substance

elaborated by various species of microorganism such as fungi, actinomycetes and bacteria. They suppress the growth of other micro-organism and may ultimately destroy them in low concentration.

Early history
 3500 BC the Sumerian doctors would give patients

beer soup mixed with snakeskins and turtle shells.  Babylonian doctors would heal the eyes by using an ointment made of frog bile and sour milk.  The Greeks used many herbs to heal ailments.  All of these "natural" treatments contained some sort of antibiotic.

Modern history
 Louis Pasteur was one of the first recognized physicians

who observed that bacteria could be used to kill other bacteria.  In 1929 Sir Alexander Fleming a Scottish bacteriologist, went on a vaction and left a petri dish of staphylococci bacteria uncovered. When he returned, he noticed that there was mold growing on it. Upon further examination, he saw that the area around the mold had no bacteria growing. He named the mold Penicillium, and the chemical produced by the mold was named penicillin, which is the first substance recognized as an antibiotic.

 Almost immediately after penicillin was introduced,

resistance in certain strains of staphylococci was noticed.  In 1935, Domagkdiscovers synthetic antimicrobial chemicals (sulfonamides).  During World War II, because of need for antibiotic agents, penicillin was isolated and further tested by injection into animals. It was found to be extremely useful in curing infections, and to have extremely low toxicity to the animals. Because of these findings, use of penicillin greatly increased. This also spurred a search of other chemical agents of similar use.

 the late 1940's through the early 1950's, streptomycin,

chloramphenicol, and tetracycline were discovered and introduced as antibiotics.  In 1953, during a Shigella outbreak in Japan, a certain strain of dysentery bacillus was found to be resistant to chloramphenicol, tetracycline, streptomycin, and the sulfanilamides.  By the 1950's it was apparant that tuberculosis bacteria was rapidly developing resistance to streptomycin, which had commonly been used to treat it.

Classification of antibiotics
Classification based on chemical structure & proposed mechanism of actions as fallows 1. Agents that inhibits synthesis of bacterial cell wall these includes a) penicillin & cephalosporin which are structurally simillar b) Cycloserine vancomycin bacitracine & the azole antifungal agent ( e.g clotrimazole, fluconazole & itraconazole which are structurally dissimilar agent

2.Agent that act directly on the cell membrane of the micro organism affecting permeablity & leading to leakage of intercelluar compound e.G polymyxin & polyene antifungal agent nystatin Amphotericin B which bind to cell wall sterolls

3 .Agent that affect the function of 30 s or 50 s ribosomal subunit to cause or reversible inhibition of protein synthesis e.G chloramphenical Tetracycline Erythromycin Clindamycin

4 .agent that bind to 30s ribosomal subunit &alter protein synthesis which eventually lead to cell death E.g. aminoglycosides

5.agent that affect bacterial nucleic acid metabolism such as rifamycin (e.g. rifampin ) which inhibit RNA polymerase & the quinilones which inhibit topoisomerase

6 . agent that block essential enzymes of folate metabolisum
E.g. trimethoprim& sulfonamide

7 . Antiviral agent which are of several classes including
Nuclic acid analog such as acyclovir or gancyclovir that selectively inhibit viral DNA polymerase and zidovidine which inhibit reverse transcriptase b) Non nucleoside reverse transcriptase inhibitors such as nevirapine c) Inhibitor of other essential viral enzyme. E.g. inhibitors of HIV protease or influenza neuraminidase
a)

classification
 According to spectra

1.Antibiotic effective against gram positive bacteria a.For systemic infection, erythromycin, lincomycin, novobiocin. b. Those employed topically e.g. bacitracin 2.Antibiotic mainly against gram negative bacteria a.For sylstemic infection e.g. strepomycin & other aminoglycosides b.Those used locally in intestine e.g.paromomycin

3.Antibiotic mainly effective against gram –ve & +ve bacteria a.Used for systemic infection e.g. ampicillin, amoxycillin, cephalosporin b.For topical application e.g. neomycin 4. Effective against rickettsial & chlamydia e.g. tetracycline & chloramphenicol 5.Effective against acid fast bacilli e.g. steptomycin, rifampicin & viomycin

