Penicillin G Potassium, Penicillin G Sodium (Monograph)

Drug class: Natural Penicillins
ATC class: J01CE01
VA class: AM110

Medically reviewed by Drugs.com on Sep 21, 2023. Written by ASHP.

Introduction

Penicillin G, a natural penicillin, is a β-lactam antibiotic.^{10 61}

Uses for Penicillin G Potassium, Penicillin G Sodium

Penicillin G potassium and penicillin G sodium are used parenterally when rapid and high concentrations of penicillin G are required, as in the treatment of endocarditis, meningitis, pericarditis, septicemia, severe pneumonia, or other serious infections caused by organisms susceptible to penicillin G.^{8 9 10 11 12 61 64 197}

For additional information on the uses of penicillin G potassium and penicillin G sodium, see Uses in the Natural Penicillins General Statement 8:12.16.04.

Endocarditis

IV penicillin G potassium or sodium is used for the treatment of endocarditis caused by susceptible Streptococcus pyogenes (group A β-hemolytic streptococci; GAS), other β-hemolytic streptococci (including groups C, H, G, L, and M), or S. pneumoniae.^{8 9 11 12} The American Heart Association (AHA) states that IV penicillin G is a reasonable regimen for the treatment of endocarditis caused by susceptible S. pyogenes, S. agalactiae^{† [off-label]} (group B streptococci; GBS), groups C and G streptococci, and highly penicillin-susceptible S. pneumoniae (penicillin MIC 0.1 mcg/mL or less), but concomitant use of gentamicin during the initial weeks of penicillin G treatment should be considered if endocarditis is caused by streptococci groups B, C, or G.⁴⁵⁰

For the treatment of endocarditis caused by viridans group streptococci^{† [off-label]} or nonenterococcal group D streptococci^{† [off-label]} (including S. gallolyticus^{† [off-label]} [formerly S. bovis]) that are highly susceptible to penicillin (penicillin MIC 0.12 mcg/mL or less), AHA states that IV penicillin G (with or without gentamicin) is a regimen of choice.^{450 452} If endocarditis is caused by viridans group streptococci^{† [off-label]} or S. gallolyticus^† relatively resistant to penicillin (penicillin MIC greater than 0.12 mcg/mL but less than 0.5 mcg/mL), AHA states that IV penicillin G should be used in conjunction with gentamicin.^{450 452} These recommendations include endocarditis involving native valves or prosthetic valves or other prosthetic material caused by these gram-positive bacteria.⁴⁵⁰

AHA states that IV penicillin G in conjunction with gentamicin is a reasonable regimen for the treatment of native valve endocarditis caused by viridans group streptococci^†, Abiotrophia defectiva^†, or Granulicatella^† with penicillin MIC 0.5 mcg/mL or greater.^{450 452}

For the treatment of endocarditis involving native valves or prosthetic valves or other prosthetic material caused by Enterococcus faecalis^†, E. faecium^†, or other enterococcal species susceptible to both penicillin G and gentamicin, AHA states that IV penicillin G in conjunction with gentamicin is a regimen of choice.^{450 452} AHA states that it is reasonable to substitute streptomycin for gentamicin in this regimen if enterococci are susceptible to penicillin and streptomycin, but resistant to gentamicin.⁴⁵⁰

IV penicillin G has been used for the treatment of endocarditis caused by nonpenicillinase-producing staphylococci.^{8 9 11 12 452} AHA states that IV penicillin G may be considered for the treatment of native valve endocarditis caused by penicillin-susceptible S. aureus or coagulase-negative staphylococci in pediatric patients;⁴⁵² however, penicillin G is not included in current AHA recommendations for the treatment of staphylococcal endocarditis in adults.⁴⁵⁰

AHA recommends that treatment of endocarditis should be managed in consultation with an infectious disease expert, especially when endocarditis is caused by S. pneumoniae, β-hemolytic streptococci, staphylococci, or enterococci.^{450 452}

For additional information on management of endocarditis, current guidelines from AHA should be consulted.^{450 452}

Syphilis

IV penicillin G potassium or sodium is used for the treatment of syphilis caused by Treponema pallidum.^{8 9 11 12 344 345 350 440 441}

For the treatment of neurosyphilis and otic or ocular syphilis, the US Centers for Disease Control and Prevention (CDC) and other clinicians state that IV penicillin G potassium or sodium is the drug of choice and IM penicillin G procaine (with oral probenecid) is an alternative if compliance can be ensured.^{344 345 440 441}

For the treatment of congenital syphilis, CDC recommends IV penicillin G potassium or sodium or IM penicillin G procaine in neonates with proven or highly probable congenital syphilis (i.e., abnormal physical examination consistent with congenital syphilis, serum quantitative nontreponemal serologic titer fourfold higher than the mother's titer, or positive darkfield test or polymerase chain reaction [PCR] of lesions or body fluids).³⁴⁴ CDC recommends IV penicillin G potassium or sodium, IM penicillin G procaine, or IM penicillin G benzathine in neonates with possible congenital syphilis (i.e., normal physical examination and serum quantitative nontreponemal serologic titer no more than fourfold higher than the mother's titer and the mother received a recommended treatment regimen less than 4 weeks before delivery; the mother was not treated or was inadequately treated, including treatment with erythromycin or any regimen not included in CDC recommendations; or there is no documentation that the mother received treatment).³⁴⁴

CDC and other clinicians state that IM penicillin G benzathine is the drug of choice for the treatment of primary syphilis (i.e., ulcer or chancre at infection site), secondary syphilis (i.e., manifestations that include, but are not limited to, rash, mucocutaneous lesions, and lymphadenopathy), and tertiary syphilis (i.e., cardiac syphilis, gummatous lesions, tabes dorsalis, and general paresis) in adults, adolescents, and children.^{344 345 350 440 441}

IM penicillin G benzathine also is the drug of choice for the treatment of latent syphilis (i.e., detected by serologic testing but lacking clinical manifestations), including both early latent syphilis (latent syphilis acquired within the preceding year) and late latent syphilis (i.e., all other cases of latent syphilis or syphilis of unknown duration) in all age groups.^{344 345 350 440 441}

Neonates with human immunodeficiency virus (HIV) infection who have congenital syphilis and HIV-infected children, adolescents, or adults who have neurosyphilis or primary, secondary, early latent, late latent, or tertiary syphilis should receive the same treatment regimens as those without HIV infection.^{344 440 441} Because serologic nonresponse and neurologic complications may be more frequent in HIV-infected individuals, close follow-up is essential in those coinfected with syphilis and HIV.^{344 440} In addition, careful neurologic examinations are indicated in all HIV-infected patients coinfected with syphilis.⁴⁴⁰

There are no proven alternatives to penicillin G for the treatment of congenital syphilis in infants and children with known or suspected penicillin hypersensitivity and no proven alternatives to penicillin G for the treatment of any stage of syphilis in pregnant women with penicillin hypersensitivity; therefore, CDC recommends that such patients be desensitized and treated with the appropriate penicillin G preparation.³⁴⁴

For additional information on management of syphilis, current CDC sexually transmitted diseases treatment guidelines available at [Web] should be consulted.³⁴⁴

Prevention of Perinatal Group B Streptococcal Disease

IV penicillin G potassium or sodium is used in pregnant women during labor (intrapartum) for prevention of early-onset neonatal group B streptococcal (GBS) disease^†.^{292 359 362}

GBS infection is a leading cause of neonatal morbidity and mortality in the US.³⁶² Pregnant women who are colonized with GBS in the genital or rectal areas can transmit GBS infection to their infants during labor and delivery, resulting in invasive neonatal infection that can be associated with substantial morbidity and mortality.^{292 359 362}

CDC, AAP, and other experts recommend routine universal prenatal screening for GBS colonization (e.g., vaginal and rectal cultures) in all pregnant women at 35–37 weeks of gestation, unless GBS bacteriuria is known to be present during the current pregnancy or the woman had a previous infant with invasive GBS disease.^{292 359} These experts state that intrapartum anti-infective prophylaxis for prevention of perinatal GBS is indicated in pregnant women identified as GBS carriers during the routine prenatal GBS screening performed at 35–37 weeks during the current pregnancy, in women with GBS bacteriuria identified at any time during the current pregnancy, and in women who had a previous infant diagnosed with invasive GBS disease.^{292 359} Intrapartum anti-infective prophylaxis also is indicated in women with unknown GBS status at the time of onset of labor (i.e., culture not done, incomplete, or results unknown) if delivery is at less than 37 weeks of gestation, the duration of amniotic membrane rupture is 18 hours or longer, or intrapartum temperature is 38°C or higher.^{292 359} If an intrapartum nucleic acid amplification test (NAAT) is performed in a woman with unknown GBS status at the time of onset of labor (may not be available in all settings) and results are positive for GBS, intrapartum anti-infective prophylaxis is indicated;³⁵⁹ if an intrapartum NAAT is negative for GBS, anti-infective prophylaxis is indicated if any of the above risk factors for perinatal GBS infection are present.³⁵⁹

When intrapartum anti-infective prophylaxis is indicated in the mother for prevention of GBS in the neonate, it should be initiated at the onset of labor or rupture of membranes.³⁵⁹ If cesarean delivery is performed before onset of labor in a woman with intact amniotic membranes, anti-infective prophylaxis is not usually indicated, regardless of the GBS colonization status of the woman or gestational age.^{292 359}

CDC, AAP, and other experts recommend IV penicillin G as the drug of choice and state that IV ampicillin is the preferred alternative for such prophylaxis.^{292 359 362} Penicillin G is considered the drug of choice because it has a narrower spectrum of activity than ampicillin and is less likely to select for antibiotic-resistant organisms.^{292 359}

Regardless of whether the mother received intrapartum anti-infective prophylaxis, appropriate diagnostic evaluations and anti-infective therapy should be initiated in the neonate if signs or symptoms of active infection develop.^{292 359 362}

For additional information regarding prevention of perinatal group B streptococcal disease, current guidelines from CDC and AAP should be consulted.^{359 362}

Penicillin G Potassium, Penicillin G Sodium Dosage and Administration

Reconstitution and Administration

Penicillin G potassium and penicillin G sodium are administered by IM injection or by intermittent IV injection or infusion or continuous IV infusion.^{8 9 11 12 61} Penicillin G has been administered by intrapleural,^{9 12} intraperitoneal,⁶¹ intra-articular,^{9 12} or other local instillations.^{9 12} Although the drug has been administered intrathecally,^{9 12 61} this route is not recommended because of possible neurotoxicity (e.g., seizures).^{61 416}

Vials containing penicillin G potassium or penicillin G sodium powder for injection should be reconstituted to the desired concentration using the amount of diluent specified by the manufacturer.^{8 9 12} Depending on the specific product and route of administration, the powders generally are reconstituted with sterile water for injection,^{8 9 12} 0.9% sodium chloride injection,^{8 9 12} or dextrose injection.⁸ The powder should be loosened in the vial and the vial held horizontally and rotated while slowly directing the stream of diluent against the wall of the vial.^{8 9 12} After the diluent has been added, the vial should be shaken vigorously.^{8 9 12} Because penicillin G is unstable in solutions at room temperature,⁶¹ reconstituted penicillin G potassium and penicillin G sodium solutions should be used immediately or refrigerated.^{8 9 12} (See Chemistry and Stability: Stability.)

