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Pharm test #3 > CEPHALOSPORINS > Flashcards

CEPHALOSPORINS Flashcards

1
Q

Cephalosporin chemical structure and significance

A

β-lactam ring with a 6-membered dihydrothiazine ring (PCN has a 5 membered ring).

provides stability against many β-lactamase enzymes that render the penicillins inactive

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2
Q

Cephamycins chemical structure and significance

A

methoxy group at position 7 of the β-lactam
ring

confers activity against anaerobes such as Bacteroides spp.

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3
Q

Mechanism of action of Cephalosporins

A

bind and inhibit PBPs which inhibits cell wall synthesis (inhibit cross-linking)

same as penicillins

Bactericidal

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4
Q

3 mechanisms of resistance to cephalosporins

A
  1. β-lactamase enzymes (most common, hydrolyzes the bond of the β-lactam ring)
  2. altered PBPs
  3. altered permeability
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5
Q

Which cephalosporins have the most β-lactamase resistance

A

3rd and 4th generations

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6
Q

SPICE bacteria

A

have the ability to produce β-lactamase enzymes when exposed to antibiotics that induce their production (inducable β-lactamases)

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7
Q

1st generation cephalosporins have activity against

A

many gram positive aerobes (the best of all cephalosporins) and some gram negative aerobes

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8
Q

gram positive bacteria that 1st generation cephalosporins have activity against

A

MSSA
penicillin-susceptible S. pneumoniae
group A and B streptococcus
viridans streptococci

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9
Q

gram negative bacteria that 1st generation cephalosporins are active against

A

PEK
Proteus mirabillis
E. coli
Klebsiella pneumoniae

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10
Q

2nd generation cephalosporin activity

A

slightly less active against gram + when compared to 1st generation.

but more active against gram negative aerobes and cephamycins have anaerobe activity

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11
Q

gram negative aerobes that 2nd generation cephalosporins have activity against

A 
HENPEK
Haemophilus influenza
Morazella catarrhalis
Enterobacter
Neisseria spp. 
P. mirabillis
E. coli
K. pneumoniae
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12
Q

cephamycin activity

A

same as the other 2nd generation cephalosporins with additional activity against some anaerobes including Bacteroides fragilis

ie cefoxitin

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13
Q

3rd generation cephalosporin activity

A

generally less gram + than 1st and 2nd gen. but expanded gram negative aerobe activity

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14
Q

ceftriaxone is what generation

A

3rd generation

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15
Q

ceftriaxone and cefotaxime are one of the only cephalosporins with activity aginst

A

penicillin resistant S. pneumoniae

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16
Q

gram negative coverage for 3rd generation cephalosporins

A

HENPECKSSS (and more)
P. mirabilis, E. coli, K. pneumoniae
H. influenzae, M. catarrhalis, Neisseria gonorrhoeae (even β-
lactamase producing strains)
Neisseria meningitidis
Citrobacter spp., Enterobacter spp. (less with oral agents)
Morganella spp., Providencia spp.,

Serratia marcescens, Salmonella spp., Shigella spp.

Pseudomonas aeruginosa - only ceftazidime and cefoperazone

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17
Q

which 3rd generation cephalosporins have activity against Pseudomonas aeruginosa

A

only ceftazidime and cefoperazone

not ceftriaxone

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18
Q

which generation has some strong inducers of extended spectrum β-lactamases

A

3rd generation

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19
Q

4th generation of cephalopsorins

A

extended spectrum of activity for many gram positive and negative aerobes (no anaerobes)

excellent stability against β-lactamases hydrolysis and is a poor inducer of ESBL

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20
Q

cefepime is given

A

via IV only

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21
Q

gram negative coverage of 4th generations

A

similar to 3rd generation including
Pseudomonas aeruginosa and
β-lactamase producing Enterobacter and E. coli

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22
Q

Cephalosporins are NOT active against

A 
methicillin-resistant Staphylococcus
aureus (MRSA) 
coagulase-negative staphylococci, Enterococcus spp., 
Listeria monocytogenes, 
Legionella pneumophila, 
Clostridium difficile, 
Stenotrophomonas maltophilia, and
 Campylobacter jejuni.
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23
Q

cephalosporins absorption

A

well absorbed but have low serum concentrations when given orally.