6.Effective against protozoa e.g. paramomycin & tetracyclin 7.Effective against fungi e.g.nystatine, amphotericin B 8.Effective against malignancy e.g. actinomycin, mitomycin

 Following are the points by which the clinician can

make a decision of when to use antibiotic, which are to select, and how to use both therapeutic and prophylactic situations. To do this one should atleast know about the following 1. Bacterial flora causing most odontogenic infections 2. The basic mechanism of host defenses 3. The variety of contemporary antibiotics and principles to choose

Bacterial flora causing most odontogenic infections
 The indigenous microbial flora of the mouth is

bacteria, which are almost always the cause of odontogenic infections. The usual flora is both aerobes and anaerobes

The basic mechanism of host defenses
 Host defense mechanism is the most important factor in

the final outcome of a bacterial insult.Each patient has many defenses against infections. 1. Physiologic depression of host defence, Shock Disturbances of circulation caused by advanced age Obesity Fluid imbalance 2. Diseases and disease state that may inhibit host defense Malnutrition syndrome Patient with cancer and leukemia Poorly controlled diabetics

 3 Congenital defect which causes defective host

mechanism Agammaglobulinemia Multiple myeloma Total body radiation therapy Children who have had splenectomy  4. Therapeutic drugs that impares host defense mechanism Cytotoxic drugs Immunosuppressive drugs

principles to choose Antibiotics
 Once the decision has been made to use antibiotics as

an adjunct to treating infection the antibiotics should be properly selected. The followingguide lines are useful 1. Identification of causative organism 2. Determination of antibiotic sensitivity 3. Choice of antibiotics

1. Identification of causative organism Causative organism can be isolated from pus blood, or tissue fluids. Based upon the knowledge of pathogenesis and clinical presentation of specific infection,antibiotic therapy will be either initial or definitive depending upon whether or not the organism is diagnosed previously.

2. Determination of antibiotic sensitivity When treating an infection that has not responded to initial antibiotic therapy or when treating a postoperative wound ,the causative agent must be previously identified and the antibiotic sensitivity must also be determined.

3 Choice of antibiotics Upon receipt of the culture and sensitivity report, there may be a choice of four or five antibiotics. Selection should be based on consideration of several factors like 1. Patients previous history of allergy 2. Antibiotics with narrow spectrum 3. Drug that cause fewest adverse reactions. 4. Drug which is least toxic 5. The well established still effective antibiotics 6. Bactericidal rather than bacteriostatic drug 7. The less expensive still effective antibotic 8. Combination antibiotics

 1. Patient`s history of allergy

Allergic reaction to drugs should be considered first. When it exists, alternative drugs must be used. Example erythromycin or clindamycin is usually use if the patient is allergic to penicillin

 2. Antibiotics with narrow spectrum

The only majour indication for use of broad spectrum antibiotics coverage is in severe life threatening infection where identification of causative agent is obsure. Each time bacteria are exposed to antibiotics, the opportunity for development of resistant strains is present. If narrow spectrum antibiotics is used ,fewer organisms have the opportunity to become resistant.

 3. Drug that cause fewest adverse reactions

The goal of antibiotic therapy is to provide an effective Drug that causes least problem to the patient  4. Drug which is least toxic Toxicity reactions are those that occur as a result of excessive dose or duration of therapy, but can occur in individual patients with normal doses.

 5. The well established still effective antibiotics

Since its initial availability, penicillin, has been used for oral infection and it has been very effective, with low incidence of adverse reaction. Newer antibiotics should be used only when they have proved advantage over the older ones .

 6. Bactericidal rather than bacteriostatic drug

Bactericidal drugs are effective during the log phase of bacterial growth the time . If growth is slowed or brought to stop,cidal drugs have a greately diminished effect. As a result, in these situations, when combination drug therapy is to be used,cidal and static combination should not be used in combination.

 7. The less expensive still effective antibotic

Most effective but less expensive drug should be considered first.  8. Combination antibiotics There are situations in which the use of antibiotic combination is clearly indicated. Example is when it is necessary to increase the antibacterial spectrum in patients with life threatening sepsis of unknown cause.

