Antibacterial Agents (1)

8/6/2019 Antibacterial Agents (1)

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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

Antibacterial Agents (1)

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