antibacterial agents (1)
TRANSCRIPT
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Mindanao State UniversityIligan Institute of Technology
COLLEGE OF NURSINGJPBSilang, RN, MAN
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1. H t le.g, Autoclave/pressurized steam-kills bacterial spores
Boiling water- kills spores (>2 hours) & vegetative (1omin)
Refrigeration- kills microbes at 5 to -10 degrees CelsiusOven- kills spores @ 160 degrees Celsius x 2 hrs
2. i tie.g, UV- kills all microbes @ 265 nm energy (not useful
in liquids)Gamma- kills all microbes (extends food shelf life)
3. iltr ti - uses materials to trap microbese.g, HEPA filters-ensures air purity by separating
99 % of particles as small as 0.3 micrograms
4. sic l cl ie.g, handwashing
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1. Phenols and phenolic compounds- skinantiseptics and ingredients in presurgicalscrubs.
Example: Lysol
2. Alcohols- effective skin antiseptic.Example: ethanol, isopropyl alcohol
3. Halogens (iodine, chlorine)- water
disinfection, wound antisepsis, sanitation
4. Heavy metals- as antiseptics anddisinfectants.
Examples: silver nitrate and copper
5. Dyes- crystal violet
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6. Soap and Detergents- effective degermining agents
7. Quaternary ammonium compounds- more effective
than soap and detergentsExample: Benzalkonium chloride
8. Aldehydes- alters the biochemistry ofmicroorganisms including nucleic acids and proteins.Example: formalin
9. Gaseous agentsExample:ethylene oxide- carcinogenic and explosivechlorine gas- for sanitation of food and hospitals
10. Chemotherapeutic agents- antimicrobials
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Drugs used to manage infections Effective in treating infections
because of their selective toxicity
Selective toxicity- the ability to killinvading microorganisms withoutharming the human cells1. Drug accumulates in microbes at higher
levels than in humans
2. Drug has specific action on cellularstructures that are unique on themicrobe.
3. Drug action on biochemical process ismore harmful to the microbe thanhuman cells.
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I. l ssific ti b sc ptibl
r ism1. Antibacterial drugs
2. Antiviral drugs
3. Antifungal drugs
4. Anti-parasitic drugs
5. Antihelmintic drugs
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Weakens the cell wall which allows cellto absorb more water causing swellingand lysis
Penicillin nd cep l sp rinbinds toproteins which causes inhibition oftranspeptidase
Penicillin nd cep l sp rinactivate
autolytic enzyme V nc m cinprevents the formation of
linear peptidoglycan units
Other drugs: Bacitracin
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Disruption of bacterial protein synthesiswithout affecting the protein synthesis inhuman cells since both ARESTRUCTURALLY DIFFERENT
T
etr c cli
nes- bind to 30S and block
transcription process
Aminogl coside- bind to 30S ondifferent receptors which blocks theformation of 70S
Er t rom cin- binds to 50 S whichinterferes the translocation reactions
Chlor mphenicol- binds to 50 S andinhibits peptidyl transferase activity
Other drug: Clindamycin
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Many bacteria uses enzymes for
replication that do not exist inhuman cells
Fl oroq inolones- inhibitsDNA gyrase causing failure ofDNA to replicate
Other drug: Rifampicin
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Antimetabolites Folic acid or folate-
important in the synthesis
of Nucleic Acid
Sulfonamides- prevents theformation of PABA (para-aminobenzoic acid) which isthe precursor of folate
Trimethoprim- selectivelyinhibit dihydrofolatereductases of bacteria and
protozoa
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Disruption of the integrity ofcell wall would lead to leakcomponents and substanceswithin the cell that are vital toits survival
Polymixin- inserts into thelipid bilayer and then
forming artificial pores
Other drugs: Nystatin
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The ability of the bacteria to developways to mutate or secrete enzymesthat make antimicrobials ineffective
CONTRI
TING
FACTORS:
1. Production of drug-inactivating
enzymes
2. Changes in receptor structure
3. Changes in drug permeation and
transport4. Development of alternative
metabolic pathways
5. Emergence of drug resistant microbes
6. Presence of factors which facilitates drugresistance
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Productionofdrug inactivating
enzymes
Beta lactamases destroys the beta-
lactam ringsResult: Cephalosporins and penicillinsbecome ineffective
Changes in receptor structure
Alteration of penicillin-bindingproteins
Result: Decreases the affinity forbinding beta-lactam antibiotics
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Changes in drug permeation andtransport The bacteria are able to hydrolyze
the antibiotics as it slow enters the
cell The production of efflux pump
which extrudes certain drugs
Development of alternative
metabolic pathways To combat the effect of
sulfonamides inhibition of synthase, the bacteria produces PABA torecover dihydropterate synthaseto form folic acid
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Emergence of drug-resistant microbes
Drug specific resistance- by spontaneousmutation
Multiple drug resistance- by conjugationprocess
Factors that facilitate resistance
Prophylactic use of antibiotics LoweringMIC will lead to antimicrobial
resistance
Example: improper dosage
improper duration
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1. ethicillin-ResistantStaphyclococcus
aureas or RSA
Resistant to all staphylococcicPenicillins
Alters penicillin-binding proteinswhich leads to reduction of the abilityof Penicillins to inhibit cell wallsynthesis
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2.Vancomycin- ResistantEnterococci or VRE
> resistant to:1. penicillin + aminoglycoside2. cephalosporin +
aminoglycoside
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3.Penicillin-ResistantStreptococcus pneumoniae
- emerged due to the frequentuse of Penicillins andCephalosporins as prophylaxisfor Otitis media
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4. ultiple Drug-ResistantTuberculosis or DR-TB> has developed due toinadequate therapy
> short duration> low dosage> patients poor adherence
Multiple drug therapy
> strategy to reduce theincidence ofMRE> starts with a number of drugs,then followed by a decrease inthe number, but no less than 4drugs are given at any time.