Bacterial resistance to antibiotic
1. When the drug does not reach it’s target 2. The drug is not active 3. Target is altered.

Selection of antibiotics
 When an antibiotic is indicated the goal is to

choose a drug that is selectivley active for the most likely infecting micro-org.& that has least potential to cause toxicity or allergic reaction in individual being treated.  Antibiotic are used in three general ways  as empirical therapy  as definative therapy  As prophylactic or preventive therapy

Pharamacokinetic factor that affect the selection of antibiotic
 Location of the infection  access of antibiotic to sites of infection

e.g. if the infection in the CSF the drug must pass the blood brain barrier

Host factors
 Host factor for the selection of antibiotics

1. Host defense mechanisms
a. action in the immunocompetant host can be cure mearly by halting multiplication of micro organism { bacteriostatic effect} b. if host defense are impaired bacteriostatic activity may be inadequate and a berteriocidal agent may be required for cure

e.g. pt with bacterial endocarditis pt with AIDS

Local factors
 Antimicrobial activity may be significantly

reduces in pus  Large accumulation of Hb in infected hematomous cab bind penecillin and tetracycline & thus may reduce the effectiveness of other drug  Penetration of antibiotic into infected areas such abscess is imparied because vascular supply is reduce  Presence of the foreign bodies reduces the effectiveness of antibiotic

Genetic factors
 A no. of drug (e.g. sulfanamides,

chloramphenicol and nalidixic acid ) may produces acute hemolysis in pt with glucose 6- phosphate dehydrogenase deficiency

pregnancy
 Pregnancy may impose an increased risk of

reaction to antibiotic for both mother & fetus  Hearing loss in child with administration of streptomycin to the mother during pregnancy  Tetracycline can affect bones & teeth of fetus , may develop fatal acute fatty necrosis of liver pancreatitis & associated renal damage.

Drug allergy
 A antibiotics especially- B-lactum are

notorious or provoking allergic reaction  Sulfonamides trimethoprim nitrofurapterin and erythromycin also has been associated with hypersentitivity reaction especially rash.  Antimicrobial agent like othe drugs can caused drug fever

Therapy with combined antimicrobial agent
 Indication  Empirical therapy of severe infections in which a cause

is unknown  Treatment of polymicrobial infection  Enhancement of antibacterial activity in the treatment of specific infection.

Disadvantage of combination of antimicrobial agents
 Risk of toxicity from two or more agent  The selection of multiple drug resistance  micro organism

 Increased cost to the patient

Some commonly used antibiotics

Penicillin
It is the extract from mould

penicilium notatum Belonging to group called beta lactum antibiotics

Classification
 1. natural penicillin  E.g. penicillin g benzyl penicillin

Procaine penicillin  Benzedrine penicillin  2.acid resistant penicillin  Phenoxymethyl penicillin  3.penicillinase resistant penicillin  Methicillin  Oxacillin  cloxacilline  Flucloxacilline  nafcillin


 4.penicillin effective against gram +ve

&some gram -ve organism
Ampicillin  Amoxicillin  Talampicin


 5.extended spectram penicillin  a.carboxypenicilin  Carbenicillins  b.amidinopenicillin  Mecillinam  pivmecilliam

Mechanism of action
 Act by inhibiting cell walll synthesis in

bacteria. they prevent sythesis & crosslinkage of peptidoglycans which is the integral part of bacterial cell wall.

Antibacterial spectrum of penicillin
 Effective mainly against gram +ve & gram –

ve cocci &and some gram +ve bacilli.

