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RATIONAL USE OF ANTIBIOTICS
AND PREVENTION OF ANTIMICROBIAL
RESISTANCEDr. S. MayaPG – I YRDepartment of Oral and Maxillofacial Surgery
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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.
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WORLD HEALTH DAY 2011
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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.
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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.
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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.
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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
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PRINCIPLES OF PRESCRIPTION
Patient Factors
Physician Factors
Antibiotic related Factors
Microbial Factors
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PATIENT-RELATED FACTORS
Infection - site and severity
Age
Immunological status
Co-morbidities
Genetic factors
Pregnancy
Allergies
Compliance
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PHYSICIAN-RELATED FACTORS
Diagnostic uncertainty
Perceived demand and
expectations from the patient
Influence from medical
representatives
Inadequate knowledge
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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
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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
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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
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SPECTRUM OF ACTIVITY
BROAD SPECTRUM NARROW SPECTRUM
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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
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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
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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
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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
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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.
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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
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PHARMACODYNAMICS
Time course of antibiotic concentrations in serum and tissue,
In vitro susceptibility (MIC),
Microbial response (inhibition of growth or rate of killing).
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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.
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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.
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COST OF ANTIBIOTIC
Materials for administration of drug
Labor costs
Expected duration of stay in hospital
Cost of monitoring levels
Expected compliance
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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.
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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
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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
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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
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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
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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
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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
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ANTIBIOTIC PRESCRIPTION
THERAPEUTICALEMPIRIC
DEFINITIVE
PROPHYLAXISSURGICAL
NON SURGICAL
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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
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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
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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
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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).
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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
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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
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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
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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
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ANTIBIOTIC MISUSE IN
DENTISTRY
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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
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ANTIBIOTICS IN DENTISTRY
THERAPEUTICPROPHYLAXIS
AmoxycillinAmoxycillin + MetronidazoleAmoxycillin + CloxacillinDoxycycline
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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
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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
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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
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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
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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
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Choose the Appropriate Antibiotic
Think before prescribing Are we using Right drug ?