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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

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