antibiotics, misuse of antibiotics
DESCRIPTION
Antibiotics, Misuse of AntibioticsTRANSCRIPT
Dr.T.V.Rao MD 1
ANTIBIOTICS Use,
Misuse andConsequences
Dr.T.V.Rao MD
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Diseases Caused by Viruses and Bacteria
Differentiate Before a DecisionVirus Common cold Diarrhea (99%) Acute Bronchitis Influenza (flu) Measles Chicken Pox AIDS Rabies Hepatitis
Bacteria Urine infections Strep Throat Boils/abscesses Gangrene Some pneumonia Ear infections (half) Sinus infections (<
half) Bubonic Plague Tuberculosis
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Bacteria are the cause of the vast majority of deaths due to infection in the United States: sepsis, meningitis, pneumonia
Most viral infections get better all by themselves in 1-3 weeks; no medications are required: colds, flu, stomach virus
Bacterial diseases are very common Health problems
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They don’t help the patient at all Expense: 75% of outpatient
antibiotics are used for respiratory infections
Patient expectations: why no better? Side effects: diarrhea, rash, allergyDevelopment of resistance:
the antibiotic won’t work when you really DO need it for a bacterial infection
Problems With Improper Use of Antibiotics
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ANTIMICROBIAL AGENT
• Any chemical or drug used to treat an infectious
disease, either by inhibiting or killing the
pathogens in vivo
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Beginning of Antibiotics with Discovery of Pencillin
The discovery of penicillin has been attributed to Scottish scientist Alexander Fleming in 1928 and the development of penicillin for use as a medicine is attributed to the Australian Nobel Laureate Howard Walter Florey
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Discovery of Pencillin Awarded Nobel Prize
Selman Waksman The term
"antibiotic" was coined by Selman Waksman in 1942 to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution
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Antimicrobial agents – that are produced synthetically but have action similar to that of antibiotics and are defined as chemotherapeutic agents
Eg Sulphonamides, Quinolones.
Chemotherapeutic Agents
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Substances derived from a microorganism or produced synthetically, that destroys or limits the growth of a living organism
ANTIBIOTICS
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Bacteriostatic - Antimicrobial agents that reversibly inhibit growth of bacteria are called as bacteriostic ( Tetracyclnes, Chloramphenicol )
Bactericidal – Those with an irreversible lethal action on bacteria are known as bactericidal ( Pencillin, Isoniazid )
Definition
1920 1930 1940 1950 1960 1970 1980 1990 2000
ertapenem
tigecyclin daptomicin linezolid
telithromicin quinup./dalfop. cefepime ciprofloxacin aztreonam norfloxacin imipenem cefotaxime clavulanic ac. cefuroxime gentamicin cefalotina nalidíxico ac. ampicillin methicilin vancomicin rifampin chlortetracyclin streptomycin pencillin G prontosil
The development
of anti-infectives …
Development of anti-infectives
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Antimicrobial agents are widely employed to cure bacterial diseases
Definition of Antibiotic – Antibiotics are substances that are derived from a various species of microorganisms and are capable of inhibiting the growth of other microorganism even in small concentrations.
Uses of Antimicrobial Agents
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ANTIBIOTICS – Sources
1. Natural
a.Fungi – penicillin, griseofulvin
b.Bacteria – Bacillus sp. (polymixin, bacitracin) ; Actinomycetes (tetracycline, chloramphenicol, streptomycin)
2. Synthetic
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ANTIMICROBIAL AGENTIdeal Qualities:
1. kill or inhibit the growth of pathogens
2. cause no damage to the host
3. cause no allergic reaction to the host
4. stable when stored in solid or liquid form
5. remain in specific tissues in the body long enough to be effective
6. kill the pathogens before they mutate and become resistant to it
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Basic Classes of Antibiotics Although a large number of antibiotics exist, they fall
into only a few classes with an even more limited number of targets.
