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Flashcards in CEPHALOSPORINS Deck (55):
1

Cephalosporin chemical structure and significance

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

2

Cephamycins chemical structure and significance

methoxy group at position 7 of the β-lactam
ring

confers activity against anaerobes such as Bacteroides spp.

3

Mechanism of action of Cephalosporins

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

same as penicillins

Bactericidal

4

3 mechanisms of resistance to cephalosporins

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

5

Which cephalosporins have the most β-lactamase resistance

3rd and 4th generations

6

SPICE bacteria

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

7

1st generation cephalosporins have activity against

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

8

gram positive bacteria that 1st generation cephalosporins have activity against

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

9

gram negative bacteria that 1st generation cephalosporins are active against

PEK
Proteus mirabillis
E. coli
Klebsiella pneumoniae

10

2nd generation cephalosporin activity

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

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

11

gram negative aerobes that 2nd generation cephalosporins have activity against

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

12

cephamycin activity

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

ie cefoxitin

13

3rd generation cephalosporin activity

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

14

ceftriaxone is what generation

3rd generation

15

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

penicillin resistant S. pneumoniae

16

gram negative coverage for 3rd generation cephalosporins

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

17

which 3rd generation cephalosporins have activity against Pseudomonas aeruginosa

only ceftazidime and cefoperazone

(not ceftriaxone)

18

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

3rd generation

19

4th generation of cephalopsorins

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

20

cefepime is given

via IV only

21

gram negative coverage of 4th generations

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

22

Cephalosporins are NOT active against

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

23

cephalosporins absorption

well absorbed but have low serum concentrations when given orally.

Food affects the absorption

24

cephalosporin distribution

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