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Thera VII > 08 Beta-Lactams Wong-Beringer > Flashcards

08 Beta-Lactams Wong-Beringer Flashcards

1
Q

What are the different classes of Beta-Lactams?

A

Penicillins. Cephalosporins. Monobactam. Carbapenems

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2
Q

What are the PCN derivatives used?

A

Penicillin (procaine). Ampicillin (amoxicillin). Oxacillin (dicloxacillin). Piperacillin

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3
Q

What is the 1st generation IV Cephalosporin?

A

Cefazolin

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4
Q

What are the 2nd generation IV Cephalosporins?

A

Cefuroxime. Cefoxitin. Cefotetan

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5
Q

What are the 3rd generation IV Cephalosporins?

A

Ceftazidime. Ceftriaxone. Cefotaxime

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6
Q

What is the 4th generation IV Cephalosporin?

A

Cefepime

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7
Q

What is the 5th generation IV Cephalosporin?

A

Ceftaroline

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8
Q

What is unique about Ceftaroline?

A

First Beta-Lactam with activity against MRSA

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9
Q

What are the different Carbapenems used?

A

DIME: Doripenem, Imipenem, Meropenem, Ertapenem

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10
Q

What are the “Natural” Penicillins?

A

Penicillin G or Pen VK. Narrow spectrum

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11
Q

What do the “Natural” Penicillins cover?

A

Gm (+) cocci (streptococci, enterococci, high rates of R with staph), Gm (+) bacilli, Gm (-) cocci (N. meningitidis (high rates of R w/ N. gonorrheae)), Spirochetes (Treponema). NOT Gm (-) bacilli

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12
Q

What is the DOC for Treponema?

A

“Natural” Penicillins

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13
Q

What are the therapeutic uses for “Natural” Penicillins?

A

DOC for infections due to susceptible bacteria. Rheumatic fever prophylaxis

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14
Q

What are the Penicillinase-Resistant Penicillins?

A

Oxacillin. Structure confers resistance to destruction by B-lactamases. Less active thatn Pen G against Gm (+) bacteria

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15
Q

What is Oxacillin used for?

A

“Narrow” - Anti STAPHYLOCOCCAL. “Natural” penicillins don’t cover this

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16
Q

What are the Aminopenicillins used?

A

Ampicillin, Amoxicillin. Broader spectrum than Pen G but not stable in the presence of B-lactamses. Combination with B-lactamase inhibitors restore activity against SOME B-lactamase producing strains

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17
Q

What do Aminopenicillins cover?

A

Gm (+) cocci: Strep, Enterococci (S. aureus (many R d/t B-lac+). Gm (+) bacilli: Listeria. Gm (-) cocci: Moraxella. Gm (-) bacilli. Anaerobes

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18
Q

How does Amoxicillin compare to Ampicillin?

A

More complete PO absorption and less frequent dosing than ampicillin

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19
Q

What are Aminopenicillins the DOC for?

A

Enterococcal infections, Group B streptococci, Listeria, Proteus mirabilis, and E. coli, H. influenzae

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20
Q

What prophylaxis is Amoxicillin used for?

A

Endocarditis prophylaxis for patients undergoing dental procedures

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21
Q

What is Amox/Clav acid (PO) used for?

A

URIs, LRIs, UTIs due to amox-resistant organisms

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22
Q

What is Augmentin?

A

Amox/Clav acid

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23
Q

What is Amp/Sulbactam (IV) used for?

A

Intraabdominal, gynecologic, skin and soft tissue infections

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24
Q

What is Unasyn?

A

Ampicillin/Sulbactam

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25
Q

What are the Carboxy- and Ureido- Penicillins?

A

Piperacillin (NOT stable in presence of B-lactamase)

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26
Q

What does Piperacillin cover?

A

Expanded Gm (-) spectrum: Pseudomonas, Klebsiella, Enterobacter, Citrobacter, Serratia. Gm (+) cocci: non-BL producing Staph, Strep, and Enterococci

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27
Q

What is Zosyn?

A

Piperacillin/Tazobactam - Restores piperacillin activity against some B-lactamase producing strains

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28
Q

What is Piperacillin the DOC for?

