Dr. S.

Maya PG I YR Department of Oral and Maxillofacial Surgery

ANTIBIOTICS THE WONDER DRUG

Antibiotic : substance produced by micro organisms and capable of destroying or inhibiting the growth of micro-organisms

Since the discovery of penicillin, the first antibiotic known, in 1929 the antibiotics became the magic drug for infectious diseases. Their remarkable healing power observed at that period led to the wide spread use and often inappropriate prescriptions and consequently the emergence of the antibiotic abuse and resistance.

WORLD HEALTH DAY 2011

OBJECTIVES
Avoid adverse effects on the patient Avoid unnecessary increases in the cost of health

care Avoid emergence of antibiotic resistance ecological or societal aspect of antibiotics

The way in which a physician uses an antibiotic can affect the response of future patients. Hence physicians have a responsibility to the society in rational utilization of antibiotics.

CONSEQUENCES OF INAPPROPRIATE ANTIBIOTIC USE

Widespread sensitization of the population, with resulting hypersensitivity, anaphylaxis, rashes, fever, blood disorders, cholestatic hepatitis, and perhaps collagenvascular diseases. Changes in the normal flora of the body, with disease resulting from "super-infection" due to overgrowth of drug-resistant organisms. Masking serious infection without eradicating it. For example, the clinical manifestations of an abscess may be suppressed while the infectious process continues.

CONSEQUENCES OF INAPPROPRIATE ANTIBIOTIC USE

Direct drug toxicity (eg, granulocytopenia or thrombocytopenia with cephalosporins and penicillins and renal damage or auditory nerve damage due to aminoglycosides). Development of drug resistance in microbial populations, chiefly through the elimination of drug-sensitive microorganisms from antibiotic-saturated environments (eg, hospitals) and their replacement by drugresistant microorganisms.

ANTIBIOTIC MISUSE- CONTRIBUTING FACTORS

Inappropriate selection of antibiotics (failure to follow guidelines) based on prescription principles
Continuation

of empiric therapy despite negative culture in a stable patient

Lack

of awareness of susceptibility patterns of common pathogens

Inappropriate

self medication

PRINCIPLES OF PRESCRIPTION

Patient Factors
Physician Factors Antibiotic related Factors Microbial Factors

PATIENT-RELATED FACTORS

Infection - site and severity Age Immunological status

Co-morbidities
Genetic factors Pregnancy

Allergies
Compliance

PHYSICIAN-RELATED FACTORS

Diagnostic uncertainty

Perceived demand and expectations

from the patient

Influence from medical

representatives Inadequate knowledge

ANTIBIOTIC-RELATED FACTORS
Mechanism of Action of the drug Spectrum of activity Broad/narrow spectrum Pharmacokinetic/pharmacodynamic (PK/PD) profile

Adverse Reactions Drug-drug Interactions Cost

Absorption Distribution Metabolism and excretion

MECHANISMS OF ACTION OF THE DRUG

SELECTIVE TOXICITY Drug is harmful to the pathogen without being harmful to the host

Inhibition Inhibition Inhibition Inhibition

of of of of

cell wall synthesis cell membrane function protein synthesis nucleic acid synthesis

BACTERICIDAL
MECHANISM INTERFERENCE WITH Cell wall synthesis Nucleic acid synthesis Host defense mechanism plays a minor role

BACTERIOSTATIC
MECHANISM INHIBITION OF Protein synthesis Retards the growth and reproduction of bacteria. Host defense mechanism plays a major role

SPECTRUM OF ACTIVITY
BROAD SPECTRUM NARROW SPECTRUM

PHARMACOKINETIC FACTORS
The pharmacokinetic profile of an antibacterial agent refers to concentrations in serum and tissue versus time and reflects the processes of absorption, distribution, metabolism, and excretion. Pharmacokinetic information is useful for
1.

Estimating the appropriate antibacterial dose and

frequency of administration
2.

Adjusting dosages in patients with impaired excretory capacity Comparing one drug with another

3.

