Pulm Lectures 17 & 18 - Pharm of Resp Infections

darodri6's version from 2016-09-15 23:28

Drug Classes & MOA

ClassDrugsMnemonicGeneral MOASpecific MOASpectrumOther
VancomycinVancomycinCell Wall Synthesis InhibitorsBinds D-ala-D-ala portion of precursors preventing peptidoglycan synthesisgram positive ONLY(Orally for C. difficile pseudomembranous colitis)
Beta-lactamase inhibitorsClavulanic Acid, Sulbactam, TazobactamCaSTCell Wall Synthesis InhibitorsBind to PBP and prevent peptidoglycan cross-linkingnone, except sulbactam vs acinetobacter
AztreonamAztreonamCell Wall Synthesis InhibitorsBind to PBP and prevent peptidoglycan cross-linkinggram – rods only
AminoglycosidesAmikacin, Gentamicin, Neomycin, Streptomycin, Tobramycin"-micin, -mycin"Protein Synthesis InhibitorsInhibit at the 30S subunitaerobic gram negatives
TetracyclinesDemeclocycline, Doxycycline, Minocycline, Tetracycline"-cyclines"Protein Synthesis InhibitorsInhibit at the 30S subunitbroad, many gram + (including CA-MRSA), gram – (resistance building), toxin secreters (cholera), rickettsiae, spirochetes, mycoplasma, and chlamydia, Borrelia burgdorferi, acne)
MacrolidesAzithromycin, Clarithromycin, ErythromycinACE
Protein Synthesis InhibitorsInhibit at the 50S subunitatypical pneumonia (Mycoplasma, Chlamydia, Legionella), streptococcal infections
ChloramphenicolChloramphenicolProtein Synthesis InhibitorsInhibit at the 50S subunitRocky Mountain spotted fever, rickettsial infections, H. influenzae, Neisseria meningitidis, S. pneumoniae
ClindamycinClindamycinProtein Synthesis InhibitorsInhibit at the 50S subunitgram +, some gram -, anarobes, CA-MRSA
OxazolidinoneLinezolidProtein Synthesis InhibitorsInhibit at the 50S subunit
FluroquinolonesCiprofloxacin, Gemifloxacin, Levofloxacin, Moxifloxacin, Nalidixic Acid"-floaxcins"DNA topoisomerase inhibitors (inhibit II and IV)gram negative aerobes

Respiratory versions cover: S. pneumoniae, M. pneumoniae, C. pneumoniae, L pneumonophillia

Moxifloxacin: covers Bacteroides but no pseudomonas
SulfonamidesSulfamethoxazoleFolic Acid Synthesis InhibitorsPABA antimetabolites inhibit dihydropteroate synthaseTMP/SMX: Pneumocystis jiroveci, Nocardia, CA-MRSA, E. coli, Klebsiella, Enterobacter, Proteus, Moraxella, Haemophilus, protozoal, shigella, salmonella
Dihydrofolate reductase inhibitorsTrimethoprimFolic Acid Synthesis InhibitorsInhibits dihydrofolate reductaseTMP/SMX: Pneumocystis jiroveci, Nocardia, CA-MRSA, E. coli, Klebsiella, Enterobacter, Proteus, Moraxella, Haemophilus, protozoal, shigella, salmonella
RifampinRifampinInhibits DNA-dependent RNA polymerase
1st Gen. CephalosporinsCefazolin, Cephalexin"1st of all, i am ZO LEXed right now"PEcK
(Proteus mirabilis, E. coli, Klebsiella pneumoniae)
2nd Gen. Ceph.Cefoxitin, Cefuroxime, CeflacorHEN PEcKS
(Haemophilus influenzae, Enterobacter aerogenes, Neisseria sp, and Serratia marcescens)
3rd Gen CephCeftazimide, Ceftriaxone, Cefotaxime"cefTRIaxone means 3"better gram – than 2nd (ceftazidime: Pseudomonas)
4th Gen. CephCefepime"its 4 o'clock, is it PIME yet"3rd generation + Pseudomonas
5th Gen. CephCeftaroline"cAROLINE is in the 5th grade"3rd generation + MRSA
PenicillinPenicillin G, Penicillin V-mostly gram-positive (S. pneumoniae, S. pyogenes, and Actinomyces)

