Pumerantz-Treatments

Front 1

Describe the curb-65=0-1 (outpatient treatments)

Back 1

I. Previously healthy and no risk for drug resistance
1. macrolide (covers both M. pneumonia and S. pneumonia) 2. doxycycline (if problem w/ macrolide)
II. Presence of co-morbidities
1. B-lactom (targets drug resistant S. pneumonia) + macrolide or doxycycline
2. respiratory flouroquinilones (RFQ)

Front 2

Describe the curb-65=2 (medical ward treatment)

Back 2

1. B-lactam + macrolide
2. RFQ (reserve for B-lactam allergic patients)
note-patients should be hospitalized and drugs given IV

Front 3

Describe the curb-65=3 or more (severe pneumonia/ICU treatment) at no risk for P. aeruginosa of MRSA

Back 3

1. Potent antipneumococcal β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) + azithromycin
2. RFQ

Front 4

Describe the treatment for P. aeruginosa

Back 4

Initial treatment with antibiotic combination (should cover, P. aeruginosa, S. pneumonia, and M. pneumonia), then adjusted once susceptibilities are known:
Antipneumococcal, antipseudomonal β-lactam (piperacillin-tazobactam cefepime, carbapenem) +
a. RFQ (ciprofloxacin or levofloxacin)
b. aminoglycoside + azithromycin
c. aminoglycoside + RFQ
note-aztreonam may substitute for β-lactam in allergic patients

Front 5

If patient has recurrent S. pneumonia infections, what should be suspected?

Back 5

Think antibody problem (immune deficiency)-can give IV immunoglobulin
potential asplenia (associated w/ sickle-cell anemia-Howell Jolly bodies)

Front 6

What are the 5 principles of antibiotic resistance?

Back 6

1. Given sufficient time and drug use, antibiotic resistance will emerge
2. Resistance is progressive, evolving from low levels through intermediate to high levels (small increases in MIC, unless acquired as transferred genetic element)
3. Organisms resistant to one drug are likely to become resistant to others
4. Once resistance appears, it doesn't decline (or does so very slowly)
5. use of antibiotics by any one person affects others

Front 7

Differentiate extracellular from intracellular markers of the lung

Back 7

extracellular-epithelial lining fluid (measured by bronchalveolar lavage)
intracellular-alveolar macrophages

Front 8

describe the blood-alveolar space

Back 8

blood-alveolar barrier composed of 2 membranes, capillary wall and alveolar wall that are separated by fluid-filled interstitial space
Antibiotics need to diffuse across alveolar capillary wall, interstitial fluid, and alveolar epithelial cells to reach epithelial lining fluid (ELF)

Front 9

What is the drug of choice for most respiratory treatments?

Back 9

B-lactams (use unless there's a good reason not to)

Front 10

Describe the lung penetration of different drug classes

Back 10

A. β-lactams: <50% of serum concentration in lung parenchyma
B. Fluoroquinolones, macrolides, and linezolid: ≥100% serum concentrations in lung, bronchial secretions, and alveolar macrophages
C. Doxycycline-good penetration into lung tissue/bronchial secretions; poor into pleural fluid
D. Vancomycin-poor penetration into macrophages and lung parenchyma
E. Aminoglycosides-poor penetration into lung and respiratory secretions

Front 11

Describe the treatment principles for treating lung infections intracellularly vs extracellularly

Back 11

B-lactams-used for infections outside cells (not concerned about tissue penetration); great for pneumococcal infections
In lung, 2 types of macrophages-alveolar macrophages, interstitial macrophages
MRSA-can cause intracellular parasitism; need a drug that has good penetration

Front 12

What are the potent anti-pneumococcal β-lactam agents

Back 12

cefotaxime
ceftriaxone
ampicillin–sulbactam
ampicillin-good despite PCN resistance; S. pneumonia doesn’t produce PCNase, rather alters binding site for PCN (ampicillin still has affinity)
note-treat based on assumption of PCN resistance

Front 13

list the antipneumoccal respiratory flouroquinolones

Back 13

Levofloxacin
Moxifloxacin
note-FQs are 2nd choice of treatment; ciprofloxacin isn't RFQ

Front 14

What is the drug of choice for M. pneumonia?

Back 14

azithromycin (based on pharmacokinetics and minimal collateral damage)

Front 15

What is the drug of choice for Legionella?