IM Injection

To prepare solutions for IM administration, vials labeled as containing 1 or 5 million units of penicillin G (as penicillin G potassium)^{9 12} or vials labeled as containing 5 million units of penicillin G (as penicillin G sodium)⁸ should be reconstituted to the desired concentration using the amount of diluent specified by the manufacturer.^{8 9 12} If not used immediately, vials reconstituted for IM use should be refrigerated (see Chemistry and Stability: Stability).^{8 9 12}

Vials labeled as containing 20 million units of penicillin G (as penicillin G potassium) are intended only for IV infusion and should not be used to prepare solutions for IM injection.^{9 12}

For IM administration, penicillin G potassium solutions containing up to 100,000 penicillin G units/mL may be used with a minimum of discomfort;^{9 12} higher concentrations are physically possible and may be used when needed.^{9 12}

If large doses of penicillin G are required, the drug should be administered IV (not IM).^{9 12}

IV Administration

To prepare solutions for IV administration, vials labeled as containing 1, 5, or 20 million units of penicillin G (as penicillin G potassium) or 5 million units of penicillin G (as penicillin G sodium) should be reconstituted according to the manufacturer's directions.^{8 9 12} If not used immediately, vials reconstituted for IV use should be refrigerated (see Chemistry and Stability: Stability).^{8 9 12}

For intermittent IV administration, the daily dosage usually is given in equally divided doses every 4–6 hours; however, daily dosage may be given in equally divided doses every 2–3 hours for the treatment of severe infections (e.g., meningitis).^{8 9 12 61}

For continuous IV infusion, the volume of IV fluid and rate of administration required by the patient in a 24-hour period should be determined and the appropriate daily dosage of penicillin G should be added to the fluid.^{9 12} For example, if an adult patient requires 2 L of fluid in 24 hours and a dosage of 10 million penicillin G units daily, 5 million units can be added to 1 L of IV solution and the rate of administration adjusted so that the liter of fluid will be infused over 12 hours.^{9 12}

Thawed solutions of the commercially available frozen premixed penicillin G potassium injection in dextrose should be administered only by IV infusion.¹¹ The commercially available frozen injection should be thawed at room temperature (25°C) or under refrigeration (5°C);¹¹ the injection should not be thawed by warming in a water bath or by exposure to microwave radiation.¹¹ Precipitates that may have formed in the frozen injection usually will dissolve with little or no agitation when the injection reaches room temperature;¹¹ potency is not affected.¹¹ After thawing at room temperature, the injections should be agitated and the container checked for minute leaks by firmly squeezing the bag.¹¹ The injection should be discarded if the container seals or outlet ports are not intact or leaks are found or if the solution is cloudy or contains a precipitate.¹¹ Additives should not be introduced into the injection container.¹¹ The premixed injection should not be used in series connections with other plastic containers since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.¹¹

Rate of Administration

Large IV doses of penicillin G potassium or sodium (greater than 10 million penicillin G units) should be administered slowly because of the potential for serious electrolyte disturbances from the potassium and/or sodium content of these preparations.^{8 9 11 12} (See Cautions: Adverse Effects.)

For intermittent IV administration, penicillin G potassium or sodium has been given by IV infusion over 1–2 hours^{8 9 11 12 61 1563} or by IV infusion over 10–30 minutes.^{61 1414} Although doses of the drug also have been injected IV over 3–5 minutes,^{8 9 11 12 61} large doses should be administered slowly.^{8 9 11 12}

Dosage

Dosage of penicillin G potassium and penicillin G sodium usually is expressed in terms of penicillin G units,^{8 9 11 12} but also has been expressed as mg of penicillin G.⁶¹

Pediatric Dosage

General Pediatric Dosage

Dosage of IM or IV penicillin G potassium or sodium for pediatric patients should be individualized and generally is based on weight and the severity of the infection.^{8 9 11 12}

The manufacturers state that penicillin G potassium or sodium should not be used in pediatric patients requiring less than 1 million penicillin G units per dose.^{8 9 11 12}

The American Academy of Pediatrics (AAP) states that the usual dosage of IV or IM penicillin G potassium or sodium in neonates 7 days of age or younger is 25,000–50,000 units/kg every 12 hours.²⁹² In neonates 8–28 days of age, AAP recommends a dosage of 25,000–50,000 units/kg every 8 hours.²⁹² Higher dosages may be necessary for the treatment of meningitis in neonates.²⁹²

In pediatric patients beyond the neonatal period, AAP states that the usual dosage of IV or IM penicillin G potassium or sodium is 100,000–150,000 units/kg daily given in 4 equally divided doses for the treatment of mild to moderate infections or 200,000–300,000 units/kg daily given in 4–6 equally divided doses for the treatment of severe infections.²⁹² AAP states that the highest dosage recommended for pediatric patients beyond the neonatal period should be used for the treatment of meningitis.²⁹²

Endocarditis

For the treatment of native valve endocarditis caused by highly penicillin-susceptible streptococci (penicillin MIC 0.1 mcg/mL or less), including Streptococcus pyogenes (group A β-hemolytic streptococci; GAS), other β-hemolytic streptococci (e.g., groups C, G), S. agalactiae^† (group B streptococci; GBS), viridans group streptococci^†, or nonenterococcal group D streptococci^† (e.g., S. gallolyticus^† [formerly S. bovis], S. equinus^†), the American Heart Association (AHA) states that pediatric patients may receive IV penicillin G in a dosage of 200,000–300,000 units/kg daily (up to 12–24 million units daily) given in divided doses every 4 hours for 4 weeks.⁴⁵²

For the treatment of native valve endocarditis caused by streptococci that are relatively resistant to penicillin^† (penicillin MIC greater than 0.1 but less than 0.5 mcg/mL), AHA states that pediatric patients may receive IV penicillin G in a dosage of 200,000–300,000 units/kg daily (up to 12–24 million units daily) given in divided doses every 4 hours for 4 weeks in conjunction with gentamicin (3–6 mg/kg daily IV in divided doses every 8 hours given concomitantly during the first 2 weeks of penicillin G treatment).⁴⁵²

For the treatment of native valve endocarditis caused by viridans group streptococci^†, Abiotrophia^†, or Granulicatella^† with penicillin MIC 0.5 mcg/mL or greater, AHA states that pediatric patients may receive IV penicillin G in a dosage of 200,000–300,000 units/kg daily (up to 12–24 million units daily) given in divided doses every 4 hours for 4–6 weeks in conjunction with gentamicin (3–6 mg/kg IV daily in divided doses every 8 hours given concomitantly during the first 2 weeks of penicillin G treatment).⁴⁵²

For the treatment of endocarditis involving prosthetic valves or other prosthetic material caused by penicillin-susceptible viridans group streptococci^†, other streptococci, Abiotrophia^†, or Granulicatella^† with penicillin MIC 0.1 mcg/mL or greater, AHA states that pediatric patients may receive IV penicillin G in a dosage of 200,000–300,000 units/kg daily (up to 12–24 million units daily) given in divided doses every 4 hours for 6 weeks in conjunction with gentamicin (3–6 mg/kg IV daily in divided doses every 8 hours given concomitantly for the entire 6 weeks of penicillin G treatment).⁴⁵²

For the treatment of enterococcal endocarditis^† (native valve or prosthetic valve or other prosthetic material), AHA states that pediatric patients may receive IV penicillin G in a dosage of 200,000–300,000 units/kg daily (up to 12–24 million units daily) given in divided doses every 4 hours in conjunction with gentamicin (3–6 mg/kg IV daily in divided doses every 8 hours).⁴⁵² The recommended duration of treatment with the 2-drug regimen is 4–6 weeks for native valve enterococcal endocarditis; a longer duration of treatment with both drugs is recommended if prosthetic valves or other prosthetic material is involved.⁴⁵²

If IV penicillin G is used for the treatment of endocarditis caused by susceptible S. aureus or coagulase-negative staphylococci (penicillin MIC 0.1 mcg/mL or less) in pediatric patients, AHA recommends a dosage of 200,000–300,000 units/kg daily (up to 12–24 million units daily) given in divided doses every 4 hours.⁴⁵²

The manufacturers recommend that pediatric patients with endocarditis caused by susceptible streptococci (including S. pyogenes, streptococci groups C, H, G, L, and M, or S. pneumoniae) receive penicillin G potassium or sodium in a dosage of 150,000–300,000 units/kg daily given in divided doses every 4–6 hours.^{8 9 11 12}

