List the organisms that 1st gen cephalosporins are effective against. Which is target?
Gram-pos: - MSSA (*target) - PCN-susc. Strep pneumo - Group streptococci - Viridians streptococci Grem-neg: (PEK) = - Proteus mirabilis - E. coli - Klebsiella pneumoniae
List the organisms that 2nd gen cephalosporins are effective against. *Which group is unique to this gen?
Gram-pos: (slightly less active than 1st gen) - MSSA (*target), PCN-susc. Strep pneumo, Group streptococci, Viridians streptococci. Gram-neg: (HENPEK) = - H. influenzae - Enterobacter spp. - Neisseria spp. - Proteus mirabilis - E. coli - Klebsiella pneumoniae (+ M. catarrhalis). Anaerobes: Bacteroides fragilis /group
List the organisms that 3rd gen cephalosporins are effective against. *Which is target?
Gram-neg (HENPECKSSS P) = - H. influenzae - Enterobacter spp. - Neisseria gonorrhoeae - Proteus mirabalis - E. coli - Citrobacter spp. - Klebsiella pneumoniae - Serretia marcescens - Salmonella spp. - Shigella spp.; *Pseudomonas aeruginosa (target) (still have gram-pos activity but less active than earlier gens)
Which 3rd gen. cephalosporin does NOT target pseudomonas, unlike the others? Which would you use instead?
Ceftriaxone - Ceftazidime
How does the activity of 4th gen cephalosporins change compared to 3rd gen?
Gram-pos: similar to ceftriaxone. Gram-neg: Similar to ceftriaxone but also adds: - Pseudomonas aeruginosa - Beta-lactamse-producing enterobacter spp.
List the categories/organisms that 5th gen cephalosporins are effective against. *Which is unique to this gen?
Resp pathogens - H. influenzae - strep. Pneumoniae - Moraxella - Staph aureus. Gram-pos + SSSI: - Strep pneumonia *MRSA*
*What important organisms are cephalosporins NOT active against? (6)
SMACLE - Stenotrophomonas maltophilia - MRSA (*except for the 5th gen) - Atypical bacteria (eg Legionella; cuz no cell wall) - C-diff - Listeria - Enterococcus spp.
All cephalosporins are eliminated via the ___________ except for ___________ and ___________ (how are each eliminated?)
- Kidney - Ceftriaxone (bile) - Cefoperazone (liver)
Which gens of cephalosporins are used for surgical prophylaxis?
1st and 2nd (2nd for more intense surgeries?)
What are some of the uses of ceftriaxone? (4 orgs)
- Uncomplicated gonorrhea (single IM dose) - CAP - PRSP - Viridans strep endocarditis
What's the most important organisms that 4th gen cephalosporins cover (that ceftriaxone doesn't)?
Pseudomonas
What are the major adverse effects of all gen cephalosporins? (2)
1. Hypersensitivity 2. C-diff
- Are Carbapenems broad or narrow spectrum? - What major groups are they effective against? - What are their target organisms?
- Most broad-spectrum available - Many gram-pos and gram-neg aerobes, as well as gram-pos/neg anaerobes. - Targets: MSSA, bacteroides.
*What organisms are carbapenems NOT effective against? (7)
*NOT effective against: MRSA, PRSP, VRE, coag-neg staph, c-dif, atypical bacteria, S. maltophila
-______________, a carbapenem, undergoes hydrolysis by a dihydropeptidase enzyme in the ________________ to a toxic metabolite. - Therefore, it's comarketed with _________, a DHP inhibitor (to prevents this)
- Imipenem - Renal brush border (hepatotoxic) - Cilastatin (not on test, but USMLE)
What major drug category do cephalosporins fall under? Carbapenems?
- Beta-lactams - Beta-lactams
What are carbapenem's mech of action? - Baciocidal or static? - Time or conc-dependent?
Inhibitors of cell wall synthesis by binding to and inhibiting PBPs; primary target is PBP-2 - Bacteriocidal - Time-dependent
Name the major carbapenems. - Which 2 are the "best"?
DIME - Doripenem (best) - Imipenem (best) - Meropenem - Ertapenem
What are the mechs of resistance for cephalosporins? (which is most important?)
- Beta-lactamase enzymes (most important) - PBP alteration - Decreased membrane penetration
Beta-lactams are all cross-allergenic except for which one?
Aztreonam
Are cephalosporins bacteriocidal or bacteriostatic?
Bactericidal
Which subset of the cephalosporins are the only ones that have activity against anaerobes? - Which generation is it in?
Cephamycins - 2nd gen
*What gen. cephalosporin is used for the treatment of meningitis?
3rd gen
When treating meningitis w/3rd gen cephalosporins, if pseudomonas is suspected or present, what specific drug would you use?
Ceftazidime
What is the main thing that 5th gen cephalosporins are used for?
Drug-resistant organisms
Why were cephalosporins developed?
Beta lactams that are less susceptable to beta-lactamase enzymes.
Why were carbapenems developed?
- Extended spectrum of activity - Further beta-lactamase stability
What are the clinical uses of carbapenems?
- Empiric therapy for HA-infections - Polymicrobial infections - Infections due to β-lactamase-producing organisms (SPICE, SPACE, others)
*If pseudomonas is suspected, which carbapenem would you avoid?
*Avoid ertapenem if pseudomonas suspected
What are the main adverse effects of carbapenems?
- CNS (e.g. seizures) - GI - Hypersensitivity
Do carbapenems have hypersensitivity/cross-reactivity w/PCNs like cephalosporins do?
Yes
What category of drug is a monobactam? - How can it be administered?
Synthetic monocyclic beta-lactam - IV
Monobactams are beta-lactams. What specific part of the cell wall do they target? - What is the main class of organisms they target?
PBP-3 - of gram-negative aerobes
Recall: what class of organisms do monobactams inhibit? - What's its main target?
Gram-neg aerobes * Pseduomonas
Recall: what is the class of drugs that aztreonam is a member of? Since aztreonam is the only beta-lactam that does have cross-allergencitiy, what clinical implications does this have?
- Monobactams - Can be used in PCN-allergic pts
What are the major adverse effects of monobactams?
N/D
What are the major adverse effects for 2nd gen cephalosporins, besides hypersensitivity and c-diff?
- Hypoprothrombinemia - Ethanol intolerance due to disulfiram-like rxn
Which gen's of cephalosporins inhibit pseudomonas?
- 3rd (except ceftriaxone) - 4th
Which gen of cephalosporins are effective against anaerobes like bacteroides?
2nd gen only
