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BIOM 4090 > Unit 06: antibacterial drug therapy and beta lactams > Flashcards

Unit 06: antibacterial drug therapy and beta lactams Flashcards

1
Q

explain the gram reaction

A

gram positive stain purple

gram negative counterstained red

  • fix cells, add crystal violet, idoine treatment which bidns to crystal violet and traps in cells, add alcohol then counterstain with safranin
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2
Q

describe the gram negative bacteria

A

have an outer membrane, asymmetirc bilayer in which the outer leadlet is comprised of lipopolysaccharide

  • structurally unusual membrane forms a permeability barrier that excludes wide bariety of mol and limits penetraiton of gram stain
  • the murein layer is thinner and is surrounded by a second, outer lipid bilayer membrane.

Hydrophilic molecules cross this outer membrane through channels, which are formed by a cylindrical arrangement of pore proteins (porins).

have lipopolysaccharide (LPS) in the outer membrane- major antigen for the immune response to Gram-negative organisms.

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3
Q

describe gram positive bacteria

A
  • have a thick peptidoglycan (murein) layer whereas gram negative only have a thin layer
  • thick later allows nutrients, waste producst and antibiotics to difuse
  • lipoteichoic acids in outer leaflet of membrane intercalate through the cell wall to the outer surface - inolved in cell adherance, feeding and envasion of host immune system
  • peptidoglycan consists of sugars (polysaccharides) and amino acids (polypeptide) that are cross linked to form the outside of the PM
  • since gram stain binds to peptidoglycan- thck layer makes it stain purple
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4
Q
A
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5
Q

what are the steps in anybacterial drug susceptibility testing

A
  1. determine the MIC - lowest conc of drug that inhibits vidible growth
  2. determine the MBC- minimum bactericidal conc, lowest conc reuqired to kill a particular bacterium

*determine by taking dilutions of the MIC and sub-culturing onto ati-bacterial free media, then test tubes for growth.

*even though may not be growth bacteria may still be alive

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6
Q

MIC/MBC testing is $$$ what is usually done instead

A
  • Kirby-Bauer disk diffusion test
  • paper disks are impregnated with drug and palced on a plate with uniform “lawn” of bacteria
  • drug idffuses into the agar and the zone of inhibition around each disk is measured after a specific time
  • zone diameter is copmared to a standard regression curve that correlates this with MIC (Ug/mL) - bacterial isolate is reported as sensitive, intermediate or resistant to drug
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7
Q

is bacterial resistant all or none?

A
  • resistance to any drug is not an all or none charcateristic
  • each infection contains a mix of bacteria of different sensitivities and therapy may leave the most resistant strains to grow
  • different strains of the same abcterium from different patients may also difer in sensitivity even in same geographic area
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8
Q

what are the 5 steps to selecting and administering antimicrobial drugs?

A
  1. if possible identify the organism
  2. initiate treatment immediately

. select a drug

  1. determine dosage
  2. assess drug safety
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9
Q

describe step 1 of selecting/administering antimicrobial drugs - identiy the organism

A
  • accomplished through Gram or other stains, using the literature or previous experience with a similar organism.
  • Culture and sensitivity testing should also be performed for most life threatening infections or when a non-critical infection is resistant to empirical therapy.
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10
Q

describe step 2 of selecting/administering antimicrobial drugs - initiate treatment

A
  • want to do immediately
  • delay may lead to other infections like meningitis or septic arthritis (v dangerous)
  • treatment can begin while you are wating on results of the culture and sensitivity teating

*at this point treatment is essentially an educated guess

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11
Q

describe step 3 of selecting/administering antimicrobial drugs - select a drug

A
  • based on bacterial sensitivity and preferable you should use narrow spectrum drugs to avoid killing comensal bacteria
  • need to determine if ebst to prescribe a bacteriostatic (stops bacteria from reproducing) or bactericidal (kills the bacteria)
  • bactericidal drugs are often used if the immune system is compromised or infection is life threatening
  • also consider safety, adverse effects, drug dsitribution (CNS and prostate are difficult tissues for drug to enter) and the cost to patient
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12
Q

describe step 4 of selecting/administering antimicrobial drugs - determine dosage

