Erdman - Cephalosporins Flashcards
What does the six member ring of cephalosporins do?
Confers greater stability against some beta-lactamase enzymes
What is the mechanism of action of cefiderocol?
Acts as a siderophere and binds to extracellular iron using it as a vessel to enter bacteria
Why are all cephalosporins bactericidal but not penicillins?
Because cephalosporins do not have activity against enterococcus, which are only bacteriostatic
Gram-positive bacteria that produce beta-lactamase enzymes that are resistant to cephalosporins
Pen-R staph aureus
Gram-negative bacteria that produce beta-lactamase enzymes that are resistant to cephalosporins
-Kleb pneumoniae
-Haemophilus influenzae
-M catarrhalis
-E. coli
-Enterobacter
-Neisseria gonorrhoeae
Anaerobes that produce beta-lactamase enzymes that are resistant to cephalosporins
-Bacteroides fragilis
How many generations of cephalosporins are there?
7 generations technically
What is the difference between the generations of cephalosporins?
-Lose gram+ activity as you increase in gram- activity as you go op in generations (1-4)
-Greater beta-lactamase stability as you go from 1-4
-Miscellaneous generations have the greatest resistance to beta-lactamase enzymes
Gram positive activity of first generation cephalosporins
-Group strep
-Viridans strep
-Pen susc S. pneumoniae
-Meth susc S. aureus* (DOC)
Gram negative activity of first generation cephalosporins
(PEK)
-P. mirabilis
-E. coli
-K. pneumoniae
What are the first gen cephalosporins?
-Cefazolin (parenteral)
-Cephalexin (oral)
Which second generation cephalosporins have activity against anaerobes?
Cephamycins
Gram positive activity of second generation cephalosporins
-Group strep
-Viridans strep
-Pen-susc S. pneumoniae
-Meth-susc S. aureus*
Gram negative activity of second generation cephalosporins
(HENPEK)
-M. catarrhalis
-H. influenzae (beta-lactam negative)
-Enterobacter spp. (some)
-Neisseria spp.
-P. mirabilis
-E. coli
-K. pneumoniae
Anaerobe activity of second generation cephalosporins
(Cephamycins only)
-Bacteroides fragilis
-Bacteroides fragilis group
What are the cephamycins?
-Cefoxitin
What are the second generation cephalosporins?
-Cefuroxime (IV and oral)
-Cefprozil (oral)
-Cefoxitin
Which third generation cephalosporins retain the best activity against gram-positive aerobes?
Ceftriaxone has the best activity against gram-positive aerobes including penicillin resistant S. pneumoniae
Gram negative activity of third generation cephalosporins
(HENPECKSSS)
-Pseudomonas aeruginosa
-M. catarrhalis
-Acinetobacter sp.
-Morganella morganii
-Providencia
-H. influenzae
-Enterobacter spp.
-N. gonorrhoeae (including beta-lactamase producing)
-N. meningitidis
-P. mirabilis
-E. coli
-Citrobacter sp.
-K. pneumoniae
-Serratia marcescens
-Salmonella sp
-Shigella sp.
Which third generation cephalosporins cover pseudomonas?
-Ceftazidime
-Cefoperazone
-NOT ceftriaxone
What are the third generation cephalosporins?
-Ceftriaxone
-Ceftazidime
-Cefpodoxime
Gram positive activity of fourth generation cephalosporins
Similar to ceftriaxone (covers PRSP)
Gram negative activity of fourth generation cephalosporins
Similar to ceftriaxone but includes pseudomonas and beta-lactamase producing spp.
How are fourth generation cephalosporins effected by beta-lactamase enzymes?
Stable against beta-lactamases and are poor inducers of AmpC inducible enzymes
What are the fourth generation cephalosporins?
Cefepime (IV)
Gram positive activity of ceftaroline (Teflaro)
Similar to ceftriaxone (PRSP) but also covers MRSA
Gram negative activity of ceftaroline (Teflaro)
Similar to ceftriaxone and does not cover pseudomonas aeruginosa
Gram positive activity of cefiderocol (Fetroja)
None
Gram negative activity of cefiderocol (Fetroja)
Similar to cefepime but includes many ESBLs, AmpCs, and CREs
Gram positive activity of ceftolozane-tazobactam (Zerbaxa)
Covers streptococcus (not good for this)
Gram negative activity of ceftolozane-tazobactam (Zerbaxa)
Similar to cefepime also includes some ESBLs and AmpCs (resistant pseudomonas aeruginosa) (most active against pseudomonas in cephalosporin class)
Gram positive activity of ceftazidime-avibactam (Avycaz)
Covers streptococcus (not good for this)
Gram negative activity of ceftazidime-avibactam (Avycaz)
Similar to cefepime but also includes many ESBLs, some AmpCs and KPC/OXA CREs (not VIM or NDMs)
What are cephalosporins dependent on to kill bacteria?
-Time dependent
-Time>MIC is PD parameter that correlates with efficacy
What synergy is used clinically to treat viridans strep?
Ceftriaxone plus gentamicin
What synergy is used clinically to treat staph aureus?
Cefazolin plus gentamicin
What synergy is used clinically to treat gram-negative aerobes?
Ceftriaxone, ceftazidime, or cefepime plus gentamicin, tobramycin or amikacin
Which cephalosporins achieve therapeutic concentrations in the CSF?
-Parenteral cefuroxime
-Third gen agents
-Fourth gen agents
Which cephalosporins are not eliminated through the kidney?
-Ceftriaxone
-Cefoperazone
What is the one cephalosporin with a long half-life?
Ceftriaxone has a half-life of 8 hours and is dosed once or twice daily
Clinical uses of first gen cephalosporins
-Bacteremia due to MSSA
-Surgical prophylaxis
Is cefuroxime still used for meningitis?
No
Which cephalosporins are used for polymicrobial infections or surgical prophylaxis for abdominal surgery?
(Cephamycins)
-Cefoxitin
-Cefotetan
Clinical uses of third gen cephalosporins
-Ceftazidime if Pseudomonas is suspected or documented
-Ceftriaxone is used for uncomplicated gonorrhea (one IM dose), community-acquired pneumonia, PRSP, viridans strep endocarditis
Clinical uses of fourth gen cephalosporins
Febrile neutropenia due to gram negative bacteria (including pseudomonas)
Clinical uses of ceftaroline
-MRSA
-Does not cover pseudomonas
Clinical uses of cefiderocol
Current place in therapy still being determined
Clinical uses of Avycaz and Zerbaxa
Current place in therapy still being determined
Cephalosporin adverse effects
-Hypersensitivity
-Hypoprothrombinemia
-Ethanol intolerance
-IV calcium precipitates with ceftriaxone
-Nonconvulsive status epilepticus
What percent of patients with a penicillin allergy will have cross-reactivity with cephalosporins?
1-5%
When should cephalosporins be avoided in penicillin allergic patients?
-Allergic reaction causing ICU admission
-Delayed severe skin reaction
When should cephalosporins with a similar R1 side chain be avoided in penicillin allergic patients?
Allergic reaction that causes general rash or itching
Which cephalosporins have a MTT side chain?
-Cefamandole
-Cefotetan
-Cefmetazole
-Cefoperazone
-Moxalactam
What does the MTT side chain cause?
-Hypoprothrombinemia
-Ethanol intolerance
How can you avoid calcium and ceftriaxone precipatates?
Calcium should not be given within 24 hours of ceftriaxone