–β-lactams (penicillins) –cell wall biosynthesis
–Glycopeptide (vancomycin) –cell wall biosynthesis
–Aminoglycosides (gentamycin) –protein synthesis
–Macrolides (erythromycin) –protein synthesis
–Quinolones (ciprofloxacin) –nucleic acid synthesis
–Sulfonamides (sulfamethoxazole) –folic acid metabolism
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Is an antibiotic necessary ? What is the most appropriate antibiotic ?
What dose, frequency, route and duration ?
Is the treatment effective ?
Prescribing an antibiotic
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Useful only for the treatment of bacterial infections
Not all fevers are due to infection Not all infections are due to bacteria
There is no evidence that antibiotics will prevent secondary bacterial infection in patients with viral infection
Is an antibiotic necessary ?
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Oral vs parenteralTraditional view
“serious = parenteral” previous lack of broad spectrum oral
antibiotics with reliable bioavailability Improved oral agents
higher and more persistent serum and tissue levels
for certain infections as good as parenteral
Choice of regimen
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Eliminates risks of complications associated with intravascular lines
Shorter duration of hospital stay
Savings in nursing time Savings in overall costs
Advantages of oral treatment
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New Resistant Bacteria
Mutations
XX
Emergence of Antimicrobial Resistance
Susceptible Bacteria
Resistant Bacteria
Resistance Gene Transfer
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Mechanisms of Resistance
Enzymatic
degradation
Decreased entry
Efflux pumpAltered target site
Bypass pathway
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Antimicrobial Resistance: Key Prevention Strategies
Optimize Use
PreventTransmission
PreventInfection
EffectiveDiagnosis& Treatment
PathogenAntimicrobial-Resistant Pathogen
Antimicrobial
Resistance
Antimicrobial Use
Infection
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings
Susceptible Pathogen
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Antibiotic resistance is a consequence of evolution via natural selection. The antibiotic action is an environmental pressure; those bacteria which have a mutation allowing them to survive will live on to reproduce. They will then pass this trait to their offspring, which will be a fully resistant generation.
Emerging Resistance
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48% of all antibiotics by weight is added to animal feeds to promote growth. Results in low, sub therapeutic levels which are thought to promote resistance.
Farm families who own chickens feed tetracycline have an increased incidence of tetracycline resistant fecal flora
Chickens at Spanish supermarkets have >90% of cultured campylobacter resistant to quinolones
39% of enterococci in the fecal flora of pigs from the Netherlands is resistant to vancomycin vs 0% in Sweden. (Sweden bans antibiotic additives in animal feed)
ANTIMICROBIAL RESISTANCE:The role of animal feed antibiotic additives
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Several studies have demonstrated that patterns of antibiotic usage greatly affect the number of resistant organisms which develop. Overuse of broad-spectrum antibiotics, such as second- and third-generation Cephalosporins, generate resistant strains.
Irrational Use of Third Generation
Cephalosporins
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The resistant strains arise either by mutation and selection or by genetic exchange in which sensitive organisms receive the genetic material ( part of DNA) from the resistant organisms and the part of DNA carries with it the information of mode of inducing resistance against one or multiple antimicrobial agents.
Origin of Drug Resistant Strains
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RESISTANCEACQUISITION OF BACTERIAL RESISTANCE
ACQUIRED RESISTANCE
Species develop ability to resist an antimicrobial drug to which it is as a whole naturally susceptible
Two mechanisms:
1. Mutational – chromosomal
2. Genetic exchange – transformation, transduction, conjugation
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The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection, the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save.
. Sir AlexanderFlemming
Self Medication
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1980s –ESBL producing GN bacteria 1990 Vancomycin resistant Enterococci emerged
2000 VISA (intermediate level resistance)
2002-VRSA (high level resistance) 2002- Linezolid resistant enterococci and Staphylococci reported
Historical aspects
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Evolution of b-LactamasePlasmid-Mediated TEM and SHV Enzymes
AmpicillinThird-GenerationCephalosporins
1963
1965
TEM-1E coliS paratyphi
1970s
TEM-1Reported in28 Gram-NegativeSpecies
1980s1983
ESBLinUnitedStates
1987
ESBL inEurope
2000
>120 ESBLsWorldwide
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Resistance to Antibiotics
•Bacteria (and viruses) are very resourceful creatures and they have developed resistance mechanisms to essentially every antibiotic that has been developed.
