Penicillin

Background

Nomenclature

• Broadly speaking, formulations of penicillin G are soluble and used for IV or IM administration, and penicillin V is used for oral administration but does not achieve high levels in the serum

Formulation	Other Names	Comments
sodium penicillin G	sodium benzylpenicillin crystalline penicillin	soluble, used for IV
procaine penicillin G	procaine benzylpenicillin procaine penicillin	less soluble, used for IM
benzathine penicillin G	DBED penicillin	less soluble than procaine, used for IM
penicillin V	phenoxymethylpenicillin	used for PO, but poor absorption

Mechanism of Action

• Directly inhibits penicillin-binding proteins

Spectrum of Activity

• Generally active against Gram-positive cocci, especially streptococci but some strains of Staphylococcus aureus, most clostridia, Neisseria, and some Haemophilus influenzae
• Not active against aerobic Gram-negative bacilli
• Penicillin G is generally more active than penicillin V across all bacteria

Clinical Breakpoints

Species	Breakpoints (μg/mL)			Breakpoints (mm)
	S	I	R	S	I	R
Anaerobes except Bacteroides	≤0.5	1	≥2
Enterococcus	≤8		≥16	≥15		≤14
Neisseria gonorrhoeae	≤0.06	0.12-1	≥2	≥47	27-46	≤26
Neisseria meningitidis	≤0.06	0.12-0.25	≥0.5
Staphylococcus	≤0.12		≥0.25	≥29		≤28
Streptococcus pneumoniae				≥20
Streptococcus pneumoniae IV (nonmeningitis)	≤2	4	≥8
Streptococcus pneumoniae IV (meningitis)	≤0.06		≥0.12
Streptococcus pneumoniae PO (pen V)	≤0.06	0.12-1	≥2
Streptococcus (β-hemolytic)	≤0.12			≥24
Streptococcus (viridans group)	≤0.12	0.25-2	≥4

Dosing

• Benzylpenicillin (penicillin G)
  • Standard dosing: 3 million units (1.8 g) IV q4h, or 4 million units (2.4 g) IV q6h
  • High dose (for critical illness, IE, and CNS penetration): 4 million units (2.4 g ) IV q4h

Renal Dosing

Benzylpenicillin (Penicillin G)

GFR (mL/min)	Standard Dose	High Dose
>50	3 MU (1.8 g) IV q4h, or 4 MU (2.4 g) IV q6h	4 MU (2.4 g ) IV q4h
10-50	3 MU (1.8 g) IV q6h	3 MU (1.8 g) IV q4h
<10	3 MU (1.8 g) IV load, then 2 MU (1.2 g) IV q8h	4 MU (2.4 g) IV load, then 2 MU (1.2 g ) IV q6h
CRRT	2 MU (1.2 g) IV q6h	3 MU (1.8 g) IV q6h

Safety

Adverse Reactions

Hypersensitivity Reactions

• Can cause any type of hypersensitivity reaction (I to IV)
• Type I: anaphylaxis and urticaria
• Type II: autoimmune hemolytic anemia
• Type III: serum sickness-like reaction
• Type IV:
  • Delayed maculopapular drug rash
    • Usually after 7 to 10 days of starting, and up to 1 to 3 days after stopping
    • Progresses over days, with lesions that are relatively fixed
    • Can worsen over a few days after stopping, then resolves over 1 to 2 weeks
    • Pruritus is variable
    • Most commonly occur in the context of a viral infection
  • Contact dermatitis