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Penicillin G

Class: Natural Penicillins
VA Class: AM110
Chemical Name: [2S-(2α,5α,6β)]-3,3-Dimethyl-7-oxo-6-[(phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid compd. withN,N′-bis(phenylmethyl)-1,2-ethanediamine (2:1) tetrahydrate
Molecular Formula: (C16H18N2O4S)2•C16H20N2•4H2OC16H18N2O4S•C13H2O•N2O2•H2OC16H18N2O4S•KC16H18N2O4S•Na
CAS Number: 41372-02-5
Brands: Permapen, Pfizerpen

Medically reviewed by Drugs.com on Sep 21, 2021. Written by ASHP.

Warning

  • Penicillin G benzathine (Bicillin L-A, Permapen) penicillin G procaine, and fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R, Bicillin C-R 900/300), are administered by deep IM injection only and should not be injected IV or admixed with other IV solutions.

  • Inadvertent IV administration of penicillin G benzathine has been associated with cardiorespiratory arrest and death.

  • Prior to administration of penicillin G benzathine, penicillin G procaine, or fixed combination of penicillin G benzathine and penicillin G procaine, carefully read the warnings, adverse reactions, and dosage and administration sections of the prescribing information.

Introduction

Antibacterial; β-lactam antibiotic; natural penicillin. Available as penicillin G benzathine, penicillin G procaine, penicillin G potassium, and penicillin G sodium.

Uses for Penicillin G

Bone and Joint Infections

Treatment of native vertebral osteomyelitis or prosthetic joint infections caused by susceptible β-hemolytic streptococci (penicillin G potassium or sodium).

Treatment of native vertebral osteomyelitis or prosthetic joint infections caused by susceptible Enterococcus (penicillin G potassium or sodium); used with or without an aminoglycoside.

Treatment of native vertebral osteomyelitis or prosthetic joint infections caused by susceptible Cutibacterium acnes (formerly Propionibacterium acnes) (penicillin G potassium or sodium).

Consult current IDSA clinical practice guidelines available at [Web] for additional information on management of bone and joint infections.

Endocarditis

Treatment of native valve endocarditis or endocarditis involving prosthetic valve or other prosthetic material caused by certain susceptible gram-positive bacteria (penicillin G potassium or sodium).

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. AHA states IV penicillin G is a reasonable regimen for treatment of endocarditis caused by susceptible S. pyogenes, S. agalactiae (group B streptococci; GBS), groups C and G streptococci, and highly penicillin-susceptible S. pneumoniae (penicillin MIC ≤0.1 mcg/mL); consider concomitant use of gentamicin for endocarditis caused by streptococci groups B, C, or G.

Treatment of endocarditis caused by viridans group streptococci or nonenterococcal group D streptococci, including S. gallolyticus (formerly S. bovis). AHA states IV penicillin G (with or without gentamicin) is a regimen of choice for such infections caused by highly penicillin-susceptible strains (penicillin MIC ≤0.12 mcg/mL); use IV penicillin G in conjunction with gentamicin if strains are relatively resistant to penicillin G (penicillin MIC >0.12 mcg/mL but <0.5 mcg/mL).

Treatment of endocarditis caused by viridans group streptococci, Abiotrophia defectiva, or Granulicatella with penicillin MIC ≥0.5 mcg/mL. AHA states IV penicillin G in conjunction with gentamicin is a reasonable regimen for such infections.

Treatment of endocarditis caused by Enterococcus faecalis, E. faecium, or other enterococci susceptible to penicillin G and gentamicin. AHA states IV penicillin G in conjunction with gentamicin is a regimen of choice for such infections; streptomycin can be substituted for gentamicin if enterococci are susceptible to penicillin and streptomycin, but resistant to gentamicin.

Has been used for treatment of endocarditis caused by nonpenicillinase-producing staphylococci. AHA states that IV penicillin G may be considered for treatment of endocarditis caused by penicillin-susceptible S. aureus or coagulase-negative staphylococci in pediatric patients; penicillin G not included in current AHA recommendations for treatment of staphylococcal endocarditis in adults.

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

Consult current guidelines from AHA for additional information on management of endocarditis.

Meningitis and Other CNS Infections

Treatment of meningitis caused by certain susceptible gram-positive or gram-negative bacteria (penicillin G potassium or sodium).