•Moreover, increased use of antibiotics results in increased resistance (the paradox of antibiotics).
•The basic resistance mechanisms are quite simple:
1.Modify the antibiotic
2.Modify the target of the antibiotic
3.Destroy the antibiotic
4.Make it more difficult for the antibiotic to get into the cell
5.Actively remove the antibiotic from the cell
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Plasmid seem to be ubiquitous in bacteria, May encode genetic information for properties
1 Resistance to Antibiotics 2 Bacteriocins production 3 Enterotoxin production 4 Enhanced pathogen city 5 Reduced Sensitivity to mutagens 6 Degrade complex organic molecules
T.V.Rao MD
Plasmids
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Plasmids – helps to spread multiple drug resistance
Discovered in 1959 Japan Infections caused due to Shigella spread
resistance to following Antibiotics Sulphonamides Streptomycin Choramphenicol, Tetracycline
Resistance Transfer FactorRTF
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RTF Shigella + E.coli
excreted in the stool resistant to several drugs in vivo and vitro
Plasmid mediated –transmitted by Conjugation
Episomes spread the resistance
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R forms may have evolved as a collection of Transposons
Each carrying Genes that confers resistance to one or several Antibiotics
Seen in Plasmids, Microorganisms AnimalsLaboratory Manipulations are called as
Genetic Engineering
Transposons and R factor
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Sulphonamides --- Reduce permeabilityErythromycin ---- Modification of
ribosome'sTetracyclnes ----- Reduced
permeabilityChloramphenicol ---- Acetylation of drugStreptomycin ----- Adenylation of drugPencillin ----- Hydrolysis of lactum ring
Plasmid Mediated Drug resistance
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Therapeutic failures and relapseFacilitates spread in the hospital under “antibiotic pressure”
Need to use more costly and toxic agents
The emergence of untreatable pathogens
Clinical Significance of Antibiotic Resistance
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RESISTANCE
ACQUIRED RESISTANCE – EXAMPLES:
1. Resistance (R) plasmids
Transmitted by conjugation
2. mecA gene
Codes for a PBP with low affinity for -lactam antibiotics
Methicillin-resistant S. aureus
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RESISTANCEORIGIN OF DRUG RESISTANCE
NON-GENETIC
1. Metabolically inactive organisms may be phenotypically resistant to drugs – M. tuberculosis
2. Loss of specific target structure for a drug for several generations
3. Organism infects host at sites where antimicrobials are excluded or are not active – aminoglycosides (e.g. Gentamicin) vs. Salmonella enteric fevers (intracellular)
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RESISTANCEGENETIC
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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RESISTANCEGENETIC
2. Extrachromosomal
a. Plasmid-mediated
Occurs in many different species, esp. gram (-) rods
Mediate resistance to multiple drugs
Can replicate independently of bacterial chromosome many copies
Can be transferred not only to cells of the same species but also to other species and genera
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Development of Resistance in Gram Positive Pathogens
1Smith TL et al. N Engl J Med. 1999;340:493-501. 2Martone WJ. Infect Control Hosp Epidemiol. 1998;19:539-545. 3Hiramatsu K et al. J Antimicrob Chemother. 1997;40:135-136. 4CDC. MMWR Morb Mortal Wkly Rep. 2002;51:565-567.
1975 1995199019851980Path
ogen
s R
esis
tant
to A
ntib
iotic
s (%
)100
90
80
70
60
50
40
30
20
10
19962000
MRSA = methicillin-resistant Staphylococcus aureusVRE = vancomycin-resistant enterococciGISA = glycopeptide-intermediate S aureusVRSA = vancomycin-resistant S aureus
MRSA1
VRE2
GISA3
Year 2002
VRSA4
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< Inappropriate specimen selection and
collection
< Inappropriate clinical tests
< Failure to use stains/smears
< Failure to use cultures and
susceptibility tests
Practices Contributing to Misuse of Antibiotics
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RESISTANCELIMITATION 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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What Is Antimicrobial Stewardship?
