Antibiotic Review Flashcards
What are the reasons for responsible prescription writing?
minimize the development of antibiotic resistant microorganisms
minimize harm to the patient caused by toxicity from unnecessary drugs
provide cost effective treatment
What are the Centor criteria and what do they tell you?
A centor score of 2 or higher, then there’s likely a bacterial infection so you should conduct a rapid antigen detection test
absence of cough = 1 age 3-14 = 1, 15-45 = 0, >45 = -1 anterior cervical LA = 1 fever = 1 tonsillar erythema or exudate = 1
What is a rapid strep test actually detecting?
C-carbohydrate on the bacteria’s outer membrane
What is the specificity and sensitivity of the rapid strep test? What does this mean in terms of diagnosis/
specificity is great - over 95%
sensitivity is relatively low at 80%
this means that you can get a lot of false negatives - need to follow any negative with sputum cultures
What’s the number one antibiotic of choice for strep pyogenes pharyngitis?
penicillin (and there really isn’t much resistance, so that’s good)
What are the 4 groups of beta-lactam meds?
penicillins
cephalosporins
carbapenems
aztreonam
What is the mechanism of action for the beta lactam ABx?
they bind to the penicillin binding protein, which is a transpeptidase required for the peptide-linking step in cell wall synthesis
you get a build-up of cell wall rpecursors, which activates autolytic enzymes
ultimately you get cell lysis = bactericidal
When would you consider using penicillin G over penicillin V? What’s the greater risk with G?
Use G if you’re concerned about compliance - you only have to give one injection in the office
the risk for anaphylaxis is higher with G than V
Amoxicillin is also used for treatment of strep pyogenes, but why is penicillin preferable?
it’s super broad spectrum so you need to worry about killing normal flora
What should you give in anaphylaxis? What is the effect on vasculature? On pulmonary system?
epinephrine - induces vasoconstriction via alpha1, tachycardia via beta1 and bronchodilation via beta2
What other drugs should you avoid if a person has a hypersensitivity to penicillin? What’s ok?
avoid cephalosporins and carbapenems = cross-sensitivity
aztreonam is okay because it’s a monobactam
Why wouldn’t aztreonam work for strep pharyngitis though?
it’s only effective against gram negatives
So what should you give a patient with a penicillin allergy if he has strep pharyngitis?
Have to go to a macrolide or clindamycin
What are the three macrolides we know?
erythromycin
azithromycin
clarithromycin
What is the mechanism of action for the macrolides?
bind to the 23s rRNA of the 50S subunit, inhibiting translocation
What’s the spectrum of macrolides?
broad coverage of respiratory pathogens
How do bacteria get resistance against macrolides? Two ways….
methylation of the 23s binding site
increased efflux
What are the adverse effects of macrolides?
GI discomfort (stimulates migratory motor complex) prolonged QT hepatic failure (inhibits CYP3A4)
Which macrolide is counterindicated in pregnancy?
clarithromycin - associated with miscarriages
Treatment failure ocurs in 15% of positive GAS cases. What are potential reasons for this?
- antibiotic resistance - rare for penicillin, but 5-8% resistant to macrolides
- lack of compliance
- had a viral pharyngitis, but was a carrier for GAS
- neighboring flora like H. flu secrete beta-lactamases
- Strep pyogenes can enter epithelial cells and hide from ABx
Treatment for influenza is usually just supportive, but what groups of people do you treat?
those with severe illness over 65 yrs old under 2 years old pregnant with chronic illnesses
What are the two groups of influenza antivirals?
adamantane (amantadine)
neuraminidases (oseltamivir and zanamivir)
What does adamantane block?
viral uncoating
Why is adamantane not really used anymore?
It was only effective against influenza A in the first place and now the vast majority of strains are resistant to it
(change in viral M2 proton ion channel)
What do oseltamivir and zanamivir do?
They block the effects of neuraminidase such that you don’t get the cleavage step necessary for viral spread
When are oseltamivir and zanamivir effective? In what strains?
when the virus is in the actively dividing phase - so treat within the first 48 hours of symptom onset
effective for influenza A and B but not C
Why can resistance develop so quickly for influenza?
high mutation rates - viral polymerase makes a lot of mistakes
leads to antigenic drift and shift
Describe oseltamivir a little more:
age for use, metabolism, excretion, side effects
use in people over 1 yr of age
prodrug needs to be activated by hepatic esterases
renal excretion (so modify for renal insufficiency)
GI side effects, HA and fatigue
Describe zanamivir in more detail:
age of use, how is it taken? why is this important?, who do you avoid it in?