Treatment of meningitis caused by susceptible Listeria monocytogenes; used alone or in conjunction with an aminoglycoside.

Treatment of meningitis caused by susceptible Neisseria meningitidis. A drug of choice for penicillin-susceptible strains.

Treatment of meningitis caused by susceptible S. agalactiae (group B streptococci; GBS). Consider concomitant use of an aminoglycoside.

Treatment of meningitis caused by susceptible S. pyogenes or other β-hemolytic streptococci, including groups C, H, G, L and M.

Treatment of meningitis or ventriculitis caused by susceptible S. pneumoniae (penicillin MIC <0.1 mcg/mL). Consider that S. pneumoniae with intermediate resistance or complete resistance to penicillin G reported with increasing frequency.

Treatment of healthcare-associated ventriculitis and meningitis caused by susceptible Cutibacterium acnes (formerly Propionibacterium acnes) (penicillin G potassium or sodium).

Has been used for treatment of meningitis caused by susceptible nonpenicillinase-producing Staphylococcus (penicillin G potassium or sodium).

Pharyngitis and Tonsillitis

Treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci; GAS) and prevention of initial attacks (primary prevention) of rheumatic fever (penicillin G benzathine).

AAP, IDSA, and AHA recommend a penicillin regimen (i.e., 10 days of oral penicillin V or oral amoxicillin or single dose of IM penicillin G benzathine) as treatment of choice for S. pyogenes pharyngitis and tonsillitis; other anti-infectives (narrow-spectrum oral cephalosporins, oral macrolides, oral clindamycin) recommended as alternatives in penicillin-allergic patients.

If signs and symptoms of pharyngitis recur shortly after initial treatment and presence of S. pyogenes documented, retreatment with original or alternative anti-infective recommended. Alternative regimens recommended for retreatment include a narrow-spectrum oral cephalosporin, oral clindamycin, oral fixed combination of amoxicillin and clavulanate, oral macrolide, or IM penicillin G benzathine.

Consider that multiple, recurrent episodes of symptomatic pharyngitis within several months to years may indicate the patient is a long-term pharyngeal carrier of S. pyogenes experiencing repeated episodes of nonstreptococcal (e.g., viral) pharyngitis.

Treatment not usually recommended for asymptomatic chronic pharyngeal carriers of S. pyogenes. Eradication of the carrier state may be desirable in certain situations (e.g., community outbreak of acute rheumatic fever, acute poststreptococcal glomerulonephritis, or invasive S. pyogenes infections; outbreak of S. pyogenes pharyngitis in a closed or partially closed community; multiple episodes of documented symptomatic S. pyogenes pharyngitis occurring within a family for many weeks despite appropriate treatment; personal or family history of acute rheumatic fever). In such situations, recommended regimens include oral clindamycin, oral fixed combination of amoxicillin and clavulanate, or oral rifampin used in conjunction with either IM penicillin G benzathine or oral penicillin V.

Respiratory Tract Infections

Treatment of mild to moderate upper respiratory tract infections caused by susceptible S. pyogenes (group A β-hemolytic streptococci; GAS) (penicillin G benzathine).

Treatment of moderately severe to severe upper respiratory tract infections caused by susceptible S. pyogenes (penicillin G procaine, fixed combination of penicillin G benzathine and penicillin G procaine).

Treatment of serious respiratory tract infections (e.g., pneumonia, empyema) caused by susceptible S. pyogenes or other β-hemolytic streptococci (including groups C, H, G, L, and M) (penicillin G potassium or sodium).

Treatment of moderately severe respiratory tract infections (pneumonia) caused by susceptible S. pneumoniae (penicillin G procaine, fixed combination of penicillin G benzathine and penicillin G procaine).

Treatment of respiratory tract infections, including community-acquired pneumonia (CAP), caused by susceptible streptococci, including S. pneumoniae (penicillin G potassium or sodium). Consider that S. pneumoniae with resistance to penicillin G reported with increasing frequency. A drug of choice if CAP caused by penicillin-susceptible S. pneumoniae (MIC ≤2 mcg/mL). IDSA states parenteral penicillin G may be used for empiric treatment of CAP in infants or school-aged children fully immunized against invasive pneumococcal and Haemophilus influenzae type b (Hib) disease if local epidemiologic data for S. pneumoniae do not show substantial high-level penicillin resistance; other anti-infectives recommended for empiric treatment of CAP in adults and other infants and children.

