Antibiotic Principles (Beta-Lactams)

What classes are examples of Gram-positives?

Streptococcus

Enterococcus

Staphylococcus aureus

What are the two categories of Streptococcus?

Alpha-hemolytic

Beta-hemolytic

What are the two main types of Enterococcus?

E. faecalis

E. faecium

What are the two main types of Staphylococcus aureus?

MSSA

MRSA

What are the two main types of Gram-negatives?

Enterobacterales

Pseudomonas aeruginosa

What are the two ways in which we categorize anaerobes?

Above diaphragm

Below diaphragm

What are the three community-acquired respiratory atypical bacteria?

Legionella

Chlamydophilia

Mycoplasma

What are the drugs of choice for MSSA infections?

Cefazolin and oxacillin/nafcillin

Which are the only beta-lactams that do NOT require renal dose adjustments?

Ceftriaxone

Nafcillin

Oxacillin

Dicloxacillin

Which beta-lactam has poor PO bioavailability?

Cefdinir

Describe the activity of penicillins

NONE HAVE MRSA ACTIVITY

Penicillins have EXCELLENT Streptococcus coverage

Which beta-lactams have excellent anaerobic activity?

Beta-lactam/beta-lactamase inhibitors

Describe the activity of natural penicillins

EXCELLENT Streptococcus coverage

Treponema pallidum (syphilis)

Some anaerobic Streptococci activity (above diaphragm)

What is the route of administration of penicillin G?

IV

What is the route of administration of penicillin VK?

PO

What is the route of administration of benzathine penicillin?

IM

What are natural penicillins the drug of choice for?

Syphilis and many Streptococcal infections

Often not used unless for syphilis (CNS penetration for neurosyphilis)

Describe the activity of aminopenicillins

Retains most activity of natural penicillins

NOT used for syphilis

Enhanced activity against Enterococcus

What may aminopenicillins have resistance against?

Alpha-hemolytic Strep

Which Enterococcus are aminopenicillins more active against?

E. faecalis compared to E. faecium

Which aminopenicillin has no IV formulation available?

Amoxicillin

Describe the oral absorption of ampicillin

Often erratic

Avoid ampicillin PO, use amoxicillin

What are aminopenicillins the drug of choice for?

Ampicillin-susceptible Enterococci

Listeria monocytogenes

Describe the activity of penicillinase-resistant penicillins

Streptococcus spp.

MSSA

What are adverse events of penicillinase-resistant penicillins?

Neutropenia

Hepatotoxicity (elevation in LFTs)

What is the route of administration of nafcillin and oxacillin?

IV

What is the route of administration of dicloxacillin?

PO

What is important to note about dose adjusting for penicillinase-resistant penicillins?

NO renal dose adjustments required!!

What are penicillinase-resistant penicillins considered the drug of choice for?

MSSA infections

What is important to note about the permeability of penicillinase-resistant penicillins?

Excellent CNS penetration

Describe the activity of beta-lactam/beta-lactamase inhibitors

Retains excellent Streptococcus spp. activity

Enterobacterales activity

Some MSSA activity

EXCELLENT anaerobic activity

Which beta-lactam/beta-lactamase inhibitors have the best enterobacterales activity?

Piperacillin-tazobactam >>> amoxicillin-clavulanic acid > ampicillin-sulbactam

Which enterobacterales does piperacillin-tazobactam have activity against?

E. coli

Proteus spp.

Klebsiella spp.

Enterobacter spp.

Citrobacter spp.

Serratia spp.

Which enterobacterales do amoxicillin-clavulanic acid and ampicillin-sulbactam have activity against?

E. coli

Proteus spp.

Klebsiella spp.

Which is the only beta-lactam/beta-lactamase inhibitor that has Pseudomonas aeruginosa activity?

Piperacillin-tazobactam

Amoxicillin/Clavulanic Acid

Augmentin

Ampicillin/Sulbactam

Unasyn

Piperacillin/Tazobactam

Zosyn

What is a notable adverse event of amoxicillin-clavulanic acid?

More upset stomach due to the clavulanic acid component

Against which bacteria does piperacillin-tazobactam have more reliable activity than other drugs in the class?

Gram-negatives (Enterobacterales)

Describe the permeability of beta-lactam/beta-lactamase inhibitors

Poor CNS penetration

Beta-lactamase inhibitor does not cross BBB well since it is bulky

Which cephalosporin has a dissimilar R1 side chain from ALL beta-lactams?

Cefazolin

This means that this drug can be used in a patient with a penicillin allergy

Which cephalosporin does penicillin, amoxicillin, and ampicillin share a side chain with?

Cephalexin

Be careful of cross-reaction!

What is an important class effect of cephalosporins?

NONE have Enterococcus activity

Which drugs are first generation cephalosporins?