Adverse effect of penicillin
 Intolerance  Thrombophlebitis  Allergy with manifestation like
 1.skin rash

 2.serum sickness like syndrome
 3.renal disturabane  4.haemopoitic disturabance  5.anaphylaxis

 Jarish herxiheimer reaction on syphilitic pt

treated with penicillin  Superinfection e.g. candida  hypermia

 Classification
 Natural penicillin

vk  Penicillinase resistance Dicloxacillin
 Nafcillin

Usual adult resgimen 250-500mg QID
250mg 6 hrly 500mg QID

Activity against oral pathogens
Gm+ve gm+ve gm–ve Arobes anarobes anarobes
+ve +ve + -ve

stap.only stap & strepto

-ve -ve

-ve -ve

 Amoxicilline  Amox/

potassium clavulanate (augmantin)  Ampicillin

250-500mg 8hrly 250-500mg 8hrly 250-500mg QID

+ve +ve

+ve +ve

-ve -ve

+ve

-ve

-ve

AMINOGLYCOSIDES
 These are group of natural & semisynthetic

drugs having polybasic amino groups & linked glycosidically to two or more amino sugars.

Mechanism of action
 The drugs combine with the bacterial

ribosomes & interfares with m-RNA ribisomes combination which ultimately prevents protien synthesis.

Absorbtion fate and excreation
 It is excreted mainly by glomerular filtration

&asmall portion in bile

spectrum
 Vibrio comma  Proteus  E-colli

 Enterobacteria
 Klebsiella  H- influenza

 This group includes drug like

Streptomycine  Gentamycine  Kanamycine


Tetracycline
 They are naphthalene derivatives  it’s nucleus is made up by the fusion of foci

partialy unsaturated cyclohexiane radius and hence named tetracycline

Mechanism of action
 Interfer with protein synthesis by blocking

the attachment of amino acyl transfer rna to acceptor site on m-RNA ribosome complex.

Absorption fate & excretion
 Tetracycline form insoluble complexes

by chelation with calcium ,magnesium & aluminium  Iron interferes with absorption excreted mainly in urine

Spectrum
 Includes both gram +ve & -ve orgamism  Dose –

orally-250-500mg TDS  Parantally- 1-2gms in two equal doses 12hrly interval.  Newer drug are Doxycycline  Demeclocycline  Methacycline  Minocycline  lymecycline


Disadvantages
 GI system

Diahrroea  Nausea  Vomiting  Suprinfection  Candida infectionis comman  Fetal hepatic disfuction  Azotemia may be agrevated to renal impairment  Chelating effect in teeth & bone


Cephalosporins
 1st generation  They are highly effective against gram +ve

but weaker against gram _ve bacteria  These are  cephalexim  Cephalethin  Cephaloridine  Cephradine  cefadroxil

Cephalexin
 Only orally active first generation cephalosporin with          

spectrum Strptococcus Staphylococci Gonococci Closridia C. diptheria Actinomyces Klebshiella Protease Salmonella shingella

Dose
 Adult – 25mg to 1gm 6 to 8 hrly.
 children – 25mg to 100mg/kg/day

Cefadroxil
 A it is close congener of cephalexim& has

good tissue penetration  B can be given 12 hrly  C spectrum is same as cephalexim  Dose 0.5gm -1gm BD.

SECOND GENARATION
 They are newer to first genaration.  They have more activity against gram –ve

organisms.  E.g. cefuroxime – it is higher activity against penicilliase producing organisms and all ampicillin resistant H-influenzae.

Other spectrum
 More active against klebsiella, E-coli,

enterobacter, indole positive protiens.  Dose – a. 0.75 – 1.5 gms/ IM or IV/9 hrly b.30- 100mg/kg/day.  Available as- supacef.

Third generation
 These were developed in end of 1980’s.  They have augmentation activity against –ve Endobactericeae.  They are resistant to β lactamase.  These are Cefotaxamine
 Ceffizoxime  Ceftriaxone

 Moxalactum
 ceftazidium

Cefotoxamine
 Potent action on gram-ve as well as gram+ve  It is not so active against anaerobic like bact. Fragillis, Staphylococcous aureus, Pseudomonas aerugemosa.  It is very important drug in teratment of

meningitis, hospital acquired diseases septicaemia and infection in immuno compromised pt.  Dose –  A.1-2gms/Imor IV/6- 12hrly  50-100mg/kg/day

 Available as  Omnatax  claforan

Ceftizaxone
 Long acing cephalosporin  One daily dose is good enough and it has good CSF penetration  Dose
 Adult - 1-2gms/IM or IV /day  Child- 75-100mg/kg/day

Ceftazidime
 Most prominent feature is high activity againt pseudomonas.  It is used in febrile pt including pt with burns.  It is less effective to staphylococcus aureus.  Dose
 Adult-0.5-2gms/IM or IV/ every 8 hours  Child- 30mg/ kg/day

Forth generation cephalosporine
 E.g. cefepime(maxipime) and cefpirome  It is new cephalosporine with properties like those of

3rd generation cephalosporine but more resistance to some beta-lactumase.  It is active against streptococci and methyciline sensetive staphylococci but not against methyciline resistance staphylococci.