Meningitis and Other CNS Infections

For the treatment of meningitis caused by susceptible Listeria monocytogenes, the Infectious Diseases Society of America (IDSA) recommends that neonates 7 days of age or younger receive IV penicillin G in a dosage of 150,000 units/kg daily given in divided doses every 8–12 hours and that those 8–28 days of age receive a dosage of 200,000 units/kg daily given in divided doses every 6–8 hours;⁴¹⁸ these experts recommend that treatment in neonates be continued for 2 weeks beyond the first sterile CSF culture or for at least 3 weeks, whichever is longer.⁴¹⁸ In infants and children with L. monocytogenes meningitis, IDSA recommends a dosage of 300,000 units/kg daily given in divided doses every 4–6 hours for a duration of at least 21 days.⁴¹⁸ Concomitant use of an aminoglycoside should be considered.⁴¹⁸

For the treatment of meningitis caused by susceptible Neisseria meningitidis (penicillin MIC less than 0.1 mcg/mL), IDSA recommends that neonates 7 days of age or younger receive IV penicillin G in a dosage of 150,000 units/kg daily given in divided doses every 8–12 hours and that those 8–28 days of age receive a dosage of 200,000 units/kg daily given in divided doses every 6–8 hours;⁴¹⁸ these experts recommend that treatment in neonates be continued for 2 weeks beyond the first sterile CSF culture or for at least 3 weeks, whichever is longer.⁴¹⁸ In infants and children with N. meningitidis meningitis, a dosage of 300,000 units/kg daily (up to 12 million units daily) given in divided doses every 4–6 hours for a duration of 7 days has been recommended.^{292 418}

For the treatment of meningitis caused by susceptible S. agalactiae ^† (group B streptococci; GBS), AAP recommends that neonates 7 days of age or younger receive IV penicillin G in a dosage of 250,000–450,000 units/kg daily given in 3 divided doses and that those older than 7 days of age receive a dosage of 450,000–500,000 units/kg daily given in 4 divided doses and states that treatment should be continued for at least 14 days.²⁹² IDSA recommends that neonates 7 days of age or younger receive IV penicillin G in a dosage of 150,000 units/kg daily given in divided doses every 8–12 hours and that those 8–28 days of age receive a dosage of 200,000 units/kg daily given in divided doses every 6–8 hours;⁴¹⁸ these experts recommend that treatment in neonates be continued for 2 weeks beyond the first sterile CSF culture or for at least 3 weeks, whichever is longer.⁴¹⁸ In infants and children with S. agalactiae meningitis, IDSA recommends a dosage of 300,000 units/kg daily given in divided doses every 4–6 hours for a duration of 14–21 days.⁴¹⁸ Concomitant use of an aminoglycoside should be considered.⁴¹⁸

For the treatment of meningitis caused by susceptible S. pneumoniae, IDSA recommends that neonates 7 days of age or younger receive IV penicillin G in a dosage of 150,000 units/kg daily given in divided doses every 8–12 hours and that those 8–28 days of age receive a dosage of 200,000 units/kg daily given in divided doses every 6–8 hours;⁴¹⁸ these experts recommend that treatment in neonates be continued for 2 weeks beyond the first sterile CSF culture or for at least 3 weeks, whichever is longer.⁴¹⁸ AAP recommends that infants and children 1 month of age or older with S. pneumoniae meningitis receive IV penicillin G in a dosage of 250,000–400,000 units/kg daily given in divided doses every 4–6 hours.²⁹² IDSA recommends that infants and children receive a dosage of 300,000 units/kg daily given in divided doses every 4–6 hours for a duration of 10–14 days.⁴¹⁸

For the treatment of healthcare-associated ventriculitis and meningitis caused by susceptible Cutibacterium acnes^† (formerly Propionibacterium acnes), IDSA recommends that pediatric patients receive IV penicillin G in a dosage of 300,000 units/kg daily given in divided doses every 4–6 hours.⁴¹⁶ The recommended treatment duration is 10 days in those with no or minimal CSF pleocytosis, normal CSF glucose, and few clinical symptoms or systemic features or 10–14 days in those with significant CSF pleocytosis, CSF hypoglycorrhachia, or clinical symptoms or systemic features.⁴¹⁶

The manufacturers recommend that pediatric patients with meningitis caused by susceptible N. meningitidis or S. pneumoniae receive penicillin G potassium or sodium in a dosage of 250,000 units/kg daily (up to 12–20 million units daily) given in divided doses every 4 hours for 7–14 days.^{8 9 11 12}

Respiratory Tract Infections

For the treatment of community-acquired pneumonia (CAP) caused by susceptible S. pyogenes (group A β-hemolytic streptococci; GAS) in pediatric patients 3 months of age or older, IDSA recommends that IV penicillin G be given in a dosage of 100,000–200,000 units daily in divided doses every 4–6 hours.⁵¹³ For severe infections, 200,000–250,000 units/kg daily may be used.⁵¹³

For the treatment of CAP caused by susceptible S. pneumoniae (penicillin MIC 2 mcg/mL or lower) in pediatric patients 3 months of age or older, IDSA recommends that IV penicillin G be given in a dosage of 200,000–250,000 units/kg daily in divided doses every 4–6 hours.⁵¹³ AAP recommends that infants and children 1 month of age or older with nonmeningeal infections caused by S. pneumoniae receive penicillin G in a dosage of 250,000–400,000 units/kg daily given in divided doses every 4–6 hours.²⁹² Penicillin G should not be used for empiric treatment of CAP if local epidemiologic data indicate that invasive S. pneumoniae have high-level penicillin resistance.⁵¹³

If penicillin G potassium or sodium is used for the treatment of serious respiratory tract infections (e.g., pneumonia) caused by susceptible S. pyogenes, streptococci groups C, H, G, L, and M, or S. pneumoniae, in pediatric patients, the manufacturers recommend a dosage of 150,000–300,000 units/kg daily in divided doses every 4–6 hours.^{8 9 11 12}

Skin and Skin Structure Infections

For the treatment of necrotizing infections of the skin, fascia, and muscle caused by susceptible S. pyogenes, IDSA recommends that pediatric patients receive a regimen of IV penicillin G given in a dosage of 60,000–100,000 units/kg every 6 hours in conjunction with clindamycin (10–13 mg/kg IV every 8 hours).⁵⁴³

Anthrax

For the treatment of anthrax (inhalational, GI, meningitis) caused by penicillin-susceptible Bacillus anthracis that occurs as the result of natural or endemic exposures to anthrax, some clinicians recommend that children receive IV penicillin G in a dosage of 100,000–150,000 units/kg daily given in divided doses every 4–6 hours.⁶⁷⁰ For the treatment of severe or life-threatening systemic anthrax (inhalational, GI, meningoencephalitis, sepsis) or the treatment of cutaneous anthrax with signs of systemic involvement, lesions on the head or neck, or extensive edema caused by penicillin-susceptible B. anthracis that occurs as the result of natural or endemic anthrax exposure, some experts recommend that children receive IV penicillin G in a dosage of 300,000–400,000 units/kg daily given in divided doses every 4–6 hours.⁶⁸⁰ Concomitant use of other anti-infectives (e.g., streptomycin or other aminoglycoside, clindamycin, clarithromycin, rifampin, vancomycin) may also be indicated.^{670 680} Treatment of naturally occurring or endemic anthrax generally should be continued for at least 14 days after symptoms abate.⁶⁷⁰

If IV penicillin G is used in a multiple-drug parenteral regimen for initial treatment of systemic anthrax (inhalational, GI, meningitis, cutaneous anthrax with systemic involvement, lesions on the head or neck, or extensive edema) caused by penicillin-susceptible B. anthracis that occurs in the context of biologic warfare or bioterrorism, AAP states that full-term neonates 7 days of age or younger should receive a dosage of 300,000 units/kg daily given in divided doses every 8 hours and those 1–4 weeks of age should receive 400,000 units/kg daily given in divided doses every 6 hours.⁶⁷¹ For the treatment of these systemic anthrax infections in premature neonates, AAP recommends that those with gestational age of 32–34 weeks receive 200,000 units/kg daily given in divided doses every 12 hours from birth until 7 days of age and 300,000 units/kg daily given in divided doses every 8 hours from 1–4 weeks of age;⁶⁷¹ those with gestational age of 34–37 weeks should receive 300,000 units/kg daily given in divided doses every 8 hours from birth until 7 days of age and 400,000 units/kg daily given in divided doses every 6 hours from 1–4 weeks of age.⁶⁷¹ In infants and children 1 month of age or older, AAP recommends that IV penicillin G be given in a dosage of 400,000 units/kg daily in divided doses every 4 hours (up to 4 million units per dose).⁶⁷¹ The multiple-drug parenteral regimen should be continued for at least 2–3 weeks until the patient is clinically stable; treatment can then be switched to an oral regimen.⁶⁷¹ Because of the possible persistence of anthrax spores in lung tissue following an aerosol exposure in the context of biologic warfare or bioterrorism, the US Centers for Disease Control and Prevention (CDC) and other experts state that the total duration of anti-infective treatment should be 60 days.^{668 671 683 686}

For additional information on the treatment of anthrax and recommendations for postexposure prophylaxis following exposure to anthrax spores, see Uses: Anthrax, in Ciprofloxacin 8:12.18.

