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Antimicrobial Drugs.pptx
1.
2. ANTIMICROBIAL DRUGS
Infection:
• The invasion and multiplication of microorganisms such as bacteria,
viruses, and parasites that are not normally present within the body.
• An infection may cause no symptoms and be subclinical, or it may
cause symptoms and be clinically apparent.
• An infection may remain localized, or it may spread through the
blood or lymphatic vessels to become systemic (body wide).
• Microorganisms that live naturally in the body are not considered
infections.
• For example, bacteria that normally live within the mouth and
intestine are not infections.
3. Types of infection:
1. Acute infection: It is characterized by rapid onset of infection, a
relatively brief period of symptoms, and resolution within days
2. Sub-acute infection: An infection intermediate between acute
and chronic.
3. Chronic infection: An infection having a protracted
coarse or prolonged duration
4. Primary infection: An initial infection is known as primary
infection
5. Secondary infection: An infection made possible by a
primary infection that lowers the host’s resistance (for
example, bacterial pneumonia following influenza).
6. Concurrent or super infection: The existence of two or more
infections at the same time.
7. Cross infection: The transfer of an infectious organism or
disease from one patient to another
4. 8. Cryptogenic infection: An infection whose source is unknown.
9. Contagious infection: It is usually refers to those that are easily
transmitted and commonly seen. Such as influenza or chicken pox
10. Droplet infection: An infection acquired by the inhalation of a
microorganism in the air, especially, one is added to the air by
someone’s breath or cough
11.Local infection: An infection that is not spread but remains contained
near the entry side
12. Nosocomial infection: An infection that is acquired during
hospitalization
13. Apical infection: An infection located at the tip of root of a tooth
14. Blood-borne infection: An infection transmitted through
contact with the blood of an individual. For example, hepatitis,
AIDS etc.
15. Air-borne infection: An infection caused by inhalation of pathogenic
organism in the air
5. 16. Oppertunistic infection: Any infection that results from a defective
immune system that cannot defends against pathogens normally found in
the environment
17. Sub-clinical infection: An infection that is immunologically confirmed
but does not show clinical symptoms in the individuals
18. Systemic infection: An infection in which the infecting agent or
organisms are throughout the body rather than restricted to a local area
19. Exogenous infection: Infection caused by Infective organism from
outside
20. Endogenous infection: Infection caused by body organism
21. Bacterial infection: An infection caused by Bacteria ( for eg T.B.)
22. Viral infection: An infection caused by virus ( for example viral fever).
23. Fungal infection: An infection caused by fungus
24. Protozoal infection: An infection caused by protozoa
25. Pyogenic infection: An infection resulting resulting from pus-
forming organism
6. Disease Caused by Infective Organism
Bacteria:
Typhoid (salmonella typhi), bacillari dysentery (bacillus of
Shigella group), amoebic dysentery ( Entamobea histolytica),
TB (Mycobacterium tuberculosis) etc.
Virus:
AIDS (HIV or retro virus), hepatitis B (hepadno virus),
hepatitis C (RNA virus
Fungi:
Ringworm, oral candidiasis (Candida albicans, Candida
tropicals, Candida slabrata) etc •
Protozoa:
Amoebic dysentery, visceral leishmaniasis or kala-a-zar
(Leishmania donovani) etc.
Parasite: Malaria (Plasmodium vivex) etc
7. CLASSIFICATION OF ANTIMICROBIAL DRUG
Classification based on chemical structure
1. Sulfonamide & related drug: sulfadiazine, sulfomethoxazole
2. Diaminopyrimidines: trimethoprim
3. Quinolones: norfloxacin, ciprofloxacin, levofloxacin, ofloxacin
4. Beta-Lactam antibiotics: penicillin, cephalosporins
5. Tetracyclines: tetracycline, oxytetracycline, doxycycline
6. Nitrobenzene derivatives : chloramphenicol
7. Aminoglycosides: streptomycin, gentamycin, kanamycin,
amikacin
8. Macrolides: erythromycin, clarithromycin, azithromycin.
9. Lincosamide: lincomycin, clindamycin
10.Glycopeptide antibiotics : vancomycin
9. Classification based on spectrum of activity
1. Narrow spectrum:
Acts only on a single or a limited group of microorganisms
are said to have a narrow spectrum. Eg isoniazid is active only
against Mycobacterium.