• A combination of infection control and antimicrobial management• Mandatory infection control compliance• Selection of antimicrobials from each class of drugs that doesthe least collateral damage• Collateral damage issues include– MRSA– ESBLs– C difficile– Stable derepression– MBLs and other carbapenemases– VRE• Appropriate de-escalation when culture results are availableDellit TH, et al. Clin Infect Dis. 2007;44:159-177.
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IDSA Guidelines – Definition ofAntimicrobial 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
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The Primary Goal ofAntimicrobial Stewardship
• The primary goal of antimicrobial stewardship is to
– Optimize clinical outcomes while minimizing unintendedconsequences of antimicrobial use
• Unintended consequences include the following– Toxicity
– The selection of pathogenic organisms, such as C difficile
– The emergence of resistant pathogens
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The Primary Goal ofAntimicrobial Stewardship
• The primary goal of antimicrobial stewardship is to
– Optimize clinical outcomes while minimizing unintendedconsequences of antimicrobial use
• Unintended consequences include the following– Toxicity
– The selection of pathogenic organisms, such as C difficile
– The emergence of resistant pathogens
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< Inappropriate specimen selection and
collection
< Inappropriate clinical tests
< Failure to use stains/smears
< Failure to use cultures and
susceptibility tests
Practices Contributing to Misuse of Antibiotics
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< Use of antibiotics with no clinical indication (eg, for viral infections)
< Use of broad spectrum antibiotics when not indicated
< Inappropriate choice of empiric antibiotics
Inappropriate Antibiotic Use
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< Inappropriate dose - ineffective concentration of antibiotics at site of infection
< Inappropriate route - ineffective concentration of antibiotics at site of infection
< Inappropriate duration
Inappropriate Drug Regimen
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If a bacterium carries several resistance genes, it is called multiresistant or, informally, a superbug. The term antimicrobial resistance is sometimes use to explicitly encompass organisms other than bacteria
Multi Drug resistant pathogens
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Antibiotic resistance has become a serious problem in both developed and underdeveloped nations. By 1984 half of those with active tuberculosis in the United States had a strain that resisted at least one antibiotic.In certain settings, such as hospitals and some childcare location
Antibiotic Resistance Threat to Humans and Animals
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Between 1962 and 2000, no major classes of antibiotics were introduced
Fischbach MA and Walsh CT Science 2009
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Physicians Can Impact
O th e r c lin ic ia n s
Patients
Optimize patient evaluation Adopt judicious antibioticprescribing practicesImmunize patients
Optimize consultations with other cliniciansUse infection control measuresEducate others about judicious use of antibiotics
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Bacteria evolve resistance to antibiotics in response to environmental pressure exerted by the use of antibiotics.
Many of these bacteria are significant pathogens.
Our responsibility to our community is to use antibiotics prudently, for appropriate indications.
Antibiotic Pressure and Resistance in Bacteria:
Conclusions
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12 Steps to Prevent Antimicrobial Resistance
12 Break the chain 11 Isolate the pathogen
10 Stop treatment when cured 9 Know when to say “no” to vanco 8 Treat infection, not colonization 7 Treat infection, not contamination
6 Use local data 5 Practice antimicrobial control 4 Access the experts3 Target the pathogen
2 Get the catheters out 1 Vaccinate
Prevent Transmission
Use Antimicrobials Wisely
Diagnose & Treat Effectively
Prevent Infections
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings
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Antibiotic resistance is a major problem world-wide
Resistance is inevitable with use
No new class of antibiotic introduced over the last two decades
Appropriate use is the only way of prolonging the useful life of an antibiotic
Conclusions
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Are we Overusing Antibiotics
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Organizations - Curb Unwarranted Antibiotics
Surveillance
Prevention and Control
Research
Product Development
Agency forHealth Care Research and
Quality Department ofDefense
Environmental Protection
Agency
Health CareFinancing
Administration
Health Resources and Services
Administration
Department ofAgriculture
Department ofVeterans Affairs
Choose the Appropriate Antibiotic
Think before prescribing Are we using Right drug for the Right bug ?
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Created by Dr.T.V.Rao MD for Medical Professionals in the
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