Term
| Who discovered/derived cephalosporin? |
|
Definition
| In 1948 Brotzu found a mold in the mediterranean sea that he took back to the lab. He found that it could kill S. aureus. |
|
|
Term
| What are the first generation parenteral cephalosporins? |
|
Definition
cefazolin*
cephalothin
cephapirin
cephradine |
|
|
Term
| second generation parenteral cephalosporins |
|
Definition
cefoxitin
cefuroxime
cefotetan |
|
|
Term
| third generation parenteral cephalosporins |
|
Definition
|
|
Term
| antipseudomonal 3rd generation cephalosporins |
|
Definition
|
|
Term
| fourth generation cephalosporins |
|
Definition
|
|
Term
| oral 1st generation cephalosporins |
|
Definition
cephalexin*
cephradine
cefadroxil |
|
|
Term
| oral 2nd generation cephalosporins |
|
Definition
cefaclor
cefuroxime axetil |
|
|
Term
| oral 3rd generation cephalosporins |
|
Definition
cefpodoxime
cefditoren
cefdinir
ceftibuten |
|
|
Term
|
Definition
imipenem+cilastatin
meropenem
ertapenem
doripenem |
|
|
Term
|
Definition
|
|
Term
|
Definition
| lab can take any first generation cephalosporin and drop it on an agar plate and then record susceptibilities and the results will be the same for all |
|
|
Term
| Which generation exhibits the "class disc"? |
|
Definition
| first generation cephalosporins |
|
|
Term
| first generation cephalosporin gram + coverage |
|
Definition
| excellent gram+ coverage (staph and strep): very good against beta-lactamase producing staph, not effective against coagulase negative staph, MRSA, enterococci |
|
|
Term
| first generation cephalosporin gram - coverage |
|
Definition
limited to: E.coli, *Klebsiella pneumoniae*, P. mirabilis
no good drug against K. pneumoniae until cephalosporins
not good against H. influenzae |
|
|
Term
| first generation anaerobic coverage |
|
Definition
active against most anaerobes except Bacteroides fragilis
so it is NOT a great anaerobic drug |
|
|
Term
|
Definition
|
|
Term
| Which first generation cephalosporin has the best antistaphylococcal activity (if you look at MICs)? |
|
Definition
|
|
Term
| Which first generation cephalosporin has the longest half life? |
|
Definition
|
|
Term
| Can the first generation cephalosporins enter the cerebral spinal fluid in effective concentrations? |
|
Definition
| No, therefore they are not good for CNS infections. |
|
|
Term
|
Definition
most widely used of all cephalosporins
used for surgical prophylaxis (effective up to 4 hrs)
alternative treatment for Staph and Strep infections, MSSA, endocarditis |
|
|
Term
| What is the most widely used (most doses given) of all the cephalosporins? |
|
Definition
|
|
Term
| What is the drug of choice for endocarditis? Which cephalosporin is used if there is an allergy to it? |
|
Definition
| nafcillin the drug of choice for endocarditis, but if patient is allergic to penicillin then cefazolin is often used (unless it is a severe allergy) |
|
|
Term
| List the second generation parenteral cephalosporins |
|
Definition
cefamandole
*cefoxitin a cefamycin
cefuroxime
*cefotetan + a cefamycin
cefonicid
cefmetazole+NMTT side chain |
|
|
Term
| list the second generation oral cephalosporins |
|
Definition
cefaclor
cefprozil
*cefuroxim axetil*
lorcarbacef |
|
|
Term
| Is the class disc effect exhibited with the second generation cephalosporins? |
|
Definition
| no, only first generation |
|
|
Term
| What is the microbiological trend of the cephalosporins? |
|
Definition
| moving from 1st to 2nd to 3rd generation cephalosporins there is an increase in gram- coverage as a result of enhanced beta-lactamase stability but a decrease in gram+ activity |
|
|
Term
| difference between 1st and 2nd generation cephalosporins |
|
Definition
increase in gram- coverage
slight loss of activity against Staph and Strep (less afinity for binding site) |
|
|
Term
Which two second generation cephalosporins are active against H. influenzae, Strep. pneumoniae, moraxella catarrhalis, and widely promoted for para-respiratory infections
take care of many common infectious diseases from community: sinusitis, bronchitis, upper respiratory infections, middle ear infections, etc.? |
|
Definition
| cefamandole and cefuroxime |
|
|
Term
| Which second generation cephalosporins have moderate activity against Bacteroides fragilis and are approved for surgical prophylaxis of colon-rectal procedures? |
|
Definition
cefoxitin
cefotetan
cefmetazole |
|
|
Term