Clostridium Infections

For the treatment of myonecrosis and gas gangrene caused by Clostridium perfringens or other clostridium in children, IDSA recommends that IV penicillin G be given in a dosage of 60,000–100,000 units/kg every 6 hours in conjunction with clindamycin (10–13 mg/kg IV every 8 hours).⁵⁴³ AAP recommends that children with myonecrosis caused by C. perfringens receive IV penicillin G in a dosage of 250,000–400,000 units/kg daily and states that concomitant use of clindamycin may be more effective than penicillin G alone.²⁹² Surgical debridement and/or surgery should be performed as indicated.^{8 9 11 12}

If IV penicillin G is used as an adjunct to tetanus immune globulin (TIG) in the management of tetanus caused by C. tetani, AAP recommends that children receive a dosage of 100,000 units/kg daily (up to 12 million units daily) given in divided doses every 4–6 hours for 7–10 days.²⁹² The role of anti-infectives in the adjunctive treatment of tetanus is unclear;¹⁰ metronidazole usually is preferred if an anti-infective is used.^{10 292}

Diphtheria

If penicillin G potassium or sodium is used as an adjunct to diphtheria antitoxin (not commercially available in the US, but may be available from CDC) for the treatment of diphtheria caused by Corynebacterium diphtheriae and prevention of the diphtheria carrier state, the manufacturers recommend that pediatric patients receive a dosage of 150,000–250,000 units/kg daily given in divided doses every 6 hours for 7–10 days.^{8 9 11 12} CDC recommends a 14-day regimen of IM penicillin G procaine if a penicillin is used for adjunctive treatment of diphtheria.¹⁶⁶ Patients usually are no longer contagious 48 hours after initiation of anti-infective treatment.¹⁶⁶ Eradication of C. diphtheriae should be confirmed 24 hours after completion of treatment by 2 consecutive negative cultures taken 24 hours apart.^{166 292}

Lyme Disease

If IV penicillin G is used as an alternative to IV ceftriaxone for the treatment of early Lyme disease^† in children with acute neurologic disease manifested as meningitis or radiculopathy, IDSA recommends a dosage of 200,000–400,000 units/kg daily (up to 18–24 million units daily) given in divided doses every 4 hours for 10–28 days.³²⁹

If IV penicillin G is used as an alternative to IV ceftriaxone or IV cefotaxime for the treatment of late Lyme disease^† in children with recurrent Lyme arthritis and objective evidence of neurologic disease, AAP and IDSA recommend a dosage of 200,000–400,000 units/kg daily (up to 18–24 million units daily) given in divided doses every 4 hours for 14–28 days.^{292 329}

For the treatment of late neurologic Lyme disease^† affecting the central or peripheral nervous system, IDSA, AAP, and others state that children can receive IV penicillin G in a dosage of 200,000–400,000 units/kg daily (up to 18–24 million units daily) given in divided doses every 4 hours for 14–28 days as an alternative to IV ceftriaxone.^{292 329 342} IDSA states that retreatment is not recommended unless relapse of neurologic disease is documented with reliable objective measures.³²⁹

Neisseria meningitidis Infections

For the treatment of serious infections (e.g. endocarditis, pneumonia) caused by susceptible N. meningitidis, the manufacturers recommend that pediatric patients receive penicillin G potassium or sodium in a dosage of 150,000–300,000 units/kg daily given in divided doses every 4–6 hours.^{8 9 11 12}

For dosage recommendations for the treatment of meningitis caused by N. meningitidis in pediatric patients, see Meningitis and Other CNS Infections under Dosage: Pediatric Dosage, in Dosage and Administration.

Rat-Bite Fever

For the treatment of rat-bite fever caused by Streptobacillus moniliformis (erythema arthriticum epidemicum, Haverhill fever) or Spirillum minus (sodoku), the manufacturers recommend that pediatric patients receive penicillin G potassium or sodium in a dosage of 150,000–250,000 units/kg daily given in divided doses every 4 hours for 4 weeks.^{8 9 11 12}

Some clinicians suggest that pediatric patients with rat-bite fever receive IV penicillin G in a dosage of 20,000–50,000 units/kg daily for 5–7 days followed by oral penicillin V (25–50 mg/kg daily [up to 3 g daily] in 4 divided doses for 7 days).³⁰ For the treatment endocarditis caused by S. moniliformis strains that are less susceptible to penicillin G (MIC greater than 0.1 mcg/mL), some clinicians state that pediatric patients should receive IV penicillin G in a dosage of 160,000–240,000 units/kg daily (up to 20 million units daily) for 6 weeks;³⁰ concomitant use of an aminoglycoside (streptomycin or gentamicin) may be indicated for initial treatment.^{10 30 292}

Syphilis

For the treatment of proven or highly probable congenital syphilis in neonates (see Uses: Syphilis), CDC recommends an IV penicillin G dosage of 50,000 units/kg every 12 hours during the first 7 days of life and 50,000 units/kg every 8 hours thereafter for a total duration of 10 days.³⁴⁴ If more than 1 day of treatment is missed in such neonates, the entire course of treatment should be restarted.³⁴⁴ If IV penicillin G is used in neonates with possible congenital syphilis (see Uses: Syphilis), CDC recommends 50,000 units/kg every 12 hours during the first 7 days of life and 50,000 units/kg every 8 hours thereafter for a total duration 10 days.³⁴⁴

In infants and children 1 month of age or older with reactive serologic tests for syphilis, CDC recommends that IV penicillin G be given in a dosage of 200,000–300,000 units/kg daily (50,000 units/kg every 4–6 hours) for 10 days.³⁴⁴

CDC, AAP, and the manufacturers recommend that penicillin G potassium or sodium be given in a dosage of 200,000–300,000 units/kg daily (50,000 units every 4–6 hours) for 10–14 days for the treatment of congenital syphilis diagnosed after the neonatal period or for the treatment of neurosyphilis in infants and children 1 month of age or older.^{8 9 11 12 292 344} Some clinicians recommend that this regimen be followed by a single dose of IM penicillin G benzathine (50,000 units/kg [up to 2.4 million units]).^{292 344}

For the treatment of neurosyphilis and otic or ocular syphilis in adolescents with human immunodeficiency virus (HIV) infection, some clinicians recommend that IV penicillin G be given a dosage of 18–24 million units daily (by continuous IV infusion or given as 3–4 million units every 4 hours) for 10–14 days.⁴⁴⁰ Some clinicians recommend that this regimen be followed by a regimen of IM penicillin G benzathine (2.4 million units once weekly for 1–3 weeks).⁴⁴⁰

HIV-infected neonates with congenital syphilis and HIV-infected children and adolescents with any stage of syphilis should receive the same treatment regimens recommended for those without HIV infection.^{344 441}

Adult Dosage

Bone and Joint Infections

For the treatment of native vertebral osteomyelitis or prosthetic joint infections caused by susceptible β-hemolytic streptococci^†, IDSA recommends that adults receive IV penicillin G in a dosage of 20–24 million units daily (by continuous IV infusion or in 6 divided doses).^{590 591} The recommended duration of treatment is 6 weeks in patients with native vertebral osteomyelitis⁵⁹⁰ or 4–6 weeks in those with prosthetic joint infections.⁵⁹¹

For the treatment of native vertebral osteomyelitis or prosthetic joint infections caused by susceptible Enterococcus ^†, IDSA recommends that adults receive IV penicillin G in a dosage of 20–24 million units daily (by continuous IV infusion or in 6 divided doses) for 4–6 weeks.^{590 591} Concomitant treatment with an aminoglycoside given for 4–6 weeks also can be considered⁵⁹¹ and is recommended if infective endocarditis also in present.⁵⁹⁰

For the treatment of native vertebral osteomyelitis or prosthetic joint infections caused by susceptible C. acnes ^† (formerly P. acnes), IDSA recommends that adults receive IV penicillin G in a dosage of 20 million units daily (by continuous IV infusion or in 6 divided doses).^{590 591} The recommended duration of treatment is 6 weeks in patients with native vertebral osteomyelitis⁵⁹⁰ or 4–6 weeks in those with prosthetic joint infections.⁵⁹¹

Endocarditis

For the treatment of native valve endocarditis caused by viridans group streptococci^† or S. gallolyticus^† (formerly S. bovis) that are highly penicillin-susceptible (penicillin MIC 0.12 mcg/mL or less), AHA recommends that adults receive IV penicillin G in a dosage of 12–18 million units daily (by continuous IV infusion or in 4 or 6 divided doses) given for 4 weeks.⁴⁵⁰ Alternatively, adults with uncomplicated endocarditis caused by highly penicillin-susceptible viridans group streptococci^† or S. gallolyticus^† who are at low risk for adverse effects related to aminoglycoside therapy may receive a 2-week regimen consisting of IV penicillin G in a dosage of 12–18 million units daily (by continuous IV infusion or in 6 divided doses) in conjunction with gentamicin (3 mg/kg daily IV or IM given as a single daily dose or as 1 mg/kg every 8 hours).⁴⁵⁰ The 2-week regimen is not recommended for patients with known cardiac or extracardiac abscesses, creatinine clearance less than 20 mL/minute, impaired eighth cranial nerve function, or infection with Abiotrophia, Granulicatella, or Gemella.⁴⁵⁰

For the treatment of native valve endocarditis caused by viridans streptococci^† or S. gallolyticus^† that are relatively resistant to penicillin G (penicillin MIC greater than 0.12 mcg/mL but less than 0.5 mcg/mL), AHA recommends that adults receive IV penicillin G in a dosage of 24 million units daily (by continuous IV infusion or in 4–6 divided doses) given for 4 weeks in conjunction with gentamicin (3 mg/kg daily IV or IM given as a single daily dose or as 1 mg/kg every 8 hours during the first 2 weeks of penicillin G treatment).⁴⁵⁰

For the treatment of native valve endocarditis caused by viridans streptococci^†, A. defectiva^†, or Granulicatella^† with penicillin MIC 0.5 mcg/mL or greater, AHA states that IV penicillin G given in a dosage of 18–30 million units daily (by continuous IV infusion or in 6 divided doses) in conjunction with gentamicin (3 mg/kg daily IV or IM in 2 or 3 divided doses) is a reasonable regimen for adults.⁴⁵⁰ AHA states that consultation with an infectious disease expert is recommended to determine the duration of treatment for such infections.⁴⁵⁰