PROPER DOSE
Administer sufficient amount to achieve the desired therapeutic effect but not enough to cause injury to the host Sensitivity testing by disk diffusion method

Minimum Inhibitory Concentration of an antibiotic for a specific

bacterium the peak concentration of the antibiotic at the site of infection should be 3-4 times the MIC

Increased Doses Generally toxic except when site of infection is isolated from the blood supply Example: Abscess
Sub therapeutic levels Mask the infection Recurrence of infection once the drug is discontinued

Drug concentrations at the site of infection should be sufficient to inhibit or kill the pathogen. ORAL ROUTE - Advantages

Route of Administration Oral vs Parenteral

Eliminates risks of complications associated with intravascular lines Shorter duration of hospital stay Savings in overall costs

Greater patient satisfaction

ABSORPTION
Parenteral route Treating serious, established infection

When oral antibacterial agents are not effective against a particular pathogen When bioavailability is uncertain When larger doses are required than are feasible with the oral route

Long-term antimicrobial therapy is required and oral

therapy is not feasible

Can be changed to oral therapy after the 5th day of antibiotic administration

DISTRIBUTION

Knowledge of anticipated antimicrobial drug concentrations at sites of infection is critical.

When the infection is located in a "protected" site where penetration is poor, such as cerebrospinal fluid (CSF), the eye, the prostate, or infected cardiac vegetations, high parenteral doses or local administration for prolonged periods may be required for cure.

ELIMINATION

Hepatic elimination (metabolism or biliary elimination) Renal excretion of the unchanged or metabolized form or by a combination of the two processes.

Adjust dosage when elimination capability is impaired

PHARMACODYNAMICS

Time course of antibiotic concentrations in serum and tissue,

In vitro susceptibility (MIC),

Microbial response (inhibition of growth or rate of killing).

PHARMACODYNAMICS
1.

Concentration dependent (fluoroquinolones, aminoglycosides), such that an increase in antibiotic concentration leads to a more rapid rate of bacterial death Time dependent (-lactams), such that the reduction in bacterial density is proportional to the time that concentrations exceed the MIC.

2.

ADVERSE REACTIONS
Common cause of morbidity Alteration in therapy Additional expense Occasionally result in death

AVOIDED by Reducing dosage Limiting the duration of therapy Reducing the rate of administration.

COST OF ANTIBIOTIC

Materials for administration of drug

Labor costs

Expected duration of stay in hospital

Cost of monitoring levels Expected compliance

DURATION OF TREATMENT

In general, the duration of therapy should be long enough to prevent relapse yet not excessive. 5-6 days sufficient Extension of therapy beyond the limit of effectiveness may increase the medication's side effects and encourage the selection of resistant bacteria.

MONITORING EFFICACY
Early review of response Routine early review Resolution of infection 5 day course/ 7 day course Serum antibiotic levels

Increasing or decreasing the level of

treatment depending on response change route change dose change spectrum of antibacterial activity stopping antibiotic

MICROBIAL FACTORS
Antimicrobial resistance is the ability of microbes, such as bacteria, viruses, parasites, or fungi, to grow in the

presence of a chemical (drug) that would normally kill it

or limit its growth.

Resistance of a microorganism to an antimicrobial medicine to which it was previously sensitive

Withstand attack of antimicrobials so that standard treatment procedures become ineffective Infection may persist or spread

MICROBIAL FACTORS
MECHANISMS OF RESISTANCE Microorganisms

Produce enzyme that destroys the drug Eg: B lactamase and resistant Staphylococci

Change their permeability to the drug Eg: Resistance to Polymixins Develop an altered structural target for the drug Eg: Altered PBP in resistant Streptococcus Altered metabolic pathway that bypasses the reaction inhibited by the drug Eg: Sulphonamide resistant bacteria do not require extracellular PABA Altered enzyme that can still perform its metabolic function but is much less affected by the drug Eg: Trimethoprim resistant bacteria Dihydrofolic acid reductase enzyme

ORIGIN OF DRUG RESISTANCE

NON GENETIC ORIGIN
Natural resistance Mechanism of action of drug does not affect the bacteria Eg: Metabolically inactive bacteria are not harmed because the antimicrobials interfere with bacterial metabolic process

ORIGIN OF DRUG GENETIC RESISTANCE

1. Chromosomal

Occurs at a frequency of 10-12 to 10-7

20 to spontaneous mutation in a locus that controls susceptibility to a given drug due to mutation in gene that codes for either: a. drug target

b. transport system in the membrane that controls drug uptake

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2.