Cefazolin

Cephalexin

Cefadroxil

Cefazolin

Ancef

Kefzol

Cephalexin

Keflex

Describe the activity of first generation cephalosporins

Excellent Streptococcal spp. and MSSA activity

Limited Gram-negative coverage

Which Gram-negatives (Enterobacterales) do first generation cephalosporins cover?

"PEcK" bacteria

Proteus mirabilis, E. coli, Klebsiella pneumoniae

Describe the permeability of first generation cephalosporins

Poor CNS penetration

What is the route of administration of cefazolin?

IV

What is the route of administration of cephalexin and cefadroxil?

PO

What are first generation cephalosporins the drug of choice for?

MSSA

What is cefazolin VERY commonly used for?

Surgical site prophylaxis

Which drugs are second generation cephalosporins?

Cefuroxime

Cefaclor

Cefuroxime

Ceftin

What is the route of administration of cefuroxime?

PO and IV

Which drugs are third generation cephalosporins?

Ceftriaxone

Cefdinir

Cefpodoxime

Ceftriaxone

Rocephin

Describe the activity of third generation cephalosporins

EXCELLENT Streptococcus spp. activity

Enhanced activity against Enterobacterales

Which Enterobacterales do third generation cephalosporins have activity against?

E. coli, Proteus spp., Klebsiella spp., Serratia spp.

Do NOT use for Enterobacter spp. or Citrobacter spp.

What do third generation cephalosporins NOT have activity against?

No P. aeruginosa activity

How often is ceftriaxone dosed?

Q24H IV

Describe the permeability of third generation cephalosporins

Excellent CNS penetration

Describe the dose adjustments of third generation cephalosporins

NO renal dose adjustments required!!

Describe cefdinir and cefpodoxime and their activity

Oral 3rd generation cephalosporins

Different spectrum of activity than ceftriaxone = more similar spectrum to cephalexin/cefazolin

Which drug is an anti-pseudomonal third generation cephalosporin?

Ceftazidime

Describe the activity of ceftazidime

POOR/NO Streptococcus spp. activity = ONLY BETA-LACTAM WITHOUT STREP COVERAGE

Enhanced activity against Enterobacterales (same as ceftriaxone)

Which Enterobacterales is ceftazidime effective against?

E. coli, Proteus spp., Klebsiella spp., Serratia spp.

Do NOT use for Enterobacter spp. or Citrobacter spp.

What is a notable part of ceftazidime activity?

P. aeruginosa activity

Only has Gram-negative activity INCLUDING P. aeruginosa

Describe the permeability of ceftazidime

Excellent CNS penetration

Which drug is a fourth generation cephalosporin?

Cefepime

Describe the activity of cefepime

EXCELLENT activity against Streptococcus spp.

EXCELLENT activity against Enterobacterales

Pseudomonas aeruginosa activity

Describe the permeability of cefepime

Excellent CNS penetration

What are adverse events of cefepime?

Potential for cefepime-induced neurotoxicity

More common in patients with renal insufficiency and advanced age

Which drug is a fifth generation cephalosporin?

Ceftaroline

Describe the activity of ceftaroline

EXCELLENT activity against Streptococcus spp.

Activity against Enterobacterales (same as ceftriaxone)

What is a unique quality of ceftaroline activity?

Excellent activity against MRSA

ONLY BETA-LACTAM WITH MRSA ACTIVITY

Basically ceftriaxone PLUS MRSA activity

What is the route of administration of ceftaroline?

IV

Describe the activity of carbapenems

Excellent activity against Streptococcus

Variable activity against Enterococcus

VERY active against Enterobacterales

Describe the activity of carbapenems against Enterococcus

Ertapenem = none

Meropenem = some

Imipenem = best

What are carbapenems the drug of choice for?

Extended-spectrum beta-lactamase (ESBL) producing bacteria

What is notable about the activity of carbapenems?

Activity against Pseudomonas aeruginosa

EXCELLENT activity against all anaerobes (including Bacteroides fragilis)

Which carbapenem does NOT have activity against Pseudomonas aeruginosa?

Ertapenem

Which bacteria does ertapenem NOT have activity against?

APE

Acinetobacter

Pseudomonas

Enterococcus

Describe the permeability of meropenem

Excellent CNS penetration

What is a notable drug interaction of carbapenems?

Carbapenems interact with valproic acid by lowering the seizure threshold

Which drug is a monobactam?

Aztreonam

Describe the activity of aztreonam

Moderate to excellent activity against Enterobacterales

Has activity against P. aeruginosa

Similar spectrum of activity to ceftazidime

What does aztreonam NOT have activity against?

Gram-positive bacteria

Anaerobes

When should aztreonam NOT be used?

In a patient with a ceftazidime allergy

Ceftazidime and aztreonam have a similar chemical structure