RATIONAL USE OF ANTIBIOTICS

AND PREVENTION OF ANTIMICROBIAL

RESISTANCEDr. S. MayaPG – I YRDepartment 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

RATIONAL USE OF ANTIBIOTICSOBJECTIVES

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 collagen-vascular 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 drug-resistant microorganisms.

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

ANTIBIOTIC MISUSE- CONTRIBUTING FACTORS

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 drugSpectrum of activity – Broad/narrow

spectrumPharmacokinetic/pharmacodynamic

(PK/PD) profile Absorption Distribution Metabolism and excretion

Adverse ReactionsDrug-drug InteractionsCost

MECHANISMS OF ACTION OF THE DRUG

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

Inhibition of cell wall synthesisInhibition of cell membrane functionInhibition of protein synthesisInhibition of nucleic acid synthesis

BACTERICIDAL

BACTERIOSTATIC

MECHANISM

INTERFERENCE WITH•Cell wall synthesis•Nucleic acid synthesis

Host defense mechanism plays a minor role

MECHANISMINHIBITION 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 FACTORSThe 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

3. Comparing one drug with another

PROPER DOSEAdminister 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 infectionRecurrence of infection once the drug is discontinued

Route of AdministrationOral vs Parenteral

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

ORAL ROUTE - Advantages

Eliminates risks of complications

associated with intravascular lines

Shorter duration of hospital stay

Savings in overall costs

Greater patient satisfaction

ABSORPTIONParenteral 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

DISTRIBUTIONKnowledge 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

2. Time dependent (-lactams), such that the reduction in bacterial density is proportional to the time that concentrations exceed the MIC.

ADVERSE REACTIONS

Common cause of morbidityAlteration in therapyAdditional expenseOccasionally result in death

AVOIDED by Reducing dosage Limiting the duration of therapyReducing 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 FACTORSAntimicrobial 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

MECHANISMS OF RESISTANCE

Microorganisms

Produce enzyme that destroys the drugEg: B lactamase and resistant Staphylococci

Change their permeability to the drugEg: Resistance to Polymixins

Develop an altered structural target for the drugEg: 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

MICROBIAL FACTORS

ORIGIN OF DRUG RESISTANCE

NON GENETIC ORIGIN

Natural resistanceMechanism of action of drug does not affect

the bacteria

Eg: Metabolically inactive bacteria are not harmed because the antimicrobials interfere with bacterial metabolic process

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GENETIC

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

ORIGIN OF DRUG RESISTANCE

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GENETIC

2. Extrachromosomal

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

ORIGIN OF DRUG RESISTANCE

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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

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

WHO 2011

Strengthen surveillance and laboratory capacity

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.

Enhance infection prevention and control.

Foster innovations and research and development for new tools

Commit to a comprehensive, financed national plan with accountability and civil society engagement

ANTIBIOTIC PRESCRIPTION

THERAPEUTICALEMPIRIC

DEFINITIVE

PROPHYLAXISSURGICAL

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 settingpharmacodynamic considerationsresistance profile of the expected

pathogens in a particular hospital or geographic area

INDICATION OF EMPIRIC THERAPY

Life threatening infectionsCommunity-acquired infectionsInfection of unknown originNeutropenic patients

MISUSE of ANTIBIOTIC:

Treatment of untreatable infectionTherapy of fever of unknown originImproper dosageInappropriate reliance on AB aloneLack 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 PROPHYLAXISNo 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).

SURGICAL

1. Considered only if the expected rate of infectious complications is 3-5%

2. Continue for no more than 1 day after the procedure and ideally should be given only intraoperatively

NON SURGICALPREVENT :

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

4. Opportunistic infection in immunocompromised

PROPHYLAXIS

COMBINATION CHEMOTHERAPY

To increase efficacy

When no single agent’s 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

THERAPEUTICPROPHYLAXIS

AmoxycillinAmoxycillin + MetronidazoleAmoxycillin + CloxacillinDoxycycline

GUIDELINESAntibiotic 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

GUIDELINESDENTAL CONDITION USE OF ANTIBIOTICS

Periodontal disease Adjuncts to mechanical therapy Acute periodontal conditions

when drainage is unsuccessful Local spread of infection Refractory/aggressive Systemic signs

Pericoronitis Analgesics and debridement/extractionAntibiotics – only if systemic symptoms present

Surgical impactions Postoperative infections from surgical extractions are low and evidence shows that antibiotics have little or no effect

Abscess Acute – Antibiotics and adjunctive therapyChronic – Entirely surgical management

Fractures Compound fractures - Antibiotics

GUIDELINES - PROPHYLAXISMEDICAL CONDITION DENTAL TREATMENT

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 EXTRACTION

ROOT CANAL TREATMENT

DEEP SCALING AND ROOT

PLANING

FLAP SURGERIES

IMPLANT PLACEMENT

IDSA Guidelines – Definition ofAntimicrobial Stewardship

Antimicrobial stewardship is an activity that promotesThe appropriate selection of antimicrobialsThe appropriate dosing of antimicrobialsThe appropriate route and duration of antimicrobial therapy

IncludesMeasuring the interventionsMonitor the effects of the interventionsCost analysis

Bailey and Scott’s Diagnostic Microbiology – 12th Edition

Harrison’s Principle of Internal Medicine

Jawetz’s 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=1119-3077;year=2012;volume=15;issue=2;spage=151;epage=155;aulast=Goud

http://jac.oxfordjournals.org/content/53/4/567.full

REFERENCES

Choose the Appropriate Antibiotic

Think before prescribing Are we using Right drug ?