A

Serious Pseudomonas infections (use in combination with an aminoglycoside)

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29
Q

What is the therapeutic use of Zosyn?

A

Mixed infections: intraabdominal, gynecologic, skin and soft tissue

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30
Q

What is the absorption like for oral Pen V?

A

Easily destroyed by gastric acid (~1/3 is absorbed from the duodenum). Administer on an empty stomach (1 hour before meals or 2 hours after)

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31
Q

What is the PK of Pen G administered IM?

A

Slow release –> low but persistent levels of antibiotic in the blood (12 hours to several days or week). Procaine Penicililn, Benzathine Penicillin

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32
Q

What is IM Pen G often used for?

A

Syphilis and Rheumatic Fever

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33
Q

What is the main route in which PCN Derivatives are eliminated?

A

Renal clearance

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34
Q

Which PCN Derivatives DO NOT need to be renally adjusted?

A

Oxacillin, Nafcillin

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35
Q

What is the dosing schedule like for PCN Derivatives?

A

Multiple times per day

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36
Q

What are the Beta-Lactamase inhibitors used?

A

Clavulanic Acid ~ Tazobactam > Sulbactam

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37
Q

What are the characteristics of Beta-Lactamase Inhibitors?

A

Minimal direct antibacterial activity. Binds IRREVERSIBLY to B-lactamase –> prevent destruction of the B-lactam ring

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38
Q

What does the inhibitor activity of B-lactamase inhibitors depend on?

A

Type and amount of B-lactamase present. Compound to be protected. pH of the environment

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39
Q

What are the susceptible B-lactamase producing strains?

A

S. aureus, Bacteroides fragilis, Most strains of E. coli, Klebsiella pneumoniae

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40
Q

What strains are B-lactamase inhibitors NOT active against?

A

B-lactamases from Pseudomonas, Enterobacter, Serratia, Citrobacter

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41
Q

What are the Adverse Effects associated with PCN Derivatives?

A

Hypersensitivity Reactions (rash most common, cross-sensitivity among all penicillins, IgE-mediated immediate type: hives, laryngeal edema, anaphylaxis). GI: diarrhea. Superinfection with C. difficile. Bone marrow suppression

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42
Q

Which PCN Derivatives can cause electrolyte imbalance?

A

Ticar, high dose Pen VK

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43
Q

Which PCN Derivatives can cause seizures?

A

High dose Pen G, Imipenem. Higher risk in renal failure, elderly, CNS disorder

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44
Q

Which PCN Derivatives can cause thrombophlebitis?

A

Nafcillin

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45
Q

How are Cephalosporins classified?

A

Classification by generation: Chronology, Antimicrobial activity

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46
Q

What are the 1st generation PO Cephalosporins?

A

Cephalexin. Cephradine. Cefadroxil

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47
Q

What are the 2nd generation PO Cephalosporins?

A

Cefuroxime. Cefaclor. Cefprozil

48
Q

What are the 3rd generation PO Cephalosporins?

A

Cefixime. Cefpodoxime. Cefdinir. Ceftibuten

49
Q

What does Cefazolin (Ancef) cover?

A

Gram (+): S. aureus, Strep, oral anaerobes. Gram (-): PEK (Proteus, E.coli, Klebsiella)

50
Q

What is Cefazolin (Ancef) indicated for?

A

Surgical prophylaxis (except colorectal procedures (doesn’t cover for bacteroides)). Cellulitis, soft tissue infections, postoperative wound infections

51
Q

What does Cefuroxime (Zinacef) cover?

A

More Gm (-) HNPEK (Hemophilus, Neisseria), less active vs. Gm (+)

52
Q

What is Cefuroxime (Zinacef) used for?

A

Respiratory tract infections! Because it covers Hemophilus

53
Q

What does Cefoxitin (Mefoxin) and Cefotetan (Cefotan) cover?

A

Additional activity vs. anaerobes (B. fragilis)

54
Q

What is Cefoxitin (Mefoxin) and Cefotetan (Cefotan) indicated for?

