Lecture 5 -2nd half Flashcards
slide 38
review at end
slide 39
review at end
What to know to select correct treatment:
-identify organism
-susceptibility of organisms to a give mobile agent
-client factors (regnanct, allergies, breastfeeding)
-safety of drugs
-cost of drug
Gram negative:
-thin peptidoglycan layer
-has outer lipid layer that has LPS: harder for antibiotics to penetrate LPS layer
-gram stain pink
Gram Positive:
-thick layer of peptidoglycan
-no outer lipid layer
-gram stain purple
Gram variable Bacteria:
-not clearly pink or purple gram stain (both)
-mobiluncus spp, and gardnerella vaginalis which are typical associated with bacterial vaginosis are gram variable
-it’s likely BV if not yeast
slide 44 labelling gram + vs -
mobiluncus and gerdnerella
mobiluncus = gram - with thin peptidoglycan cell wall and an outer membrane
gernerella = gram + with thick cell wall and absence of external membrane
antibiotic resistance
-antibiotic resistance rapidly increased (superbugs, MRSA as examples)
-how to avoid:
1.Use antibiotics properly and avoid when possible
2.Start with narrow-spectrum (narrow treats single group of microbes, extended/medium treat more globally, broad spectrum is a wide range)
3.Culture and sensitivity tests (helpful with drug allergies)
4.Counsel clients appropriately (complete entire course of treatment)
-**slide 47 = white circles are different antibiotics, yellow is bacteria. Circles with big green circles are effective antibiotics for that specific bacteria
Antibiotic Resistance causes:
-occurs when antibiotics that have historically killed a given strain of bacteria no longer work
-arises from alteration sin bacterial DNA (mutations or takes on DNA from another strain)
Antibiotic Resistance Mechanisms:
-microbes can become antibiotic resistant by take DNA from another drug resistant strain (horizontal gene transfer)
-drug resistance genes often coded on plasmid dna
horizontal gene transfer occurs in 3 ways:
- transformation
-pieces of dna are taken up from the external environment - conjugation
-transfer of plasmid dna via direct cell to cell contact (via a pilus) - transduction
-a bacteriophage (virus that infects bacteria) performs the gene transfer
slide 50 antibiotic resistance mechanisms
Antibiotic Resistance Types
- Enzymatic inactivation of antibiotic
-most common mechanism
-bacteria make enzymes that metabolize antibiotics
-ex beta-lactamases - Decreased antibiotic uptake
-gram - organisms can be resistant to some antibitoics as drug cannot pentrate outer cell membrane
-decrease number of porins/protein channels
-ex cephalopsporins - increased antibiotic efflux
-energy dependent pumps transport the drug out of cells
-ex quinolones - modification of antibiotic targets
-receptors for drugs, target molecules, enzymes are modified
-ex. s. aureus became resistant to methicillin because the penicllin-binding protein changed shape
slide 52 antibiotic resistance - types
Antibiotics:
-anti life - inhibit growth of bacteria without hammering host
-bacteriocidal = kill directly, ex penicillins make holes in bacteria, bacteria die, immune system clears up the cellular fragments
-bacteriostatic = stop growth or division of bacteria
-need an actively fighting immune system to resolve the infection
slide 54 modes of antibiotic action
cell wall synthesis inhibitors
-peptidoglycan cell wall is in bacteria is made of a carbohydrate backbone linked together by amino acid side chains and cross bridges
-the beta-lactam antibtioics (ex peniciilins and cephalosporins) inhibit the formaion of the peptide cross-bridges
-the peptidoglycan cell wall is thus incomplete and weakened, and the cell may undergo autolysis
slide 56 cell wall synthesis inhibitors
slide 57 protein synthesis inhibitors
yt video
Protein synthesis inhibitors - 50s subunit
50s subunit
-clindamycin
-macrolide class - azithromycin and erythromycin
Protein synthesis inhibitors - 30s subunit
30s subunit:
-aminoglycoside class - gentamicin
-tetracycline class - doxycycline
-trna interference:
-mupirocin (part of apno)
dna synthesis inhibitors
fluroquinolones inhbit dna synthesis:
-most common is cirprofloxacin
-gets inside bacteria via porins and inhibits DNA gyrase
-dna gyrase is the enzyme responsible for relaxing/uncoilin DNA so it can be replicated
nitrofurantoin is a prodrug:
-activated by susceptible bacteria when excreted into urine
-reactive intermediates have many functions, including inhibit bacterial DNA synthesis but also:
inhibit protein synthesis, inhibit aerobic energy metabolism, inhibit RNA synthesis, inhibit cell wall synthesis
bacterial dna synthesis slide 60
yt vid
folate synthesis inhibitors slide 61
yt vid
why do we care about folic acid in humans
-need dietary folic acid to make bases for DNA (we dont make our own folic acid)
-without proper bases, dna cant divide
-if dna cant divide then cells cant divide
-since the neural tube is formed very early in development and requires tons of cell division, deficiency in folic acid leads to nerual tube defects (aren’t enough cells to close the neural tube properly)
folic acid in bacteria
-principle is the same as in humans except that bacteria make their own folic acid
-use p-aminobenzoic acid (PABA) for de novo synthesis
fungal anatomy
-usually multicallular eukaryotic organsims
-cells have cell walls containting chitin (as oposed to cellulose or peptidoglycan)
-cannot make their own food (heterotrophic) and obtain nutrients from organic material
-most infections (actually more of a dysbiosis) in the midwifery context are caused by candida albicans
-this is a yeast that lives in the resp., gi and repro tracts
-member of the family ascomycota, part of the normal human microbiome
antifungals
-inhibit growth of fungi without harmin host
5 classes: azoles, polyenes, echinocandins, allylamines, pyrimidine analogs
-effective against candida species
antifungals on 188/24
azoles:
-clotrimazole (cannesten)
-fluconazole
-miconazole (monistat)
polyenes:
-nyastatin
Azoles
-are an antifungal
-inhibit sterol 14alpha-demethalase
-essential enzyme in sterol biosynthesis
-prevents the formation of ergosterol - a vital component in fungal cell membranes
polyenes
-an antifungal
-acts on the fungal cell membrane through hydrophobic interactions
-sequester membrane sterols, creating membrane pores - cell death
slide 65
slide 66
nipple pain
-all purpose nipple ointment APNO
-mupirocin-betamethasone valerat-miconazole
-mupirocin = a topical antibiotic
-betamethasone valerate = a steroidal anti-inflammatory
-miconazole = antifungal, effective against yeasts and also some gram + bacteria
-ibuprofen can be added for pain relief PRN
-made at compounding pharmacy
slide 70 APNO prescription
APNO - mupirocin (topical)
-mupirocin inhibits protein production in cell (inhibits trna production)
-can be absorbed by the infant PO but majroty sticks to nipple
-often suspended in polyehtylene glycol (PEG) - some people have allergies to PEG
APNO - betamethasone valerate (topical)
-high potency steroidal anti-inflammatory
-purpose in apno is to decrease pain caused by tissue inflammation
-side effects from long-term use, not in short term topical use
APNO - miconazole
-antimycotic/antifungal - inhibits formation of ergosterol which is necessary for fungal cell walls
protection against thrush
-effective against some gram + bacteria - useful as staphylococcus may lead to mastits in an inflammed cracked areola/nipple
-side effects (unlikely as less than 1% absorbed into maternal cicrualtion)
-on skin - stinging, eryhtmea and local irritaion, contact dermatitis is rare
-unclear how much reaches baby when breastfeeding
APNO - ibuprofen
-and dont forget ibuprogen can be added
-practioners vary on their managment regarding when they add to the prescription
-ibuprofen is an NSAID
-inhibits inflammation by inhibiting the cox enzymes in the prostaglandin pathway