-also N. meningitidis and T. pallidum
AminopenicillinsAmpicillin, AmoxicillinHaemophilus influenzae, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococciadding beta-lactamase inhibitor increases coverage of H. influenzae and Enterobacteriaceae
Antistaphlococcal Penicillin (Penicillinase-Resistant)Oxacillin, NafcillinS. aureus (NOT MRSA due to altered PBP)(NO coverage for MRSA due to altered PBP)
Antipseudomonal PenicillinTicarcillin, PiperacillinPseudomonas and gram – rodsUse with beta lactamase
CarbapenemsDoripenem, Ertapenem, Imipenem/Cilastatin, Meropenemgram positve cocci, ESBL gram negatives, Pseudomonas, Acinetobacter, anarobes-Ertapenem doesn’t cover Pseudomonas, Enterococcus, and Acinetobacter

-NOT effective vs atypical pneumonia, Legionella, MRSA

Mechanisms of Drug Resistance & ADE's

Drug/Drug ClassMeans of Bug ResistanceADEsOther
Beta-lactamsbeta lactamases, ESBL, Carbapenemase, MRSA has altered PBPhypersensitivity rxns, Type I IgE mediated reactions, rash, hemolysisCarbapenems also cause SEIZURES! (esp Imipenem)
Vancomycinbacterial modification of D-ala D-ala to D-ala D-lactateNephrotoxic, Ototoxic, Red Man SyndromeOritavancin binds to both forms of D-ala !!!!
Sulfonamidesaltered bacterial dihydropteroate synthase, decreased uptake or increased PABA synthesisStevens-Johnson Syndrome, Rash, Crystaluria, Photosensitivity, Hemolytic anemia in G6PD deficiency, Neprotoxicity, Kernicterus in infants
Fluoroquinolonesmutation in DNA gyrase, plasmid-mediated resistance, efflux pumpsPhotosensitivity, Chelation, QT prolongation, Tendonitis
Aminoglycosidesenzymatic inactivationNephrotoxicity, Neuromuscular Blockade, Ototoxicity, Teratogenic
Tetracyclinesdecreased uptake or increased effluxGI distress, discoloration of teeth & inhibition of bone growth, Photosensitivity, contraindicated in pregnancy
Macrolidesmethylation of 23S rRNA binding site to prevent bindingGI (motilin receptor agonists), prolonged QT interval, HepatotoxicErythro & Clarithro inhibit CYP450
Chloramphenicolplasma encoded enzymatic inactivationPseudomembranous colitis (C. difficile overgrowth), diarrhea, fever
TrimethoprimLeukopenia, Megaloblastic anemia

Common Respiratory Infections

-Majority of infections are caused by VIRUSES
-Bacterial infections are more prominent in acute otitis media & pneumonia (Strep. pneumo, Moraxella catarrhalis, Mycoplasma, H. Influenza, Strep pyogenes, Chlamydophilia)
Question Answer Column 3 Column 4 Column 5
Acute Pharyngitis-Viruses in 80-95% of cases
-Reserve abx for those with confirmed Group A strep
-Penicillin or amoxicillin
-1st generation cephalosporin (minor allergy)
-Clindamycin or macrolide (if anaphylaxis)
No resistance to penicillin has been reported for Group A Strep
Acute Bacterial Rhinosinusitiscommonly caused by H. influenzae, S. pneumoniae, and Moraxella catarrhalisAmoxicillin/Clavulanate (combo)

-For kids with non-type I penicillin allergies, use combo 3rd gen Ceph + Clindamycin
-For kids with Type I allergy (uncommon) to penicillin, use Levofloxacin
We give the A/C combo because this infection is usually caused by H. influenzae, which is known for producing beta lactamase (Clavulanate is a beta lactamase inhibitor, as well as Sulbatam & Tazobactam...only Sulbactam has direct activity vs. Acinetobacter)

Fluoroquinolone (i.e. Moxifloxacin, Levofloaxcin) would also work, but are typically reserved for patients who do not respond to first-line agents & those at risk for S. pneumoniae infection (concerns about resistance).
-Macrolides are not recommended first line due to high rates of resistance among S. pneumoniae
-TMP/SMX not recommended for empiric therapy due to high rates or resistance among both S. pneumoniae and H. influenzae
-Doxycyline can be used in adults as an alternative to amoxicillin/clavulanate
-2nd and 3rd generation oral cephs are no longer recommended due to variable rates of resistance to S. pneumoniae.
Community Acquired Pneumonia (in Adults)commonly caused by S. pneumoniae (esp among hospitalized patients) & Mycoplasma pneumoniae