Treatment of serious respiratory tract infections (e.g., pneumonia, empyema) caused by susceptible nonpenicillinase-producing staphylococci (penicillin G potassium or sodium).

Consult current IDSA clinical practice guidelines available at [Web] for additional information on management of respiratory tract infections, including CAP.

Septicemia

Treatment of septicemia caused by susceptible S. pyogenes, other β-hemolytic streptococci (including groups C, H, G, L, and M), S. pneumoniae, or nonpenicillinase-producing staphylococci (penicillin G potassium or sodium).

Skin and Skin Structure Infections

Treatment of moderately severe to severe skin and skin structure infections caused by susceptible S. pyogenes (penicillin G procaine, fixed combination of penicillin G benzathine and penicillin G procaine).

Treatment of necrotizing infections of the skin, fascia, and muscle caused by susceptible S. pyogenes (penicillin G potassium or sodium). IDSA recommends IV penicillin G in conjunction with IV clindamycin for treatment of documented S. pyogenes necrotizing fasciitis.

Treatment of moderately severe to severe skin and skin structure infections caused by susceptible staphylococci (penicillin G procaine). Because of high incidence of resistant strains, perform in vitro culture and susceptibility testing when treating suspected staphylococcal infections.

Treatment of myonecrosis and gas gangrene caused by Clostridium perfringens or other clostridium (penicillin G potassium or sodium). (See Clostridium Infections under Uses.)

Consult current IDSA clinical practice guidelines available at [Web] for additional information on management of skin and skin structure infections.

Actinomycosis

Treatment of actinomycosis (penicillin G potassium or sodium).

IV penicillin G is a drug of choice for all forms of actinomycosis, including respiratory (pulmonary, bronchial, laryngeal), abdominal, genitourinary, CNS, and cervicofacial infections.

Anthrax

Inhalational anthrax (postexposure) to reduce the incidence or progression of disease following suspected or confirmed exposure to aerosolized Bacillus anthracis spores (penicillin G procaine). Ciprofloxacin or doxycycline are initial drugs of choice for prophylaxis following suspected or confirmed exposure to aerosolized anthrax spores, including exposures that occur in the context of biologic warfare or bioterrorism. If penicillin susceptibility confirmed, consideration can be given to changing prophylaxis to a penicillin (oral amoxicillin or penicillin V) in infants and children, pregnant or lactating women, or when drugs of choice not tolerated or not available; oral amoxicillin may be preferred, especially in infants and children.

Treatment of mild, uncomplicated cutaneous anthrax caused by susceptible B. anthracis that occurs as the result of naturally occurring or endemic exposure to anthrax (penicillin G procaine). If cutaneous anthrax occurs in the context of biologic warfare or bioterrorism, initial drugs of choice are ciprofloxacin and doxycycline. If penicillin susceptibility confirmed, consideration can be given to changing to a penicillin (oral amoxicillin or penicillin V) in infants and children, pregnant or lactating women, or when drugs of choice not tolerated or not available; oral amoxicillin may be preferred, especially in infants and children.

Treatment of anthrax (inhalational, GI, or meningitis) caused by penicillin-susceptible B. anthracis that occurs as the result of natural or endemic exposures to anthrax (penicillin G potassium or sodium).

Alternative for use in multiple-drug parenteral regimens 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 (penicillin G potassium or sodium).

Clostridium Infections

Treatment of myonecrosis and gas gangrene caused by Clostridium perfringens or other clostridium (penicillin G potassium or sodium). IV penicillin G is a drug of choice; some experts recommend concomitant use of IV clindamycin. Anti-infectives are an adjunct to debridement and excision of the infected area.

Adjunct to tetanus immune globulin (TIG) in management of tetanus caused by C. tetani (penicillin G potassium or sodium). Anti-infectives cannot neutralize toxin already formed and cannot eradicate C. tetani spores, which may revert to toxin-producing vegetative forms. Role of anti-infectives in treatment of tetanus unclear; if anti-infective used for adjunctive treatment, metronidazole usually preferred.