Use in people over 7 years
you inhale it, but only 10-20% reaches the lung
the remainder in the oropharynx can cause bronchospsm, so avoid in patients with asthma and other pulmonary diseases
Why do we treat the high-risk flu cases? Is it because of flu complications?
it’s not necessarily the flu we’re worried about - it’s the secondary bacterial pneumonia that kills people
What is another term for secondary infection after a previous infections?
superinfection
Why does influenza promote secondary pneumronia?
causes apoptosis of airway epithelial cells so you have inhibition of mucocilliary clearance
also, the neuraminidase enhances bacterial growth
What are the organisms to think of for secondary pneumonia after influenza? According to Amy…
strep pneumoniae
staph aureus
GAS
CXR confirmation is often unnecessary for a diagnosis of community-acquired pneumoniae, so any antibiotic treatment you initiate without a CXR is considered what? What should you do before that though?
empiric
take a sputum sample for gram stain and culture first though
What are the common etiologies of community-acquired pneumonia?
mycoplasma neumoniae respiratory viruses strep pneumoniae chlamydia pneumoniae legionella hamemophilus influenzae
Do empiric and definitive ABx treatment really differ in terms of pneumoniae treatment?
no differences in mortality rates or length of hospitalization
What are examples of broad spectrum ABx?
carbapenems chloramphenicol 3rd gen fluoroqhinolones 2nd, 3rd and 4th gen caphalosporins tetracyclines
What are examples of narrow spectrum ABx?
penicillin lincosamides glycopeptides streptogramins Rifamycin
What are the two main antibiotic choices for comunity-acquired pneumoniae uncomplicated by other lung pathology?
doxycycline or a macrolide
What ABx should you use for CAP in patients with comorbidities or ABx use within the past 3 months?
a respiratory fluoroquinolone
or a high-dose beta-lactam plus macrolide
What are the 4 general mechanisms of drug resistance?
- Alteration in drug target
- enzymatic inactivation
- decreased uptake
- increased efflux
For strep pneumoniae, what is the cause of the penicillin resistance?
mutation in penicillin binding protein (so can’t really use a beta lactam with a betalactamase)
For strep pneumoniae, what is the cause of macrolide resistance? Two things…
- alteration of ribosomal binding site
2. increased efflux
The pneumococcal vaccine was introduced in about 2000. What effect did the vaccine have on resistance to macrolides?
it wasn’t really effective against drug-resistant serotypes, so now 90% of strains are now resistant to macrolides
What are the three respiratory fluoroquinolones?
gemifloxacin
levofloxacin
moxifloxacin
What is the mechanism for the fluoroquinolones? Bactericidal or static?
they directly inhibit DNA replication by binding bacterial DNA topoisomerase II (gyrase - gram neg) and topo IV (gram pos)
bactericidal!
What is the spectrum of coverage for the respiratory fluoroquinolones?
broad: gram positive, negative and atypicals like mycoplasma
What are the two causes of resistance to fluoroquinolones?
active efflux
mutation of topoisomerase binding sites
What are the side effects of the fluoroquinolones? Counterindicated in what groups?
GI discomfort
tenindopathies
Don’t use in pregnancy, lactation or children
What two antibiotics are typically used for mycoplasma pneumoniae?
doxyxycline or azithromycin
can’t use a betalactam obviously bc it doesn’t have a cell wall
Mycoplasma pneumoniae is hard to culture, so how do you make diagnosis?
test for cold agglutinins (IgM)
What is the mechanism of action for the tetracyclines like doxycycline? Cidal or static?
They bind to the 30S subunit preventing attachment of aminoacyle tRNA, disrupting protein synthesis
bacteristatic
Why is spectrum of tetracyclines so limited? What can you use it for?
Resistance is so widespread
use for B. burgdorferi (lyme disease), H. pylori and mycoplasma pneumoniae. Will NOT work against gram negative rods
What are the two main mechanisms of resistance to tetracyclines?
- reduced uptake
2. increased efflux
What are the adverse effects of tetracycline? Contraindicated in what groups?
photosensitivity, discoloration of teeth, inhibition of bone growth
avoid in pregnancy and children
don’t take with milk - oral absorption limited by cations
Does doxycycline exhibit concentration-dependent killing or time-dependent killing? What does this mean for treatment strategy?
concentration-dependent
means you need to get the concentration over 10 times the minimum inhibitory concentration
What group of ABx are especially time-dependent and how does this affect treatment strategy?
the beta lactams - this is why you need to have multiple doses for a longer course
What are the three main nosocomal pneumonias?