2. Extended-spectrum antibiotics:
antibiotics that are effective against gram+ve organisms and
also against a significant number of gram-ve bacteria eg.
ampicillin is considered to have an extended spectrum,
because it acts against gram+ve and some gram-ve bacteria
3. Broad spectrum:
Drugs such as tetracycline and chloramphenicol affect a wide
variety of microbial species and are referred to as broad-
spectrum antibiotics
10. Classification based on types of action
According to the types of action, antimicrobial drugs are
divided into two classes:
1. Bacteriosatic:
The antimicrobials that stop the growth of microorganism.
For example sulfonamides, tetracyclines, erythromycin,
chloramphenicol etc
2. Bactericidal:
The antimicrobials that kill the microorganism, e.g.
penicillins, ciprofloxacin, co-trimoxazole etc
11. Classification based on types of organism
According to types of organism by which the antimicrobial
are active are classified in to following types:
1. Antibacterial:
Penicillin, aminoglycosides etc.
2. Antiviral:
Acyclovir, amantadine
3. Antifungal :
Ketoconazole, griseofulvin, terbinafine
4. Antihelmenthics:
Albendazole, mebendazole etc.
5. Antiprotozoals:
Metronidazole, tinidazole, chloroquine
12. Classification based on mechanism of action
1. Interfere with cell wall synthesis: Penicillin,
cephalosporins, vancomycin and cyclosporine
2. Damage to the cytoplasmic membrane: Polymyxins,
colistin, polyene antibiotics and detergents
3. Inhibition of protein synthesis and impairment of
function of the ribosomes: Aminoglycosides, tetracyclines,
chloramphenicol, macrolides and lincomycin
4. Interfere with transcription/translation of genetic
information: Quinolones, metronidazole and rifampicin
5. Antimetabolic action: Sulfonamide, sulfones, para amino
salicylate (PAS) and trimethoprim
6. Binding to viral enzymes essential for DNA synthesis:
Protease inhibitors and acyclovir
13. GENERAL PRINCIPLE OF ANTIMICROBIAL THERAPY
1. Selection of anti-microbial agents
Identification of the infecting organism:
It is generally necessary to culture the infective organism to
arrive at a conclusive diagnosis and determines the
susceptibility to antimicrobial agents.
Patient factors:
In selecting an antibiotic, attention must be paid to the
condition of the patient. For eg, the status of the patient’s
immune system, kidneys, liver, circulation, and age must be
considered. In women, pregnancy or breast-feeding also
affects selection drug
14. Empiric therapy prior to identification of the organism:
the antimicrobial agents are used to treat an infection is
selected after the organism has been identified and its drug
susceptibility established. However, in the critically ill
patient, such a delay could prove fatal, and immediate
empiric therapy is indicated.
Determining antimicrobial susceptibility of infective
organisms:
After a pathogen is cultured, its susceptibility to specific
antibiotics serves as a guide in choosing antimicrobial
therapy.
Safety of the agent:
Antibiotics such as the penicillin are among the least toxic of
all drugs.
Cost of therapy:
Often several drugs may show similar efficacy in treating an
infection but vary widely in cost
15. 2. Route of administration
The oral route of administration is appropriate for mild
infections that can be treated on an outpatient basis.
In hospitalized patients requiring IV therapy initially, the
switch to oral agents should occur as soon as possible.