ORIGIN OF DRUG RESISTANCE Extrachromosomal

GENETIC

a. Plasmid-mediated Mediate resistance to multiple drugs Control the formation of enzymes capable of destroying antimicrobial drugs Eg: B Lactamase Genetic material and plasmids can be transferred by transduction, transformation and conjugation

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CLINICAL SIGNIFICANCE OF ANTIBIOTIC RESISTANCE

Therapeutic failures and relapse Need to use more costly and toxic agents

The emergence of untreatable pathogens

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LIMITATION OF DRUG RESISTANCE

1. Maintain sufficiently high levels of the drug in the tissues inhibit original population and first-step mutants. 2. Simultaneous administration of two drugs that do not give cross-resistance delay

emergence of mutants resistant to the drug

(e.g. INH + Rifampicin) 3. Limit the use of a valuable drug avoid exposure of the organism to the drug

Commit to a comprehensive, financed national plan with accountability and civil society engagement Foster innovations and research and development for new tools Strengthen surveillance and laboratory capacity

Enhance infection prevention and control.

Ensure uninterrupted access to essential medicines of assured quality. Regulate and promote rational use of medicines, including in animal husbandry, and ensure proper patient care; reduce use of antimicrobials in food-producing animals.

ANTIBIOTIC PRESCRIPTION
THERAPEUTICAL
EMPIRIC DEFINITIVE

PROPHYLAXIS
SURGICAL NON SURGICAL

EMPIRIC AB THERAPY
Giving antibiotic directly without identification and sensitivity test of bacteria, but obtaining specimen for lab. analysis before giving antibiotic. Empiric AB therapy based on identifying the usual pathogens at that site or in that clinical setting pharmacodynamic considerations resistance profile of the expected pathogens in a particular hospital or geographic area

INDICATION OF EMPIRIC THERAPY

Life threatening infections Community-acquired infections Infection of unknown origin Neutropenic patients

MISUSE of ANTIBIOTIC:

Treatment of untreatable infection Therapy of fever of unknown origin Improper dosage Inappropriate reliance on AB alone Lack of adequate bacterial information

DEFINITIVE THERAPY
It is the most effective, least toxicity and the narrowest selection Based on : * identification of bacteria * sensitivity test

* interpretation in the content of the

overall clinical picture * the antibiotic of choice directed to M.O

ANTIBIOTIC PROPHYLAXIS
No evidence of infection but who have been or are expected to be exposed to bacterial pathogens under circumstances that constitute a major risk of infection (1) The risk or potential severity of infection should outweigh the risk of side effects from the antibacterial agent.

(2) The antibacterial agent should be given for the shortest period necessary to prevent target infections.
(3) The antibacterial agent should be given before the expected period of risk (e.g., within 1 h of incision before elective surgery) or as soon as possible after contact with an infected individual (e.g., prophylaxis for meningococcal meningitis).

PROPHYLAXIS
NON SURGICAL
SURGICAL
1.

PREVENT :

Considered only if the expected rate of infectious complications is 3-5% Continue for no more than 1 day after the procedure and ideally should be given only intraoperatively

1. Streptococcal infection in patient with a history of RHD

2. In pre-dental extraction who have implanted prosthetic devices 3. TB/meningitis in close contact individual

2.

