B-Lactams Part 2

Question 1

Type I Hypersensitivty

Answer 1

• Most important AE for PCNs
• PCN Haptenization is the cause
• Metabolite opens the B-lactam ring and serves as a hapten to cause IgE medicated immune reaction
• Ranges from rash to anaphylaxis
• Blood levels not monitored since PCNs considered safe

Question 2

PCN Cross Sensitivity

Answer 2

• Rare cross allergic reactions

- Aminopenicllins < 2%, cephalosporins 3%, Carbapenems < 1%, and monobactams 0%

Question 3

Cephalosporins

Answer 3

• Most widely prescribed and largest selling class of B-lactams
• EX: Keflex (Ceohalexin), Omnicef (Cefdinir), Ceftin (Cefuroxime)
• Same MoA as PCNs
• PKPD Efficacy: T>MIC
• Side chain modification allows for increased cell penetration and resistance to B-lactamase
• Water soluble and pH stable
• Useful alternative for those allergic to PCNs
• 5 generations

Question 4

Ceph. Generation Differences

Answer 4

• 1st: Don’t cross BBB (cefazolin)
• 2nd: covers important gut anaerobe B. fragilis
• 3rd: drug of choice for S. pneumoniae (Cefotaxime, Ceftriaxone), IV forms reach adequate CNS levels, causes de-repression of chromosomal B-lactamases
• 4th: Cefepime cover P. aeruginosa
• 5th: Ceftaroline (Teflaro) covers MRSA, ONLY CEPHALOSPORIN

Question 5

Ceftriaxone

Answer 5

• Metabolized in the liver
• Eliminated in bile and can get “stuck” from portal hypertension
• Biliary sludging in neonates

Question 6

Ceftazidime

Answer 6

• Covers important Gram “-“ (P. aeruginosa)

- Doesn’t cover Gram “+”

Question 7

Cephalosporin PK

Answer 7

• Low CNS penetration for all oral forms, but parenteral versions of gen. 3 and 4 reach adequate levels
• Elimination: most are eliminated by kidney, Ceftriaxone being an exception

Question 8

Cephalosporin AE/Monitoring

Answer 8

• Similar to PCN
• Lower frequency of allergic reactions or hematologic/renal toxicity
• Monitoring: renal fxn, anaphylaxis with first dose, CBCs and LFTs

Question 9

Monobactams

Answer 9

• Expected to be resistant to B-lactamases
• Aztreonam is a good alternative when allergic to PCNs
• Potential cross-reactivity with Ceftazidime (side chain)
• No GI absorption, given IV and IM
• Renally excreted
• Active against Gram “-“ organisms like P. aeruginosa
• No activity against Gram “+” and anaerobes

Question 10

Carbapenems

Answer 10

• Broadest spectrum
• Gram “+”, Gram “-“, and anaerobe coverage
• Charge characteristics allow access to specific Gram “-“ porins and increases affinity to a broader range of PBP
• Expected to be resistant to B-lactamases
• Used for infections resistant to other B-lactams and enterobacter infections
• ALL associated with seizures (imipenem especially)
• Mero/Imi/Doripenem have anti-pseudomonal activity
• Cross-reactivity reports are variable

Question 11

Primaxin IV

Answer 11

• Imipenem + Cilastatin
• Cilastatin prevents degradation of imipenem by dehydropeptidase-I in the kidneys
• Imipenem is a strong B-lactamase inducer

Question 12

Carbapenem Monitoring

Answer 12

• Renal fxn
• Signs of anaphylaxis with first dose
• CBCs
• LFTs
• Confusional states

Question 13

Abx Therapy Monitoring

Answer 13

• Temperature
• WBC count (differential)
• Repeat cultures
• Symptom progression/resolution
• AE like renal function and LFTs