Spectrum
 It’s main use is in serious gram –ve infection (H-

influenza, Neisseria- gonorrhoae and Neissera meningities) including infection of CNS inti which it has exelent penetration.  Half life is of 2hrs.  Dose -2gm I.V. every 12hrs

Fifth generation cephalosporine
 Ceftobiprole has been described as "fifth

generation",though acceptance for this terminology is not universal.  Ceftobiprole (and the soluble prodrug medocaril) are on the FDA fast-track. Ceftobiprole has powerful antipseudomonal characteristics and appears to be less susceptible to development of resistance.

 These cephems have progressed far enough to be


      

named, but have not been assigned to a particular generation. Cefaclomezine Cefaloram Cefaparol Cefcanel Cefedrolor Cefempidone Cefetrizole Cefivitril

 Cefmatilen  Cefmepidium  Cefovecin  Cefoxazole  Cefrotil

 Cefsumide
 Ceftaroline  Ceftioxide

 Cefuracetim

Adverse effect
 Pain after injection.  Diarrhoea due disturbance in Gut ecology  Hypersensitivity reaction- anaphylaxis,

angiodema, asthma, urticaria.  Nephrotoxicity  Neutropenia or thrombocytopenia  Hyperprothombinemia  A flase +ve cmbs test may occur in as many as 60%of pt or cephalathin therapy.

Macrolides
 They are antibiotics having a macrocyclic

lactone ring with attached sugars  They are bacteriostatic drug

Erythromycin
 Used as aternative in penicillin sensitive individuals  CONTRAINDICATIONS
 Hypersensiivity  Liver dieases- ester salt is avoided

 Available as –tablet & syrup  Dose ADULT- 250-500mgQID

CHILDREN-30-50mg kg/day in form of divided doses.

Adverse reaction
 Nausea

 Vomiting
 Diahrroea  Hypertention

 Cardiac arrythmias
 Revesible hearing loss  ONSET OF ACTION- 2to4hrs

Azithromycin
 This new azalide longer of erytromicin has

an expanded spectrum, hyper…, Pharmacokinetics, better tolerability and drugs interation profile however it is not effective against erythromycin resistant bacteria.

Indications
Respiratory track infection
Urenary track infection. Otitis media

Contraindications
 Hypersensitivity  Hepatic impairment

DOSE- ADULT-500mg OD for 3days OR 500mg OD on days one followed by 250mg OD for 4 days. CHILDREN- 10mg/kg/ day for 3 days OR 10mg/kg/day followed by 5mg/kg/day OD for 5day. ONSET OF ACTION- one to two hrs

Adverse effect
 Mild gastric upset  Abdominal pain  Headache

 Dizziness

Imidazoles
 Metronidazole
 Prototype netroimidazole  Active against anarobes

Mode of action
 In anarobic micro-organisms metronidazole

is converted into an active form by reduction of it’s nitro group.  This binds to DNA and prevents formation of nuclic acid.

Absoption fate and excretion
 The drug is well absorbed after oral or rectal

administration.  It is elimanated urine, partly unchanged & party metabolized

Contraindications
 Neurogenic diseases  Blood dyscrasias  first trimester of pregnancy

Uses
 Acute ulcerative gingivitis
 Dental infections  Amoebiasis  Giardiasis  Trichomoniasis

Dose
 Orally 400mg 8hrly  IV infusion 0.5gms/8hrs.  Treatment should be continue for 7 days.