MRSA
pseudomonas aeruginosa
klebsiella pneumoniae
What are the two drugs you can give to treat MRSA pneumonia? Why not daptomycin?
give vancomycin or linezolid
can’t use daptomycin because it’s inactivated by pulmonary surfactant
What ABx can you give for pseudomonas aeruginosa?
piperacillin/taxobactam with cefepime (4th gen ceph)
imipenem/cilastatin, aztreonam
How do you treat klebsiella pneuoniae if it has carbapenemases?
extended spectrum beta-lactamase with colistin-polymixin E
How does vancomycin work?
spectrum?
it’s a glycopeptide that inhibits cell wall synthesis by binding to the D-ala D-ala dipeptide , inhibiting the transglycosylation reaction
mainly effective against gram positives
What is the mechanism of action for linezolid? Spectrum?
it’s an oxazolidone that targets the 50S ribosome and inhibits protein synthesis
mainly effective against gram-positive organisms like staph, enterococci, and strep
Infections with gram negative bacilli are particularly common in what group?
CF patients
What is the mechanism of polymyxin E/colistin? Spectrum?
it binds phosphatidylethanolamine in the membrane, creating holes
used for multidrug resistant gram negatives like klebsiella
What’s the side effect of polymyxin E/colistin that makes it a drug of last resort?
nephrotoxicity
How does resistance to polymyxin E develop?
trick question - resistance is super infrquent and slow to develop - no cross-resistance with any other ABx
Describe the general pathogenesis of histoplasmosis? What kind of fungus is it?
It’s dimorphic:
In the environment it is a mold with hyphae and connidia. The connidia are released as spores, which we inhale into our lungs. In the lungs the spores bud into a yeast.
What will you see microscopically in a histo infection?
reticuloendothelial cells
Where is histo most common?
the mississippi/ohio river valleys
What will blastomyces dermatitidis look like microscopically?
broad-based yeast
Where is blastomyces endemic?
inhabits rotting wood in the eastern US
What will coccidioides immitis look like microscopically?
endospores in a spherule
Where is coccidioides endemic?
in the US southwest - needs dry climates
Where can fungal pneumonias disseminate in immunosuppressed individuals?
bones, joints and CNS
What is the mechanism of action for amphotericin B?
It’s a polyene that binds ergosterol to create holes in the fungal membrane allowing leakage of electrolytes
What is the spectrum for amphotericin B?
used for invasive systemic fungal infections in immunocompromised patients - active against both yeasts and molds
What are the adverse effects of amphotericin B and why does basically everyone have side effects?
it’s super toxic because it can bind to cholesterol (which is everywhere for us).
decreases renal blood flow and can lad to permanent destruction of the basement membrane - 80% will have nephrotoxicity
How does resistance develop against amphotericin B?
It rarely happens, but you can have degreased ergosterol in the membrane
What are the four general issues aspergillus fumigatus can cause?
- allergic bornchopulmonary aspergillosis - just a hypersensitivity reactions (reaction to brown mucous plugs containing fungi and eosinophils) - most common in asthma or CF
- aspergillomas - fungal balls in lungs
- fungal sinusitis
- systemic disease in immunocompromised
If the aspergillus is systemic, how do you treat it?
with voriconazole
Why is mortality rate between 45-80% with systemic disease even with voriconazole?
patients are often severely neutropenic due to immune compromise and just can’t clear the infection
Why is prednisone sufficient for treating the alelrgic bronchopulmonary aspergillosis?
it’s just a hypersensitivity reaction - no fungus has actually invaded the body
What is the mechanism of action of the axoles like voriconazole and itraconazole?
they bind the fungal p450 enzyme Erg11, thus blocking the production of ergosterol and causing the accumulation of a toxic intermediate called lanosterol
What are the major toxicities of the azoles?
drug-drug interactions, hepatotoxicity, neurotoxicity, altered hormone synthesis (so avoid during pregnancy)
What are the 2 main causes of resistance against the azoles?
altered Erg11
upregulation of efflux
What agents can be used for symptomatic treatment of respiratory infections?
- antitussives to block cough refluex
- expectorants to thin mucus
- NSAIDs for analgesia and fever reduction
- decongestants - constrict blood vessels in nasal mucosa
- anti-histamines
- bronchodilators
- supplemental O2
- nebulized cold steam
- corticosteroids
What are some home-substances that can be effective prophylaxis against respiratory infections?
garlic
vitamin C
Echinacea
probiotics
What are some reasons by patients should be careful about consuming combination or products?
- decongestants and antiH1 = make mucus thicker
- might end up taking too much analgesics!
- may help symptoms, but the symptoms like cough may have been helping them clear the infection
- no better at relieving symptoms than blacebo (alcohol, benzocaine, expectorants, codeine, antihistamine monotherapy)
Why shouldn’t you give cough medicines to kids under 4?
the risk of ovredose is too high and you don’t get much benefit
