Z Abx important Flashcards
FLUOROQUINOLONES
Mechanism: DNA Gyrase and Topoisomerase inhibitors àbactericidal
Side effects: QT prolongation (recent NEJM article suggested increased risk of cardiovascular death with Levofloxacin, but not Ciprofloxacin), tendon rupture (esp if on steroids), GI intolerance, cartilage damage, rare dysglycemias (Gatifloxacin removed from market for this reason), dizziness/HA’s, rashes, teratogenicity, transaminitis. Fluoroquinolones also recently associated with increased risk of retinal detachment. High rate of c.diff.
Fluoroquinolones also have excellent TB coverage (Moxifloxacin > Levofloxacin > Ciprofloxacin). If patient has PNA, but suspect TB, do not use FQ’s!!(Do not want to use monotherapy against TB à will develop resistance)
All fluoroquinolones have atypical coverage (but Cipro – relatively weaker against Chlamydia and Mycoplasma, but good vs Legionella).
All fluoroquinolones have excellent bioavailability (except Norfloxacin), so use PO whenever possible.
Ciprofloxacin (PO and IV)
Spectrum: best gram negative coverage of FQs, but virtually no gram positive coverage.
Lacks good anaerobic coverage.
Used for: many purposes including UTIs, double coverage of Pseudomonas including for HAP/HCAP/VAP, bone and joint infections, prostatitis
, GI/intraabdominal coverage - often with Flagyl, traveler’s diarrhea.
Also effective vs anthrax.
Common myth is that it does not “penetrate” the lungs. This is false – it is not used in community-acquired PNA due to lack of Strep pneumo coverage. It is routinely used for HAP/HCAP/VAP as double-coverage for Pseudomonas (note more frequent dosing for PNA – 400 mg IV q8 hours)
Levofloxacin (Levaquin)(PO and IV)
Spectrum: “Respiratory Fluoroquinolone” - excellent activity vs. Strep pneumo, slightly less reliable Pseudomonas coverage than Cipro. Good for atypicals.
Used for: Community Acquired PNA (can use as monotherapy), sinusitis/bronchitis, UTI’s, and double coverage of Pseudomonas including hospital acquired PNA.
Moxifloxacin (Avelox) (PO and IV)
Also a Respiratory FQ, but main difference vs. Levofloxacin is virtually NO urine activity (can’t use for UTIs) and NO Pseudomonas activity à no role in hospital/healthcare associated PNA.
Best gram positive, atypical, and anaerobic coverage out of FQs à approved for complicated intraabdominal infections, although significant rate of resistance in Bacteroides (either avoid for serious intraabdominal infections, or combine with Metronidazole).
Both Moxifloxacin and Levofloxacin are not typically used for Staph aureus infections due to rapid emergence of resistance.
Both Moxifloxacin and Levofloxacin have excellent Pneumococcal activity, but are 2nd-line at best for most other streptococcal infections (beta-lactams preferred).
Norfloxacin (PO) – unlike the other Fluoroquinolones, poorly absorbed. Main use is for spontaneous bacterial peritonitis (SBP) prophylaxis
CEPHALOSPORINS
higher resistance to beta-lactamases à better anti-staph activity
Spectrum (General Rules):
No cephalosporin covers Enterococcus (except Ceftaroline).
Only Ceftazidime and Cefepime cover Pseudomonas.
Only Cefoxitin and Cefotetan have good anaerobic coverage.
1st Generation - Cefazolin (Ancef, Kefzol) - IV, Cephalexin (Keflex) - PO
PEKs GM+
Spectrum: Excellent Gram positive (MSSA and strep), minor Gram negative = Proteus, E.coli, Klebsiella.
Used for: Mild-moderate nonpurulent cellulitis (if do not suspect MRSA). Cefazolin ofted used for prophlaxis during surgery.
Sometimes used for UTIs as well (especially during pregnancy).
In PCN-allergic patients, Cefazolin is drug of choice for severe MSSA infections (bacteremia, endocarditis, etc). Some use it preferentially in prolonged treatment courses over Nafcillin/Oxacillin due to overall better tolerance (less rash, diarrhea, interstitial nephritis, hepatitis)
2nd Generation
Cefuroxime (PO and IV)
”Cephamycins” - Cefoxitin, Cefotetan (IV)
HEN PEKs GM+/GM-
Cefuroxime (PO and IV)
Spectrum: Gram positive and more gram negative’s than 1st generation - gains activity vs H.influenza, Enterobacter, Neisseria.
Used for: respiratory infections (upper and lower tract), gonorrhea, UTIs, Lyme disease (alternative to Doxycycline), and more.
”Cephamycins” - Cefoxitin, Cefotetan (IV)
Spectrum: get anaerobes and gram negatives, but no Pseudomonas and weak/unreliable gram positive coverage.
Used for: UTI’s, non-severe intraabdominal infections, pelvic/GYN infections.
Bacteroides fragilis has high rates of resistance to Cefotetan (Cefoxitin is a bit better) – for serious intrabdominal infections, should use other agents.
Cefotetan can cause elevated INR.
3rd Generation
a. Ceftriaxone (Rocephin) – IV, Cefotaxime - IV, Cefpodoxime - PO
b. Ceftazidime (IV) (3rd/4th Generation Cephalosporin)
a. Ceftriaxone (Rocephin) – IV, Cefotaxime - IV, Cefpodoxime - PO
Spectrum: Good gram positive (although possibly worse than 1st generation) and excellent gram negative coverage (E.coli, Proteus, Klebsiella, Neisseria, H.influenza, and most SPACE organisms, but not Pseudomonas), no anaerobes .
Used for: Ceftriaxone used in many situations including community acquired PNA (with Azithromycin), meningitis (CTX has excellent CSF penetration), spontaneous bacterial peritonitis, some skin/soft tissue infections, bacteremia/endocarditis from susceptible strep, urinary tract infections/pyelonephritis, bone and joint infections, late Lyme disease, gonorrhea, pelvic infections, and more.
Note small but important rate of resistance in Strep pneumo.
Ceftriaxone usually once daily dosing (1-2 g) except for meningitis (2 g IV q12 hours). Cefotaxime is more frequent dosing (often used preferentially for spontaneous bacterial peritonitis due to good track record and high levels achieved in ascitic fluid, but Ceftriaxone probably equivalent).
Cefpodoxime useful as a step-down to oral after IV Ceftriaxone, but like all beta lactams note poor serum bioavailability (so not suitable for bacteremia, deep-seated or serious infections).
Ceftriaxone can cause biliary sludging and cholecystitis.
b. Ceftazidime (IV) (3rd/4th Generation Cephalosporin)
Spectrum: only has Gram negative coverage (including Pseudomonas). Virtually no Gram positive or anaerobic coverage.
Used for: Pseudomonal infections, also can be used for neutropenic fever (but beware lack of staph/strep coverage, so Cefepime often preferred).
Most experts will avoid using Ceftriaxone or Ceftazidime (and any lower generation cephalosporin) for serious infections due to SPICE organisms, due to concern for inducible resistance from chromosomal beta-lactamase (AmpC ). Preferable to use Cefepime, Piperacillin/Tazobactam, or Carbapenem (best) in those situations as they are more stable, or non-beta lactams if susceptible