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1. Identification of Pathogen2. Drug Susceptibility
3. Drug Spectrum4. Drug Dose
5. Duration
6. Site of infection7. Patient (health status, lifespan and gender,
environment, culture and inherited traits)
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Drugs must be specific to the type ofpathogen involved
Steps in identifying pathogens1. Staining Techniques
> check if G+(often aerobic) orG- (mostly anaerobic)
2. Visualization under the microscope> check the shape of the pathogen3. Cultivating microorganisms in culture
media4. Biochemical Testing
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Perform culture and sensitivity
Culture determines the identity of themicrobe
Sensitivity- determines whichantimicrobial agent is therapeutic
1. Disk Diffusion Method- MIC are basedon the zone of inhibition afterinoculating bacteria on an agar platewith a standardized amount ofantimicrobial agent.
2. Broth Dilution MIC directlydetermined by inoculating bacteria intoliquid media containing graduatedconcentrations of the antimicrobial.
It also exhibitsMBC (minimum bactericidal
concentration)
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SPECTRUM- the range of microbes against which a drug is active
1.Narrow spectrum- affects few microbes> limits the potential for adverse effects like superinfectionExamples: Isoniazid- forMycobacteria ; Cloxacillin- for Staphylococci and Streptococci
2.Broad spectrum- affects a wide variety of microbial speciesExamples: Chloramphenicol, Tetracyclines
3.Extended spectrum- effective against G+ and some G- microorganismsExamples: Ticarcillin, Carbenicillin
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Rule: Choosing the drug withthe narrowest spectrum isvital
Combination therapy- alternative to broadspectrum therapy- used in severe infection inwhich the pathogen is
unknown- used in mixed infection(more than one species ofpathogen)- used to prevent
antimicrobial resistance
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Depends on: Type of pathogen Site of infection
Presence or absence of hostdefenses
General duration: 7-10 days; but mayextend to 30 days or more for
severe infections
Early withdrawal of antimicrobialtherapy may lead to REINFECTIONwith the same pathogen which will
have becomeMORE RESISTANT
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1. Antimicrobial activity- bactericidal or bacteriostatic?
2. Selective toxicity- must only affect the infective agent and
not the host cell3. Solubility in water or solvents4. Stability
- able to perform its action in a relativelyshort time to minimize toxicity
5. Homogeneity
- useful in diluted form to minimize toxicity6. Capacity
- broad or narrow spectrum?7. Non-corroding and non-staining8. Availability
-must be easy to obtain and not expensive
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1. Type of microorganisms> spores? vegetative form?
2. Physiologic state of the cell
3. Environmental factorspH favorable in alkaline or acidicTemperature - @ what temperaturedisinfection takes placeConsistencyConcentrationof theagentPresenceofextraneous organic matter
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1.Health Status
2.Life Span3.Gender
4.Environment
5. Culture
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Patients with hypersensitivity Must be assessed for previous
allergic responses to a particular drugclass
TRUE ALLERGIC symptoms- rash,itching, hives, periorbital swelling,shortness of breath
Patients with compromisedimmune system Must have bactericidal agents since
patients immune responses arelimited
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Infants and elderly- the most
vulnerable to drug toxicity
Infants- due to immature liverand kidneys
Elderly- due to aging liver andkidneys
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Lactating mothers Drugs may combine with the
breastmilk
Example: sulfonamides causingKernicterus (type of brain damage)
PregnantWomen
Drugs may cross the placenta andmay damage the developing fetus
Example: Tetracycline- causing graymottled discoloration of the rudiments
of the teeth of the fetus.
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In the blood (intravenous)
Achieves the highest drugconcentration
Has high potential for adverseeffects
Example: Amphotericin B- causes an infusion
reaction when administered intravenously
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Genetic factors that are
influenced by antimicrobialtherapy
Example:
Glucose-6-phosphate deficiency- has
RBC lysis Sulfonamides should not be given since it
also induce RBC lysis
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For infants and elderly clients, monitorthe renal and hepatic function tests
For long term therapy, other laboratory
tests are needed CBC for drugs that can induce
anemia
Monitor serum drug levels
especially those that have highpotential for severe adverseeffects IM- an hour after infusion IV- 30-45 minutes after infusion
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1.Penicillins- inhibit of cell wallsynthesis
Penicillin G
Ampicillin Cloxacillin
Amoxicillin
2.Cephalosporin- inhibit of cellwall synthesis Cephalexin Cefuroxime Ceftriaxone
Ceftazidime
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3. Aminoglycosides- inhibits ofprotein synthesis
Gentamicin
Amikacin Neomycin
4.Macrolides- inhibits protein
synthesis Erythromycin
Azithromycin
Clarithromycin
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5. Tetracyclines- inhibitsof protein synthesis Tetracyclines
Doxycycline
6. Fluoroquinolones- inhibitsof nucleic acid synthesis
Ofloxacin Levofloxacin Moxifloxacin Nalidixic acid
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7. Sulfonamides- inhibition of
metabolic pathways
Sulfisoxazole
Sulfamethoxazole-
trimethoprim
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PREPARE FOR POST TEST:
GET YELLOW PAPER
PREPARE FOR THE EXAMONMONDAYSCHEDULE:
SET 1 6 8 AMSET 2 12 NOON- 2 PMSET 3 6 8 PM