A

Surgical prophylaxis (colorectal d/t B. fragilis coverage), intraabdominal infections, diabetic foot ulcers

55
Q

What does Cefixime (Suprax) and Cefpodoxime (Vantin) cover?

A

Less vs. Gm (+), more vs Gm (-): Hemophilus, Neisseria, Enterobacteriaceae

56
Q

What does Cefotaxime (Claforan), Ceftriaxone (Rocephin), and Ceftizoxime (Cefizox) cover?

A

Active vs. Staph (< 1st gen), EXCELLENT vs. Strep, oral anaerobes. HNPEK plus CAPES (Citrobacter, Acinetobacter sp, Providencia spp., Enterobacter sp, Serratia sp)

57
Q

What are the indications for Cefotaxime (Claforan), Ceftriaxone (Rocephin), and Ceftizoxime (Cefizox)?

A

Meningitis d/t enterics. Pneumonia or bacteremia d/t Strep pneumoniae (except Ceftizoxime), Hemophilus, CAPES

58
Q

What does Ceftazidime (Fortaz) cover?

A

“Antipseudomonal” + HNPEK + CAPES. Not reliable vs. Gm (+)

59
Q

What are the indications for Ceftazidime (Fortaz)?

A

Meningitis d/t Gm (-) enteric pathogens (except cefoperazone), nosocomial infections - pneumonia, bacteremia, febrile neutropenia

60
Q

What does Cefepime (Maxipime) cover?

A

Activity: Cefotaxime + Ceftazidime. More resistant to some B-lactamases (Enterobacter sp)

61
Q

What are the indications for Cefepime (Maxipime)?

A

Nosocomial infections d/t B-lactamse producing organisms which are resistant to 3rd generation CEPHs

62
Q

What does Ceftaroline cover?

A

Gm (+): MRSA, S. epidermidis, and PCN-R S. pneumoniae. Gm (-): Hemophilus and PEK. Mouth anaerobes: Peptostreptococcus, Fusobacterium

63
Q

How is Ceftaroline dosed?

A

600mg Q12h

64
Q

What are the indications for Ceftaroline?

A

Documented MRSA skin soft tissue infection involving other mixed organisms

65
Q

What are 1st-5th generation Cephalosporins INACTIVE against?

A

Gm (+): Enterococci, Listeria sp, Clostridium difficile. MRSA (EXCEPT Ceftaroline). Gm (-): Stenotrophomonas maltophilia (Xanthomonas)

66
Q

What should be done whenever Cephalosporins are EFFECTIVE?

A

Use the lowest generation with the narrowest spectrum –> preserves normal flora. Lower cost

67
Q

What is the PK like for ORAL Cephs?

A

Many are easily hydrolized by gastric acid. More than 10 oral agents available

68
Q

What is the distribution like for 1st and 2nd gen IV Cephs?

A

Widely distributed EXCEPT for eye and CSF

69
Q

What is the distribution like for 3rd and 4th gen Cephs?

A

Penetrate CSF in presence of inflamed meninges

70
Q

What is the elimination like for CEPHs?

A

ALL undergo glomerular filtration and/or tubular secretion; PRIMARILY excreted unchanged in urine EXCEPT: Ceftriaxone, no dose adjustment in renal disease

71
Q

How are CEPHs usually dosed?

A

Relatively short t1/2, therefore dose at Q8h for most agents

72
Q

Which CEPHs are not dosed Q8h?

A

IV: Cefotetan, Ceftriaxone, Cefepime, Ceftaroline. Oral: 2nd and 3rd gen

73
Q

What are the ADRs associated with CEPHs?

A

Relatively low direct toxicity. Hypersensitivity reactions (major): skin rash most common. Direct toxicities: thrombophlebitis, painful IM injection; GI: N/V/D. Increase bleeding (cefotetan). Superinfections: Enterococci, C. difficile

74
Q

Which IV CEPHs are best for S. aureus?

A

1st gen

75
Q

Which IV CEPHs are best for S. pneumoniae?

A

3rd/4th gen

76
Q

Which IV CEPHs are best for MRSA?

