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Infectious Disease > Beta Lactam Antibiotics > Flashcards

Beta Lactam Antibiotics Flashcards

1
Q

What does the main structure of the beta lactam consist of?

How do they work?

A

consist of the beta-lactam ring, essential for the activity of the antibiotic against a pathogen.

Most β-lactam antibiotics work by inhibiting cell wall biosynthesis in the bacterial organism.

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2
Q

Struture of penicillins?

3

A

thiazolidine ring,
beta-lactam ring,
a secondary amino group on the beta-lactam ring where substituents can attach to form different compounds

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3
Q

MOA of Penicillin?

3

A
  1. Bactericidal to growing bacteria
  2. Interferes with transpeptidation of cell wall synthesis
  3. cell wall is destroyed and the bacterial cell dies
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4
Q

What do beta lactam bacteria bind to?

A

bind to a family of related enzymes that are called—penicillin binding proteins (PBPs)‏

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5
Q

What do beta lactam antibiotics bind to?

A

the PBPs and inhibit transpeptidation which stops the cross-linking of polysaccharides

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6
Q

What step is inhibited by beta-lactam antibiotics?

A

the linear
polymers are being
cross-linked by
transpeptidation

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7
Q

HOw do Bacteria often develop resistance to β-lactam antibiotics ?

A

synthesizing β-lactamase (penicillinase), an enzyme that breaks down the beta-lactam ring and inactivates the antibiotic (essentially this is metabolism of the drug)

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8
Q

How do we overcome Beta-lactam resistance?

A

β-lactam antibiotics are often given with β-lactamase inhibitors such as clavulanic acid.

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9
Q

What are the Beta-Lactam Compound classes?

3

A

Penicillins
Cephalosporins
Beta-Lactamase Inhibitors- combined w/ PCN’s

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10
Q

Penicillin classifications?

3

A

Penicillin G
Antistaphlococcal PCNs
Broad Spectrum PCNs

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11
Q

NAme the types of Antistaphlococcal PCNs?

4

A

nafcillin,
dicloxacillin,
oxacillin,
cloxacillin

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12
Q

What are the types of broad spectrum PCNs?

A

Second generation
Third generation
Fourht generation

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13
Q

What are some second generaton broad spectrum pcns?

2

A

ampicillin, amoxicillin

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14
Q

What are some of the third generation broad spectrum pcns?

2

A

carbenicillin, ticarcillin

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15
Q

Fourth generation broad spectrum pcns?

A

piperacillin

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16
Q

Combinations w/ beta-lactamase inhibitors?

4

A
  1. amoxacillin/potassium clavulanate (Augmentin)
  2. ampicillin/sulbactam (Unasyn) -broader coverage-sicker pts
  3. Ticarcillin/potassium clavulanate (Timentin)
  4. Piperacillin & tazobactam sodium (Zosyn)
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17
Q

All PCNs should be given on an empty stomach except which one?

A

oral amoxacillin

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18
Q

Giving PCNs with probenecid (500mg q 6 hrs) does what?

A

increases blood levels of all PCNs

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19
Q

Allergic reactions to one PCN will be what to others?

What can these reactions range from?

A

cross reactive to others,

reactions can be urticarial to anaphylaxis to serum sickness

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20
Q

PCNs can cause what complications?5

These are rare but mainly seen with what?

A 
encephalopathy: 
somnolence, 
stupor, 
coma, 
seizures; 
(NEUROTOXICITY)
rare, mainly seen with high doses
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21
Q

What side effect is the most frequent complaint with PCNs?

A

GI reactions, especially diarrhea

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22
Q

What GI complication do we have to worry about with all antibiotics?

A

C.Diff

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23
Q

What is the use of Penicillin G?

6

A 
Treatment of infections (including 1. sepsis, 
2. pneumonia, 
3. pericarditis, 
4. endocarditis, 
5. meningitis, 
6. anthrax
caused by susceptible organisms
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24
Q

What groups of bacteria is Penicillin G active against?
4

Penicillin VK/oral form is the drug of choice for which infections?

A
  1. Gram-positive cocci (streptococci, staphylococci)
  2. Gram-positive rods (Listeria, actinomyces)
  3. Gram-negative cocci (Neisseria)
  4. Most anaerobes (clostridium)

strep pharyngitis

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25
Q

What are the dosage form of Penicillin G?

Which ones do we want to use the most?

A

IM
IV
PCN VK is oral form (has poor bioavailability, narrow spectrum)

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26
Q

What are the IM forms of Penicillin G?

How long does one injection last?