Adverse effects
 Anorexia  Nausea  Metalic taste

 Headache
 Glossitis  Dryness of mouth  Thromphlebitis of injected veins

Indication for antibiotic used
A. Systemic indications 1. Congnital or acquired heart

a. Rheumatic heart disease b. Valvular diseases c. Pt with ventricular defects 2. Severe kidney diseaes a. chronic glumerulonephritis b. pt undergoing dialysis

3. Active leukemia, agranulocytosis, aplasia ,

anemia 4. Metabolic disturbances – diabetes 5. Pt on chemotherapeutic drugs 6. Pt with vascular graft

B. Maxillo- facial trauma 1.Hard tissue trauma-the consensus is that antibiotic convert should be used for any mandibular or maxillar fracture compented into mouth or paranasal sinus through mouth. 2.Soft tissue trauma 3.Orthognathic & recontructive maxillo- facial surgery. 4.Odontogenig infection 5.Pericoronities 6.Osteomylitis

contraindication
 Minor chronic localised abscess.  Well localised vesibular abscess .  Localised ostitis

 For sterilizing root canal
 Pt with mild pericoronitis, minor gingival

oedema & mild pain which do not required antibiotcs

Prophylactic antibiotic therapy
 Standard recommendation

 A cephalosporin cefadroxil preferred
 1preoperatively 500 mg orally 1hr before surgery  2 post operatively 250 mg orally 6hr after initial

dose


or  Clindamycin in penicillin allergic pt  1 pre operatively 300 mg orally 1 hr before surgery  2 post operatively 150 mg orally 6hr after initial dose

Principles of antibiotic prophylaxis
 1 antimicrobial agent t is chosen on basis of

most likely micro organisum to cause infection  2 an antibiotic loading dose should be employed  3 antibiotic should present in sufficient concentration in blood and targate tissue prior to dissemination of offending micro organisum

 4 antibiotics should be continued only as

long as microbial contamination from operative site persist  5 patient benefits from prophylaxis should out high risk of antibiotic included allergy , toxicity , superinfection.

Dental procedure that require endocardititis prophylaxis
 Tooth extraction  Periodontal suergery  Subgingival dental prophylaxis

 Endodontic surgery
 Incision & Drainage of infection

Dental procedures that do not require endocardiatis prophylaxis
 Supragingival prophylaxis  Restorative tooth preparation  Placement of orthodontic appliances

 Conserative endodontic theraphy

REASONS FOR ANTIBIOTIC FAILURE
 INAPPROPIATE choice of antibiotics  Too low blood concentration  Poor penetration to infected site

 Limited or decreased vascularity
 Impaired host defence  Unfavourable local factors

 Increased plasma protein binding  Antibiotic antagonism  Slow microbial growth

 Antibiotic resistant organisms
 Patient failure to take antibiotics  Failure to eradicate sorce of infection

Myths &misconception in antibiotic th erapy
 Myth- antibiotics cure pt 1

except in immunocompramised pt antibiotics are not curative but rather function to provide time for normal host defence initially overwhelmed by micro organisum to gain and control &eventually eliminate the in fectious process

 2 .Antibiotics are substitute for surgical

drainage - never are antibiotics a substituted for eradication of the source of infection ( extraction, incision, drainage ) unless the infection is too diffuse
(pericoronitis)

 3 culture and sensitivity test are required -

orofacial infection are characteristically acute in nature, polymicrobial in cause, short in duration with proper treatment. These infection require immediate attention and a dealy of 18 to 36 hrs for result of culture & sensitivity tests prior to initiation of antibiotics therapy is usually not appropriate because the microbial cause Is commly such that common antibiotics are effective, incision &drainage are relatively easy.

Myth – antibiotics incresed host defence to infection
 The followoing condition appear valid at present  1 antibiotic that can peenetrate into the mammelion cell (tetracycline , eryt hromycin) are more likely to affect host defence than those that can not (beta lactum)  2 tetracycline may supress white cell chemotaxis where as betta lactum do not  3 most antibiotics (except tetracycline) do not depress phagocytosis  Tnb lymphocyte transformation may be depressed by trtracyclines

Multiple antibiotics are superior to as single antibiotics.
 It is often assume that antbiotic combination are superior to single antibiotic such as not commonly the case.  The primary clilical indication for antibiotic

conbination therapy is severe infection in which ofending organism is unknown and major conciquences may ensue if antibiotic therapy is not instituted immediatey before culture and sensetivity test are available.