A

5th gen

77
Q

How does bacteria coverage change as CEPH generation goes up for IV?

A

More Gm (-) coverage: PEK –> HNPEK –> CAPES, Pseud

78
Q

How does bacteria coverage change as CEPH generation goes up for PO?

A

More Gm (-) coverage: PEK –> HNPEK (no CAPES, no Pseud)

79
Q

Which PO CEPHs are best for Gm (+)?

A

1st gen

80
Q

What are the different Carbapenem formulations?

A

IV: Imipenem, Meropenem, Doripenem. IM and IV: Ertapenem

81
Q

What are the general features of Carbapenems?

A

Most active agents available (spectrum). Most resistant to hydrolysis by B-lactamases compared to other beta-lactams. Imipenem combined with cilastatin to prevent metabolism by renal dehydropeptidase I

82
Q

What is the spectrum of activity for Doripenem, Imipenem, Meropenem (DIM)?

A

Very board spectrum (GP, GN, aerobes, anaerobes). BacterioSTATIC against enterococus

83
Q

What is not covered by Doripenem, Imipenem, Meropenem (DIM)?

A

Stenotrophomonas maltophilia. S. epidermidis. MRSA. E. faecium. Memorize what they DON’T cover, much less than what they do cover

84
Q

What activity is Imipenem better for?

A

Gram (+) activity

85
Q

What activity is Meropenem better for?

A

Gram (-) and anaerobic activity

86
Q

What activity is Doripenem better for?

A

Slightly more potent vs. Pseudomonas

87
Q

What is the activity like for Ertapenem compared to DIM?

A

NOT Pseudomonas, Acinetobacter, and Enterococcus

88
Q

What is resistance like for Carbapenems?

A

Gram (+) develop resistance generally as result of altered penicillin binding proteins (PBPs). Gram (-) eg. Pseudomonas aeruginosa: result of decreased permeability due to loss of outer membrane porin protein, metallo-beta lactamases (carbapenemases)

89
Q

What is the PK like for Carbapenems?

A

Primarily RENALLY cleared. Adequate CSF penetration with inflamed meninges (imip and mero)

90
Q

Which Carbapenem has the longest half-life and dosed QD?

A

Ertapenem

91
Q

What are the ADRs associated with Carbapenems?

A

PCN allergy. Local: inflammation at injection site. N/V/D. Pruritis, rash, drug fever

92
Q

What is a class effect of Carbapenems that should be watched for?

A

Seizure incidence. I > M, D > E

93
Q

What is the DDI like between Carbapenems and Valproic acid?

A

Significant decrease of valproic acid levels, interferes with absorption

94
Q

What are the indications for Carbapenems?

A

RESERVED for tx of documented multi-drug resistant organisms. Used for mixed bacterial infections. Aerobic GN bacteria NOT susceptible to other beta-lactams

95
Q

What is renal adjustment like for Carbapenems?

A

ALL need to be adjusted

96
Q

What are the general characteristics of Monobactam?

A

Principal side chain = sulfamic moiety resembles that of ceftazidime. Minimal cross-reactivity with PCNs, CEPHs

97
Q

What is Aztreonam (Azactam)?

A

Monobactam

98
Q

What is the spectrum of coverage with Aztreonam (Azactam)?

A

Active vs. aerobic Gm (-) Enterobacteriaceae and Pseudomonas aeruginosa (like an aminoglycoside). NOT active vs. Gm (+) or anaerobes

99
Q

What is the PK of Aztreonam (Azactam)?

A

IV only. Primarily renally cleared. T1/2 = 1h; prolonged in renal failure (CrCl < 10: Q24h). Adequate CSF penetration w/ inflamed meninges

100
Q

What are the different types of reactions to Penicillin Allergy?

A

Immediate (Type I): < 1 hr after PCN administration. Accelerated (Type I): 1-72 hr. Late (Type II, III, IV): > 72 hr. Other (idiopathic): usually > 72 hr

101
Q

What are the characteristics of Immediate Penicillin Allergy?