Adjunct in management of botulism (penicillin G potassium or sodium). Botulism immune globulin IV (BIG-IV) is standard of care for infant botulism and anti-infectives not indicated unless clearly necessary for a concurrent infection. Botulism antitoxin (not commercially available in US, but may be available from CDC) is recommended treatment for other forms of botulism (e.g., foodborne and wound botulism) and for botulism that occurs in the context of biologic warfare or bioterrorism. Although role of anti-infectives in management of wound botulism unclear, penicillin G potassium or sodium has been used as adjunct to antitoxin and surgical debridement in wound botulism, including when antitoxin could not be administered.

Diphtheria

Adjunct to diphtheria antitoxin (not commercially available in US, but may be available from CDC) for treatment of diphtheria caused by Corynebacterium diphtheriae (penicillin G procaine, penicillin G potassium or sodium). Anti-infectives are not a substitute for diphtheria antitoxin. If a penicillin used for adjunctive treatment of diphtheria, CDC recommends IM penicillin G procaine. Patients usually no longer contagious 48 hours after initiation of anti-infective treatment. Confirm eradication of C. diphtheriae 24 hours after completion of treatment by 2 consecutive negative cultures taken 24 hours apart. Because diphtheria infection may not confer immunity, initiate or complete immunization with a preparation containing diphtheria toxoid adsorbed during convalescence.

Prevention of diphtheria in asymptomatic, household or close contacts of patients with respiratory or cutaneous diphtheria (penicillin G benzathine). If a penicillin used for prevention of diphtheria in contacts, CDC and AAP recommend IM penicillin G benzathine. Prompt initiation of prophylaxis indicated in all household or other close contacts of individuals with suspected or proven diphtheria, regardless of vaccination status of exposed individual. An immediate dose of age-appropriate preparation containing diphtheria toxoid adsorbed also indicated in contacts if inadequately immunized against diphtheria, immunization status unknown, or last booster dose received ≥5 years previously.

Elimination of diphtheria carrier state in identified carriers of toxigenic C. diphtheriae (penicillin G benzathine, penicillin G procaine). If a penicillin used to eliminate diphtheria carrier state, CDC and AAP recommend IM penicillin G benzathine. Obtain follow-up cultures ≥2 weeks after treatment of diphtheria carriers; if cultures positive, give a 10-day course of oral erythromycin and obtain additional follow-up cultures.

Erysipelothrix rhusiopathiae Infections

Treatment of erysipeloid caused by Erysipelothrix rhusiopathiae (penicillin G procaine).

Treatment of Erysipelothrix endocarditis (penicillin G potassium or sodium).

Fusobacterium Infections

Treatment of moderately severe infections of the oropharynx caused by Fusobacterium, including Vincent’s gingivitis and pharyngitis (penicillin G procaine).

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 (penicillin G potassium or sodium). Not recommended for empiric treatment of such infections; although penicillin G may be effective against Fusobacterium, other organisms may also be involved (e.g., Bacteroides fragilis, Prevotella, Porphyromonas) that usually are resistant to the drug.

Leptospirosis

Treatment of severe leptospirosis (penicillin G potassium or sodium).

Leptospiral infections often result in asymptomatic or subclinical illness that is self-limited; however, severe, life-threatening infections can occur. Initiate anti-infective therapy as soon as possible after symptom onset; benefits of anti-infectives uncertain, especially if initiated in patients with late and/or severe disease.

Listeria Infections

Treatment of serious infections caused by susceptible L. monocytogenes (e.g., infections during pregnancy, granulomatosis infantiseptica, septicemia, meningitis, endocarditis, pneumonia) (penicillin G potassium or sodium). Ampicillin used alone or in conjunction with gentamicin or streptomycin generally considered treatment of choice for invasive infections caused by L. monocytogenes.

For information on treatment of meningitis caused by L. monocytogenes, see Meningitis and Other CNS Infections under Uses.

Lyme Disease

Treatment of early Lyme disease in patients with acute neurologic disease manifested as meningitis or radiculopathy (penicillin G potassium or sodium). Alternative to IV ceftriaxone.

Treatment of late Lyme disease in patients with recurrent Lyme arthritis and objective evidence of neurologic disease (penicillin G potassium or sodium). Alternative to IV ceftriaxone.