Name two infections that its used for and one that is now resistant?

Name two infections that the IV form of penicillin G is used to treat?

A

PCN G benzathine & *PCN G procaine

10-12 days

strep and sometimes syphilis
(gonorrhea is now resistant)

IV form used to treat meningitis and endocarditis

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27
Q

How would we treat Erysipelas with penecillin G?

How would we treat Neurosyphilis with penicillin G?

In general IV penecillin G?

(how much and how often)

A

IV: 1-2 million units every 4-6 hours x 7-10 days

IV: 18-24 million units/day in divided doses every 4 hours (or by continuous infusion) for 10-14 days

1-24 million units/day divided every 4-6 hours

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28
Q

Pregnancy category for Penicillin G?

Safe for lactation?

Renal dosing?

Hepatic dose?

A

B (presumed safety based on animal studies)

Yes

Adjust dose for creatinine clearance

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29
Q

Local adverse rxn for penicillin G?

Significant adverse reactions to penicillin G?

A

Local: Injection site reaction

  1. Cardiovascular: Localized phlebitis, local thrombophlebitis
  2. Central nervous system (high doses): Coma, hyperreflexia, myoclonus, seizure
  3. Dermatologic: Contact dermatitis, skin rash
    Endocrine & metabolic: Electrolyte disturbance (high doses)
  4. Gastrointestinal: Pseudomembranous colitis
  5. Hematologic & oncologic: Neutropenia, positive direct Coombs test (rare, high doses)
  6. Hypersensitivity: Anaphylaxis, hypersensitivity reaction (immediate and delayed), serum sickness
  7. Immunologic: Jarisch-Herxheimer reaction
  8. Renal (high doses): Acute interstitial nephritis, renal tubular disease
Cardiovascular
CNS
Dermatologic
Endocrine and metabolic
GI
Hematologic
Hypersensitivity
Immunologic
Renal
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30
Q

Contraindications for Penicillin G?

A

Hypersensitivity to penicillin or any component of the formulation

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31
Q

Warnings and precautions for Penicllin G?

6

A
  1. Anaphylactoid/hypersensitivity reactions
  2. Superinfection
  3. Disease-related concerns
  4. Seizure disorders
  5. Special populations: 6. Pediatrics/Neonates will have decreased renal clearance of PCN
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32
Q

Drug interactions with Penicillin G?

7

A

BCG : Causes Dimish Effect Risk X: Avoid combination

Methotrexate: Increase Effect. Risk C: Monitor therapy

Probenecid: Increase Effect. Risk C: Monitor therapy

Sodium Picosulfate: Dimish Effect. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification

Tetracycline Derivatives: Dimish Effect. Risk D: Consider therapy modification

Vitamin K Antagonists (eg, warfarin): May enhance effect. (monitor INR)

OBCP’s: pcn may decrease contraceptive efficacy

BCG
Methotrexate
Probenecid
Sodium Picosulfate
Tetracycline Derivatives
Vitamin K Antagonists (eg, warfarin)
OBCP’s
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33
Q

Antistaphylococcal PCNs
use and activity?
2

WHo is it inactive against? 2

Name the three exmaples given of Antistaphylococcal PCNs?

A

semisynthetic PCNs used for infection with

  1. beta-lactamase-producing staph, also used against
  2. PCN susceptible strains strep & pneumococci

Inactive against Enterococci &; methicilliin resistant strains (MRSA)

Dicloxacillin,
oxacillin, and
nafcillin

(antibiotics that are not affected by beta-lactamase enzyme)

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34
Q

Antistaphylococcal PCNs dosage forms?
Dicloxacillin
Oxacillin
Nafcillin

A

PO
IM; IV
IV

35
Q

Antistaphylococcal PCNs:
Pregnancy Category?
Lactation?
Renal dosing/Hepatic dosing?

A

Pregnancy Cat: B
Lactation: Safety Unknown

Renal Dosing/Hepatic Dosing
No dosage adjustment required. However, the manufacturer’s labeling recommends consider decreasing. dose if concomitant renal and hepatic impairment

36
Q

Main adverse effects of Antistaphylococcal PCNs?

A

1% to 10%: Gastrointestinal (dicloxacillin only): Nausea, diarrhea, abdominal pain

37
Q

Antistaphylococcal PCNs drug interactions?