A

Occurs in less than 1 hr of exposure. IgE-mediated by PCN-specific antibodies. Systemic s/sxs of anaphylaxis. Incidence = 0.004% - 0.015% of penicillin courses. Most common - adults age 20-49 years

102
Q

What are the characteristics of Accelerated Penicillin Allergy?

A

Occurs 1-72 hrs after exposure. IgE-mediated. S/sx: urticaria, angioedema, laryngeal edema, and wheezing. Life-threatening reactions occurring beyond 1 hr of PCN administration - rare

103
Q

What are the characteristics of Late Penicillin Allergy?

A

Occurs in > 72 hrs after PCN admin. NOT IgE-mediated –> skin testing not useful to confirm allergy. Type II - IgE, complement mediated (Increased clearance of RBC, platelets by lymphoreticular system). Type III - IgE, IgM immune complex (serum sickness (joint pain, fever), tissue injury, drug fever). Type IV - contact dermatitis

104
Q

What are the characteristics of Idiopathic Penicillin Allergy?

A

Usually > 72 hrs after PCN administration. Maculopapular or morbilliform rash. Most common. Symmetric, often confluent erythematous macules and papules on extremities of ambulatory pts or overlie pressure areas of bedridden pts. Rash generally spare the palm and soles

105
Q

What are some rashes that are unrelated to PCN?

A

Viral infections: HIV, hepatitis B, mumps, echovirus, coxsackie virus. Infections associated with numerous bacteria. Other concurrent medications (including other antibiotics)

106
Q

What is the Cross-Reactivity like for Cephalosporins?

A

Frequency of allergic reactions w/in 24 hrs of ceph admin for pts w/ history of PCN allergy and + skin test = 5.6% (if no alternative drug, Ceph desensitization is required). For pts w/ history of PCN allergy and (-) skin test = 1.7% (cephalosporin may be used)

107
Q

What is the Cross-Reactivity like for Carbapenems?

A

1-10% (up to 47% in pts w/ history of PCN allergy and + skin test has been reported in small study). Pts w/ + skin test or history of Type I allergy to PCN (skin test with carbapenem or graded challenge if a carbapenem is needed)

108
Q

What is the Cross-Reactivity like for Aztreonam?

A

Least cross-reactive with PCN

109
Q

What is the clinical decision for PCN use based on?

A

Detailed history. If a pts reaction to PCN indicates that the rash was strictly maculopapular, with no signs of a Type I reaction (safe to readminister an antibiotic containing penicillin or cephalosporin). If pts reaction to PCN suggests Type I allergy: skin testing if penicillin therapy is warrented, NO skin testing if equally effective antibiotic alternatives are available or if the clinician would still withhold PCN therapy regardless of skin test results

110
Q

What are the characteristics of Penicillin Skin Testing?

A

DO NOT skin test pts with a history of exfoliative dermatitis or SJS attributable to B-lactam drugs. NOT useful for pts with history of non-Type I allergy to PCN

111
Q

What is the Penicillin Skin Testing procedure?

A

Average time ~40 minutes. Positive skin test results based on pts history of allergic reactions

112
Q

What is done after a positive skin test?

A

Pts should undergo desensitization if need penicillin

113
Q

What is done after a negative skin test?

A

Pts may receive a medically supervised oral PCN challenge

114
Q

When do IgE-mediated reactions occur?

A

IgE-mediated reactions occur when drug-hapten complex crosslinks IgE antibodies bound to circulating mast cells –> release of mediators (i.e. histamine)

115
Q

What is Desensitization?

A

Performed by dose escalation of the drug starting with a very small dose (1:100,000 of final dose) given every 15 minutes to deplete mast cell content in a controlled manner to avoid an acute full anaphylactic reaction. Oral provides less risk than IV in causing a rxn during the desensitizing process

116
Q

What are some general patient education points for oral beta-lactam agents?

A

PO penicillin derivatives: take on empty stomach at least 1 hr prior or 2 hours after meals. If severe or watery diarrhea, or skin rash develops, do not self-treat. Call prescriber or health care professional for advice. Birth control pills may not work properly while taking this medicine (use another method of contraception for at least one month)

Thera VII (37 decks)

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