Rational use of antimicrobials

RATIONAL USE OF ANTIBIOTIC

Dr. Rajat SR Biswas, MD Resident Physician

Medicine Department Chittagong Maa Shishu O General

Hospital

Introduction

• Antibiotics are substances produced by micro-organisms that are antagonistic to the growth of life or other micro-organisms

• Infection is the entry, multiplication and development of micro-organism into host resulting in disease

Introduction

• Infection is one of the most important cause of morbidity and mortality in medical practice

• And the introduction of antimicrobials has greatly revolutionized the patient outcome suffering from infection

• As the list of antimicrobial is vast and its

irrational use is may cause unnecessary morbidity and mortality

Introduction

• So the rational use antimicrobials is vital in management of patient with infection with special attention to newer antimicrobials

History of chemotherapy

• Chemotherapy were practiced since ancient time

• The ancient Greeks used male fern and Aztecs chenopodium, as intestinal antehelmintics


• For hundreds of years moulds have been applied to wounds

• Despite the introduction of mercury as a treatment for syphilis (16th century) and the use of cinchona bark against malaria (17th century), the history modern chemotherapy doesn't begin until the late19th century


• By 1906, chemotherapy was a practical proposition

• In 1935 first sulphonamide was introduced and were used in puerperal sepsis, pneumonia, and meningitis

• In 1930 Alexander Fleming (1881-1955) accidentally discovered penicillin

• 1938, Florey and Chain undertook an investigation of antibiotics as an academic exercise. They prepared penicillin, discovered its systemic effects and confirmed its remarkable lack of toxicity


• In 1941,the clinical trial of penicillin was started. Penicillin treatment was started on 12th February 1941, with 200mg (10,000 units) initially, and then 300mg every three hours

• Since 1939, large programmes of screening fungi and bacteria for antibiotic production have been conducted

General description of antibiotics

Antimicrobials in clinical use

• Antibacterial

• Antiviral

• Antiprotozoal

• Antihelmintic

Indication of antimicrobial use

• Cure of infection

• Control of infection

• Prevention of infection

• Non infectious indication

Spectrum of activity of antimicrobials

• Narrow spectrum antibiotic

• Extended spectrum antibiotic

• Broad spectrum antibiotic

Rational use of antimicrobials

• Appropriate patient

• Appropriate indication

• Appropriate drug/s

• Appropriate administration– Dose,route, duration etc

• Appropriate combination

• Cost of antibiotics

Administration of antimicrobials

• Oral – Convenient – Pleasant – Adequate– Food influence the absorption

• Parenteral – Intramuscular – Intravenous

Duration of therapy

• Duration of therapy – Single dose – gonococcal urethritis – 3 days– 7-10 days– 2 weeks– 3 weeks– 4 weeks – >4 weeks

Mode of action of antimicrobials

• Bacteriostatic • Bactericidal

Bacteriostatic activity is adequate – for treatment of most infections

Bactericidal activity may be necessary– for cure in patient with altered immunity (neutropenia)– protected infectious foci (endocarditis or meningitis)– infections like complicated staphylococcal aureus

bacteremia

Site of action of antimicrobials

• On cell wall

• Cytoplasmic membrane

• Protein synthesis

• Nucleic acid metabolism

• Intermediary metabolism

Mechanism of action of antmicrobials

• Inhibit cell wall synthesis – Beta lactum– Glycopeptides– Bacitracin

• Cytoplasmic membrane – Colistin – Amphotericin B

• Inhibit protein synthesis– Aminoglycosides– Macrolides– Chloramphenicol– Tetracycline

Mechanism of action of antmicrobials

– Inhibition of bacterial metabolism• Sulphonamide • trimethoprim

– Inhibit nucleic acid synthesis or activity• Rifampicin• Metronidazole• Nitrofurantoin

– Alter cell wall permeability• Polymixin

Classification of antimicrobial

According to molecular structure– Beta lactum – Quinolones – Aminoglycosides– Microlides – Tetracyclines – Sulphonamides – Glycopeptides – Othesrs

Main classes of antimicrobials

• Beta lactams– Penicillin– Cephalosporin– Monobactam– Carbapenem

• Quinolones– Nalidixic acids– fluroquinolones


• Amino glycosides– Gentamycin – Tobramycin– Amikacin

• Macrolides– Erythromycin– Azithromycin– clarithromycin


• Tetracycline– Oxytetracycline– Doxycycline

• Glycopeptide– Vancomycin

• Sulphonamide– Sulphadimidine – Sulphathiazine


• Other antibiotic– Chloramphenicol– Clindamycin– Metronidazole

Newer antimicrobials

• Third and fourth generation cephalosporin

• Third generation fluroquinolones

• Newer microlide

Criteria for using newer antimicrobials

• Therapeutic advantage

• Improved efficacy

• Improved Pharmacokinetic

• Decreased toxicity

• Better tolerance

• Lower cost

General principles of use

• Make a diagnosis defining – Site of infection– Type of organism responsible – Antimicrobial sensitivity

• Decide whether chemotherapy is at all necessary (Indication)– Acute infection – Chronic infection