For the treatment of endocarditis involving prosthetic valves or other prosthetic material caused by viridans streptococci^† or S. gallolyticus^† that are highly penicillin-susceptible (penicillin MIC 0.12 mcg/mL or less), AHA states that adults can receive IV penicillin G in a dosage of 24 million units daily (by continuous IV infusion or in 4–6 divided doses) given for 6 weeks with or without gentamicin (3 mg/kg daily IV or IM as a single daily dose or as 1 mg/kg every 8 hours given concomitantly during the first 2 weeks of penicillin G treatment).⁴⁵⁰ When endocarditis involving prosthetic valves or other prosthetic material is caused by viridans streptococci^† or S. gallolyticus^† relatively or highly resistant to penicillin G (penicillin MIC greater than 0.12 mcg/mL), AHA states that it is reasonable to extend the duration of concomitant gentamicin to 6 weeks.⁴⁵⁰

For the treatment of enterococcal endocarditis^† (native valve or prosthetic valve or other prosthetic material) caused by Enterococcus susceptible to penicillin and gentamicin, AHA states that adults may receive IV penicillin G in a dosage of 18–30 million units daily (by continuous IV infusion or in 6 divided doses) in conjunction with gentamicin (3 mg/kg daily IV or IM in 2 or 3 divided doses; dose adjusted to achieve gentamicin peak serum concentrations of 3–4 mcg/mL and trough concentrations less than 1 mcg/mL).⁴⁵⁰ In patients with native valve enterococcal endocarditis, treatment with both drugs should be continued for 4 weeks in those who had symptoms of infection for less than 3 months prior to treatment or for 6 weeks in those who had symptoms for 3 months or longer prior to treatment.⁴⁵⁰ In patients with enterococcal endocarditis involving prosthetic heart valves or other prosthetic material, continuation of both drugs for 6 weeks is reasonable.⁴⁵⁰ If endocarditis is caused by enterococci resistant to gentamicin but susceptible to penicillin and streptomycin, AHA states that streptomycin (15 mg/kg daily IV or IM in 2 divided doses; dose adjusted to achieve streptomycin peak serum concentrations of 20–35 mcg/mL and trough concentrations less than 10 mcg/mL) can be substituted for gentamicin in recommended regimens.⁴⁵⁰ Alternative regimens (e.g., double β-lactam regimens) should be considered in patients with creatinine clearance less than 50 mL/minute.⁴⁵⁰

The manufacturers state that penicillin G potassium or sodium can be given in a dosage of 5–24 million units daily in divided doses every 4–6 hours for the treatment of endocarditis caused by susceptible staphylococci.^{8 9 11 12} However, penicillin G is not included in current AHA recommendations for the treatment of staphylococcal endocarditis in adults.⁴⁵⁰

The manufacturers state that penicillin G potassium or sodium can be given in a dosage of 12–24 million units daily in divided doses every 4–6 hours for the treatment of endocarditis caused by susceptible streptococci, including S. pyogenes, streptococci groups C, H, G, L, and M, and S. pneumoniae.^{8 9 11 12}

Meningitis and Other CNS Infections

For the treatment of meningitis caused by susceptible L. monocytogenes, IDSA and other clinicians recommend that adults receive IV penicillin G in a dosage of 24 million units daily (4 million units every 4 hours).^{418 475} IDSA recommends a treatment duration of at least 21 days and states that concomitant use of an aminoglycoside should be considered.⁴¹⁸ The manufacturers recommend that adults with meningitis caused by susceptible L. monocytogenes receive a penicillin G dosage of 15–20 million units daily given in divided doses every 4–6 hours for 2 weeks.^{8 9 11}

For the treatment of meningitis caused by susceptible N. meningitidis, IDSA recommends that adults receive IV penicillin G in a dosage of 24 million units daily (4 million units every 4 hours) for 7 days.⁴¹⁸ The manufacturers recommend that adults receive a dosage of 24 million units daily (2 million units every 2 hours).^{8 9 11 12}

If meningitis is caused by susceptible S. agalactiae^† (group B streptococci; GBS), IDSA recommends that adults receive IV penicillin G in a dosage of 24 million units daily (4 million units every 4 hours) for 14–21 days.⁴¹⁸ IDSA states that concomitant use of an aminoglycoside should be considered.⁴¹⁸

For the treatment of meningitis caused by susceptible S. pneumonia (penicillin MIC less than 0.1 mcg/mL), IDSA and other clinicians recommend that adults receive IV penicillin G in a dosage of 24 million units daily (4 million units every 4 hours) for 10–14 days.^{418 475} The manufacturers recommend that adults receive a dosage of 12–24 million units daily given in divided doses every 4–6 hours.^{9 11 12} One manufacturer recommends a dosage of 5–24 million units daily given in divided doses every 4–6 hours.⁸

For the treatment of healthcare-associated ventriculitis and meningitis caused by C. acnes^† (formerly P. acnes), IDSA recommends that adults receive IV penicillin G in a dosage of 24 million units daily given in divided doses every 4 hours.⁴¹⁶ Treatment should be continued for 10 days in those with no or minimal CSF pleocytosis, normal CSF glucose, and few clinical symptoms or systemic features or for 10–14 days in those with significant CSF pleocytosis, CSF hypoglycorrhachia, or clinical symptoms or systemic features.⁴¹⁶

Respiratory Tract Infections

If penicillin G potassium or sodium is used for the treatment of serious respiratory tract infections (e.g., empyema, pneumonia) caused by susceptible nonpenicillinase-producing staphylococci, the manufacturers recommend that adults receive a dosage of 5–24 million units daily in divided doses every 4–6 hours depending on severity.^{8 9 11 12}

If penicillin G potassium is used for the treatment of serious respiratory tract infections (e.g., empyema, pneumonia) caused by susceptible S. pyogenes, streptococci groups C, H, G, L, and M, or S. pneumoniae, the manufacturers recommend that adults receive a dosage of 12–24 million units daily in divided doses every 4–6 hours depending on severity.^{9 11 12} If penicillin G sodium is used for the treatment of these infections, the manufacturer recommends a dosage of 5–24 million units daily in divided doses every 4–6 hours depending on severity.⁸

Septicemia

If penicillin G potassium or sodium is used for the treatment of septicemia caused by susceptible nonpenicillinase-producing staphylococci, the manufacturers recommend that adults receive a dosage of 5–24 million units daily in divided doses every 4–6 hours depending on severity.^{8 9 11 12}

If penicillin G potassium is used for the treatment of septicemia caused by susceptible S. pyogenes, streptococci groups C, H, G, L, and M, or S. pneumoniae, the manufacturers recommend that adults receive a dosage of 12–24 million units daily in divided doses every 4–6 hours depending on severity.^{9 11 12} If penicillin G sodium is used for the treatment of these infections, the manufacturer recommends a dosage of 5–24 million units daily in divided doses every 4–6 hours depending on severity.⁸

Skin and Skin Structure Infections

For the treatment of necrotizing infections of the skin, fascia, and muscle caused by susceptible S. pyogenes, IDSA recommends that adults receive a regimen of IV penicillin G given in a dosage of 2–4 million units every 4–6 hours in conjunction with clindamycin (600–900 mg IV every 8 hours).⁵⁴³

Actinomycosis

For the treatment of actinomycosis caused by Actinomyces in adults, the manufacturers recommend that penicillin G potassium or sodium be given in a dosage of 1–6 million units daily in divided doses every 4–6 hours for cervicofacial disease or 10–20 million units daily in divided doses every 4–6 hours for thoracic or abdominal disease.^{8 9 11 12}

Some clinicians state that, although dosage and duration of therapy should be individualized, a reasonable treatment regimen for pulmonary actinomycosis or other severe infections caused by Actinomyces is IV penicillin G given in a dosage of 18–24 million units daily (3–4 million units every 4 hours) for at least 2–6 weeks followed by 6–12 additional months of an oral regimen (penicillin V or amoxicillin).^{10 27 28 898 901} A shorter duration of treatment may be sufficient for less extensive disease (e.g., cervicofacial region).^{10 27 28 29} Surgical procedures should be performed as indicated.^{8 9 10 11 12 27}

Anthrax

For the treatment of anthrax (inhalational, GI, meningitis) caused by penicillin-susceptible B. anthracis that occurs as the result of naturally occurring or endemic anthrax exposure, some clinicians recommend that adults receive IV penicillin G in a dosage of 8–12 million units daily given in divided doses every 4–6 hours.⁶⁷⁰ For the treatment of severe or life-threatening systemic anthrax (inhalational, GI, meningoencephalitis, sepsis) or the treatment of cutaneous anthrax with signs of systemic involvement or extensive edema caused by penicillin-susceptible B. anthracis that occurs as the result of natural or endemic anthrax exposure, some clinicians recommend that adults receive IV penicillin G in a dosage of 4 million units every 4–6 hours (16–24 million units daily).⁶⁸⁰ Concomitant use of other anti-infectives (e.g., streptomycin or other aminoglycoside, clindamycin, clarithromycin, rifampin, vancomycin) may also be indicated.^{670 680} Treatment of naturally occurring or endemic anthrax generally should be continued for at least 14 days after symptoms abate.⁶⁷⁰

If IV penicillin G is used in a multiple-drug parenteral regimen for initial treatment of systemic anthrax (inhalational, GI, meningitis, cutaneous anthrax with systemic involvement, lesions on the head or neck, or extensive edema) caused by penicillin-susceptible B. anthracis that occurs in the context of biologic warfare or bioterrorism, CDC recommends that adults (including pregnant and postpartum women) receive a dosage of 4 million units every 4 hours.^{672 673} The multiple-drug parenteral regimen should be continued for at least 2–3 weeks until the patient is clinically stable; treatment can then be switched to an oral regimen.^{672 673} Because of the possible persistence of anthrax spores in lung tissue following an aerosol exposure in the context of biologic warfare or bioterrorism, CDC and other experts state that the total duration of anti-infective treatment should be 60 days.^{668 672 673 683 686}

The manufacturers state that the minimum dosage of penicillin G potassium or sodium for the treatment of anthrax in adults is 8 million units daily given in divided doses every 6 hours and that higher dosage may be required depending on susceptibility of the organism.^{8 9 11 12}

For additional information on the treatment of anthrax and recommendations for postexposure prophylaxis following exposure to anthrax spores, see Uses: Anthrax, in Ciprofloxacin 8:12.18.

