Beta lactams and cell wall synthesis inhibitors (Fitz)

Question 1

Because B-lactams resemble ___, they inhibit cross-linking enzyme(s)/Transpeptidases

Answer 1

D-ala-D-ala

Question 2

Which enzyme is a target of Pencillins (and other B lactams)?

Answer 2

transpeptidase

Question 3

These penicillins are narrow spectrum but potent and effective drugs against sensitive strains of gram + cocci, certain gram - cocci, certain gram + anaerobic species, spirochetes

Answer 3

Natural penicillins –> G and V

Question 4

What gram + cocci and diseases are clinically indicated for use of natural penicillins?

Answer 4

S. pneumo –> pneuomococcal pneumonia (resistant)
S. pypgenes –> pharyngitis, scarlet fever
S viridans group –> endocarditis

Question 5

What are routes of Penicillin G? Penicillin V?

Answer 5

G –> IV, IM, PO (low bioavailability); distributed into CNS with inflamed meninges

V–> PO, stable at gastric, acidic pH and has good oral bioavailability

Question 6

What is a complication of natural penicillins?

Answer 6

Hypersensitivity –> includes life-threatening anaphylaxis

Question 7

This enzyme produced by bacterial pathogens renders them penicillin resistant

Answer 7

B lactamase –> cleaves B lactam rings, inactivating penicillin G and conferring drug resistance

Question 8

B lactamase enzymes efficiently degrades these natural penicillins:

Answer 8

Penicillin G and V

Question 9

B lactamase enzymes efficiently degrades these extended spectrum abx:

Answer 9

ampicillin, amoxicillin

Question 10

B lactamase enzymes efficiently degrades these anti-pseudomonals:

Answer 10

ticarcillin and piperacillin

Question 11

Name the anti-staphylococcal penicillins:

Answer 11

Methicillin, Nafcillin, Oxacillin, Dicloxacillin

Question 12

Methicillin, Nafcillin, Oxacillin, and Dicloxacillin are drugs of choice for ___

Answer 12

penicillin-resistant BUT methicillin-sensitive organisms S aureus (MSSA)

Question 13

Methicillin is not used clinically d/t this toxicity:

Answer 13

interstitial nephritis

Question 14

What is the route, clearance, and toxicity associated with Nafcillin/

Answer 14

IV

hepatic, biliary

Hypersensitivity, Increase P450 induction

Oxacillin and Dicloxacillin each are PO, Renal/biliary, and both cause hypersensitivity

Question 15

Methicillin and related anti-staphylococcal penicillins bind to __ involved in cell wall synthesis in MSSA

Answer 15

penicillin binding proteins

Question 16

Alteration of __ gene and __ in S. aureus confers high-level resistance to Methicillin, oxacillin and other anti-staph penicillins despite the fact that they are not substrates for B lactamase. This is known as MRSA

Answer 16

mec A

PBP2

Question 17

MRSA is due to alteration of ___ and not caused by B lactamase enzymes

Answer 17

PBPs (PBP2)

Question 18

what is the drug of choice for MRSA?

Answer 18

Vancomycin

Question 19

what are vancomycin uses for Gram +?

Answer 19

MRSA (S aureus)
MRSE (S epidermidis)
Enterococci (E faecalis, E faecium) –> avoid overuse to avoid vancomycin resistance
Special use to treat C difficile –> oral admin for topical effect in bowel (if metronidazole failed)

Question 20

what activity does vancomycin have against gram - aerobes or anaerobes

Answer 20

no activity

Question 21

Vancomycin binds to D-ala-D-ala blocking ___ elongation and cross-linking

Answer 21

peptidoglycan

Question 22

list some vancomycin adverse effects:

Answer 22

Vanc-induced erythroderma or shock
Neprhotoxicity and ototoxicity
Dermatologic-rash
Phlebitis at injection site

Question 23

These penicillins enter via porins, bind to PBPs in periplasm and disrupt cell wall integrity

Answer 23

extended spectrum Aminopenicillins –> Ampicillin and Amoxicillin

Question 24

What gram + cocci and diseases are clinically indicated for extended spectrum aminopenicillins?