8

A

Aripiprazole: decrease Management: Risk D: Consider therapy modification

Calcium Channel Blockers: Increase the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification

Contraceptives (Estrogens): increase the metabolism of Estrogens. Management: Use of an alternative, nonhormonal form of contraception during nafcillin therapy is recommended. Risk D: Consider therapy modification

BCG: Decrease
Risk X: Avoid combination

Methotrexate: Increase
Risk C: Monitor therapy

Probenecid: May increase the serum concentration of Penicillins. Risk C: Monitor therapy

Saxagliptin: CYP3A4 Inducers may decrease the serum concentration of Saxagliptin. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Dicloxacillin may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Aripiprazole
Calcium Channel Blockers
Contraceptives (Estrogens)
BCG
Methotrexate
Probenecid
Saxagliptin
Vitamin K Antagonists (eg, warfarin)
38
Q

Use and treatment with second generation PCNs?
(Name three infections)

Amoxicillin can be combined with clavulanic acid (Augmentin) which is a beta-lactamase inhibitor so expands coverage to cover what?3

A

treat otitis, sinusitis, lower RTI

gram positive, gram-neg and anaerobic organisms

39
Q

Second Generation PCNs:
Pregnancy Cat?
Lactation?

Renal Dosing?

Hepatic Dosing?

A

B
Safe
Adjust dose if CrCl

No hepatic adjustments needed

40
Q

Second Generation PCN
Adverse effects?
7

A 
CNS
Dermatologic
Gastrointestinal
Hematologic
Hepatic
Renal
Allergy
41
Q

Second Generation PCN disease related concerns?

A

Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients.

-wasnt strep, treated with amoxicillin and they broke out in rash because it was mono

42
Q

Second generation PCN drug interactions?

8

A

Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
OCP’s: pcn may decrease contraceptive efficacy

Allopurinol
BCG
Methotrexate
Probenecid
Sodium Picosulfate
Tetracycline Derivatives
Vitamin K Antagonists (eg, warfarin)
OCP’s
43
Q

Activity and use for third generation PCNs?

4

A

strep,
enteric gram-neg bacilli

(E. coli, Klebsiella pneumoniae, Enterobacter cloacea, Enterobacter aerogenes and Proteus miriabilis),

Pseudomonas and
anaerobes

44
Q

Dosing for third generation PCNs?2

A

IV only

Standard therapy as anti-Pseudomonal medication in hospitals

45
Q

Ticarcillin available in combination w/ Clavulanate K+ (Temectin) broadens spectrum to include? 4

A

gram-neg aerobes:
Actinobacter sp.,
Pasteurella,
Proteus sp.

46
Q

Fourth generation PCN covers the same as third generation but more active against who?3

A

more active against strains Klebsiella, enterococci and Bacteroides

47
Q

Clinical failures have occurred when piperacillin used alone against what?

A

Pseudomonas

48
Q

Piperacillin w/ tazobactam(Zosyn): broad spectrum; used for?5

A

cellulitis,
postpartem endometritis, peritonitis,
community-acquired pneumonia, noscomial pneumonia

BIG GUN. Used for really sick pts

49
Q

SE of fourth generation PCN?3

A

bleeding problems,
rash,
GI symptoms

50
Q

PCN Pearls:
can cause what kind of adverse affects?
4

A

bleeding problems
interstitial nephritis—autoimmune reaction to a penicillin-protein complex
PCN in high doses can cause neurological complications and seizures
Common to see secondary infections such as vaginal candidiasis (consider prophylactic treatment with oral antifungal medication if this has been a problem in the past)

51
Q

What are the Beta-Lactamase Inhibitors?

3

A

clavulanic acid,
sulbactam,
tazobactam

52
Q

What is the activity of the Beta-Lactamase Inhibitors?

2

A

inhibitors of many bacterial beta-lactamases

Inactivate aminoglycosides

53
Q

How are Beta-Lactamase Inhibitors used?

3

A

only in combination with a PCN, activity spectrum determined by that PCN

  • -Intra-abdominal/gynecological infections
  • -Skin and soft tissue infections
  • -RTI, sinusitis and lung abscesses
54
Q

As we progress from 1st to 3rd generation Cephalosporins what happens?

What helps enhance absorption in Cephalosporins?

A

An increase in gram-negative coverage
A loss in gram-positive coverage

Well absorbed from the GI tract—food enhances absorption

55
Q

Structure of cephalosporins?

A

7-aminocephalosporanic ring is the nucleus; there are two areas where various R1 an R2 groups can attach which gives the compound its antimicrobial activity

Beta-lactam ring

56
Q

What are the 1st generation cephalosporins?

3

A

Cephalexin (Keflex) and
Cefazolin (Ancef)-IV version– still used a lot
Cefadroxil oldest,*

57
Q

What kind of bacteria is 1st gen cephalosporins active against?3

Who does it not work against?