| Are second generation cephalosporins used for CNS infections? |
|
Definition
| No, cefuroxime could enter the CNS but it failed treatment tests. |
|
|
Term
| Which second generation cephalosporins have extended half-lives? |
|
Definition
cefonicid (3.5-4.0 hr)
cefuroxime (1.7 hr) |
|
|
Term
| What are the side effects of the second generation cephalosporins? |
|
Definition
interference with production of prothrombin (inability to clot)
disulfuram-like reaction
can have allergic reactions (not as reactive as penicillins) |
|
|
Term
| What interferes with production of prothrombin to cause the inibility to clot? |
|
Definition
| N-methyl-thiotetrazole (NMTT) side chain |
|
|
Term
| How do you correct the side effect caused by the NMTT side chain of some second generation cephalosporins? |
|
Definition
| vitamin K (important for clotting precursors): stimulates production of prothrombin |
|
|
Term
| What is the cross-hypersensitivity between penicillins and second generation cephalosporins? |
|
Definition
| 3-5%, about 1 in 20 patients |
|
|
Term
| What is the difference between the 2nd and 3rd generation cephalosporins? |
|
Definition
"quantum-leap" in activity against gram- organisms due to enhanced beta-lactamase stability and the ability to penetrate the gram- cell wall
poor activity against gram+ organisms |
|
|
Term
| Is there a class disc effect for the third generation cephalosporins? |
|
Definition
|
|
Term
| What are the three subgroups of third generation cephalosporins? |
|
Definition
1. enterobacteriaceae
2. enterobacteriaceae + anti-pseudomonal
3. enterobacteriaceae + anti-anaerobic |
|
|
Term
| Which third generation cephalosporins are effective against enterobacteriaceae? |
|
Definition
cefotaxime
ceftriaxone
ceftizoxime |
|
|
Term
| Which third generation cephalosporins are effective against enterobacteriaceae and pseudomonas? |
|
Definition
|
|
Term
| Which third generation cephalosporins are effective against enterobacteriaceae + anaerobes? |
|
Definition
| ceftizoxime good against B. fragilis |
|
|
Term
| Can any third generation cephalosporins penetrate the CNS? |
|
Definition
Yes, ceftriaxone
cefotaxime |
|
|
Term
| Which two third generation cephalosporins are approved for use in gram- meningitis? |
|
Definition
ceftriaxone
cefotaxime
they can penetrate CNS and are effective at lower MICs |
|
|
Term
| list the oral third generation cephalosporins |
|
Definition
cefixime
cefpodoxime
cefditoren
cefdinir |
|
|
Term
| How do the 4th generation cephalosporins compare to the other generations in regards to antimicrobial spectrum of activity? |
|
Definition
1st to 3rd generation better gram- activity at the expense of gram+ activity
4th generation about the same gram- activity as 3rd generation but increase the gram+ activity |
|
|
Term
| name fourth generation cephalosporins |
|
Definition
|
|
Term
| cefepime (4th generation cephalosporin) |
|
Definition
dipolar molecule, zwitterion (improves cell wall penetration)
good beta-lactamase stability
poor inducer of beta-lactamases
good activity against enterobacteriaceae, P. aeruginosa, H. influenzae, N. gonorrhea, N. meningiditis, gram+ organisms
not good against MRSA, enterococci, and anaerobes like B. fragilis
primarily intended for hospital-acquired infections and meningitis |
|
|
Term
| Which generation of cephalosporins are notorious for turning on beta-lactamase enzyme genes? |
|
Definition
|
|
Term
| What is a stably derepressed organism |
|
Definition
produces a lot of beta-lactamase enzymes
gene switch cannot be turned back off |
|
|
Term
| Can fourth generation cephalosporins penetrate the CNS? |
|
Definition
| Yes, cefepime can be used in the treatment of meningitis. |
|
|
Term
| What are the two main organisms that the fifth generation cephalosporins cover? |
|
Definition
|
|
Term
| list the 5th generation cephalosporins |
|
Definition
|
|
Term
|
Definition
only available in Canada
injectable drug
structure engineered to bind to PBP2a of MRSA
modest activity against E. faecalis (notE. faecium)
gram-activity similar to ceftriaxone (3rd generation) |
|
|
Term
| Why are ceftobiprole and ceftaroline effective against MRSA? |
|
Definition
| their structure was specifically engineered to bind the penicillin binding protein 2a (PBP2a) receptor of MRSA |
|
|
Term
|
Definition
structure engineered to bind to PBP2a of MRSA
FDA approved for complicated skin and soft tissue infections and community acquired pneumonia (CAP)