Clostridium Infections

For the treatment of myonecrosis and gas gangrene caused by C. perfringens or other clostridium, IDSA recommends that adults receive IV penicillin G in a dosage of 2–4 million units every 4–6 hours in conjunction with clindamycin (600–900 mg IV every 8 hours).⁵⁴³ The manufacturers recommend that adults receive penicillin G potassium or sodium in a dosage of 20 million units daily given in divided doses every 4–6 hours.^{8 9 11 12} Surgical debridement and/or surgery should be performed as indicated.^{8 9 11 12}

If penicillin G potassium or sodium is used as an adjunct to TIG in the management of tetanus caused by C. tetani, the manufacturers recommend that adults receive 20 million units daily given in divided doses every 4–6 hours.^{8 9 11 12} The role of anti-infectives in the adjunctive treatment of tetanus is unclear;¹⁰ metronidazole usually is preferred if an anti-infective is used.^{10 292}

If penicillin G potassium or sodium is used as an adjunct in the management of botulism caused by C. botulinum, the manufacturers recommend that adults receive 20 million units daily given in divided doses every 4–6 hours.^{8 9 11 12} Although the role of anti-infectives is unclear,^{10 61} some clinicians recommend a penicillin G dosage of 10–20 million units daily for adjunctive management of wound botulism.¹⁰ Botulism antitoxin (not commercially available in the US, but may be available from CDC) is the recommended treatment for foodborne and wound botulism and for botulism that occurs in the context of biologic warfare or bioterrorism.^{10 292 683 746 747 751 753}

Diphtheria

If penicillin G potassium or sodium is used as an adjunct to diphtheria antitoxin (not commercially available in the US, but may be available from CDC) for the treatment of diphtheria caused by C. diphtheriae, the manufacturers recommend that adults receive a dosage of 2–3 million units daily given in divided doses every 4–6 hours for 10–12 days.^{8 9 11 12} CDC recommends a 14-day regimen of IM penicillin G procaine if a penicillin is used for adjunctive treatment of diphtheria.¹⁶⁶ Patients usually are no longer contagious 48 hours after initiation of anti-infective treatment.¹⁶⁶ Eradication of C. diphtheriae should be confirmed 24 hours after completion of treatment by 2 consecutive negative cultures taken 24 hours apart.^{166 292}

Erysipelothrix Infections

If penicillin G potassium or sodium is used for the treatment of Erysipelothrix endocarditis, the manufacturers recommend that adults receive 12–20 million units daily given in divided doses every 4–6 hours for 4–6 weeks.^{8 9 11 12}

Fusobacterium Infections

If penicillin G potassium or sodium is used for the treatment of severe Fusobacterium infections of the oropharynx (including acute necrotizing ulcerative gingivitis [Vincent’s infection], trench mouth, Fusobacterium gingivitis or pharyngitis), lower respiratory tract, or genital area, the manufacturers recommend that adults receive 5–10 million units daily in divided doses every 4–6 hours.^{8 9 11 12} Penicillin G is not recommended for empiric treatment of such infections because, although the drug may be effective against Fusobacterium, other organisms may also be involved (e.g., Bacteroides fragilis, Prevotella, Porphyromonas) that usually are resistant to penicillin G.¹⁰

Leptospirosis

For the treatment of severe leptospirosis^†, IV penicillin G has been given in a dosage of 6 million units daily (1.5 million units every 6 hours) for 7 days.^{10 98 99} Anti-infective treatment should be initiated as soon as possible after symptom onset;^{10 292} however, the benefits of anti-infective therapy are uncertain,^{10 544 545 546} especially if initiated in patients with late and/or severe disease.^{544 545 546}

Listeria Infections

For the treatment of serious infections caused by susceptible L. monocytogenes (e.g., endocarditis, meningitis) in adults, the manufacturers recommend that penicillin G potassium or sodium be given in a dosage of 15–20 million units daily in divided doses every 4–6 hours.^{8 9 11 12}

For additional dosage recommendations regarding the treatment of meningitis caused by L. monocytogenes in adults, see Meningitis and Other CNS Infections under Dosage: Adult Dosage, in Dosage and Administration.

Lyme Disease

If IV penicillin G is used as an alternative to IV ceftriaxone for the treatment of early Lyme disease^† in adults with acute neurologic disease manifested as meningitis or radiculopathy, IDSA recommends a dosage of 18–24 million units daily given in divided doses every 4 hours for 10–28 days.³²⁹

If IV penicillin G is used as an alternative to IV ceftriaxone for the treatment of late Lyme disease^† in adults with recurrent Lyme arthritis and objective evidence of neurologic disease, IDSA recommends a dosage of 18–24 million units daily given in divided doses every 4 hours for 14–28 days.³²⁹

For the treatment of late neurologic Lyme disease^† affecting the central or peripheral nervous system, IDSA and others state that adults can receive IV penicillin G in a dosage of 18–24 million units daily given in divided doses every 4 hours for 14–28 days as an alternative to IV ceftriaxone.^{329 342} IDSA states that retreatment is not recommended unless relapse of neurologic disease is documented with reliable objective measures.³²⁹

Neisseria meningitidis Infections

For the treatment of septicemia and/or meningitis caused by susceptible N. meningitidis, the manufacturers recommend that adults receive penicillin G potassium or sodium in a dosage of 24 million units daily (2 million units every 2 hours).^{8 9 11 12}

For additional dosage recommendations regarding the treatment of meningitis caused by N. meningitidis in adults, see Meningitis and Other CNS Infections under Dosage: Adult Dosage, in Dosage and Administration.

Pasteurella multocida Infections

For the treatment of serious infections caused by Pasteurella multocida, including bacteremia and meningitis, the manufacturers recommend that adults receive penicillin G potassium or sodium in a dosage of 4–6 million units daily given in divided doses every 4–6 hours for 2 weeks.^{8 9 11 12}

Rat-Bite Fever

For the treatment of rat-bite fever caused by susceptible S. moniliformis (erythema arthriticum epidemicum, Haverhill fever) or S. minus (sodoku), the manufacturers recommend that adults receive penicillin G potassium or sodium in a dosage of 12–20 million units daily given in divided doses every 4–6 hours for 3–4 weeks.^{8 9 11 12}

CDC recommends that adults with rat-bite fever caused by S. moniliformis receive IV penicillin G in a dosage of 1.2 million units daily for 5–7 days; if improvement occurs, treatment can be switched to oral penicillin V or oral ampicillin (500 mg 4 times daily for 7 days).³¹ Some clinicians suggest that adults with rat-bite fever can receive IV penicillin G in a dosage of 400,000–600,000 units daily for at least 7 days, but that dosage should be increased to 1.2 million units daily if there is no response to the lower dosage within 2 days.³⁰

For the treatment of S. moniliformis endocarditis caused by a strain that is less susceptible to penicillin G (MIC greater than 0.1 mcg/mL), some clinicians recommend that adults receive IV penicillin G in a dosage of 20 million units daily for 4 weeks;^{10 30} concomitant use of an aminoglycoside (streptomycin or gentamicin) may be indicated for initial treatment.^{10 30}

Syphilis

For the treatment of neurosyphilis and otic or ocular syphilis, CDC and other clinicians recommend that adults receive IV penicillin G in a dosage of 18–24 million units daily (by continuous IV infusion or given as 3–4 million units every 4 hours) for 10–14 days.^{344 440} Some clinicians recommend that this regimen be followed by a regimen of IM penicillin G benzathine (2.4 million units once weekly for up to 3 weeks).^{344 440}

The manufacturers recommend that adults with neurosyphilis receive penicillin G potassium or sodium in a dosage of 12–24 million units daily (2–4 million units every 4 hours) for 10–14 days;^{8 9 11 12} this may be followed by a regimen of IM penicillin G benzathine (2.4 million units once weekly for up to 3 weeks).^{8 9 11 12}

HIV-infected adults with any stage of syphilis should receive the same treatment regimens recommended for those without HIV infection.^{344 440}

Whipple's Disease

For initial treatment of Whipple’s disease^† caused by Tropheryma whipplei, some clinicians recommend that IV penicillin G be given in a dosage of 10 million units daily.¹⁰ Others recommend a dosage of 12–24 million units daily (2–4 million units every 4 hours).⁷²⁴ A regimen of IV penicillin G given in a dosage of 1.2 million units daily in conjunction with parenteral streptomycin (1 g daily) also has been recommended.⁷¹⁶ The initial parenteral regimen usually is continued for 2–4 weeks and should be followed by 1–2 years of treatment with an oral regimen (e.g., co-trimoxazole).^{10 716 724}

Optimal regimens for treatment of Whipple's disease have not been identified and relapses may occur, even after adequate and long-term anti-infective treatment.^{10 717 718 719 720}

Prevention of Perinatal Group B Streptococcal Disease

When intrapartum anti-infective prophylaxis for prevention of perinatal group B streptococcal (GBS) disease^† is indicated in the mother to prevent early-onset GBS disease in her neonate (see Uses: Prevention of Perinatal Group B Streptococcal Disease), CDC and AAP recommend that an initial dose of 5 million units of penicillin G be given IV at the onset of labor or rupture of membranes followed by 2.5–3 million units IV every 4 hours until delivery.^{292 359 362}

Regardless of whether anti-infective prophylaxis was administered to the mother, appropriate diagnostic evaluations and anti-infective therapy should be initiated in the neonate if signs or symptoms of active infection develop.^{292 359 362}

Dosage in Renal and Hepatic Impairment

In patients with impaired renal function, doses and/or frequency of administration of penicillin G may need to be modified in response to the degree of impairment.^{8 9 11 12 61 348 369 384 385}