A
  1. gram positive organisms such as streptococcus and staphylococcus
    WILL COVER MOST SORE THROATS
  2. good against anaerobic cocci (eg, peptococcus, peptostreptococcus)
  3. (not MRSA), some gram negative activity;
58
Q

Side effects of 1st gen cephalosporins to remember?

A

GI mostly, allergic reactions, as with all anti-biotics may cause Clostridium difficile colitis

59
Q

What is Cephalexin used most for?

A

uncomplicated cellulitis

60
Q

What is Cefazolin used most for?

2

A

more complicated cellulitis or IV prophylaxis prior to surgery

61
Q

What are the 2nd generation cephalosporins?

4

A

cefaclor (Ceclor)
cefuroxime (Ceftin)
cefoxitin (Mefoxin)
cefotetan (Cefotan IV 1-2g q12h)‏

62
Q

What kind of bacteria are 2nd generation cephalosporins active against?

Who does it better cover than 1st gen (2) and who does it not cover?

A

gram-positive cocci, but also better gram negative coverage for Klebsiellae, H. influenzae, none against Pseudomonas

63
Q

What is Cefuroxime used for?

4

A

treat sinusitis, otitis, RTI

CAP

64
Q

Cefoxitin is used for what?

2

A
  1. anaerobic activity-most commonly used in prophylaxis of GI surgeries
  2. treat peritonitis & diverticulitis because active against gram-neg rods & Bacteroides
65
Q

What are the 3rd generation cephalosporins?

3

A

cefotaxime

  • ceftazidime
  • ceftriaxone
66
Q

What is the activity of the 3rd generation cephalosporins?

3

A

expanded gram-neg coverage against
meningicoccus,
citrobacter,
beta-lactamase strains of haemophilus and neisseria,

67
Q

What bacteria is ceftazidime active against?

A

Pseudomonas aeruginosa

68
Q

Which 3rd Generation
Cephalosporins cross the BBB?
2

A

Cefotaxime & ceftriaxone

69
Q

Ceftriaxone (Rocephin) & cefotaxime are used to treat what?

A

used to treat meningitis,

70
Q

Empirical therapy for serious infections because why?

A

effective against PCN-resistant strains pnemonococci

71
Q

ceftriaxone is used to treat two other diseases first line. What are they?

A

gonorrhea/Lyme disease

72
Q

S/E of 3rd generation cephalosporins?

5

A 
rash, 
N/V, 
elevated LFTs, 
eosinophilia, 
headache
73
Q

What is the 4th generation cephalosporin?

A

cefepime (Maxipime)

74
Q

What kind of bacteria is 4th Generation Cephalosporin, cefepime active against?
5

A

Gram positive and negative, including
pseudomonas,
Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus and
Neisseria

75
Q

Uses for 4th gen cehpalosporins?

4

A

penetrates BBB well… used to treat meningitis, other serious infections and sepsis

sometimes use with an aminoglycoside when treating pseudomonas

76
Q

Side effects of 4th generation cephasporins?

A

diarrhea, N/V, HA, rash

77
Q

In general what are 2nd generation cephaolsporins used for?

A

cephalosporins are used to treat otitis, sinusitis and RTI (Ceftin)

78
Q

What are 3rd & 4th generation cephalosporins the drug of choice for?

A

drugs of choice for gram-neg meningitis

- good alternative to aminoglycosides

79
Q

What is the drug or choice for gonorrhea?

A

Ceftriaxone

80
Q

What drug is effetcive against pseudomonas menigitis?

A

Ceftazidime

81
Q

What drugs are the Carbapenems?
2
Which one has better coverage?

A

Imipenem/cilastatinhas better coverage than meropenem, Meropenem (IV

82
Q

What bacteria are Carbapenems active against?

3

A
  1. effective against gram +(including Enterococcus faecalis & listeria),
  2. gram-neg (H influenzae, N gonorrhoeae, Enterobacter & Pseudomonus),
  3. Anerobes (including Bacteroides)‏
83
Q

Meropenem is used for?

5

A
  1. meningitis,
  2. intra-abdominal infections,
  3. resistant UTI’s,
  4. pseudomonus and
  5. with or without an aminoglycoside for neutropenic patient
84
Q

Side effects of Carbapenems?

4 and two specifically for imipenem

A

N/V,
diarrhea,
rashes,
reactions at infusion sites,

imipenem… renal failure & seizures

Infectious Disease (29 decks)

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