A
  • usualy done by commerical government labs
  • label recommendations or consultation with a reference text is advised
  • dose can be adjusted according to patients needs
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13
Q

describe step 5 of selecting/administering antimicrobial drugs - safety

A

imp to consider when need for drug is not critical

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14
Q

what disease processes require special consideration and basic principles cannot be applied

A

osteomyelitis, foreign bodies, abcesses, intracellular pathogens and immunodeficiency

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15
Q

why does osteomyelitis reuqire special consideraition before antibiotic prescription

A
  • type of infection and inflammation of the bone or bone marrow
  • in chronic osteomyelitis patients, antibitic therapy is unually prolonged compared to toher infections -lasting 6-12 weeks

despite this recurrence of infection is common

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16
Q

why do foreign bodies reuqire special consideraition before antibiotic prescription

A
  • foreign bodies like quils, slivers, nails or plant awns always come with risk of subsequent bacterial infection
  • the foreign material must first be removed and then prophylactic antimicrobials are administered (generally broad spectrum) before any signs of infection appear
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17
Q

why do abscesses reuqire special consideraition before antibiotic prescription

A
  • abcess is a collection of pus (neutrophils) that has accumulated in tissue as a response to ifnection agent
  • before treatment can be administered, abscess needs to be drained
  • in some cases dont need antimicrobial after
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18
Q

why do intracellular pathogen reuqire special consideraition before antibiotic prescription

A
  • mycobacteria, salmonella and legionells surive inside cells therefore it is necessary to use a drug that enter cells readily
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19
Q

why do immunodeficiencies reuqire special consideraition before antibiotic prescription

A
  • deficient host defences sucha s those that are the result of infectious disease, stres,autoimmune or inherited diseases and idopathic immunodeficiency may reuqire drug conc that are much higher than normal
20
Q

describe prophylactic treatment usign antimicrobials

A
  • refers to use of pharmacologic agents fr prevention rather than treatment
  • used in situations where there is high risk of serious infection following trauma like meningitis and/or when a patients condition predisposes them to more serious infection like UTI
  • risk period must be known and covered in order for this treatment to be successful
  • ex prophylactic therapy could be used following radiation therapy in some cases where the individuals immune system may be compromised as the benefits during period outweigh risks adn ride effects
21
Q

prophylactic treatment during surgical situations

A
  • microbes could enter body during procedure
  • includes the opening of any portion of GI tract or major abdominal or thoracic organ (gut resection, hysterectomy, C-section, cardiac surgery), opening a joint, major proedures of head/neck or placement of prosthesis
22
Q

appropriate antimicrobal drug selection for prophylactic sue requires knowledge on

A

General spectrum of activity

Major adverse effects

Distribution/elimination

First line, second line, or emergency classification

Cost

Possible routes of administration

23
Q

what are the 6 main categories of antimicobial drugs

A

beta-lactams, aminoglycosides, tetracyclines, sulfonamides, fluoroquinolones, and macrolides.

24
Q

what are the 5 main sites of action for antimicrobial drugs

A

Inhibition of cell wall assembly

Damage to cell membrane

Inhibition of protein synthesis

Inhibition of nucleic acid synthesis

Damage to DNA

25
Q

what are the 3 general groups of antibacterial drugs

A

those that inhibit eznymes in DNA synthesis and integrity

  • those targeting transcription and translation to inhibit bacterial processes that meidate RNA and protien synthesis
  • those that inhibit steps in bacterial cell wall synthesis
26
Q

what is a beta lactam

A
  • common systemic antimicrobial agent that is very safe and effective
  • only works for actively growing bacteria
  • contain a four membered lactam (cyclic amide) which confers antibacterial activivty but sensitive to destruction by bacteria expressing beta-lactamases
27
Q

what are commonly prescribed beta lactams

A
  • penicillins and cephalosporins
28
Q

how are bacteria resistant to B lactams

A
  • able to cleave the B lactam bond reuqired for antibiotic action
  • B lactamase inhibiots like clavulanic acid and sulbactam act as decoys by binding to (inhibiting) B-lactamase enzymes

*structural similarity between B lactamase inhibitos and the B lactam antibioitcs

29
Q

what is clavulanic acid

A

act as decoys by binding to (and thereby inhibiting) β-lactamase enzymes.