Antibiotic prophylaxis usually effective
 It is commonly assume that antibiotics

administered prior to invasive surgical procedure remain post operative infection.  The reality based on laboratoru studies is that antibiotic prophalaxis is only some time effective.

Bacteriocidal agents are always superior to bacteriostatic agent
 Bacteriocidal antimicrobials are

required in pt with impaier host defenses (nutropenia, meningitis) but bacteriostatic agent are uaually satisfactory, if host defence against infection are adequqte.

Antimicrobials are effective in chronic infectious disease
 Antimicrobials are never been

successful in the eradication of a chronic infection because the prolong exposure of micro-organism to chemical leads to eventual dominance of drug resistance organism

Antibiotics are safe and non toxic
 Most antimicrobials are among safest drug

yet all are associated with allergy, ecological damage to human and microbial environment.


Infection require a complete course of therapy
 There is no such things as predetermine complete

course of antibiotic therapy.  The only guide for determining the effectiveness of antibiotic therapy and hence duration of treatment is related to clinical improvement of pt.

Misconceptions
 Prolong therapy destroy resistant micro-organism.  Prolong therapy is necessary for rebound infection that recur as organism is suppresed but not eliminated (orofacial infections do not rebound if

the sourse of infection is properly eliminated)  Antibiotic doseges and duration of therapy can be extra polated from one infection to another

REFERENCE—
 GOODMAN & GILLMAN  TEXTBOOK OF PHARMACOLOGY
 

BY TRIPATHI BY SATOSKAR

INTRODUCTION:
 Infections and their consequences are a considerable problem inorthopedic      

surgery. Despite systemic prophylaxis, infection rates after orthopedic surgery are above1%. Antibiotic loaded PMMA bone cements have been shown to enhance the efficiency of intravenous prophylactic treatments for total hipreplacement1. However, less than 10% of the load is released during the first 5-10 days ofimplantation2: the remaining antibiotic is released at low levels over many months3 and could select antibiotic-resistant strains2. The recommendations for the use of antibiotic in prophylactic applications are to obtain high levels, with treatment duration inferior to 48 hours. A new HAP/TCP bone substitute loaded with 125 mg of Gentamicin was designed for prophylactic use in bone filling applications. Its aim was to enhance the efficacy of systemic prophylactic treatments by increasing the local antibiotic concentration without selecting resistant strains.

Methods
 A commercial bone substitute composed of 70%

Hydroxyapatite and 30% β- Tricalcium Phosphate4 containing 125 mg of Gentamicin (ATLANTIK Genta, Medical Biomat, France) was used in this study.  The release rate of Gentamicin from the bone substitute was investigated after implantation in the femoral condyle of 5 sheep. In order to investigate the local and systemic Gentamicin concentrations, synovial fluids and blood samples were assessed by immunoassay over a 5 day period.

 There were differences in local Gentamicin

concentrations between individuals but for all animals, the local Gentamicin concentrations measured during the first 8 hours were higher than the minimal bactericidal concentration of the majority of the germs responsible for infections in orthopedic surgery, i.e. 612 μg/ml. After 48 hours, the concentration in blood and synovial fluids was less than 0.5 μg/ml.

 The mean Gentamicin concentration peak obtained in

blood was 4.2 μg/ml and then mean local Gentamicin concentration obtained in synovial fluids during the first 8 hours was305 μg/ml  The Gentamicin amount remaining in the implant explanted at day 8 was less than 0.003% of the initial amount

 It is a fact that selection of multi-drug-resistant

bacteria has occurred throughout history. Unfortunately, however, drug-resistant bacteria have been met with antibiotics that are nothing more than recapitulations of earlier drugs. There has been an urgent need for new avenues of therapeutic treatment, and a new era of prophalytic (preventative) treatment has begun. Here the most plausible approaches are described:  bacterial interference

 bacteriophage therapy  bacterial vaccines  cationic peptides  cyclic D,L-a-peptides

One way is to inoculate hosts with nonpathogenic bacteria.
 Bacterial interference, also known as bacteriotherapy,

is the practice of deliberately inoculating hosts with nonpathogenic (commensal) bacteria to prevent infection by pathogenic strains. To establish an infection and propagate disease, pathogenic bacteria must find nutrients and attachment sites (adhesion receptors). .

