• Penicillin G and Penicillin V Pharmacology and Therapeutics

  • Therapeutic uses

    • Streptococcal Infections

      Streptococcal Infections:  Audio Overview

      • Penicillin is the first-line treatment for streptococcal pharyngitis (strep throat) caused by Streptococcus pyogenes (Group A strep).¹ 

        • Dosing regimens for penicillin as well as amoxicillin have been described.² 

          • Penicillin eradicates S. pyogenes and prevents complications like rheumatic fever.³ 

            • Penicillin V is also used for mild to moderate streptococcal skin infections such as erysipelas or uncomplicated cellulitis.^4,5,6

              • Facial erysipelas infection

                Facial erysipelas infection, a disease characterized by superficial layer skin infection (upper dermis). Erysipelas is a type of cellulitis and may be serious.5  Attribution CDC/Dr. Thomas F. Sellers/Emory University, Public domain, via Wikimedia Commons https://commons.wikimedia.org/wiki/File:Facial_erysipelas.jpg

            •  Group B Streptococcus (S. agalactiae) infections for example in. neonatal sepsis and prophylaxis in obstetrics may be treated with IV penicillin. In women with penicillin allergy clindamycin may be an alternative.⁷  

            • Penicillin G (often in combination with gentamicin or another agent) is also a drug of choice for enterococcal endocarditis caused by Enterococcus faecalis (if susceptible), using high-dose IV penicillin G plus an aminoglycoside (gentamicin)  for synergy.⁸

    • Syphilis and Spirochetal Infections

      Syphilis and Spirochetal Infections:  Audio Overview

      • Penicillin G is the gold-standard therapy for syphilis, in all stages.⁹  

        • Treponema pallidum

          Histopathology of Treponema pallidum spirochetes using modified Steiner silver stain. (Obtained from the CDC Public Health Image Library) Attribution CDC, Public domain, via Wikimedia Commons Image credit: CDC/Dr. Edwin P. Ewing, Jr, 1986.

        • Treponema pallidum is exquisitely sensitive to penicillin G.⁹ 

        • Early syphilis is treated in primary care or infectious disease clinics with a single IM dose of benzathine penicillin G (2.4 million units) to achieve sustained low-level penicillin in the blood.¹⁰ 

        • Late latent syphilis requires three weekly IM doses, and neurosyphilis or ocular syphilis requires high-dose IV penicillin G for 10–14 days.^11,12

      • Penicillin G (IV) is also recommended for neonatal congenital syphilis¹³ and, along with azithromycin, for Treponema pertenue infections (yaws).¹⁴  

      • Other spirochetal infections treated with penicillin include Leptospirosis (IV penicillin G).¹⁵ 

    • Pneumococcal Infections

      Pneumococcal Infections:  Audio Overview

      • Streptococcus pneumoniae (pneumococcus) historically was penicillin-sensitive and penicillin G was first-line for pneumococcal pneumonia²³, meningitis, and otitis media.

        • Streptococcus pneumoniae

          "Scanning Electron Micrograph of Streptococcus Pneumoniae." Attribution Janice Haney Carr, Public domain, via Wikimedia Commons https://commons.wikimedia.org/wiki/File:Streptococcus_pneumoniae-263.jpg

        • Due to resistance resulting from genetic mutations that alter penicillin-binding protein structure, management now depends on local susceptibility.^16,17 

      • Penicillin G IV is still used for pneumococcal meningitis (Streptococcus pneumoniae) if the isolate is susceptible (MIC ≤0.06 μg/mL for meningitis); otherwise, third-generation cephalosporins, such as cefotaxime or ceftriaxone, may be appropriate.¹⁸ 

      • For pneumococcal pneumonia, penicillin G IM or IV can be used if the strain is confirmed sensitive.¹⁹ 

        • In outpatient primary care, amoxicillin (an oral aminopenicillin) has often replaced penicillin V for empiric treatment of community-acquired pneumonia, noting that Streptococcus pneumoniae is the bacteria most frequently isolated.²⁰

          • Amoxicillin remains an antibiotic of preference in treating acute otitis media.²²

             

            Otitis Media Audio Overview

            •  

              Otitis Media

              Attribution BruceBlaus, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons https://commons.wikimedia.org/wiki/File:Otitis_Media.png

            • Second-line alternatives in case of treatment failure include oral cefuroxime or amoxicillin-clavulanate.²¹ 

August, 2025