good activity against MSSA, MRSA, Strep and enteric gram- rods
moderate activity against Acinetobacter, Enterococcus faecalis (not faecium)
poor activity against P. aeruginosa, E. faecium and anaerobes
gram - activity similar to ceftriaxone |
|
|
Term
| What is the mechanism of action for a MRSA cephalosporin? |
|
Definition
high affinity for PBP 2a
vinylpyrrolidone moiety at the 3 position aids in the interaction at PBP 2a |
|
|
Term
| What are the two approaches to beta lactamase nomenclature? |
|
Definition
strucural approach
functional approach |
|
|
Term
| structural approach to beta-lactamase nomenclature |
|
Definition
molecular class based on protein sequence
limits clinical utility
Classes A, B, C, and D
A, C, and D hydrolyze substrate by formin and acyl enzyme through an active serine site (open beta lactam ring)
B hydrolyze substrate metalloenzymes that utilize zinc ion as catalyst (open beta-lactam ring) |
|
|
Term
| functional approach to beta-lactamase nomenclature |
|
Definition
uses a numbering system that groups enzymes according to their ability to hydrolyze different classes of beta lactam substrates
groups 1, 2a, 2be, 2br, 2c, 2d, 2f, 3a, 4, etc. |
|
|
Term
| What are the different types of beta-lactamases produced by bacteria? |
|
Definition
penicillinases
cephalosporinases
broad spectrum (more than one type)
extended spectrum beta-lactamases(ESBLs)
carbapenemases |
|
|
Term
| What are extended spectrum beta lactamases (ESBLs)? |
|
Definition
| beta-lactamases that mediate resistance to extended spectrum cephalosporins (ceftazidime, cefotaxime, and ceftriaxone) and monobactams but do not affect cephamycins (cefoxitin and cefotetan) or carbapenems |
|
|
Term
| Which organisms produce ESBLs? |
|
Definition
K. pneumoniae
K. oxytoca
E. coli
P. aeruginosa
Salmonella
P. mirabilis |
|
|
Term
| What drug is the most consistently effective against ESBL-producing organisms? |
|
Definition
|
|
Term
| What should be done to minimize the developmet of ESBL producing organisms? |
|
Definition
limit the empiric use of ES cephalosporins
use penicillins first (ex. piperacillin) |
|
|
Term
| list the carbapenems on the US market |
|
Definition
imipenem
meropenem
ertapenem
doripenem |
|
|
Term
| When should you use carbapenems? |
|
Definition
use when susceptibilities say you need to
don't use empirically |
|
|
Term
|
Definition
combination of thienamycin (antibiotic) plus cilastatin
first carbapenem to hit the market
broad spectrum, b-lactamase stable
seizures noted with high doses/decreased renal function |
|
|
Term
|
Definition
blocks hydrolysis of thienamycin in kidney
restores antibiotic activity
stops renal toxicity
component of imipenem |
|
|
Term
| Do carbapenems induce beta-lactamases? |
|
Definition
| Yes, they are potent inducers. They turn AmpC and other enzymes on in the bacteria. |
|
|
Term
| If an organism is capable of producing carbapenemases then is it resistent to other beta-lactam antibiotics? |
|
Definition
| Yes, if carbapenemases produced by bacteria then it is resistent to all beta-lactam antibiotics |
|
|
Term
| When should you use carbapenems? |
|
Definition
Only when necessary
ex. Acinetobacter |
|
|
Term
| What is one of the only drugs you can use when acinetobacter is resistant to beta-lactamases--including carbapenemases? |
|
Definition
|
|
Term
|
Definition
similar to imipenem
less seizure potential
pretty good against Staph (not MRSA), good against strep, enterobacteriaceae, pseudomonas, effective against anaerobes including B. fragilis |
|
|
Term
|
Definition
long half-life, once daily dosing
excellent gram+ activity, enterobacteriaceae, anaerobes
minimal pseudomonas activity
not good for prophylactic use
poor choice for intensive care hospital infections (b/c not effective against Pseudomonas) |
|
|
Term
|
Definition
broad spectrum of activity against gram+ organisms, enterobacteriaceae and pseudomonas
extended infusion time (4 hours) takes advantage of interval dependent killing characteristic
more like imipenem and merepenem |
|
|
Term
| What are the monobactams? |
|
Definition
|
|
Term
|
Definition
gram-, aerobic spectrum only!
anti-pseudomonal activity
can be used safely in patients with penicillin allergy |
|
|
Term
| What is the only drug that can safely be used in patients with a penicillin allergy? |
|
Definition
|
|
Term
|
Definition
|
|
