What is the recommended dosage and administration of Penicillin G (penicillin G) for treating bacterial infections?

Penicillin G Dosing and Administration for Bacterial Infections

For serious bacterial infections in adults, Penicillin G should be administered at 12-24 million units per day divided every 4-6 hours intravenously, with specific dosing determined by infection type and severity. 1

Standard Adult Dosing by Infection Type

Streptococcal Infections (Including Endocarditis)

• For highly penicillin-susceptible viridans group streptococci and S. bovis (MIC ≤0.12 μg/mL): Administer 12-18 million units/24 hours IV either continuously or in 4-6 equally divided doses for 4 weeks 2
• For native valve endocarditis: The same 12-18 million units/24 hours regimen is appropriate, with treatment duration of 4 weeks 2
• For prosthetic valve endocarditis: Increase to 24 million units/24 hours IV for 6 weeks 2
• For relatively penicillin-resistant strains (MIC >0.12 to <0.5 μg/mL): Use 24 million units/24 hours IV in divided doses every 4 hours, combined with gentamicin 3 mg/kg/day for the first 2 weeks 2

Staphylococcal Infections

• For penicillin-susceptible staphylococci (rare, MIC ≤1 μg/mL): Administer 200,000-300,000 units/kg/day IV divided every 4 hours, up to 12-24 million units daily 2
• For serious staphylococcal infections (septicemia, empyema, pneumonia, endocarditis): Use 5-24 million units/day depending on severity, divided every 4-6 hours 1, 3

Central Nervous System Infections

• For meningococcal meningitis/septicemia: Administer 24 million units/day as 2 million units every 2 hours (note the shorter interval) 1, 3
• For pneumococcal meningitis: Use 12-24 million units/day in divided doses every 4 hours 1
• For neurosyphilis: Administer 12-24 million units/day as 2-4 million units every 4 hours for 10-14 days, with many experts recommending additional benzathine penicillin G 2.4 million units IM weekly for 3 doses after IV therapy completion 1, 3

Other Serious Infections

• For anthrax (adjunctive to antitoxin): Minimum 8 million units/day in divided doses every 6 hours; higher doses may be required based on organism susceptibility 1, 3
• For Listeria meningitis: 15-20 million units/day for 2 weeks 1, 3
• For Listeria endocarditis: 15-20 million units/day for 4 weeks 1, 3
• For disseminated gonococcal infections (meningitis, endocarditis, arthritis): 10 million units/day with duration dependent on infection type 1, 3

Pediatric Dosing

General Principles

• This product should not be administered to patients requiring less than one million units per dose 1
• For serious infections (pneumonia, endocarditis) in children ≥45 kg: Use adult dosing of 10 million units/day in 4 equally divided doses 1

Specific Pediatric Indications

• For arthritis: 100,000 units/kg/day in 4 equally divided doses for 7-10 days 1
• For meningitis: 250,000 units/kg/day in equal doses every 4 hours for 10-14 days 1
• For endocarditis: 250,000 units/kg/day in equal doses every 4 hours for 4 weeks 1
• For congenital/neurosyphilis (after newborn period): 200,000-300,000 units/kg/day (administered as 50,000 units/kg every 4-6 hours) for 10-14 days 1
• For diphtheria: 150,000-250,000 units/kg/day in equal doses every 6 hours for 7-10 days 1
• For rat-bite fever with endocarditis: 150,000-250,000 units/kg/day in equal doses every 4 hours for 4 weeks 1

Administration Routes and Techniques

Intravenous Administration

• For continuous IV drip: Add the appropriate daily dosage to the patient's required 24-hour fluid volume; for example, if a patient requires 2 liters in 24 hours and 10 million units of penicillin, add 5 million units to each liter and adjust flow rate accordingly 1
• The 20,000 units (20 million units) dosage may be administered by intravenous infusion only 1
• Penicillin G is administered in divided doses, usually every 4-6 hours, with the exception of meningococcal meningitis/septicemia (every 2 hours) due to its short half-life 1, 3

Intramuscular Administration

• Solutions containing up to 100,000 units of penicillin per mL may be used with minimal discomfort 1
• Keep total injection volume small; no more than 2 g should be given at any one injection site 1
• The intramuscular route is the preferred route when feasible 1

Reconstitution Guidelines

For proper reconstitution, the amount of solvent required varies by desired concentration 1:

• For 50,000 units/mL: Use 20 mL solvent for 1,000 units
• For 100,000 units/mL: Use 10 mL solvent for 1,000 units
• For 250,000 units/mL: Use 4 mL for 1,000 units; 18.2 mL for 5,000 units
• For 500,000 units/mL: Use 1.8 mL for 1,000 units; 8.2 mL for 5,000 units

Renal Impairment Dosing

Penicillin G is relatively nontoxic, and dosage adjustments are generally required only in cases of severe renal impairment 1:

• For creatinine clearance <10 mL/min/1.73m²: Administer full loading dose followed by one-half of the loading dose every 8-10 hours 1
• For uremic patients with creatinine clearance >10 mL/min/1.73m²: Administer full loading dose followed by one-half of the loading dose every 4-5 hours 1
• Additional dosage modifications should be made in patients with both hepatic disease and renal impairment 1

Treatment Duration and Monitoring

General Duration Principles

• For most acute infections: Continue treatment for at least 48-72 hours after the patient becomes asymptomatic 1
• For Group A β-hemolytic streptococcal infections: Maintain antibiotic therapy for at least 10 days to reduce the risk of rheumatic fever 1

Storage and Stability

• All reconstituted solutions should be stored in a refrigerator 1
• When refrigerated, penicillin solutions may be stored for seven days without significant loss of potency 1
• Sterile solution may be left in refrigerator for one week without significant loss of potency 1

Critical Considerations and Common Pitfalls

Pharmacokinetic Variability

• Penicillin G plasma concentrations vary notably between patients and are associated with age, weight, serum creatinine, and estimated creatinine clearance 4
• An increase in penicillin concentration during treatment shows strong correlation with advanced age, low creatinine clearance, low weight, and low albumin 4

Organism-Specific Cautions

• For enterococcal endocarditis: Standard dosing of 3 g every 6 hours may be insufficient; therapeutic drug monitoring should be applied to optimize dosing and exposure, as only 71% of patients achieve 100% fT > MIC with standard dosing 4
• For streptococci and penicillin-susceptible staphylococci: Penicillin G 3 g every 6 hours is suitable, with 96% of patients achieving 50% fT > MIC 4

Intrathecal Use Warning

• The intrathecal use of penicillin in meningitis must be highly individualized and should be employed only with full consideration of possible irritating effects 1
• The preferred route of therapy in bacterial meningitides is intravenous, supplemented by intramuscular injection 1

Drug Stability Concerns

• Penicillins are rapidly inactivated in the presence of carbohydrate solutions at alkaline pH 1
• Use Sterile Water for Injection, USP or Sterile Isotonic Sodium Chloride for Parenteral use for reconstitution 1