Cephalosporins Flashcards
Cephalosporins chemistry
Great stability against some b-lactamase enzymes
MOA
Bactericidal
interfere with cell wall synthesis by binding to PBP located in the bacterial cell wall which leads to inhibition of final transpeptidation step of peptidoglycan synthesis
Mechanism of resistance
- Production of B-lactamase enzymes
- alteration in the PBP leading to decreased affinity (MRSA, PRSP)
- Alteration of outer membrane leading to decreased penetration to the PBP
Classification of cephalosporins
grouped in 4 generations
based on structure/ antimicrobial activity and resistance to B-lactamase enzymes
Generalization of spectrum of activity
Lose gram positive activity with an increase gram negative as you go from 1 to 2 to 3 to 4
Greater b-lactamase stability as you go from 1 to 2 to 3 to 4
Cefazolin and Cephalexin
First generation Cephalosporins
First generation cephalosporin activity
Best with gram positive
Gram positive:
Group steptococci
Viridans streptococci
Pen-susc S. Pneumoniae
Meth-susc S. Aureus
Gram Negative (PEK)
Pseudomonas Mirabilis
E. Coli
Klebsiella Pneumoniae
Cefuroxime and Cefprozil and Cefoxitin
Second generation Cephalosporins
Cefoxitin is a cephamycin but grouped with second generation due to activity
Second generation Cephalosporins
Cefuroxime, Cefproxil, Cefoxitin
Gram positive:
Group Streptococci
Viridans Streptococci
PSSP
MSSA
Gram Negative (HENPEK)
Pseudomonas Mirabilis
E. Coli
Klebsiella Pneumoniae
H. Influenzae (BL -)
Enterobacter Spp. (some)
Neisseria spp.
M.Catarrhalis
Aerobes (ONLY CEFOXITIN)
bacteroides Fragilis
Bacteroides fragilis group
Ceftriaxone, Ceftazidime, Cefpodoxime
Third Generation Cephalosporins
Third generation Cephalosporins Coverage
Ceftriaxone, Ceftazidime, Cefpodoxime
CEFTRIAXONE IS ONLY ONE THAT COVERS GRAM POSITIVE AEROBES - PEN-RESISTANT S. PNEUMONIAE
Gram negative aerobes: (HENPEK-CSSS)
H. Influenziae
Enterobacter spp
Niessiria gonorrhoeae
Pseudomonas mirabilis
E. Coli
Klebsiella
Citrobacter spp.
Salmonella
Shigella
Serratia marcescens
Pseudomonas aeruginosa (ONLY CEFTAZIDIME) -EXAM Q
Cefepime
Fourth generation Cephalosporin
Fourth generation Cephalosporin coverage
Cefepime
Gram positive:
PEN-RESISTANT S. PNEUMONIAE
Gram negative: (HENPEK-CSSS)
H. Influenziae
Enterobacter spp (BL+)
Niessira
psuedomonas mirabilis
E. Coli (BL+)
Klebsiella
Citrobacter
Shigella
Salmonella
Serratia
Psuedomonas Aeurginosa
Ceftaroline
Anti-MRSA cephalosporin
Anti-MRSA Cephalosporin
Ceftaroline
Gram positive: pen-resistant s. pseumoniae, meth-resistant s. aeureus
Gram negative aerobes: (HENPEK-CSSS)
H. Influenziae
Enterobacter spp
Niessiria gonorrhoeae
Pseudomonas mirabilis
E. Coli
Klebsiella
Citrobacter spp.
Salmonella
Shigella
Serratia marcescens
Cefiderocol
Does not cover gram positive
Gram negative aerobes: (HENPEK-CSSS)
H. Influenziae
Enterobacter spp
Niessiria gonorrhoeae
Pseudomonas mirabilis
E. Coli
Klebsiella
Citrobacter spp.
Salmonella
Shigella
Serratia marcescens
Pseudomonas Aeruginosa
Covers ESBLs, AmpC, CREs, KPCs, NDMs, VIM, OXA-48
Ceftolozane-Tazobactam (Zerbaxa)
Cephalosporin-b-lactamase inhibitor
Cephalosporin-b-lactamase inhibitor
Ceftolozane-Tazobactam (Zerbaxa)
Ceftazidime-Avibactam (avycaz)
Gram positive: streptococcus
Gram negative aerobes: (HENPEK-CSSS)
H. Influenziae
Enterobacter spp
Niessiria gonorrhoeae
Pseudomonas mirabilis
E. Coli
Klebsiella
Citrobacter spp.
Salmonella
Shigella
Serratia marcescens
Pseudomonas Aeruginosa
Zerbaxa Includes ESBLs and AmpC
Avycaz includes ESBLs, AmpC, KPCs, OXA
Which cephalosporin is considered a potential drug of choice for infections due to MSSA?
A. Ceftazidime
B. Cefotetan
C. Cefazolin
D. Ceftolozane-Tazobactam
E. Cefonicid
Cefazolin - first generation Cephalosporin
Which cephalosporin does NOT have activity against Pseudomonas aeruginosa?
A. Ceftriaxone
B. Ceftazidime
C. Cefepime
D. Ceftolozane-Tazobactam
E. Ceftazidime-Avibactam
A. Ceftriaxone - 3rd gen cephalosporin
Pharmacology
Time dependent
clinical efficacy is Time above MIC (T>MIC)
Absorption
Oral cephalosporins are well absorbed but have lower concentration than parental products - food can decrease absorption
Distribution
Widely distributed through out the tissues and fluids
CSF concentration acheived only with Parental Cefuroxime, Cefepime, Ceftiaxone, Ceftazidime
Elimination
Most eliminated unchanged by the kidney
Ceftriaxone biliary
Cefoperazone through liver
Short elimination half lives around 2 hours
ceftriaxone has half life of 8 hours
First generation Clinical use
MSSA
Streptococci skin and soft tissue infections
Surgical prophylaxis
Second generation clinical use
Cefuroxime and Cefprozil and Cefoxitin
No longer recomended for treatment of meningitis
Bacteroides fragilis - Cefoxitine
Polymycrobial infections
Third generation clinical use
Ceftazidime if Pseudomonas suspected infection
Ceftriaxone is used for uncomplicated gonorrhea (One IM dose), PRSP
Fourth generation clinical use
Cefepime - Antipseudomonal activity
Anti-MRSA cephalosporin clinical use
Ceftaroline - Skin and soft tissue infection including those cause by MRSA
Adverse effects
- Hypersenitivity reaction - Patients who had severe reaction to penicillin needed ICU admission should avoid ALL Cephelosporins those with other reaction and NO ICU admission should avoid Cephalopsorins with similar R1 chain
- Hematologic - Anemia, Leukopenia, Thrombocytopenia
- Gastrointestinal- increased bili (ceftriaxone), C. diff
- other - IV calcium and ceftriaxone orecipitation(never mix the two), Nonconvulsive status epilepticus (can happen in those with renal insufficiency)
Adverse reaction specific to Cefamandole, Cefotetan, Cefmetazole, Cefoperazone, Moxalactam
Due to MTT side chain (Nitromethylthiotetrazole)
Causes
-hypoprothrombinemia due to reaction in Vitamin K producing bacteria in GI
- Ethanol intolerance - pts should not drink while on these drugs
True/False: A patient who developed anaphylaxis to penicillin requiring ICU admission can safely receive any cephalosporin.
FALSE
All beta-lactams (including all cephalosporins) should be avoided in a patient who developed anaphylaxis to penicillin requiring ICU admission
