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Respiratory antivirals/antibiotics

Terms in this set (53)

Which anti-influenza therapies are no longer used and why?
Amantadine and Rimantadine
No longer used due to resistance
Mechanism of action for oseltamivir and zanamivir
Inhibition of Influenza A/B neuraminidase --> conformational changes within the enzyme's active site
How is resistance to oseltamivir/zanamivir acquired?
Mutations to hemagglutinin or neuraminidase. These variants also have reduced infectivity/virulence.
Adverse effects of oseltamivir
GI upset
Adverse effects of zanamivir
Wheezing/bronchospasm due to administration through oral inhalation
Clinical use of oseltamivir and zanamivir
Prophylaxis in individuals who cannot receive vaccine
Early treatment of flu --> decreased symptoms in 1-3 days
Treatment for RSV
Ribavirin
Ribavirin MOA
Inhibits both RNA and DNA viruses secondary to alterations of the cellular nucleotide pools + inhibition of viral mRNA synthesis
Adverse effects of Ribavirin
Transient wheezing and rash w/ aerosolized tx
Increased bilirubin, anemia, and rigors w/ systemic tx
Teratogenic
Pathogens that can cause outpatient CAP
Typicals: S. pneumo and H. flu
Atypicals: Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella spp.
Major characteristics of atypicals
No cell wall (except Legionella--fastidious Gram neg)
Obligate intracellular pathogens
Mycoplasma and Chlamydia --> mild infections "walking pneumonia"
Antimicrobials that have "atypical" activity
Macrolides
Fluoroquinolones
Tetracyclines
Antimicrobials that can be used to treat CAP
B-lactams + B-lactam inhibitors
Macrolides
Tetracyclines
Respiratory fluoroquinolones (not cipro)
Empiric treatment options for CAP
For S. pneumo (not PRSP) + H. flu: B-lactam + B-lactam inhibitor
S. pneumo (not PRSP) + H. flu + atypicals: Macrolides + Tetracyclines (not doxycycline)
S. pneumo (including PRSP) + H. flu + atypicals: Respiratory FQ's (not cipro)
B-lactam + B-lactam inhibitor MOA
B-lactam: binds to penicillin-binding proteins on inner surface of cell wall, blocks transpeptidation --> cell lysis
B-lactamase inhibitor needed for H. Flu, Staph, Kleb--those produce beta-lactamases
Resistance for B-lactams
Beta-lactamases
Alterations in PBPs
Cell wall changes
Adverse effects of B-lactams/BLIs
Diarrhea
Amoxicillin causes rash if concurrent mononucleosis
Hypersensitivity (cross reactivity with PCN and majority of B-lactams)
Serum sickness
Examples of B-lactams/BLI combinations
Ampicillin + sulbactam (IV)
Amoxicillin + clavulanic acid (PO)
Ceftriaxone
MOA for macrolides
Bind to sites on 50S ribosome --> inhibits bacterial protein synthesis --> blocks transpeptidation and translocation reactions
Macrolide resistance
Dec. permeability of cell membrane/active efflux
Esterases that hydrolyze macrolides
Modificiation of ribosomal binding site
Adverse effect of macrolides
N/V/abd pain
Cholestatic hepatitis
Prolonged QTc interval
Skin rash
Examples of macrolides
Azithromycin or erythromycin
Tetracycline MOA
Binds reversibly to sites on the 30S ribosome --> misreading of genetic code
Tetracycline resistance
Enzymatic inactivation
Impaired influx/increased efflux
Ribosome protection by proteins
Tetracycline adverse effects
N/V/D
Photosensitivity
Teeth discoloration/bone deformities
Liver toxicity

Do not use in pregnant women/children!
Examples of tetracyclines
Doxycycline: non-PRSP S. pneumo, H.flu, atypicals
Tigecycline: can treat PRSP S. pneumo
Fluoroquinolone MOA
Inhibits bacterial topoisomerases --> prevents DNA supercoiling/transcription/repair
Fluoroquinolone resistance
Altered target sites
Altered cell wall permeability
Active efflux pump
Adverse effects of FQs
Photosensitivity
QT prolongation
Tendonitis/tendon rupture! (never use again if that happens)
Do not use in pregnant women or children
Why can't use you use ciprofloxacin in CAP?
Reaches the lungs, but only works for Gram neg infections, so only used for HAP/VAP
Treatment options for CAP according to severity:
ICU: Ceftriaxone + azithromycin + vanco (covers MRSA)
Hospital/non-ICU: Ceftriaxone + azithromycin
Outpatient: either oral levofloxacin alone or amox/clav + azithromycin
When is the patient typically admitted to the ICU?
If they are likely to have infection due to resistant Gram negs:
-PSA
-CA-MRSA
-Legionella spp.
Risk factors for CA-MRSA colonization
-contact sport participants
-injection drug users
-people living in crowded conditions
-MSM
-prisoners
Duration of CAP Tx
-Minimum 5 days
-Afebrile for 48-72 hrs
-<1 sign for clinical instability associated with CAP
Criteria for switching from IV to oral Abx
-Functioning GI tract
-Clinical improvement: negative blood cultures, temperature <38 deg C, RR < 24, HR < 100 bpm
Potential pathogens for HAP/VAP/HCAP
-S. pneumo
-H. flu
-MSSA (methicillin susceptible S. aureus)
-antibiotic sensitive enteric GNRs: E. coli, Enterobacter, Proteus, Serratia
-MDR pathogens (PSA, ESBL GNRs, Acinetobacter)
-MRSA
-Legionella
Empiric treatment recommendations for HAP/VAP/HCAP
-Anti-PSA cephalosporin or carbapenem or B-lactam/BLI
+
-Anti-PSA fluoroquinolone or aminoglycoside
+
-Anti-MRSA therapy (vanco or linezolid)
Examples of beta-lactams/BLIs (penicillin) used for HCAP
Piperacillin + tazobactam (IV)
Adverse effects of Anti-PSA cephalosporins
Diarrhea, enterocolitis, vaginitis
Rash
Interstitial nephritis
Hypersensitivity rxns that can lead to cross reactivity
Examples of Anti-PSA cephalosporins
Cefepime
Ceftazadime
Carbapenem resistance
Carbapenem-specific beta lactamase enzymes
Mutation resulting in absence of outer membrane porin
Adverse effects of carbapenems
-Diarrhea, rash, hypersensitivity
-Leukopenia/neutropenia/thrombocytopenia
-Decreased seizure threshold with Imipenem (do not use in pts w/ hx of seizures or traumatic brain injury)
Examples of carbapenems
Iminpenem
Meropenem
Doripenem
FQs used in HAP/HCAP
Levofloxacin
Ciprofloxacin (good Gram neg coverage)
When is FQ monotherapy not okay?
Severe CAP
HAP
Aminoglycoside MOA
Irreversible binding to sites on 30S ribosome --> misreading of genetic code --> no protein synthesis
Adverse effects of aminoglycosides
Neuromuscular blockade
Ototoxicity (auditory and vestibular damage)
Nephrotoxicity
CN VIII toxicity
Examples of aminoglycosides
Amikacin
Tobramycin
Gentamicin
Vancomycin MOA
Inhibits formation of peptidoglycan
Adverse effects of Vanco
Chills, fever, rash
Red neck sndrome
Nephrotoxicity at high doses
Linezolid MOA
Binds to 23S ribosome subunit to prevent formation of the ribosome subunit that initiates protein synthesis
Adverse effects of Linezolid
Serotonin syndrome (be careful if pts are on SSRIs)
Thrombocytopenia and neutropenia
Why can't you use Daptomycin for pneumonia tx?
It breaks down surfactant
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