Cephalosporins Flashcards
How do cephalosporins compare chemically and structurally to penicillins?
Chemically and structurally similar to penicillins
What two drugs are included in the cephalosporin class but technically cephamycins?
Cefoxitin and cefotetan
What is the MOA of cephalosporins?
inhibit mucopeptide synthesis in the bacterial cell wall, making the bacterium osmotically unstable. Like penicillins, cephalosporins inhibit PBPs involved in cross-linking peptidoglycans in the cell wall
What are Penicillin Binding Proteins (PBPs)?
subgroup of enzymes of transpeptidases. Essential for bacterial cell wall synthesis. involved in the final stages of synthesizing peptidoglycan.
Inhibition of PBPs leads to defects in cell wall structure and irregularities in cell shape
What are cephalosporins most effective against?
They are most effective against rapidly growing organisms forming cell walls and when antibiotic concentrations exceed the pathogen’s MIC for at least 50% of the dosing interval
What is the only intravenous first-generation cephalosporin?
Cefazolin
What are the most commonly used first-generation cephalosporins?
cephalexin & cefadroxil
What species are intrinsically resistant to cephalosporins?
Enterococcus species
Do 1st gen cephalosporins readily enter the CSF?
No
What are the three 2nd gen. cephalosporins?
cefaclor, cefprozil, and cefuroxime
2nd gen cephalosporins are active against?
active against the same organisms as the first generation but with increased activity against H. influenzae
Cephamycins are included in what generation of cephalosporins?
2nd generation
What are the two cephamycins?
cefotetan and cefoxitin
What needs to be performed before ordering a second gen. cephalosporin?
2nd gens have variable activity, so susceptibility tests need to be performed
What are three 3rd gen. cephalosporin abx?
Cefotaxime, Cefpodoxime, and Ceftriaxone
Ceftazidime is what generation of cephalosporin, and what bacteria does it have increased activity against?
3rd generation. increased gram-negative activity such as Pseudomonas aeruginosa
What generation of cephalosporins are used to treat meningitis?
Because they cross the blood-brain barrier, third-generation parenteral cephalosporins are used to treat meningitis
What is the 4th gen. cephalosporin?
cefepime
What is the 5th gen. cephalosporin?
ceftaroline
What are the most common mechanisms of resistance to cephalosporins?
beta-lactamase production and altered target sites.
are cephalosporins stable in the presence of penicillinases produced by S. aureus?
yes
Which generation(s) are the most stable in the presence of most beta-lactamases produced by enteric gram-negative bacteria?
Third- and fourth generation cephalosporins
How well are cephalosporins absorbed through GI?
have oral formulations are well-absorbed from the GI tract
How are cephalosporins distributed? What needs to be considered with ceftriaxone?
Protein binding varies, but ceftriaxone is so highly bound to albumin that it should be avoided in neonates at risk for hyperbilirubinemia, especially preterm infants
What generations of cephalosporins readily enter the CSF in the presence of meningeal inflammation
Third and fourth-generation drugs
How significant is hepatic metabolism for cephalosporins?
Hepatic metabolism is not significant for cephalosporin drug elimination.
How are most cephalosporins excreted? What is one exception?
Most cephalosporins are excreted via the kidney in varying degrees as unchanged drug. Renal impairment significantly extends the half-life of these drugs.
Ceftriaxone elimination is mainly extrarenal, via biliary, making its half-life stable to changes in renal function
What lab value signifies a renal dosing adjustment is needed for cephalosporins?
Dosage adjustments are recommended for most oral agents when the glomerular filtration rate reaches less than 30 mL/min
How does renal impairment affect cephalosporin elimination?
Renal function impairment significantly affects the half-life of most cephalosporins
Are cephalosporins safe in pregnancy?
Generally safe in pregnancy. Does cross placenta and small portions into breast milk.
Are cephalosporins recommended for those who have had a type 1 (immediate, anaphylactic) reaction to any penicillin?
Despite this low cross-reactivity (1%), cephalosporins are still generally not recommended
What adverse event has occurred when renal impairment is not adjusted for when administering cephalosporins?
Several parenteral cephalosporins have been associated with induction of seizure activity, especially in the presence of renal impairment when the dose was not adjusted
Who are at risk for coagulation abnormalities from cephalosporin administration?
those with impaired renal function, cancer, impaired vitamin K synthesis, low vitamin K stores, or malnutrition.
Is C. diff development a possible sequela of cephalosporin admin?
yes
What are some clinical uses for cephalosporins?
Active against many respiratory pathogens, including those that cause acute otitis media, sinusitis and group A streptococcal pharyngitis, pneumonia, and chronic bronchitis
Active against most UTI pathogens
What cephalosporin is used to treat gonorrhea?
Ceftriaxone (IM) is the recommended treatment for gonorrhea - resistant to others
Staphylococcal skin infections often respond to which generation of cephalosporins?
first-generation cephalosporins such as cephalexin.
What is the drug of choice for surgical prophylaxis?
Parenteral cefazolin
What is the “definitive approach” to drug selection?
the microbial diagnosis is based on valid and reliable tests such as culture or antigen assays, and drug selection is based on laboratory and susceptibility results. The goal of susceptibility testing is to identify the most effective antibiotics.
What is the “empirical approach” to drug selection?
the microbial diagnosis and drug regimen are determined with epidemiological studies. These references identify the drug with the narrowest spectrum that covers the most likely microbiological pathogens for a specific clinical diagnosis.
Which generation of cephalosporins is the preferred empirical treatment for skin and tissue infections?
Second-generation oral cephalosporins are slightly less active against gram-positive cocci than first-generation oral cephalosporins, so the latter are the preferred empirical treatment
What cephalosporins are effective against the most resistant strains of pneumococcus
Parenteral ceftriaxone and cefotaxime are used empirically in serious infections presumed to be caused by these strains.