• Select the best drug considering – Sensitivity and specificity

• From available informations • Best guess

– Pharmacokinetic factor– Patients appropriateness

• Sensitivity• Organ failure

– Optimum dose, frequency,route, and duration


• Remove the barrier to cure – Abscess– Obstruction to the passage

• Continue therapy till apparent cure

• Test for cure – Clinical cure – Microbiological cure

Factors influencing the selection of antimicrobials

• Clinical and microbiological diagnosis

• Severity of illness

• Host factor

• Physician knowledge and attitude

• Availability of antimicrobials

• Cost of the antibiotic

• Patient attitude

Factors influencing the selection of antimicrobials

• Pattern of antimicrobial resistance

• Antimicrobial policy

• Commercial influence

PROBLEMS WITH ANTIBIOTIC

Problems with antimicrobials

• Irrational use

• Drug resistance

• Adverse reaction

• Drug interaction

• Treatment failure

• Opportunistic infection

• Masking of infection

Irrational use

• No indication for antibiotic use

• Wrong selection of antibiotic

• Use of antibiotic in inappropriate dose, route, duration etc

• Inappropriate combination

• Unnecessary use of the costly antibiotic

Antimicrobial Resistance

• Microbial resistance to drug is a matter of great concern

• Mechanism of resistance to antimicrobial drugs– Inactivation of the drugs by enzymes

produced by bacteria– Change of the site of antibacterial action


– Impaired access to the site of antibacterial action

– Spontaneous mutation with selective multiplication of resistant strain

– By transmission of genes from other organism• By conjugation – plasmid • By transduction – through bcateriophage


• Types of drug resistance – Drug tolerant – Drug destroying

• Origin of drug resistance – Primary – Secondary


• Prevention of antibiotic resistance may be achieved by

– Avoiding indiscriminate use

– by ensuring the appropriate dose and duration of therapy

– using antimicrobial combination in selected circumstances


– By Constant monitoring of the resistance patterns in a hospital or community

– Restricting control of drug use, which involves agreement between clinicians and microbiologist

• e.g. limiting the use of newest antimicrobials so long the currently used drugs are effective

Adverse reactions

• Allergic reaction

• Organ toxicity

Treatment failure with antmicrobials

Treatment failure may be due to• Irrational use of antibiotics• Drug resistance

– The way the drug is used – Some factors peculiar to the patients– Treatment begin too late– Sub optimal use of drugs

• Too small dose• Too long interval • Too short duration


– Unsuitable route

– Adjuvant medication not used

• Organism present in altered state

• Substances antagonizing effect of drug present in the patients


• Barrier to adequate access of the drug to the organism

• Reduced host defense

• The organism isolated is not causing the disease

Drug interaction with antibiotics

• Antimicrobials may interact with each other and with other drugs

• Antimicrobial are a common cause of drug-drug interaction

• Recognition of the potential for the drug interaction before the administration is of crucial to the rational use of drugs


• On absorption

• On metabolism

• On elimination

• On organs


• Antibiotics that usually interact with other drugs are – Erythromycin– Fluroquinolones– Tetracycline – Rifampicin– Metronidazole

Antimicrobial combination

Advantage• To obtain potentiation

• To broaden the spectrum of antibiotic activity

• To reduce the severity or the incidence of adverse reaction

• To delay drug resistance

Antimicrobial combination

Disadvantage• Increased incidence and variety of

adverse reaction

• Suppression of normal flora

• False sense of security

Empiric /blind antibiotic therapy

• In many situations, antibacterial therapy is begun before a specific bacterial pathogen has been identified

• The choice of agents is guided by – The result of studies identifying the usual

pathogens at the site of or in that clinical setting

– Pharmacodynamic consideration – Resistance profile of the expected pathogens

in a particular hospital or geographical area

Empiric /blind antibiotic therapy

• Situation in which empirical therapy is appropriate – Life threatening infections– Treatment of community acquired infections

Chemoprophylaxis and suppression

• Prevention of infection

• Suppression of infection

• Prevention of exacerbation

• Prevention of opportunistic infection

• Epidemic control

• Protection of contact

Antibacterial cost & inappropriate use

• While some newer antimicrobials agents undeniably represents advances in therapy, many newer drugs offer no advantage over the older less expensive agents

• With the rare exception, newer drugs are usually found to be no more effective than the comparison antibiotic in controlled trails


• Despite the high prevalence of resistance is often touted to market the advantage of the new antibiotic over the older therapies

• Clinicians become confused by the bewildering competing claims of superiority

• Numerous survey have reported that ~50%antibiotic in some way “inappropriate”


• The following suggestions are intended to provide guidance through the antibiotic mage

– First objective evidence regarding the merits of newer drugs is available through publications which offer current information

– Secondly the clinicians should become comfortable using new drugs recommended by independent experts and professional organizations and should resist the temptation of prescribing the new drugs since the merits are clear


• A new antimicrobial agent with– a broader spectrum and greater potency – A longer half life and higher tissue level or – a higher serum concentration to MIC ratio

does not necessarily translate into greater clinical efficacy

• Third the clinician should familiar with local bacterial susceptibility profile


• Finally with regard to in patient use of antimicrobials, appropriate empirical treatment with one or more broad spectrum agents may often be simplified with narrower spectrum agent or even an oral drug once the result of culture and susceptibility are available


• While there is understandable temptation not to alter effective therapy, switching to a more specific agent once the patient has improved clinically doesn't compromise outcome

How to overcome irrational use of antimicrobials?

• Appropriate knowledge and attitude of the physician

• Local and national antibiotic policy• Most frequently used drugs should made

available • Bacteriologic confirmation of infection

should be easily available• Appropriate information regarding the

newer antimicrobials should be available

CONCLUSION

Conclusion

• Antibiotics are key to the management of infection

• Microbiologic diagnosis not always possible

• Empirical treatment on best guess is the appropriate alternative

Conclusion

• Rational use of antimicrobials can overcome the problems with antimicrobials

• Continued education and motivation of the physician is essential to ensure the rational use of antimicrobials

THANK YOU ALL

Health & Medicine

Rational use of antimicrobials