Treatment of late neurologic Lyme disease affecting central or peripheral nervous system (penicillin G potassium or sodium). Alternative to IV ceftriaxone.

Neisseria Infections

Treatment of serious infections caused by susceptible N. meningitidis (e.g., meningococcal sepsis, meningitis, pneumonia, arthritis) (penicillin G potassium or sodium). (See Meningitis and Other CNS Infections under Uses.) A drug of choice for most invasive meningococcal infections.

May not eliminate nasopharyngeal carriage of N. meningitidis. Chemoprophylaxis with ceftriaxone, ciprofloxacin, or rifampin usually recommended to eradicate nasopharyngeal carriage of N. meningitidis after treatment of invasive disease and prior to hospital discharge.

Do not use for treatment of gonorrhea. Was used in the past for infections caused by penicillin-susceptible N. gonorrhoeae (penicillin G potassium or sodium). Penicillins no longer recommended by CDC or others for gonococcal infections (high incidence of penicillinase-producing strains of N. gonorrhoeae).

Pasteurella Infections

Treatment of serious infections caused by Pasteurella multocida, including bacteremia and meningitis (penicillin G potassium or sodium). A drug of choice for local infections, septicemia, osteomyelitis, endocarditis, or other serious infections.

Rat-bite Fever

Treatment of rat-bite fever caused by susceptible Streptobacillus moniliformis (erythema arthriticum epidemicum, Haverhill fever) or Spirillum minus (sodoku) (penicillin G procaine, penicillin G potassium or sodium).

IV penicillin G usually drug of choice. Concomitant aminoglycoside (streptomycin or gentamicin) may be indicated for initial treatment of S. moniliformis endocarditis.

Syphilis

Treatment of syphilis (penicillin G benzathine, penicillin G procaine, penicillin G potassium or sodium).

CDC and other experts state IM penicillin G benzathine is drug of choice for 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.

IM penicillin G benzathine also drug of choice for 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.

For treatment of neurosyphilis and otic or ocular syphilis, CDC and other experts state IV penicillin G potassium or sodium is drug of choice; IM penicillin G procaine (with oral probenecid) is an alternative if compliance can be ensured.

For 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). IV penicillin G potassium or sodium, IM penicillin G procaine, or IM penicillin G benzathine recommended 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).

CDC states that syphilis diagnosed in infants and children ≥1 month of age should be managed by a pediatric infectious disease specialist.

HIV-infected neonates with congenital syphilis and HIV-infected children, adolescents, and adults with neurosyphilis or any stage of syphilis: Use same treatment regimens recommended for those without HIV infection. 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. In addition, careful neurologic examinations indicated in all coinfected patients.

Infant or child with congenital syphilis and known or suspected penicillin hypersensitivity: No proven alternatives to penicillin G; CDC recommends desensitization and treatment with appropriate penicillin G preparation.

Nonpregnant patient with primary, secondary, or latent syphilis and penicillin hypersensitivity: Can consider certain alternatives to penicillin G (e.g., doxycycline, tetracycline); if compliance with alternatives or follow-up cannot be ensured, CDC recommends desensitization and treatment with IM penicillin G benzathine.

Nonpregnant patient with neurosyphilis and penicillin hypersensitivity: No proven alternatives to penicillin G, but can consider ceftriaxone in certain circumstances; if compliance with alternatives or follow-up cannot be ensured, CDC recommends desensitization and treatment with appropriate penicillin G preparation.

Pregnant woman with any stage of syphilis and penicillin hypersensitivity: No proven alternatives to penicillin G; CDC recommends desensitization and treatment with appropriate penicillin G preparation.

Do not use a fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R, Bicillin C-R 900/300) for treatment of any form of syphilis; inadvertent use of a fixed combination may not provide the sustained serum concentrations of penicillin G required for syphilis treatment and could increase risk of treatment failure and neurosyphilis, especially in HIV-infected patients.

Consult current CDC sexually transmitted diseases treatment guidelines available at [Web] for additional information regarding management of syphilis.

Whipple's Disease

Treatment of Whipple’s disease caused by Tropheryma whipplei.

Optimal regimens for treatment of Whipple’s disease not identified; relapses may occur, even after adequate and long-term anti-infective treatment. