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Drugs for Respiratory Infections

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5 first-line drugs for tx TB
1. isoniazid
2. rifampin
3. ethambutol
4. pyrazinamide
5. rifabutin, rifapentine
CAP: tx outpatient with no risk factors
azithromycin, clarithromycin, or antipneumococcal fluoroquinolone (levofloxacin or moxifloxacin)
CAP: tx outpatient if thinking aspiration pneumonia
augmentin or clindamycin, or metronidazole
CAP: tx outpatient if b/w age 17-50, consider
doxycycline
CAP: tx outpatient if suspecting S. pneumoniae
amoxicillin or 2nd-3rd gen. ceph
Empirical tx if severity score > 90 and neg gram stain/no sputum
2nd or 3rd gen ceph + macrolide (e.g. clarithromycin, clindamycin, erythromycin, or azithromycin) or antipneumococcal fluoroquinolone (e.g. levofloxacin or moxifloxacin)
3 classes of drugs used for drug-resistant S. pneumoniae
1. anti-pneumococcal fluoroquinolones (e.g. levofloxacin)
2. oral beta-lactam (e.g. amoxicillin-clavulanate/augmentin)
3. oral macrolide (e.g. azithromycin)
DOC for older, co-morbid COPD pts against CAP
anti-pneumococcal fluroquinolone
Two reasons why oral cephs aren't be used for CAP
1. pneumococcal resistance
2. lack of activity against atypical organisms
2 options for normal CAP requiring hospitalization
1. IV/PO anti-pneumococcal fluoroquinolone (e.g. levofloxacin)
2. IV beta-lactam (e.g. 3rd gen ceph--ceftriaxone) + IV macrolide (e.g. azithromycin)
What drug can be added for suspected aspiration pneumonia if patient requires hospitalization?
clindamycin
Tx for severely ill, ICU patients with CAP
IV beta lactam (e.g. ceftriaxone) + IV anti-pneumococcal fluoroquinolone (e.g. levofloxacin)
If P. aeroginosa is suspected, what drug to add?
aminoglycoside (e.g. gentamicin)
In general, to improve gram negative coverage when treating CAP, what options are there?
ticarcillin/clavulanate (e.g. Timentin) or piperacillin/tazobactam (e.g. Zosyn) PLUS macrolide or fluroquinolone to cover atypicals (e.g. Mycoplasma or Chlamydia)
Tx for sensitive strain of pneumococcal pneumonia
pen G, pen V, or amoxicillin
Tx for intermediate resistant strain of pneumococcal pneumonia
ceftriaxone, high dose of pen G IV, or levofloxacin IV
Tx for highly resistant strain of pneumococcal pneumonia
add vancomycin or linezolid; or an IV fluoroquinolone
Two options for MRSA pneumonia
vancomycin or linezolid
HAP: three options for initial treatment
ticarcillin/clavulanate (e.g. Timentin), piperacillin/tazobactam (e.g. Zosyn), or carbapenem (e.g. imipenem)
HAP: add-on for severely ill patient
aminoglycoside (e.g. gentamicin)
HAP: pen-resistant pt
ciprofloxacin or aztreonam PLUS clindamycin or vancomycin
HAP with multi-drug resistant P. aeroginosa
cefepime (4th gen ceph) or carbapenems (e.g. imipenem or meropenem) PLUS an aminoglycoside (e.g. gentamicin)
Tx for atypical pneumonia (M. pneumoniae or C. pneumoniae)
macrolide (e.g. azithromycin, clarithromycin, or erythromycin) or tetracycline (e.g. doxycycline)
OR i thought could also use fluoroquinolone???
Tx for Chlamydia psittaci
doxycycline
Two options for tx H. influenzae pnuemonia
2nd or 3rd gen ceph (e.g. cefuroxime)
Augmentin (amoxicillin + clavulanate)
3 options for tx Legionella pneumonia
azithromycin +/- rifampin
fluoroquinolone +/- rifampin
erythromycin +/- rifampin
Tx for Klebsiella spp. pneumonia (or other gram neg bacilli e.g E.coli, Proteus, or Enterobacter); also, what to add in severely ill patients
3rd or 4th gen ceph
add aminoglycoside (e.g. gentamicin or tobramicin)
Tx for methicillin-sensitive S. aureus
penicillinase-resistant penicillin (e.g. PO cloxacilin or IV nafcillin/oxacillin)
Tx for MRSA pneumonia
vancomyin +/- rifampin
Tx for anaerobic mouth flora pneumonia (e.g. Bacteroides, Fusobacterium, Peptostreptococcus)
clindamycin or metronidazole
Tx for PCP in HIV/AIDS pts
trimethoprim/sulfamethoxazole (bactrim DS)
3 options for tx Influenza A pneumonia
oseltamivir, amantidine, or rimantidine
DOC for RSV pneumonia
ribavirin
3 mechanisms of resistance to penicillin
beta-lactamase
decreased permeability (e.g. decreased porins in g- bacteria)
altered PBP (e.g. MRSA, PRSP)
Mnemonic for activity of extended spectrum penicillins
ampicillin and amoxicillin HELPS kill enterococci
Haemophilus, E. coli, Listeria, Proteus, Salmonella, and enterococci
MOA for vancomycin
tricyclic glycopeptide that inhibits cell wall mucopeptide formation, bactericidal, but not penicillin or lactam.
Vancomycin toxicity
ototoxic, nephrotoxic, thrombophlebitis, "red man syndrome" of flushing
2 mechanisms of resistance against fluoroquinolones
mutated DNA gyrase
decreased permeability through porins
Fluoroquinolones not very effective against what category of bacteria?
anaerobes
DOC against Bacillus anthracis
ciprofloxacin, also add clindamycin +/- rifampin
Fluoroquinolones contraindicated in what two groups of patients
1. preg and nursing mothers
2. pts over 60 yo due to increased risk of tendonitis
Rifampin: MOA
inhibits DNA-dependent RNA polymerase specific for prokaryotes
Side-effect of rifampin
discolors urine, sweat, tears to orange
MOA of aminoglycosides
binds 30S to prevent ribosomal assembly and/or reading
MOA of chloramphenicol
binds 50S to inhibit peptidyl transferase reaction
MOA of clindamycin
binds irreversibly to 50S to inhibit translocation
Macrolides: bacteriocidal or static?
static at low concentrations; cidal at high concentrations
Macrolides: adverse effects
epigastric distress common; also liver problems and P-450 interactions
Mechanism of resistance against tetracycline
R-factor that reduces accumulation of active drugs
Tetracycline contraindicated in
children, b/c bone, teeth problems
Synergism between gentamicin and
beta-lactams which damage the cell wall
3 mechanisms of resistance against aminoglycosides
producing deactivating enzyme
impaired entry (mutant porins or pH, o2)
mutant 30S subunit
Aminoglycosides effect only against what category of bacteria
gram negative aerobes
What is unique about clinical action of gentamicin?
Postantibiotic effect: antibacterial activity continues beyond the time that measurable drug is present
2nd line drug for TB
streptomycin
TB: latent infection by positive PPD
INH x 9 months single dose or daily rifampin alone for 4 months
TB: active clinical TB
INH, rifampin, ethambutol, pyrazinamide for 6 months
Timeline of therapy for susceptible TB
2 month initial-phase, with a continuation phase for 4-7 months depending on sputum results at 2 months
What drug combo is used for continuation phase of TB?
INH + rifampin x 4 months
MOA of isoniazid
inhibits mycolic acid synthesis in outer membrane of Mycobacterium
Side effects of isoniazid
drug-induced hepatitis, peripheral neuritis, immunologic reactions
MOA of pyrazinamide and ethambutol
inhibits mycolic acid synthesis
Side effects of ethambutol
optic neuritis and impaired color vision
DOC for systemic mycoses
amphotericen B
MOA of amphotericen
binds ergosterol to increase fungal membrane permeability
Side effect of pyrazinamide
hepatotoxicity
2 drugs for prophylaxis of influenza A infection
rimantidine and amantidine
When should influenza prophylaxis be given?
within 48 hours after initial symptoms
MOA for influenza A prophylaxis rx
inhibits uncoating of viral nucleic acids and viral replication
DOC for RSV infection
ribavirin
MOA for RSV infection rx
synthetic guanosine analog; inhibits viral mRNA synthesis
2 rx influenza A resistant to rimantidine and amantidine
zanamivir and osletamivir
MOA of zanamivir and osletamivir
viral neuraminidase inhibitors