However, some antibiotic, such as vancomycin, amphotericin
B ,aminoglycoside are so poorly absorbed from the GI tract
that adequate serum levels cannot be obtained by oral
3. Determinants of rational dosing
Rational dosing of antimicrobial agents is based on their and
pharmacokinetic properties. Three important properties that
have a significant influence on the frequency of dosing are :
I. Concentration dependent killing
II. Time-dependent killing
III. Post-antibiotic effect (PAE).
16. 4. Combination of anti-microbial agents
It is advised to treat patients with a single agent that is most
specific to the infecting organism as well as it minimizes
resistant and toxicity. However, some situations require
combinations of antimicrobial drugs eg anti-TB
5. Prophylactic use of anti-microbial agents
Pre-surgical antimicrobial prophylaxis:
It is used to reduce the incidence of postoperative surgical
site infections.
Antimicrobial prophylaxis in immunocompromise pts.
Patients with HIV infection/AIDS, immunosuppressive
therapy after organ transplanting, are at increased risk of
infection. In these specific settings, evidence supports the
use of prolonged antimicrobial prophylaxis until immune
markers are restored.
17. Antimicrobial prophylaxis to prevent transmission of
communicable pathogens to susceptible contacts:
Eg ciprofloxacin can be given to close contacts of a patient
with meningitis caused by N. meningitidies.
Antimicrobial prophylaxis before dental and other
invasive procedures in patients susceptible to bacterial
endocarditis:
Traumatic injuries with a high probability of infections
complications
6. Non-antimicorbial therapy for infections
Systemic corticosteroids, used in conjunction with
antimicrobial therapy for the treatment of bacterial
meningitis, tuberculous meningitis,
18. 7. Complication of antimicrobial therapy
i. Hypersensitivity:
Hypersensitivity to antimicrobial drugs or their metabolic
product frequently occur. eg penicillin can cause serious
hypersensitivity
ii. Direct toxicity:
High serum levels of certain antibiotics may cause toxicity by
directly affecting cellular processes in the host. Eg
aminoglycosides can cause ototoxicity
iii. Super infections:
Broad-spectrum antimicrobial or combinations of agent, can
lead to alterations of the normal microbial flora of upper
respiratory, intestinal, permit the overgrowth of
opportunistic organisms
iv. Nutritional Deficiency:
Some Vit b-complex, vit K are synthesized by the intestinal
flora, Prolonged use of antimicrobial may alter the flora
19. 8. Judicious use of antimicrobial agents
Cost considerations in antimicrobial selection:
Cost of agent is dependent on many such as administration
costs, prolonged hospitalization, consequence of adverse
effects, and clinical efficacy. One strategy that can
significantly reduce cost is the switch from IV to oral therapy.
Oral therapy is generally less expensive, less adverse effect
Preventing emergence of antibiotic resistance:
The inappropriate-use of antimicrobial agents is most
important cause of the emergence of drug resistance, It can
be prevented or delayed through judicious prescribing, such
as:
i. Avoidance of antibiotic treatment for community-acquired
i.e viral
ii. Use of narrow-spectrum antibiotics when possible
iii. Use of antibiotics for the shortest duration that is effective
for the treatment of a particular clinical syndrome
20. Common misuses of antibiotics:
Use of antibiotics when a patient don’t appear to be
responding to therapy, even though there is no clear evidence
of infectious disease.
The frequent use of antimicrobial agents can result in
resistant to that particular antibiotic
9. Conclusion Appropriate use of antimicrobial agents
includes:
Obtaining and accurate diagnosis
Determining the need for and time of antimicrobial activities
of different agents
Tailoring (adapting) Treatment of host characteristics
Using the narrowest spectrum and shortest duration of
therapy
Switching to oral agent as soon as possible
21. MICROBIAL RESISTANCE (Drug resistance)
The ability of microorganism to develop mechanism that
block the action of drug
Antibiotic resistance refers to bacteria resisting antibiotics.