30
Q

what is sulbactam

A

act as decoys by binding to (and thereby inhibiting) β-lactamase enzymes.

31
Q

what is the mechanism of action for beta lactams

A
  • inhibition of cell wall synthesis
  • bacterial cell wall is made up of cross linked peptidogylcans
  • enzyme bacterial transpeptidase catalyzes the cross linking of sugars with the amino acids to form the outer layer of the cell wall

*beta lactams inhibit cell wall synthesis by inactivating bacterial transpeptidase which results in a defective cell wall and ultimately cell lysis

32
Q

how do penicillins work

A
  • bind covalently to bacterial transpeptidase and result in the destruction of enzyme
  • inhibits cell call synthesis
33
Q

what is penicillin G

A
  • narrow spectrum of activity but highly effective
  • penicillin G is used to treat serious infections with Gram positive bacteria (rod and cocci) as well as some anaeobes
  • not very stable in acidic conditions so reuqired to injection rather than oral admin
34
Q

what is penicillin V

A

Gastric acid stable counterpart

Can be taken oraly but less effective

35
Q

what penicillians are resistant to penicillinase

A
  • dicloxacilin, oxacilin and cloxacilin
  • have little activity against baceria other than gram positive bacteria
  • stable in acidic environments
36
Q

what is dicloxacilin used to treat

A

stubborn S. aureus infections which are resistant to most penicillins

37
Q

what is amoxicillin

A

penicillin with borad spectrum of action

  • target gram positive aerobes, anerobes and several important gram neg pathogens
  • high bioavailability comparied to other penicillins (~80%)
  • much more effective in combination with penicillinase inhibitors like clavulanic acid
38
Q

pharmacokinetics of beta lactams

A
  • distribution involes most tissues except for the CNS and prostate (unless they are inflammed)
  • elimination of agent occurs via urine excretion
  • 10% filtered while other 90% is actively secreted into the tubules
  • half life of penicillines might increase as much as 20 fold in cases of renal failed
39
Q

resistnace to beta lactams

A
  • poor to no penetration of beta lactam complex in gram negatie cell walls, making most penicillins ineffective against gram neg bacteria
  • bacteria can acquire bacterial penicillinases during growth- plasmid encoded and can be transferred to other bacteria
  • altered penicillin binding protein (such as those in staph infections) can reduce the binding affinity of penicillin for transpeptidase
40
Q

adverse effects of penicillins

A
  • hypersensitivity reactions - mild allergy to anaphylactic rxn (rare)
  • various subgroups of penicillins thet are all corss sensitixing - approx 5% of all humans have reported haivng a penicillin allergy at some point
  • non allergic skin rashed have been reported with amoxicillin
  • seizures may occur following admin of b lactams bc they lower seizure threshhold
  • avoid high doses in patients with renal disease or epileptic episodes
  • certain animals can experience colitis which can cause diarrhea and be life threatening
41
Q

what are cephalosporins?

A
  • v similar to penicillins in terms of mechanisms, distribution, elimination and fact they cause hypersensitivity reactions

**cephalosporinsa re not susceptible to penicillinases

  • 5-10% of humans with a penicillin allergy are also allergic to cephalosporins, and should thus these should also be avoided to be safe.
42
Q

describe spectrum of actiivty of cephalosporins

A

classified by “generations”, indicating changes and/or improvements to their structure and activity since the first cephalosporin was discovered in 1945.

  • first genertion v similar to amoxicillin
  • used to treat gram postive aerobes, anerobes and some medically ipmortnat gram neg aerobes like E.coli

cephalexin is common ex of first gen

43
Q

Cefuroxime

A

Second gen

Also used against anerobes

Most second gen drugs are more effective against gram neg bacteria than first gen

44
Q

cefotaxime

A
  • example of third gen
  • greater affinity for gram negative aerobes
  • can cross BBB in CNS readily so use to treat meningitis (specific to cefotaxime)
45
Q

fourth generation cephalosporins

A

reserved for life threatening infections

  • rapidly penetrate through the outer memrbane of gram negatie bacteria enhancing their activity
  • aslo active against B lactamase producing bacteria which amy inactivate third gen cephalosporins

BIOM 4090 (27 decks)

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