4. Opportunistic infection in immunocompromised

COMBINATION CHEMOTHERAPY

To increase efficacy When no single agents spectrum covers all potential pathogens (polymicrobial

infections and empiric treatment of sepsis)

To reduce antimicrobial resistance

DISADVANTAGES OF COMBINATION CHEMOTHERAPY

Relaxation of effort to establish a diagnosis Greater chance of adverse drug reactions The cost is unnecessarily high Not necessarily effective than monotherapy Very rarely, one drug may antagonize a second drug given simultaneously

Steps in Approaching Patients When Considering Antibiotic Therapy

Make a tentative diagnosis based on the history and physical examination Determine if antibiotic therapy is necessary for the given infection Choose the individual agent for the infection based on the following:

In vitro activity of the antibiotic against the most likely pathogens in the disease (Dilution and Diffusion Methods) Clinical trial results demonstrating efficacy and safety of the antibiotic in that disease and in patient populations similar to that of the presenting patient

Side effect profile of the drug:

Allergic reactions Direct adverse effects of drug Drug-drug interactions Drug-food interactions Use least expensive and narrowest-spectrum drug possible

ANTIBIOTIC MISUSE IN DENTISTRY

Dentists -10% of all antibiotic prescriptions

Antibiotic misuse in dentistry mainly involves prescribing them in 'inappropriate situations' or for too long, which includes - giving antibiotics after a dental procedure is complete in an otherwise healthy patient to 'prevent' an infection, which in all likelihood will not occur
CAUSES FOR MISUSE Using antibiotics instead of surgical incision and drainage of infections

Using antibiotics as instead of mechanical debridement of teeth in apical periodontitis

Employing antibiotics for prophylaxis in patients not at risk for metastatic bacteremia

Using antimicrobials to treat chronic adult periodontitis, which is

almost totally responsive to mechanical treatment

Using antibiotics to 'prevent' claims of negligence

ANTIBIOTICS IN DENTISTRY
THERAPEUTIC PROPHYLAXIS

Amoxycillin Amoxycillin + Metronidazole Amoxycillin + Cloxacillin Doxycycline

GUIDELINES

Antibiotic therapy should be used as an adjunct to dental treatment and never used alone as the first line of care Antibiotics are indicated when systemic signs (fever, malaise, lymphadenopathy , trismus) are evident. Pain and swelling alone are not indications Usually short course antibiotics with appropriate dental treatment results in resolution of most dental infections. Longer duration may result in development of resistant strains and superinfection

GUIDELINES
DENTAL CONDITION Periodontal disease Pericoronitis USE OF ANTIBIOTICS Adjuncts to mechanical therapy Acute periodontal conditions when drainage is unsuccessful Local spread of infection Refractory/aggressive Systemic signs

Analgesics and debridement/extraction Antibiotics only if systemic symptoms present Postoperative infections from surgical extractions are low and evidence shows that antibiotics have little or no effect Acute Antibiotics and adjunctive therapy Chronic Entirely surgical management Compound fractures - Antibiotics

Surgical impactions

Abscess

Fractures

GUIDELINES - PROPHYLAXIS
MEDICAL CONDITION Risk of infective endocarditis Prosthetic heart valve Facial fracture Compound skull fractures or cerebral rhinorrhoea Immunocompromised patients Patients who have recently received radiotherapy to head and neck Prosthetic hips Ventriculoarterial shunts DENTAL TREATMENT DENTAL EXTRACTION

ROOT CANAL TREATMENT

DEEP SCALING AND ROOT PLANING FLAP SURGERIES IMPLANT PLACEMENT

IDSA Guidelines Definition of Antimicrobial Stewardship

Antimicrobial stewardship is an activity that promotes The appropriate selection of antimicrobials The appropriate dosing of antimicrobials The appropriate route and duration of antimicrobial therapy
Includes Measuring the interventions Monitor the effects of the interventions Cost analysis

REFERENCES Bailey and Scotts Diagnostic Microbiology 12th Edition Harrisons Principle of Internal Medicine Jawetzs Medical Microbiology

Web Sources: http://www.aafp.org/afp/2001/0915/p999.html

Journals: Factors influencing primary care physicians to prescribe antibiotics in Delhi India Kotwani A, Wattal C, Katewa S, Joshi PC, Holloway K. http://www.njcponline.com/article.asp?issn=11193077;year=2012;volume=15;issue=2;spage=151; epage=155;aulast=Goud http://jac.oxfordjournals.org/content/53/4/567.full

Choose the Appropriate Antibiotic

Think before prescribing Are we using Right drug ?