The manufacturers state that dosage of IM or IV penicillin G potassium or sodium should be adjusted in patients with severe renal impairment.^{8 9 11 12} These manufacturers and others recommend that patients with creatinine clearance less than 10 mL/minute per 1.73 m² receive a loading dose of penicillin G using the usually recommended dose followed by 50% of the usually recommended dose given every 8–10 hours.^{8 9 11 12 348} In uremic patients with creatinine clearance greater than 10 mL/minute per 1.73 m², the manufacturers and others recommend a loading dose of penicillin G using the usually recommended dose followed by 50% of the usually recommended dose given every 4–5 hours.^{8 9 11 12 348}

Alternatively, some clinicians suggest that if the usual dosing interval for penicillin G potassium or sodium in patients with normal renal function (creatinine clearance greater than 50 mL/minute) is every 6 or 8 hours, then the usual dose should be given every 8–12 hours in those with creatinine clearance of 10–50 mL/minute or every 12–18 hours in those with creatinine clearance less than 10 mL/minute.^{61 385}

Some clinicians suggest a maximum daily dosage of 4–10 million penicillin G units in adults with severe renal failure.^{369 384}

In patients with impaired hepatic function in addition to impaired renal function, further dosage reductions may be advisable.^{8 9 11 12 61 348}

Cautions for Penicillin G Potassium, Penicillin G Sodium

Adverse Effects

Adverse effects reported with penicillin G potassium and penicillin G sodium are similar to those reported with other natural penicillins.^{8 9 11 12 61}

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, have been reported with penicillins.^{8 9 10 11 12 61 611 615 713 769} Hypersensitivity reactions to penicillins may be immediate reactions (usually occurring within 20 minutes after administration) that range in severity from urticaria and pruritus to angioedema, laryngospasm, bronchospasm, hypotension, vascular collapse, and death;^{8 9 11 12} accelerated reactions (usually occurring between 20 minutes and 48 hours after administration) that may include urticaria, pruritus, fever, and, occasionally, laryngeal edema; or delayed reactions (usually occurring within 1–2 weeks after initiation of penicillin therapy) that may include serum sickness-like symptoms (i.e., fever, malaise, urticaria, myalgia, arthralgia, abdominal pain) and rash ranging from maculopapular eruptions to exfoliative dermatitis.^{8 9 11 12}

Jarisch-Herxheimer reactions may occur in patients receiving penicillin G potassium or sodium for the treatment of syphilis or other spirochetal infections (e.g., leptospirosis^†, Lyme disease^†, relapsing fever^†).^{8 9 11 12 61}

Because of the potassium and sodium content, penicillin G potassium and penicillin G sodium may cause serious and potentially fatal electrolyte disturbances, particularly if high IV dosage is used.^{8 9 11 12 61} Penicillin G potassium powders for injection contain approximately 66 mg (1.7 mEq) of potassium and approximately 7 mg (0.3 mEq) of sodium in each 1 million units of penicillin G.^{9 12} Frozen premixed penicillin G potassium injections in dextrose contain approximately 1.7 mEq of potassium and approximately 1 mEq of sodium in each 1 million units of penicillin G.¹¹ Penicillin G sodium powder for injection contains approximately 1.7 mEq of sodium in each 1 million units of penicillin G.⁸

For additional information on adverse effects reported with penicillin G, see Cautions in the Natural Penicillins General Statement 8:12.16.04.

Precautions and Contraindications

Penicillin G potassium and sodium are contraindicated in patients hypersensitive to any penicillin.^{8 9 11 12}

The manufacturer of the commercially available frozen premixed penicillin G potassium injections in dextrose states that dextrose-containing solutions may be contraindicated in patients with known allergy to corn or corn products.¹¹

Penicillin G potassium and sodium share the toxic potentials of the penicillins, including the risk of hypersensitivity reactions, and the usual precautions of penicillin therapy should be observed.^{8 9 11 12}

Prior to initiation of therapy with penicillin G potassium or sodium, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs.^{8 9 11 12} There is clinical and laboratory evidence of partial cross-allergenicity among penicillins and other β-lactam antibiotics including cephalosporins and cephamycins.^{8 9 11 12 611 615 769 770 779}

Hypersensitivity reactions to penicillins are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens.^{8 9 11 12} Penicillin G potassium or sodium should be used with caution in individuals with a history of allergies and/or asthma.^{8 9 11 12}

If a hypersensitivity reaction occurs, penicillin G should be discontinued immediately and appropriate therapy instituted as indicated (e.g., epinephrine, maintenance of an adequate airway and oxygen, corticosteroids).^{8 9 11 12} Desensitization has been used to enable a penicillin to be administered to penicillin-hypersensitive patients who have life-threatening infections for which other effective anti-infective agents are not available (e.g., endocarditis, neurosyphilis or congenital syphilis, syphilis during pregnancy).^{61 64 344 345 350 450 611 615 761 762 763 779} Such procedures are usually performed in a hospital setting and expert consultation may be indicated.³⁴⁴ Specialized references should be consulted for specific information on sensitivity testing and desensitization protocols.^{344 761 763}

During prolonged therapy with high dosage of penicillin G potassium or sodium, the patient’s organ system functions should be assessed periodically, including frequent evaluation of hepatic, renal, and hematologic systems, electrolyte balance, and cardiac and vascular status.^{8 9 11 12} If any impairment of function is suspected or known to exist, a reduction in total dosage should be considered.^{8 9 11 12} (See Dosage and Administration: Dosage in Renal and Hepatic Impairment.)

For a more complete discussion of these and other precautions associated with the use of penicillin G potassium or sodium, see Cautions: Precautions and Contraindications, in the Natural Penicillins General Statement 8:12.16.04.

Pediatric Precautions

Renal clearance of penicillin G may be delayed in neonates and premature or young infants because of incompletely developed renal function.^{8 9 10 11 12 61} Appropriate reductions in dosage and frequency of administration should be made in such patients.^{8 9 11 12}

Neonates receiving penicillin G potassium or sodium should be monitored closely for clinical and laboratory evidence of toxic or adverse effects.^{8 9 11 12}

Geriatric Precautions

Clinical studies of penicillin G potassium did not include sufficient numbers of patients 65 years of age or older to determine whether geriatric patients respond differently than younger patients.^{9 11 12} Other clinical experience has not identified differences in responses between geriatric and younger patients.^{9 11 12}

Penicillin G is substantially eliminated by the kidneys and the risk of adverse effects may be greater in those with impaired renal function.^{9 11 12} Because geriatric patients are more likely to have reduced renal function, dosage should be selected with caution, usually starting at the low end of the dosage range, and renal function monitoring may be useful.^{9 11 12}

The potassium and/or sodium content of penicillin G potassium or sodium preparations and the potential for electrolyte imbalance should be considered.^{8 9 11 12} Geriatric patients may respond to salt loading with a blunted natriuresis that may be clinically important in those with certain conditions (e.g., congestive heart failure).^{9 11 12}

Pregnancy and Lactation

Pregnancy

Reproduction studies evaluating penicillin G in mice, rats, and rabbits have not revealed evidence of impaired fertility or harm to the fetus.^{8 9 11 12 25} Although experience with use of penicillins during pregnancy has not shown any evidence of adverse effects on the fetus, there are no adequate or controlled studies using penicillin G in pregnant women.^{8 9 11 12}

Some clinicians state that penicillin G is considered low risk²⁵ and safe for use during pregnancy.⁶¹ The drug is included in the US Centers for Disease Control and Prevention (CDC) recommendations for the treatment of syphilis during pregnancy.³⁴⁴

The manufacturers state that penicillin G potassium or sodium should be used during pregnancy only when clearly needed.^{8 9 11 12}

Lactation

Penicillin G is distributed into milk.^{8 9 11 12 61 64 355 364 374} Some clinicians state that penicillin G is usually considered compatible with breast-feeding.²⁵ The manufacturers and others state that penicillin G potassium or sodium should be used with caution in nursing women.^{8 9 11 12 24}

Spectrum

Based on its spectrum of activity, penicillin G is classified as a natural penicillin.^{10 61 64} For information on the classification of penicillins based on spectra of activity, see the Preface to the General Statements on Penicillins 8:12.16.

For specific information on the spectrum of activity of penicillin G and resistance to the drug, see the sections on Spectrumand on Resistance in the Natural Penicillins General Statement 8:12.16.04.

Penicillin G Potassium, Penicillin G Sodium Pharmacokinetics

For additional information on the absorption, distribution, and elimination of penicillin G, see Pharmacokinetics in the Natural Penicillins General Statement 8:12.16.04.

Absorption

Penicillin G potassium and penicillin G sodium are rapidly absorbed followed IM administration,^{9 61 64 70 72} and serum concentrations of penicillin G generally are the same following IM administration of equivalent doses of either salt.⁶⁴ Following IM administration in adults of a single dose of 600,000 or 1 million units of penicillin G (as either salt), peak serum concentrations of penicillin G generally are attained within 15–30 minutes^{61 64 70 72} and average 6–8 or 20 units/mL, respectively.⁶¹ In one study in neonates 6 days of age or younger who received IM penicillin G in a dosage of 25,000 units/kg every 12 hours as the potassium salt, serum penicillin G concentrations ranged from 12.5–36, 7.8–35.1, 4.4–35.1, 0.7–21.9, and 0.3–9.2 mcg/mL at 30 minutes, 1 hour, 2 hours, 4 hours, and 12 hours, respectively, after a dose.³⁶⁸

Following IV infusion of penicillin G, peak serum concentrations are attained immediately after completion of the infusion.^{8 9 11 12} In a study in 10 patients who received 5 million units of penicillin G given IV over 3–5 minutes, mean serum concentrations were 400, 273, and 3 mcg/mL at 5–6 minutes, 10 minutes, and 4 hours after administration, respectively.^{8 9 11 12} In a study in 5 healthy adults who received 1 million units of penicillin G given IV over 4 minutes or 60 minutes, mean serum concentrations 8 minutes after administration were 45 or 14.4 mcg/mL, respectively.^{8 9 11 12}

Following intermittent IV infusion of 2 million units of penicillin G every 2 hours or 3 million units of penicillin G every 3 hours (as either salt), serum penicillin G concentrations reportedly average 20 mcg/mL.⁶¹