Answer 24

Gram + cocci: S pneumo, S pyogenes, S viridans, Enterococci

Respiratory infx –> CAP, sinusitis, bronchitis, pharyngitis. Amoxicillin is active against penicillin sensitive S pneumonia and often used for pharyngitis in children because of “taste”

Question 25

what gram - org and diseases are clinically indicated for extended spectrum aminopenicillins?

Answer 25

H influenza: bronchitis in COPD

Question 26

what would you add to ampicillin if there is resistance d/t B lactamase?

Answer 26

Sulbactam --> irreversibly inactivates enzyme; depletes B lactamase activity; spares ampicillin; Sulbactam has no inrinsic Abx effect Ampicillin plus sulbactam - IV

Question 27

what would you add to amoxicillin if there is resistance d/t B lactamase?

Answer 27

Clavulanic acid Amoxicillin plus clavulanic acid - PO

Question 28

List the antipseudomonal penicillins:

Answer 28

Ticarcillin | Piperacillin

Question 29

What populations are at risk for Pseudomonas aeruginosa infx?

Answer 29

Burn pts CF pts Injection drug users immunosuppressed

Question 30

Ticarcillin and Piperacillin cover these orgs in addition to pseudomonas aeruginosa

Answer 30

Gram - rods Enterobacter spp., E coli, proteus mirabilis, H influenza

Question 31

which anti-pseudomonal is most potent?

Answer 31

piperacillin

Question 32

what are some resistance mechanisms employed by pseudomonas aeruginosa?

Answer 32

altered PBPs | porin deficit- multi-drug resistance (MDR)

Question 33

In what clinical scenarios would you use ticarcillin and piperacillin together with a B lactamase inhibitor?

Answer 33

Severe pneumonia in hospitalized pt with structural lung disease (COPD) Neutropenic fever-sepsis Aspiration pneumonia in hospitalized pt, or stroke victim For empirical therapy of serious infx

Question 34

Which B lactamase inhibitor can you add to Ticarcillin? Pipericillin?

Answer 34

Ticarcillin plus clavulanic acid Pipericillin plus tazobactam

Question 35

All Gen 1-3 cephalosporins are ineffective and lack activity against:

Answer 35

- Listeria monocytogenes - Legionella spp - Atypical mycoplasma - MRSA - Enterococci

Question 36

what are the 1st generation cephalosporins?

Answer 36

Cefazolin (parenteral, IV, IM) --> penetrates well into bone CEPHALEXIN (PO) --> 2x daily for pharyngitis Cephradrine (Parenteral and PO)

Question 37

1st generation cephalosporins have a useful spectrum of activity against:

Answer 37

gram + cocci, streptococci and staph aureus NOT active against: MRSA, MRSE, enterococci

Question 38

what are clinical uses of 1st generation cephalosporins?

Answer 38

Surgical prophylaxis if skin flora are likely pathogens; soft tissue and skin infx d/t S aureus, S pyogenes

Question 39

what are the 2nd generation cephalosporins?

Answer 39

Cefoxitin (IV, IM)--> active vs anaerobes, eg, B fragilis Cefotetan (IV, IM) --> same as above CEFACLOR (PO) --> serum sickness in peds CEFUROXIME AXETIL (PO) --> poor substrate for B lactamase

Question 40

2nd generation cephalosporins have a useful spectrum of activity against

Answer 40

Enhanced activity against Gram - orgs, i.e., E coli, Klebsiella, H influenza; Moraxella cattharalis, proteus spp

Question 41

what are clinical uses of 2nd generation cephalosporins?