Back 15

1. Macrolide-targets Legionella
2. FQs-cover Legionella as well as S. pneumonia

Front 16

What are the specific drug treatments for P. aeruginosa?

Back 16

A. Cephalosporins-Cefepime, Ceftazidime
B. Carbapenems-Imipenem; Meropenem
C. β-lactam/β-lactamase inhibitor: Piperacillin-tazobactam (give high dose IV)
D. Aminoglycosides-Gentamicin, Tobramycin, Amikacin
E. Fluoroquinolones-Ciprofloxacin, Levofloxacin
note-if diagnosis hasn't been made, but P. aeruginosa is suspected, treatment should cover both P. aeruginosa and S. pneumonia

Front 17

What B-lactams cover both P. aeruginosa and S. pneumonia?

Back 17

piperacillin-tazobactam
cefepime
carbapenem
note-if B-lactam allergic, use aztreonam; doesn’t cover S. pneumonia, so add vancomycin

Front 18

Describe how to treat MRSA infection in the lungs

Back 18

Vancomycin and linezolid-2 approved treatments for MRSA lung infection treatments; neither works very well (low rate of reaching target, high rate of nephrotoxicity)
By reforming vancomycin (making exterior capsule lipophilic), significantly increases lung penetration and killing of MRSA (PEGylated liposomal vancomycin works best)

Front 19

Describe the 5 axioms of treating active TB

Back 19

1. Treatment requires at least 2 effective drugs
2. Resistance develops commonly during monotherapy
3. Resistance less common with combination therapy
4. Development of resistance associated with worse prognosis and more severe disease
5. Never add single drug to failing regimen; re-treatment requires 2 drugs patient never had

Front 20

What are the treatment options for M. pneumonia?

Back 20

Since mycoplasmas lack proper cell wall, antibiotics that inhibit cell wall synthesis (B-lactams) are ineffective; DOCs include macrolides (azithromycin) or tetracyclines (doxycycline)

Front 21

Describe the MOA and pharmacokinetics of azithromycin

Back 21

MOA: bacteriostatic; inhibit protein synthesis by binding reversibly to 50S ribosomal subunits of sensitive microorganisms
Pharmacokinetics: Rapidly absorbed orally; widely distributed, except brain/CSF
≥100% serum concentrations in lung, bronchial secretions, and macrophages
Elimination: hepatically metabolized to inactive metabolites and excreted in bile; 12% unchanged in urine

Front 22

Describe MOA and pharmacokinetics of doxycycline

Back 22

MOA: bacteriostatic; inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to acceptor site on mRNA-ribosome complex
Pharmacokinetics:
95% absorbed from empty stomach and proximal small bowel
Widely distributed to tissues and secretions; accumulate in reticuloendothelial cells
good penetration into lung tissue/bronchial secretions, but poor into pleural fluid
Elimination: hepatobiliary (feces); no accumulation in renal failure

Front 23

Describe the MOA of ampicillin and amoxicillin

Back 23

bactericidal against actively growing bacteria; bind and inhibit PCN-binding proteins to inhibit cell wall synthesis
Active against penicillin-resistant S. pneumoniae, H. influenzae and E. coli
Frequently administered w/ β-lactamase inhibitor

Front 24

Describe the pharmacokinetics of ampicillin and amoxicillin

Back 24

Ampicillin-stable in acid and well absorbed
Amoxicillin-absorbed more rapidly; excreted unchanged in urine
both-20% protein bound

Front 25

Describe the MOA and pharmacokinetics of moxifloxacin

Back 25

MOA: rapid concentration-dependent killing by inhibiting DNA gyrase of GNRs
Pharmacokinetics: ≥100% serum concentrations in lung, bronchial secretions, and macrophages
Elimination: 52% hepatically metabolized via glucuronidation and sulfate conjugation; 22% urinary excretion

Front 26

Describe the MOA and pharmacokinetics of Ceftriaxone

Back 26

MOA: bactericidal against actively growing bacteria; bind and inhibit PCN-binding proteins to inhibit cell wall synthesis
Pharmacokinetics:
Widely distributed, highly protein-boud
<50% of serum concentration in lung parenchyma
Elimination: primarily liver and biliary system; 50% recovered in urine

Front 27

Describe the MOA and pharmacokinetics of Tigecycline

Back 27

MOA: similar to tetracycline but avoids efflux pumps of Enterobacteriaceae, staphylococci (MRSA), and Acinetobacter
Pharmacokinetics:
highly protein-bound (70-90%)
Elimination: 59% in feces; 33% in urine