Penicillin G potassium or sodium is absorbed from the peritoneal cavity following local instillation^{61 64} and also is absorbed from pleural surfaces, pericardium, and joint cavities.⁶⁴

Distribution

Penicillin G is widely distributed throughout the body in varying amounts following parenteral administration.^{8 9 11 12 61 64 70 81 320} Penicillin G is distributed into the lungs,^{8 9 11 12} liver,^{8 9 11 12} kidneys,^{8 9 11 12} muscle,^{8 9 11 12} bone,^{8 9 11 12} and pleural,^{8 9 11 12} pericardial,^{9 61} peritoneal,^{8 9 11 12} ascitic,^{9 61} synovial,^{8 9 11 12 61} and interstitial fluids.⁹ The volume of distribution of penicillin G is reportedly 0.53–0.67 L/kg in adults with normal renal function.³⁴⁰

Minimal concentrations of penicillin G generally are attained in CSF following administration of penicillin G potassium or sodium in patients with uninflamed meninges;^{8 9 11 12 61 70 320 349 360} however, higher penicillin G concentrations are attained in CSF when the meninges are inflamed.^{8 9 11 12 61 320 349} Following IV administration of penicillin G sodium, concentrations of penicillin G in CSF reportedly range from 0–10% of concurrent serum concentrations of the drug in patients with normal meninges.³⁶⁰ In 2 adults with syphilis who received a daily IV dosage of 5 or 10 million units of penicillin G (as the potassium salt) for at least 10 days, penicillin G concentrations in CSF immediately following completion of therapy were 0.3 or 2.4 mcg/mL, respectively.³⁶⁰ In one study in children 2 weeks to 11 years of age with meningitis who received penicillin G potassium in a dosage of 250,000 units/kg daily given in 6 divided doses by IV infusion over 15 minutes, penicillin G concentrations in CSF specimens obtained between doses averaged 0.8, 0.7, and 0.3 mcg/mL on the first, fifth, and tenth days of therapy, respectively.³⁴⁹

Penicillin G is approximately 45–68% bound to serum proteins.^{61 63 64 67 70 81 320 336 337 340 361}

Penicillin G crosses the placenta,^{8 9 11 12 40 61 70 320 362} although cord blood concentrations of the drug may be less than maternal serum concentrations.³⁶²

Penicillin G is distributed into milk.^{8 9 11 12 61 64 355 364 374}

Elimination

The serum half-life of penicillin G in adults with normal renal function is 0.4–0.9 hours.^{8 9 11 12 61 64 67 81 320 338 340 348 361}

Approximately 16–30% of an IM dose of penicillin G sodium is metabolized to penicilloic acid which is microbiologically inactive.³⁶⁶ Small amounts of 6-aminopenicillanic acid (6-APA) have also been found in the urine of patients receiving penicillin G.^{64 70} In addition, the drug appears to be hydroxylated to a small extent to one or more microbiologically active metabolites which also are excreted in urine.⁶¹

Penicillin G and its metabolites are excreted in urine mainly by tubular secretion.^{8 9 11 12 61 64 70 81 320 348 369} Small amounts of the drug are also excreted in bile.^{8 9 11 12 61 64 70 81} Following IM or IV administration of a single dose of penicillin G in adults with normal renal function, 58–85% of the dose is excreted in urine as unchanged drug and active metabolites within 6 hours.^{8 9 11 12 61}

Serum concentrations of penicillin G may be higher and the serum half-life prolonged in patients with impaired renal function.^{8 9 11 12 64 70 81 320 348 369} The serum half-life of the drug is reportedly 1–2 hours in azotemic patients with serum creatinine concentrations less than 3 mg/dL^{8 9 11 12 348} and ranges from 6–20 hours in anuric patients.^{8 9 12 64 81 320 348 369} In anuric patients with hepatic impairment, the serum half-life of penicillin G may be 2–3 times more prolonged than in anuric patients with normal hepatic function.^{70 320 348}

Renal clearance of penicillin G is delayed in neonates and premature or young infants.^{8 9 10 11 12 61} The serum half-life of penicillin G varies inversely with age^{8 9 11 12 61} and appears to be independent of birthweight.³⁶⁸ The serum half-life of the drug is reportedly 3.2–3.4 hours in neonates 6 days of age or younger, 1.2–2.2 hours in neonates 7–13 days of age, and 0.9–1.9 hours in neonates 14 days of age or older.^{8 9 11 12 61 368}

Renal clearance of penicillin G may be delayed in geriatric patients because of diminished tubular secretion ability.⁶¹

Renal clearance of penicillin G may be increased in pregnant women^{40 61} during the second and third trimesters.⁴⁰

Penicillin G is removed by hemodialysis^{8 9 10 11 12 61 63 320 369} and may be removed to a lesser extent by peritoneal dialysis.¹⁰

Chemistry and Stability

Chemistry

Penicillin G is a natural penicillin produced by fermentation of Penicillium chrysogenum in a medium containing phenylacetic acid.^{61 64 70 72} Penicillin G potassium and penicillin G sodium are frequently referred to as aqueous, crystalline forms of penicillin G.^{10 61 64 63 72}

Penicillin G potassium occurs as colorless or white crystals or a white, crystalline powder that is odorless or practically odorless and moderately hygroscopic.^{9 12} Penicillin G potassium is very soluble in water.^{9 12} Penicillin G potassium is commercially available as a sterile powder for injection in vials containing the equivalent of 1, 5, or 20 million units of penicillin G.^{9 12} Each 1 million units of penicillin G (as penicillin G potassium) contains approximately 66 mg (1.7 mEq) of potassium and approximately 7 mg (0.3 mEq) of sodium.^{9 12} The sterile powders are buffered with sodium citrate^{9 12} and/or citric acid.⁹ Following reconstitution according to the manufacturer's directions, penicillin G potassium solutions have a pH of 6–8.5.^{9 12} Penicillin G potassium also is commercially available as a frozen premixed solution in dextrose.¹¹

Penicillin G sodium occurs as a white to almost white, crystalline powder that is almost odorless.⁸ Penicillin G sodium is commercially available as a sterile powder for injection in vials containing the equivalent of 5 million units of penicillin G.⁸ Each 1 million units of penicillin G (as penicillin G sodium) contains approximately 1.7 mEq of sodium.⁸ Following reconstitution according to the manufacturer's directions, penicillin G sodium solutions are colorless and have a pH of 5–7.5.⁸

Commercially available frozen premixed penicillin G potassium injections in dextrose are sterile, iso-osmotic, nonpyrogenic solutions of the drug provided in single-dose plastic containers (Galaxy containers) fabricated from specially formulated multilayered plastic (PL 2040).¹¹ The frozen injections containing 1, 2, or 3 million units of penicillin G contain approximately 2, 1.2, or 350 mg of dextrose hydrous, respectively, to adjust osmolality and also contain sodium citrate as a buffer.¹¹ Hydrochloric acid and/or sodium hydroxide may have been added to adjust pH to 5.5–8.¹¹ The frozen premixed penicillin G potassium injections in dextrose contain approximately 1.7 mEq of potassium and approximately 1 mEq of sodium in each 1 million units of penicillin G.¹¹

Potency of penicillin G potassium and penicillin G sodium generally is expressed in terms of penicillin G units,^{8 9 11 12} but also has been expressed as mg of penicillin G.⁶¹ Each mg of penicillin G potassium has a potency of 1440–1680 USP penicillin G units;¹ each mg of penicillin G potassium powder for injection buffered with sodium citrate has a potency of 1355–1595 USP penicillin G units.¹ Each mg of penicillin G sodium has a potency of 1500–1750 USP penicillin G units.¹

Stability

Commercially available penicillin G potassium sterile powder for injection should be stored at less than 30°C.^{9 12} Following reconstitution, penicillin G potassium solutions should be stored at 2–8°C and are stable for 7 days at this temperature.^{9 12}

Commercially available penicillin G sodium powder for injection should be stored at 20–25°C.⁸ Following reconstitution, penicillin G sodium solutions should be stored at 2–8°C and are stable for 3 days at this temperature.⁸

The commercially available frozen premixed penicillin G potassium injections in dextrose should be stored at -20°C or lower.¹¹ The frozen premixed injections should be thawed at room temperature (25°C) or under refrigeration (5°C) and, once thawed, should not be refrozen.¹¹ Thawed solutions of the commercially available frozen injections are stable for 24 hours at room temperature (25°C) or 14 days when refrigerated at 5°C.¹¹ The commercially available frozen injections of the drug are provided in a plastic container fabricated from specially formulated multilayered plastic PL 2040 (Galaxy containers).¹¹ Solutions in contact with the polyethylene layer can leach out some of its chemical components in very small amounts within the expiration period of the injection; however, safety of the plastic has been confirmed in tests in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies.¹¹

Penicillin G is unstable in solution at room temperature⁶¹ and is rapidly inactivated in carbohydrate solutions at alkaline pH.^{8 12} Small amounts of polymer conjugation products reportedly form in solutions of penicillin G during in vitro storage, especially when high concentrations of the drug are stored at room temperature.^{95 96 577} Penicillin degradation products may be more potent antigens than penicillin G and may play a role in hypersensitivity reactions to the drug.^{61 95 96} Therefore, reconstituted solutions of penicillin G potassium or penicillin G sodium should be refrigerated as directed by the manufacturer^{8 9 12} or used shortly following reconstitution.^{61 95 96}

Penicillin G is potentially physically and/or chemically incompatible with some drugs, including aminoglycosides and tetracyclines, but the compatibility depends on several factors (e.g., concentrations of the drugs, specific diluents used, resulting pH, temperature).^{61 300} Specialized references should be consulted for specific compatibility information.³⁰⁰

Additional Information

For further information on chemistry and stability, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, laboratory test interferences, and dosage and administration of penicillin G potassium or sodium, see the Natural Penicillins General Statement 8:12.16.04.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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