Prunuske: Antibiotic Discussion Flashcards
A 8-year-old child had a sore throat, difficulty swallowing, and fever for 5 days. Examination was remarkable for fever; and an extensive red rash on the neck, groin, armpit. A bright red lingual papillae superimposed on a white coat, exudative tonsillitis and cervical lymphadenopathy. The mother is asking for an antibiotic.
What is your differential?
Group A Streptococcus Corynebacterium diphtheriae- grey pseudomembrane Mycoplasma pneumoniae Coronavirus Influenza Rhinovirus Epstein-Barr Virus Coxsackie virus
What causes most pharyngitis/URI? How do we treat them?
Viruses
DO NOT GIVE AN ANTIBACTERIAL DRUG
What factors in presentation suggest infection is bacterial in nature?
A centor scor of 2 or 3:
Absence of cough= 1 3-14 = 1 14-45 = 0 >45 = -1 Anterior cervical lymphadenoaphy = 1 Fever = 1 Tonsillar erythema/exudates = 1
What do you do if a centor score is 2 or 3?
Conduct a rapid antigen detection test (recognizes C carbohydrate)
What is the specificity and sensitivity for a positive rapid antigen detection test?
Specificity (>95%) (SPin) but sensitivity is (80%) (SNout)
What does a lower sensitivity mean?
People will have the disease bon’t DONT test positive
What does a high specificity mean?
If you test positive you can be fairly confident that the pt streptoccous in their throats but they may be asymptomtic carriers
What is the gold standard for treatment if a pt has a centor score of 2 or three and a negative rapid antigen detection test?
Take a culture
A patients throat culture shows a gram + cocci in chains that is also beta hemolytic. What is it?
S. Pyogenes
What are the virulence factors for s. pyogenes?
M protein and hyaluronic capsule prevent phagocytosis, invasins and toxins are also secreted
Why do we treat s. pyogenes?
Treatment prevents sequelae, alleviates symptoms, and decreases spread.
What sequaela are associated w/ s. pyogenes?
RF Glomerulonephritis Hemorrhagic cystitis Scarlet Fever Skin infection
Which of the following were more likely to prescribe early antibiotics without a positive culture?
Men Family Physicians, Practicing more than 12 yrs, Rural
*more likely to get antibiotics on a Friday
What is the appropriate antibiotic treatment for Group A strep infections?
Penicillin
What is the MOA of Penicillin?
Cell wall inhibitor (our cells don’t have cell walls so the med isn’t toxic)
Penicillins, cephalosporins, carbapenems, aztreonams are all what?
Beta lactams
What do beta lactams do?
Bind to PENCILLIN BINDING PROTEINS which are TRANSPEPTIDASES required for cell wall synthesis.
This leads to a BUILD UP of cell wall precursors that activates autolytic enzymes.
What beta lactams bactericidal or bacteriostatic?
bactericidal
When would you consider using penicillin G over Penicillin V?
G is single dose in clinic where as oral form needs to be taken 2-3 times a day for ten days.
Amoxicillin is a BIG gun and could also kill normal flora, so it’s not your first choice.
You give the patient an IM injection of penicillin G. Five minutes later she is in respiratory distress with audible wheezing. Her skin is mottled and cool. She is tachycardic and her blood pressure has fallen. What do you do?
Administer a subcutaneous injection of epinephrine
What is a major side effect associated w/ betalactams?
Anaphylactic reaction
What affect does epi have on a pt’s vascular system?
vasooconstriction> increased in bp
Which adrenoceptor primarily mediates the vascular response?
alpha 1
What effect will epinephrine have on her respiratory system?
bronchodilation
Which adrenoceptor primarily mediates the respiratory system response?
beta 2
What do you use to treat less severe allergic reactions to penicillin?
antihistamines
corticosteroids
What should you avoid if a pt is hypersensitive to penicillin?
avoid other penicillin-subclasses and if severe avoid cephalosporins and carbapenems
What drug is safe to use in pts w/ penicillin allergies but is not a good choice for treating s. pharyngitis?
Aztreonam
That drug is only affective against gram - organisms and we have a gram + organism
Erythromycin, Azithromycin, Clarithromycin are all….
macrolides!
What is the MOA of a macrolide?
Binds 23S rRNA of 50S subunit inhibiting translocation
What is the spectrum of a macrolide?
broad coverage of respiratory pathogenes
What causes resistance to macrolides?
methylation of 23S rRNA where drug is binding so it can’t bind anymore
binding site and increased efflux
What adverse affects are associated w/ macrolides?
GI discomfort, Prolonged QT interval, Hepatic failure- inhibits CYP3A4,
What macrolide is associated w/ miscarriages?
Clarithromycin
Treatment failure occurs in 15% of positive GAS cases so you reculture and switch therapy. What might be some causes of treatment failure?
- Antibiotic resistance- rare for penicillin, 5-8% of strains are resistant to macrolides
- Lack of compliance- patient feels better after 3-4 days and doesn’t finish 10 day course
- Had viral pharyngitis but was a carrier for GAS
- Neighboring flora like Haemophilus influenzae can secrete beta-lactamases
- Streptococcus pyogenes can enter epithelial cells
In December, a 73-year-old man from a nursing home was brought to the hospital in acute respiratory distress. He had been in his usual state of health until 10AM the previous day when he suddenly developed fever, chills, muscle aches, cough, and prostration. Several other nursing home residents had developed a similar illness during the previous week. His past history is unremarkable and he had not seen a physician in the past year.
Rapid Influenza test comes back positive. How do you approach the treatment?
Generally supportive treatment
Treat with antivirals if:
severe illness,
> 65 years,
What are two influenza antivirals?
Adamantane (only active against influenza A)
Neuraminidase (oseltamivir= tamiflu, zanamivir)
Are influenza antivirals active against a dividing virus?
Yes if you treat early (<48 hrs)
What is a preferred influenza prophylaxis?
Vaccine
Antivirals work but SE are common b/c treatment is longer than therapy
What blocks uncoating of the influenza virus once it has entered the cell?
Amantadine
Rimantadine
What blocks the release of influenza from a cell?
Neuraminidase inhibitors
Why is resistance to adamantanes extremely high?
change in viral M2 proton ion channel
Why is resistance to neuraminidases currenly low?
change in viral hemaglutinin or neuraminidase
Why are rates of mutation in influenza so high?
Mutation rate is HIGH for RNA virus
Antigenic SHIFT and DRIFT
What causes new strains of influenza?
Antigenic shift and drift
What is antigenic shift?
gene reassortment leading to altered surface proteins and antigenic profile
What causes antigenic drift?
small gene mutations/changes leading to altered Ab binding sites and escape from immunity
What does a neuraminidase inhibitor do?
prevents viral release
What are two types of neuraminidase inhibitors?
- Oseltamivir: ALL AGES
> 1yr, oral prodrug activated by HEPATIC ESTERASES
Renal excretion- modify for renal insufficiency
GI side effects, headache, fatigue - Zanamivir
> 7yrs, poor oral bioavailability
inhaled 10-20% reaches lung don’t use if other airway diseases
remainder of drug in oropharynx can cause bronchospasms
avoid in patients with asthma and pulmonary disease
A 73 year old man presented with a 7-day history of cough and high fever, in the month of January. He had a flu-like illness 1 week prior to this episode but had otherwise maintained good health. A chest x-ray revealed alveolar infiltrate in the posterior segment of the left lower lobe.
Secondary bacterial pneumonia
What is a superinfection?
secondary infection occurring after previous infection
What causes a secondary infection?
Induce by broad spectrum antibiotic killing off normal flora
How does an influenza infection predispose you to a superinfection?
apoptosis of airway epithelial cells>
inhibition of mucocilliary clearance
viral neuraminidase enhances bacterial growth
What are the MCC of superinfections following influenza?
S. pneumoniae> S. aureus> group A streptococcal
What is community acquired pneumonia?
Spread of orgs normally in the URT into the lower RT
What are the MCC of infection related mortality in the US?
Pneumonia and influenza
How do you diagnose community acquired pneumonia?
Cough, fever, pleuritic chest pain
Infiltrate on chest radiography
Chest -xray positive determining etiology is often unnecessary for CAP. Therefore you begin which of the following types of therapy?
Empiric
Empiric treatment versus treatment based on knowledge of pathogen does
not result in differences in mortality rates or length of hospitalization.
What are common etiologies of CAP?
Mycoplasma
Respiratory viruses
s. pneumoniae
c. pneumoniae
What are examples of broad spectrum antibiotics?
carbapenems chloramphenicol 3rd gen fluoroquinolone Cephalosporins Tetracycline
What are examples of narrow spectrum antibiotics?
Penicillin Lincosamides glycopeptides streptogamins rifamycin
What is used as initial therapy for CAP in previously healthy outpatients w/ no antibiotic use in the past three months?
Macrolide or doxycycline
What is used to tx CAP in outpts w/ comorbidities or antibiotic use in the past three months?
Respiratory fluoroquinolone (levofloxacin, gemifloxacin, moxifloxacin)
OR
Beta lactam antibiotic (high dose AMOXICILLIN, amoxicillin/clavulanate or cefopodoximine)
plus a macrolide
Why must you consider prior antibiotic use when treating CAP?
increases likelihood of having drug resistant s. pneumonia
What are mechanisms of drug resistance?
- increased elimination
- drug inactivating enzyme
- decreased uptake (porins in gram - cells)
- alteration in target molecule (change in PBP)
What is the mechanism for macrolide resistance in s. pneumonia?
macrolide resistance due to change in ribosomal binding site or efflux
What is the mechanism for penicillin resistance in s. pneumonia?
penicillin resistance due to mutation in penicillin binding protein
What effect did the vaccine have on resistance to macrolides?
Did not significantly decrease drug resistant serotypes
What are the three types of respiratory fluoroquinolones that you may use in a pt w/ comorbidities?
Gemifloxacin
levofloxacin
moxifloxacin
What is the mechanism of respiratory fluoroquinolones?
Bactericidal- Direct inhibitor of DNA replication by binding bacterial DNA topoisomerase II (gyrase) and IV
What is the spectrum of fluoroquinolones?
Broad spectrum- Gram+, Gram-, and atypical organisms like Mycoplasma
What causes resistance to fluoroquinolones?
Overprescribed, Active efflux of the drug
Mutations in topoisomerases
What SE are associated w/ Fluoroquinolones?
GI discomfort, tendinopathies
Avoid pregnancy, lactating individuals, children
A 21 year old female college student presented with a 5-day history of low-grade fever, myalgia, headache, and nonproductive cough. Gram stain had a few inflammatory cells but did not show any significant pathogen. Which of the following is the most likely cause of her illness?
Mycoplasma pneumonia
No cell wall
Hard to culture
More common in youger pts
Which of the following classes of antibiotics would you predict to be ineffective for Mycoplasma pneumonia?
Aminoglycosides Cephalosporins Fluoroquinolones Macrolides Tetracyclines
Cephalosporins (Cell wall inhibitors that work like Beta-lactams)
*Antibiotics may speed up recovery but most people recover w/out them
What causes atypical pneumonia?
Mycoplasma pneumoniae
How do you treat Mycoplasma pneumonia?
Doxycycline
Azithromycin
Why are beta lactams not affective in treating Mycoplasma pneumonia?
Adhere to epithelial cells
How do you diagnose Mycoplasma pneumonia?
Test for IgM
What is an example of a tetracycline?
Doxycline
What is the MOA of tetracyclines?
Bacteriostatic-bind 30S preventing attachment of aminoacyl-tRNA
What is the spectrum of tetracycline?
limited by resistance
B. burgdorferi, H. pylori, Mycoplasma pneumoniae, not good against GNRs
What causes resistance to tetracyclines?
Reduced uptake and increased efflux*
What adverse affects are associated w/ doxycycline?
Photosensitivity, Discoloration of teeth,
Inhibits bone growth- avoid pregnancy, children
Oral absorption limited by cations
What concentrations of doxycyline are most effective at killing the organism?
> 10 times above the MIC
What is a time dependent drug?
Effect depends on time above MIC so beta lactams need to have MULTIPLE doses
What type of antibiotics are NOT advisable for immunocompromised or life-threatening acute infections?
BACTERIOSTATIC
chloramphenicol erythromycin clindamycin sulfonamides trimethoprim tetracyclines
A 75-year-old female is admitted to an intensive care unit (ICU) for complications following open-heart surgery. During the first two weeks of her ICU stay, cefazolin (a 1st generation cephalosporin) is given to prevent subsequent wound infection. Soon after, she develops hospital acquired pneumonia due to Klebsiella pneumoniae resistant to all penicillins, cephalosporins, fluoroquinolones, and aminoglycosides, but susceptible to carbapenems. Which of the following is the most likely reason that this patient developed an infection due to multidrug resistant Klebsiella after receiving cefazolin therapy?
Selection and replication of a colonizing organism that contained a PLASMID encoding several resistance determinate genes
How is antibiotic resistance transferred from enterococcus to staphylococcus?
Enterococcus plasmid is transferred by CONJUGATION.
Transposon jumps from one plasmid to the other.
How do you treat Methicillin resistant Staphylococcus aureus (MRSA)?
Vancomycin or Linezolid
Avoid daptomycin which is inactivated by pulmonary surfactant
How do you treat pseudomonas aeruginosa?
two antibiotics including-
Piperacillin/tazobactam, Cefepime (4th gen), Imipenem/Cilastatin- PREVENTS TOXID RENAL METABOLIATE
Aztreonam
How do you treat KPC (klebsiella)?
Extended spectrum beta lactamase
treat w/ colistin-polymyxin E
What are three types of hospital acquired pneumonia?
MRSA and Gram - rods
- Meth resistant s. aureus
- pseudomonas aeruginosa
- KPC
What is the MOA for vancomycin?
Glycopeptide that inhibits CELL WALL synthesis
Binds to the D-Ala D-Ala dipeptide and inhibits transglycosylation reactions.
What is the spectrum of vancomycin?
Mainly effective against gram-positive organisms
What is the mOA of linezolid?
Oxazolidone that targets the 50S ribosome and inhibits PROTEIN SYNTHESIS
What is the spectrum of linezolid?
Mainly effective against gram-positive organisms (especially staphylococci, enterococci, and streptococci)
What are the gram negative bacili that cause hospital acquired pneumonia?
P. aeruginosa
K. pneumoinae
Hospital acquired pneumonia caused by Pseudomonas aeruginosa and Klebsiella pneumoniae are common in what populations?
Infections are common in individuals with cystic fibrosis and concern that chronic antibiotic treatment of CF patients is not only selecting for drug resistance but also decreasing diversity of lung microbiome
What causes drug resistant pneumonia in CF pts?
efflux
biofilms- MAKE IT HARD FOR ANTIBIOTICS TO PENETRATE
porins
Where are porins located?
Gram - cell wall
Hard to get drugs through porin channels and there is an extra membrane layer
What is the MOA of Polymyxin E/Colistin?
Binds phosphatidylethanolamine creating holes in membrane
What is the spectrum of Polymyxin E/Colistin?
Multidrug resistant Gram negatives
What are the SE of Polymyxin E/Colistin?
Nephrotoxicity- used as last resort
What is resistance to Polymyxin E/Colistin?
Infrequent and slow to develop
Cross resistance does not develop with any other presently used antibiotics
A student in a town near the Ohio River presents to the local hospital with headache, fever, malaise, and nonproductive cough. He became ill several days after cleaning and moving a chicken coop where hundreds of chickens had roosted for many years. Which of the microorganism is most likely responsible for his illness?
Histoplasma capsulatum (fugal infection)
dimorphic- mold in environment and yeast inside your lung
How do you treat system and dimorphic fungal mucoses?
amphotericin or itraconazole
Where is histoplasma capsulatum found?
Reticuloendothelial cells
Mississippi/Ohio river valleys
Where is blastomyces dermatitidis found?
Rotting wood, EASTERN U.S.
Broad based yeast
Where is coccidiodes immits found?
“valley fever”
Endospores in spherule
SW US, dry climates
Pulmonary lesions may calcify
Where can systemic and dimorphic fungal mycoses spread w/ out proper treatment?
bones, joints, and CNS especially in immunosuppressed individuals
What is the MOA of Polyenes: Amphotericin B?
Binds ergosterol, creating holes in membrane allowing leakage of electrolytes.
What is the spectrum of coverage of Polyenes: Amphotericin B?
Used for invasive systemic fungal infections in immunocompromised patients. Active against yeast and molds.
What is the distribution of Polyenes: Amphotericin B?
Small fraction of drug is excreted and has a long tissue half life.
What are the SE of Polyenes: Amphotericin B?
TOXIC because able to bind cholesterol. Decreases renal blood flow and can lead to permanent destruction of the basement membrane. 80% patients have nephrotoxicity
What causes resistance to Polyenes: Amphotericin B?
Rarely decrease ergosterol in membrane
What is a ubiquitous fungi in the environment that primarily infects the lungs through the respiratory tract or enters through the skin?
Aspergillus fumigatus
Septate hyphae
What does Aspergillus fumigatus cause?
- Allergic bronchopulmonary aspergillosis- hypersensitivity: brown mucous plugs- containing fungi and eosinophils, asthma or cystic fibrosis
- Asperigillomas (fungal ball), Fungal sinusitis
- Systemic disease in immunocompromised
How do you treat systemic aspergillus fumigatus?
voriconazole
*mortality rate is still between 45 and 80 percent since patients
are often neutropenic
Why might treatment with Prednisone be sufficient for ABPS?
It’s just a hypersensitivity reaction
What is the MOA of Azoles- Voriconazole, Itraconazole?
binds fungal P-450 enzyme(Erg11) blocking the production of the membrane protein ergosterol and causing the accumulation of lanosterol which is TOXIC
What is the spectrum of Azoles- Voriconazole, Itraconazole?
widely used and spectrum varies by agent
What is the distribution of Azoles- Voriconazole, Itraconazole?
Orally available
What is the toxicity of Azoles- Voriconazole, Itraconazole?
Drug-Drug interactions, hepatotoxicity, neurotoxicity, alters hormone synthesis- avoid during pregnancy.
What is the resistance of Azoles- Voriconazole, Itraconazole?
Altered cytochrome P-450, Upregulation of efflux transporters
When should antibiotics be used for bacterial caused pharyngitis?
confirm group A strep
How do you treat penicillin induced anaphylaxis and what should you AVOID?
Epinephrine
Beta lactams
What drugs are NOT effective against mycoplasma?
beta lactams
What can be used to treat gram - rods that express extended beta lactamases?
polymyxin E
What symptomatic treatments help the common col?
Acetylcystein Inhaled corticosteroids Honey Nasal irrigation Garlic Vitamine C Echinacea Probiotics