 Infection by pathogenic bacteria is prevented by

commensal bacteria, which compete with pathogenic bacteria for nutrients and adhesion receptors or spur attack through secretion of antimicrobial compounds

 This treatment has had promising results in infections

of the gut, urogenital tract, and wound sites. The major advantage of using bacteria in a positive way to benefit health, known as “probiotic” usage, is that infection is avoided without stimulating the host’s immune system and decreases selection for antibiotic resistance. Understanding how bacterial species compete, an essential criterion for research, has been known for at least 20 years but its practical application has yet to be realized.

 Bacteriophages (commonly called “phages”) are

viruses that infect bacteria and were recognized as early as 1896 as natural killers of bacteria. Bacteriophages take over the host’s protein-making machinery, directing the host bacteria to make viral proteins of their own. Therapeutically, bacteriophages were used as a prophylaxis against cholera, typhoid fever, and dysentery from the 1920s to the early 1940s.

 The practice was abruptly stopped when synthetic

antibiotics were introduced after World War II. Now that there is a plethora of multi-drug-resistant bacteria, bacteriophage therapy once again has become of keen interest.

Pathogens may be targeted through manipulation of phage DNA.
 Bacteriophage therapy is quite attractive for the

following reasons:  phage particles are narrow spectrum agents, which means they posses an inherent mechanism to not only infect bacteria but specific strains

 Other pathogens may be targeted through

manipulation of phage DNA  exponential growth and natural mutational ability make bacteriophages great candidates for thwarting bacterial resistance.  Development of bacterial vaccines has become an increasingly popular idea with the advent of complete genomic sequencing and the understanding of virulence regulatory mechanisms.

 Bacterial genomics allows scientists to scan an entire

bacterial genome for specific sequences that may be used to stimulate a protective immune response against specific bacterial strains. This approach expedites the drug discovery process and, more importantly, provides a more rational, target-based approach.  The best targets are essential bacterial genes that are common to many species of bacteria, which code for proteins with the ability to gain accesses through lipid membranes, and possess no homology to human genes.

 Regulatory genes that control virulence protein

production are excellent vaccine candidates for priming the human immune system or inhibiting virulence production.  Bacterial genomics can also detect conserved sequences from bacterial species and strains worldwide. This technology will inevitably yield superior clinical vaccine candidates.

 These diverse peptides are natural compounds that

posses both hydrophobic and hydrophilic characteristics, which means portions of the molecule are water avoiding or water loving. Cationic peptides are found throughout nature in the immune systems of bacteria, plants, invertebrates, and vertebrates

Other Peptides are synthetic, and are engineered to kill bacterial cells.
 These peptides are not the usual synthetic drugs

encountered in pharmaceutical drug design; however, they do exhibit antibacterial effects. Cationic peptides have several mechanisms of action, all of which involve interaction with the bacterial cell membrane leading to cell death. From a therapeutic standpoint, these proteins have great promise, as they have coevolved with commensal bacteria yet have maintained the ability to target pathogenic bacteria.

Other peptides are synthetic, or engineered, to kill bacterial cells.
 Unlike cationic peptides, cyclic D,L-a-peptides are

synthetic and amphipathic (molecules having both water loving and water hating characteristics) cell membrane disruptors. As the name implies these peptides are cyclic in nature and are composed of alternating D and L amino acids. Cyclic D,L-a-peptides are engineered to target gram-positive and negative membranes (not mammalian cell membranes).

 In contrast to any other known class of peptides, these

peptides can self-assemble into flat ring shaped conformations forming structures known as nanotubes, which specifically target and puncture bacterial cell membranes resulting in rapid cell death