Front 28

Describe the MOA and pharmacokinetics of Piperacillin-Tazobactam

Back 28

MOA: bactericidal against actively growing bacteria; bind and inhibit PCN-binding proteins to inhibit cell wall synthesis
Pharmacokinetics:
Widely distributed; high biliary concentration
<50% of serum concentration in lung parenchyma
Elimination: renal; 60%-80% in 24 hours; 20%-30% biliary

Front 29

Describe the MOA and pharmacokinetics of Cefepime

Back 29

MOA: bactericidal against actively growing bacteria; bind and inhibit PCN-binding proteins to inhibit cell wall synthesis
Pharmacokinetics:
<20% protein-bound
<50% of serum concentration in lung parenchyma
Elimination: >80% in urine

Front 30

Describe the MOA and pharmacokinetics of ciprofloxacin

Back 30

MOA: rapid concentration-dependent killing by inhibiting DNA gyrase of GNRs; potent post-antibiotic effect
Pharmacokinetics:
Well-absorbed orally, widely distributed in body tissues
≥100% serum concentrations in lung, bronchial secretions, and macrophages/neutrophils
Elimination: renal

Front 31

Describe the MOA and pharmacokinetics of gentamicin

Back 31

MOA: rapidly bactericidal; concentration-dependent; inhibit protein synthesis and decrease ribosomal mRNA
Pharmacokinetics:
do not penetrate into most cells; low concentration in secretions and tissues
Poor penetration into lung and respiratory secretions
Elimination: excreted almost entirely by glomerular filtration; large fraction excreted unchanged during the first 24 hours; minor excretory route is active hepatic secretion

Front 32

Describe the MOA and pharmacokinetics of aztreonam

Back 32

MOA: interacts with PCN-binding proteins and induces formation of long filamentous bacterial structures; resistant to many B-lactamases; resembles aminoglycoside; has activity only against aerobic gram-negative bacteria
Pharmacokinetics:
Widely distributed
<50% of serum concentration in lung parenchyma
Elimination: unchanged in urine

Front 33

Describe the MOA of carbapenems

Back 33

Inhibits bacterial cell wall synthesis by binding to several of the PCN-binding proteins, which in turn inhibits the final transpeptidation step of peptidoglycan synthesis; bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested

Front 34

Describe the pharmacokinetics of carbpenems

Back 34

A. Imipenem-cilastatin:
Hydrolyzed rapidly by dipeptidase (cilastatin is inhibitor of dehydropeptidase)
Rapidly and widely distributed to most tissues and fluids (exception-low concentrations in CSF)
Elimination: 70% active drug recovered in urine
B. Meropenem-Resistant to renal dipeptidase
C. Ertapenem-longer serum half-life than imipenem/meropenem that allows once-daily dosing
D. Doripenem:
Non-CYP-mediated metabolism via dehydropeptidase-I to doripenem-M1 (inactive metabolite)
Excretion: Urine (70% as unchanged drug; 15% as doripenem-M1 metabolite)

Front 35

Describe the MOA and pharmacokinetics of vancomycin

Back 35

MOA: inhibits cell wall synthesis by high affinity binding to the D-alanyl-D-alanine terminus of cell wall precursor units
Pharmacokinetics:
30% bound to plasma protein
poor penetration into macrophages and lung parenchyma (aggressive dosing recommended)
90% excreted by glomerular filtration

Front 36

Describe the MOA and pharmacokinetics of linezolid

Back 36

MOA: inhibits protein synthesis by binding to the P site of the 50S ribosomal subunit and preventing formation of larger ribosomal-fMet-tRNA complex that initiates protein synthesis; bacteriostatic for staphylococci
Pharmacokinetics:
30% protein-bound and distributes widely to well-perfused tissues
≥100% serum concentrations in lung, bronchial secretions, and macrophages
Degraded by nonenzymatic oxidation to aminoethoxyacetic acid and hydroxyethyl glycine derivatives
80% appears in urine; 10% appears as oxidation products in feces

Front 37

Describe the MOA and pharmacokinetics of metronidazole

Back 37

MOA: electron acceptor results in toxic free radicals that damage anaerobic and microaerophilic microbial DNA and other vital biomolecules
Pharmacokinetics:
<20% protein-bound
Concentrates well in all tissues (especially pus and hepatic abscesses)
Elimination: metabolized in liver accounting for >50% of systemic clearance