Answer 41

If facultative gram - bacteria and anaerobes are likely pathogens, i.e., intra-abdominal and gynecological sepsis, surgical prophylaxis for intra-abdominal & colorectal surgery

Question 42

List the 3rd generation cephalosporins:

Answer 42

Ceftriaxone --> Long t1/2 ~8 hrs, 1x daily; Penetrates CSF and bone; Activate vs N gonorrhea; Biliary clearance Cefotaxime --> Enters CSF; useful for meningitis d/t H influenza, S pneumonia, N meningitidis Cetazidime --> active vs pseudomonas aeruginosa Cefaperzone --> Disulfiram like alcohol intolerance

Question 43

3rd generation cephalosporins have a useful spectrum of activity against:

Answer 43

comparable to 1st generation vs S aureus, S pneumo, S pyogenes. Enhanced activity vs Gram - rods, enteric orgs

Question 44

This 3rd gen cephalosporin is given IV, IM with a t1/2 ~8 hrs, recommended for therapy of penicillin-resistant gonorrhea, Lyme disease involving the CNS or joints, meningitis d/t ampicillin-resistant H influenza and meningitis in children

Answer 44

Ceftriaxone Biliary excretion

Question 45

This 3rd gen cephalosporin is given IV, IM, penetrates well in CNS and is useful for bacterial meningitis from covered orgs such as H influenza, S pneumo, N meningitis, and Gram - enteric bacteria

Answer 45

Cefotaxime renal elimination tubular secretion

Question 46

This 3rd gen cephalosporin is particularly active against P aeruginosa and is an effective therapy for serious infx d/t P aeruginosa when the org is resistant to anti-pseudomonal penicillins or the pt is penicillin allergic.

Answer 46

Ceftazidime

Question 47

Ceftazidime should generally be given in combo with __ for tx of serious P aeruginosa

Answer 47

aminoglycoside (Tobramycin)

Question 48

What is a 4th generation cephalosporin?

Answer 48

Cefepime (IV, IM) --> activity greater than or equal to cefotaxime vs Gram - bacteria, H influenza, N gonorrhea, N meningitidis; Excellent penetration into CSF; Its activity is about = to Ceftazidime vs pseudomonas aeruginosa

Question 49

What is Cefepime (4th gen cephalosporin) insensitive to?

Answer 49

many B lactamases

Question 50

why is Cefepime able to better penetrate through outer membrane of gram - bacteria?

Answer 50

+charged quaternary ammonium

Question 51

What are adverse effects of cephalosporins?

Answer 51

Hypersensitivity (immediate=anaphylaxis, bronchospasm, urticaria; DTH=rash) Disulfiram-like rxn: nausea, flushing, headache; Disulfirm inhibits aldehyde dehydrogenase

Question 52

Cefotetan and Cefaperazone should be used with caution in these pts:

Answer 52

pts taking warfarin or with coagulation abnormalities --> MTT side chain causes reduction in vitamin K-producing bacteria in GI tract - Hypoprothrombinemia and bleeding

Question 53

Name a Monobactam:

Answer 53

Aztreonam

Question 54

Aztreonam binds to __ of gram - rods

Answer 54

PBP3

Question 55

What is the activity spectrum (which Gram - rods) of Aztreonam and when are they taken?

Answer 55

Gram - rods: Klebsiella, Pseudomonas, Serratia, etc Substitute for extended spectrum penicillin or gen 3,4 cephalosporins if these are contraindicated b/c of hypersensitivity

Question 56

what are your options for empirical therapy covering serious gram - infections if the pt has a severe allergy to penicillins?

Answer 56

Aztreonam (IV, IM; it is a monobactam) inactive vs Gram + spp and anaerobes

Question 57

Name Carbapenems:

Answer 57

Imipenem/Cilastatin (not a carbepanem but given alongside to avoid nephrotoxicity)

Question 58

This type of abx is the broadest spectrum of abx available and cover gram + (including Enterococcus faecalis and listeria); gram - orgs (including H influenza, N gonorrhea, Enterobacteriaceae and P aeruginosa); anaerobes, including B fragilis

Answer 58

Carbapenems not degraded by B lactamases

Question 59

This carbapenem is metabolized by the kidney to a nephrotoxic metabolite

Answer 59

Imipenem

Question 60

what are adverse effects of Carbapenems?

Answer 60

Hypersensitivity and rash CNS toxicity-seizures, confusion Nephrotoxicity-Imipenem. Always used with cilastatin

Question 61

This drug is used in combo with Imipenem and inhibits the dipeptidase enzyme in the proximal tubule to minimize nephrotoxicity of Imipenem

Answer 61

Cilastatin