Food affects the absorption

24
Q

cephalosporin distribution

A

most are widely distributed except 1st and 2nd generations do not achieve adequate CSF concentrations

25
cephalosporin elimination
mostly eliminated unchanged by the kidneys must adjust the dose in the presence of renal insufficiency • exceptions: ceftriaxone - bilary system, and cefoperazone - liver
26
cephalosporin half lives
most are short - need multiple doses per day, exceptions include: ceftriaxone which has an 8 hr half-life
27
clinical uses for 1st generation cephalosporins
Skin and soft tissue infections, septic arthritis, osteomyelitis, endocarditis, surgical prophylaxis*, urinary tract infections, bacteremia
28
clinical uses for 2nd generation cephalosporins
* Sinusitis, otitis media, upper and lower respiratory tract infections * Polymicrobial infections or surgical prophylaxis for abdominal surgery – (cephamycins - cefoxitin, cefotetan)
29
clinical uses for 3nd generation cephalosporins
* Bacteremia, pneumonia, complicated urinary tract infections, peritonitis, intra-abdominal infections, skin and soft tissue infections, bone and joint infections, meningitis** * Ceftriaxone is used for uncomplicated gonorrhea (single IM dose), CAP, PRSP, viridans strep endocard
30
what would you use for a meningitis where Pseudomonas was suspected
ceftazidime or a 4th generation (cefepime)
31
clinical uses for 4th generation cephalosporins
* Pneumonia, bacteremia, urinary tract infections, skin and soft tissue infections, intraabdominal infections, Gram-negative meningitis, febrile neutropenia * Covers Pseudomonas**
32
clinical uses for 5th generation cephalosporins
Community acquired bacterial pneumonia | Skin and skin structure infections
33
adverse effects of cephalosporins
* hypersensitivity (up to 15% of pts w/ pcn allergies) * MTT side chain * Hematologic - leukopenia, thrombocytopenia * GI - ↑ bili; C. difficile colitis * IV calcium and ceftriaxone precipitates, cefepime/ceftaz and nonconvulsive status epilepticus
34
MTT side chain
* Hypoprothrombinemia - due to enzyme inhibition of vitamin K metabolism or reduction in vitamin K-producing bacteria in GI tract (impaired blood clotting) * Ethanol intolerance (inhibits alcohol dehydrogenase)
35
Carbapenems (4 of them)
imipenem, meropenem, erta-penem, and doripenem
36
Carbapenems primary binding target
PBP-2
37
carbapenems mechanism of action
bactericidal - time depended | inhibits cell wall synthesis
38
carbapenems mechanisms of resistance
β-lactamase production, decreased permeability, alteration in PBPs
39
carbapenems spectrum of activity
* most broad specturm agents available ** | * Have activity against gram-positive and gram-negative aerobes AND anaerobes
40
bacteria NOT covered by carbapenems
MRSA, PRSP, VRE, coagulase-negative staph, C. difficile, atypical bacteria, S. maltophilia,
41
which carbapenems have the greatest spectrums of activity
imipenem, and doripenem
42
pseudomonas aeruginosa is killed by which carbapenems
imipenem, meropenem, and doripenem NOT ERTAPENEM
43
which carbapenem has the best CSF penetration?
meropenem
44
how are carbapenems eliminated
* kidney (need dosage adjustment with renal dysfunction) * Imipenem undergoes hydrolysis by a dihydropeptidase enzyme in the renal brush border to a nephrotoxic metabolite; comarketed with cilastatin, a DHP inhibitor (otherwise it would be cleared too quickly) * Short elimination half-lives (ertapenem 4 hours- longest can be given once a day)
45
what is impenem is always given with
cilastatin (inhibits DHP which would otherwise inactivate impenem)
46
clinical uses of carbapenems
* Empiric therapy for hospital acquired infections * Polymicrobial infections (broad spec) * Infections due to β-lactamase-producing organisms (SPICE, SPACE, others) * Febrile neutropenia – imip and mero * Meningitis – meropenem * If Pseudomonas is known or suspected – NOT ertapenem**
47
adverse effects of carbapenems
* hypersensitivity (cross-reactive w/ pcn) * GI * CNS - Confusion, dizziness, hallucinations, seizures. Risk factors for seizures include preexisting CNS disorder, high doses, renal insufficiency
48
Monobactam drug name
Aztreonam is the only monobactam currently available
49
Monobactam preferred binding target
PBP-3 of gram negative aerobes - inhibits cell wall synthesis like other β-lactams
50
monobactams are affective against
Gram-Negative Aerobes ONLY E. coli, K. pneumoniae, P. mirabilis, S. marcescens, H. influenzae, M. catarrhalis, Enterobacter, Citrobacter, Providencia, Morganella, Salmonella, Shigella, Pseudomonas aeruginosa**
51
Monobactams (Aztreonam)
 distribution
only available IV Widely distributed into body tissues and fluids Penetrates the CSF in the presence of inflamed meninges
52
Monobactams (Aztreonam) Elimination
* Excreted in the urine as unchanged drug * Short elimination half-life of 1.3 to 2.2 hours * Doses need adjustment with renal dysfunction; is removed by hemodialysis
53
Aztreonam clinical uses
Clinical uses include urinary tract infections, respiratory tract infections, meningitis, bacteremia, skin and soft tissue infections, and intraabdominal infections due to susceptible gram-negative aerobes
54
Aztreonam adverse effects
* Gastrointestinal: nausea, diarrhea | * Hypersensitivity: no cross-reactivity with penicillins, can be used in penicillin-allergic patients
55
what would you give to a pt with a suspected gram negative infection who is allergic to penicillin?
aztreonam - no cross-reactivity w/ pcn

Pharm test #3 (17 decks)

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