Uncomplicated skin and soft tissue infections in immunocompetent persons are most commonly caused by?
Staph aureus and Strep pyogenes
Complicated skin infections (e.g. with burns, diabetes, ulcers, etc) are more likely be caused by what?
more commonly polymicrobial and often include anaeobes and gram neg rods, such as E. coli and Pseudomonas
What are the drug options for uncomplicated non-MRSA infections?
these are typically susceptible to beta-lactamase resistance penicillins (dicloxacillin, nafcillin, and oxacillin) and 1st-gen cephalosporins (cephalexin, cefazolin)
What if a patient with uncomplicated non-MRSA infections has an allergy to a penicillin or cephalosporins?
Clindamycin (50s inhibitor) or Vanco can be used
What is the typical allergy to penicillins?
this is typically an IgE-mediated allergy (histamine release causing urticaria, angioedema, anaphylaxis). Remember that historically, patients who are truly allergic to a penicillin would also display symptoms to a 1st or 2nd gene cephalosporin (due to related R1 side chain rather than beta-lactam structure)
Again, it is hypothesized that the R1 side chain of both penicillins and cephalosporins is responsible for cross-reactive hypersensitivity. Which drugs possess this adduct?
-penicillin G, ampicillin, amoxicillin
-cefoxitin, cefaclor, cephalexin, cefadroxil, cefprozil
Most penicillins are eliminated renally and require dose-adjustment in renal failure, except which drugs?
nafcillin (mostly hepatic and only requires dose adjustment if hepatic AND renal involvment present)
-Oxacillin (hepatic elimination)
-Dicloxacillin (renal elim but no adjustment needed)
Does clindamycin require dose adjustment in RF? Vanco? What about cephalosporins
While vanco and cephalosporins DO require dose adjustment in RF, clindamycin is eliminated hepatically and does not
What is a common AE for beta-lactams?
Hypersensitivity and GI distress
What is another common AE for penicillinase-resistant penicillins (like nafcillin, dicloxacillin, and oxacillin)
AEs of vanco?
Red man syndrome and hypotension with rapid IV injection
Nephro (reversible) and ototoxicity
What are some illnesses associated with CA-MRSA?
cellulitis, abscesses, necrotizinf fasciitis, and sepsis rarely
How would simple CA-MRSA induced abscesses and less serious skin and soft tissue infections be treated?
What drug class SHOULD NOT be used empirically to treat MRSA? Why?
Fluoroquinolones due to increasing resistance
How does Linezolid work?
Binds to the 23S of the 50S subunit and prevents initiation complex formation with the 70S subunit
What are the AEs of Bactrim?
Fetal risk in 1st and 3rd trimester
How is Bactrim eliminated?
Renal (dose-adjustment needed)
How are the tetracyclines eliminated?
Hepatic and renal (dose adjustment required in RF)
AEs of tetracyclines?
How is clindmaycin eliminated?
Hepatic (no dose adjustment in LF/RF)
AEs of Clinda?
AEs of Linezolid?
-optic neuropathy and vision loss
-serotonin syndrome and seizures
What causes optic neuropathy with linezolid?
thought to be casued by mitochondrial dysfunction in the optic nerve (reversible upon discontinuing the drug)
What is serotonin syndrome?
mental status changes and autonomic hyperactivity caused by excessive levels of serotonin (that is a common effect of co-administration of serotonin increasing drugs such as isoniazid, linezolid, and SSRIs for depression)
How should patients with complicated MRSA skin and soft tissue infections be treated?
they should be hospitalized and given IV vanco (or linezolid/dapto if toxin production is an issue)
How should complicated polymicrobial infections be treated?
add a MRSA drug to a broad spectrum penicillin (piper/tazo) or imi/cilastatin OR give a 5th generation cephalosporin called CEFTAROLINE (if co-infection with P. aeruginosa or anaerboes is not suspected)
Metabolism of Ceftaroline?
IV drug that is predominantly renally eliminated (dose adjustment in RF)
AEs of Ceftaroline?
hypokalemia and phlebitis
C. difficile, ALT/AST elevation, and hemolytic anemia rarely reported
How does Dapto work?
IV drug that binds to and depolarizes the abcterial membrane, inhibiting DNA/RNA?protein synthesis
AEs of Dapto?
rhabdomyolysis (monitor serum creatine kinase levels)
AEs of piperacillin/tazo?
AEs of carbapenems?
seizures at high doses
T or F. Dapto, Piperacillin, and carbapenems should be dose-adjusted in RF