Micro - Antimicrobials (Other Antibiotics affecting bacterial cell walls) Flashcards
Pg. 181-182 in First Aid 2014 Sections include: -Cephalosporins (generations I, II, III, IV, V) -Aztreonam -Carbapenems -Vancomycin
What kind of drugs are cephalosporins, and what is their general mechanism? How do they compare to Penicillin in terms of susceptibility to penicillinase? Are they bacteriostatic or bactericidal?
Beta-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal.
What are the generations of cephalosporins?
Cephalosporins (generations I, II, III, IV, V)
What organisms are typically not covered by cephalosporins? What is the exception?
Organisms typically not covered by cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci; Exception: ceftaroline covers MRSA
What are 2 examples of 1st generation cephalosporins?
1st generation (cefazolin, cephalexin)
What coverage do 1st generation cephalosporins provide?
1st generation (cefazolin, cephalexin) - gram-positive cocci, Proteus mirabilis, E. coli, Klebsiella pneumoniae; Think: “1st generation - PEcK”
What type of drug is cefazolin? How is it used clinically?
1st generation cephalosporin; Cefazolin used prior to surgery to prevent S. aureus wound infections
What are 3 examples of 2nd generation cephalosporins?
2nd generation (cefoxitin, cefaclor, cefuroxime)
What coverage do 2nd generation cephalosporins provide?
Gram-positive cocci, Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcensens; Think: “2nd generation - HEN PEcKS”
What are 3 examples of 3rd generation cephalosporins?
3rd generation (ceftriaxone, cefotaxime, ceftazidime)
In general what kind of coverage do 3rd generation cephalosporins provide?
Serious gram-negative infections resistant to other Beta-lactams
What kind of drug is ceftriaxone? What 2 conditions does it treat?
3rd generation cephalosporin; Ceftriaxone - Meningitis and gonorrhea
What kind of drug is ceftazidime? What organism does it classically cover?
3rd generation cephalosporin; Ceftazidime - Pseudomonas
What is an example of a 4th generation cephalosporin?
Cefepime
What advantage in coverage do 4th generation cephalosporins have?
Increased activity against Pseudomonas and gram-positive organisms
What is an example of a 5th generation cephalosporin?
Ceftaroline
What coverage do 5th generation cephalosporins have? Which organism do they not cover?
Broad gram-positive and gram-negative organism coverage, including MRSA; does not cover Pseudomonas
What are 2 toxicities of cephalosporins?
(1) Hypersensitivity reactions (2) Vitamin K deficiency
What are 2 interactions that cephalosporins have with other drugs?
(1) Low cross-reactivity with penicillins (2) Increase nephrotoxicity of aminoglycosides
What kind of drug is aztreonam? Is it susceptible or resistant to Beta-lactamases?
A monobactam; Resistant to Beta-lactamases
What is the specific mechanism of aztreonam?
Prevents peptidoglycan cross-linking by binding to penicillin-binding protein 3
With what other antimicrobial is aztreonam synergistic? With what other antimicrobial does it have no cross-allergenicity?
Synergistic with aminoglycosides. No cross-allergenicity with penicillins
What is versus is not the coverage of aztreonam?
Gram-negative rods only - no activity against gram-positives or anaerobes
What are 2 patient populations for which aztreonam may be used?
For penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides
What toxicity is associated with Aztreonam?
Usually nontoxic; occasional GI upset
What are 4 examples of Carabapenems?
(1) Imipenem (2) Meropenem (3) Ertapenem (4) Doripenem
What kind of drug is Imipenem? What kind of spectrum for coverage does it have? Is it Beta-lactamase susceptible or resistant?
Imipenem is a broad-spectrum, Beta-lactamase resistant carbapenem
With what other drug is Imipenem always administered, and why? What is the mechanism of this other drug?
Always administered with cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules; Think: “With imipenem, ‘the kill is lastin’ with cilastatin’”
What are 2 newer carbapenems? Which has limited Pseudomonas coverage?
Newer carbapenems include ertapenems (limited Pseudomonas coverage) and doripenem
What is the clinical use/coverage for carbapenems?
Gram-positive cocci, gram-negative rods, and anaerobes
What kind of spectrum do carbapenems have? What is their limitation in clinical use, and why?
Wide spectrum, but significant side effects limit use to life-threatening infections or after other drugs have failed
What are 2 advantages of Meropenem?
Meropenem has a decreased risk of seizures and is stable to dehydropeptidase I
What are 3 toxicities associated with Carbapenems?
(1) GI distress (2) Skin rash (3) CNS toxicity (seizures) at high plasma levels
What is the specific mechanism of Vancomycin? Is it bacteriostatic or bactericidal?
Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors; Bactericidal
What is the coverage/clinical use of vancomycin?
Gram positive only - serious, multi-drug resistant organisms, including MRSA, enterococci, and Clostridium difficile (oral dose for pseudomembranous colitis)
What are 4 toxicities associated with vancomycin?
(1) Nephrotoxicity (2) Ototoxicity (3) Thrombophlebitis (4) Diffuse flushing - Red Man syndrome (can largely prevent by pretreatment with antihistamines and slow infusion rate); Think: “Well tolerated in general - but NOT trouble free”
Which toxicity associated with vancomycin can be prevented? What is another name for this toxicity? How can it be prevented?
Diffuse flushing - Red Man syndrome (can largely prevent by pretreatment with antihistamines and slow infusion rate)
What is the mechanism of resistance to vancomycin?
Occurs in bacteria via amino acid modification of D-ala D-ala to D-ala D-lac. Think: “Pay back 2 D-alas (dollars) for vandalizing (vancomycin”)