-other causes include H. influenzae, Chlamydophila pneumop, S. aureus (MRSA in severe cases), Legionella (inpatients)
-S. pneumo in those >65, DM, smokers, alcohol abuse, chronic dz (CV, pulm, renal, liver)
-Mycoplasma = "walking" pneumo
Outpatient =
-Healthy: macrolide or doxycycline
-Comorbidities: respiratory fluoroquinolone or beta-lactam + macrolide

Inpatient (non-ICU)=
Respiratory fluoroquinolone or beta-lactam + macrolide

Inpatient (ICU)=
Beta-lactam + (azithromycin or respiratory fluoroquinolone)

Pseudomonas consideration=
-Antipneumococcal, antipseudomonal beta-lacatam + ciprofloxacin or levofloxacin
-Antipneumococcal, antipseudomonal beta-lacatam + aminoglycoside and azithromycin
-Antipneumococcal, antipseudomonal beta-lacatam + aminoglycoside and antipneumococcal fluoroquinolone
-“antipneumococcal, antipseudomonal beta-lactam” means 1 drug that is both antipneumococcal AND antipseudomonal AND a beta lactam

CA-MRSA consideration=
Add Vancomycin or Linezolid
S. pneumoniae is associated with higher rates of morbidity & mortality, so important to make sure its covered (check local prevalence of macrolide resistance)

"Atypical"pathogens more common in older children & adults
Hospital-Acquired/Healthcare-associated/Ventilator -Associated Pneumonias =
-often caused by Klebsiella, E. coli, Enterobacter, Serratia, P aeruginosa & Acinetobacter
-may be caused by S. aureus (usually MRSA) in those with DM, head trauma or admitted to ICU
-HCAP due to Legionella common in immunocompromosed patients
Community Acquired Pneumonia (in Infants & Children)Pneumonia in babies up to 1 month, consider vaginal flora =
-Group B strep
-H. influenzae
-E. coli
-S. aureus
-L. monocytogenes

for babies 1-3 months, consider =
S. aureus
S. pneumoniae

for kids (outpatient), antimicrobial therapy not usually needed b/c CAP commonly caused via a VIRUS. But if it is bacterial, most common pathogen is S. pneumoniae

for kids (inpatient), usuallt caused by S. pneumoniae, but one must consider if they are fully immunized, & whether local data says S. pneumoniae is susceptible or resistant.
for babies up to 1 month =
Cephalosporin (if not listeria… remember they’re LAME)

For babies 1-3 months =

For kids (outpatients) with S. pneumo cause = Amoxicillin. If atypical suspected = Macrolides.

For kids (outpatient) with full immunization and/or S. pneumo susceptible = Amicillin or Penicillin G

For kids (inpatient) with no immunizations and/or local strains of S. pneumo are resistant = 3rd Gen Ceph (Ceftriaxone or cefotaxime)
-if suspected M. pneumo or C. pneumo causation = ADD Macrolide
-if confirmed S. aureus = ADD Vancomycin or Clindamycin
Cystic FibrosisCommonly caused by:
-Pseudomonas aeruginosa (initial cultures realted to increased morbidity and mortality)
-Staphlococcus Aureus
-Haemophilus influenza
-Stentrophomonas maltophilia
-Burkholderia cepacia

Acute exacerbations usually cause d by S. aureus or H. influenzae early on, and P. aeruginosa later in dz
Anti-infective therapy:
-To improve lung function & reduce exacerbations, and if patient >6 y/o with P. aeruginosa causation = INHALED Tobramycin (an aminoglycoside) (Aztrenonam also active against P. aeruginosa)

-To improve lung function & reduce exacerbations, and if patient >6 y/o with P. aeruginosa causation = ORAL Azithromycin

Acute exacerbations:
Goal is to eliminate bacterial proliferation, reduce bacterial load, decrease sputum production & restore lung function to baseline
-IV treatment = give 2 anti-pseudomonal agents (Aminoglycoside + extended spectrum penicillin/beta lactamase inhibitor)
-Oral = TMP/SMX, Amoxicillin/Clav, Oral Cephalosporins
InfluenzaOseltamivir, Zanamivirthese anti-VIRALS work to INHIBIT INFLUENZA NEURAMINIDASE, which results in clumping of newly released virions to each other and membrane of infected cell. Ultimately leads to decrease release of progeny virus
-Early administration is crucial as replications peaks 24-72 hours after onset of illness.