Antimicrobial resistance (AMR) refers to microbs resisting
antimicrobial agent
AMR occurs when microorganism change over time and no
longer respond to medicines, making infections harder to
treat and increasing the risk of disease spread, severe illness
and death.
As a result of drug resistance, drug become ineffective and
infections become increasingly difficult or impossible to
treat.
Antibiotic resistance affect people at any stage of life, as well
as the healthcare, veterinary, and agriculture industries
22.
23. Causes of resistance
1. Microbial behavior
Mutation:
When microbes reproduce, genetic mutations can occur.
Sometimes, this will create a microbe with genes that help it
survive in the face of antimicrobial agents.
Selective pressure
Microbes that carry these resistance genes survive and replicate.
The newly generated resistant microbes eventually become the
dominant type.
Gene transfer:
Microbes can pick up genes from other microbes. Genes
conferring drug resistance can easily transfer between microbes.
Phenotypic change:
Microbes can change some of their characteristics to become
resistant to common antimicrobial agents
24. 2. People’s behavior
Inexact diagnosis:
Doctors sometimes prescribe antimicrobials “just in case,” or
they prescribe broad spectrum antimicrobials when a specific
drug would be more suitable.
Inappropriate use:
If a person does not complete a course of antimicrobial drugs
Resistance can also develop if people use drugs for conditions
that they cannot treat. Eg. people sometimes take an antibiotic
for a viral infection.
Agricultural use:
Using antibiotics in farm, animals can promote drug resistance.
Hospital use:
People who are critically ill often receive high doses of
antimicrobials. This encourages the spread of AMR microbes,
particularly in an environment where various diseases are present
25. Mechanism of resistance
1. Drug Inactivation or Alteration
Many bacteria produce enzymes that irreversibly modify and
inactivate the antibiotics
One of the well-characterized enzymes is β-lactamases. They
hydrolyze the βlactam ring which is present in penicillins are
essential to their activity
2. Modification of Drug Binding Sites
Some resistant bacteria avoid recognition by antimicrobial
agents by modifying their target sites eg. Alternation of
penicillin-binding proteins (PBPs)
3. Reduced Drug accumulation:
By decreasing drug permeability and/ or increasing active
efflux( pumping out) of the drug across the cell surface
26. 4. Alteration of metabolic pathway:
Some sulfonamide-resistant bacteria don’t require para-
aminobenzoic acid(PABA) which is important precursor for
the synthesis of folic acid and nucleic acids in bacteria
inhibited by sulfonamides, instead like mammalian cell they
turn to utilized preformed folic acid
Types of resistance
1. Natural resistance :
particular microbes are inherently resistant to particular
agents eg. aminoglycoside resistance in strict anaerobes,
inability of penicillin G to penetrate Gram-negative cell
wall
27. 2. Acquired resistance
If a microorganism is initially sensitive to an anti-
microbial agent develops resistance later.
Due to change in genetic materials, e.g. Staphylococci to
rifampicin
Change in structure of cell wall eg. aminoglycoside
resistance to Streptococcus.
3. Cross resistance
If the resistance of one drug causes the resistance of next
drug, the process is said to be called a cross resistance
This type of resistance is mainly associated with among
chemically and mechanically related drugs
Eg. if one sulfonamide have resistant then all groups
develop resistance i.e. gentamicin resistant
microorganisms may have sensitive to amikacin
28. 4. Super infection
Normal flora in alimentary canal produces substance
bacteriocins
If a person takes many antibiotics for longer period of time,
then the normal microbial flora of the canal may decrease or
loss due to decrease in immunity power of the individuals
In this case pathogenic bacteria may cause infection which is
commonly known as super infection
Safety measures to resist infection
i. Use of specific antibiotics
ii. Should not used broad spectrum antibiotics unless
required
iii. Avoid use of antibiotics in viral infection
iv. Avoid long term of antibiotics unless required
v. Avoid multi antibiotic therapy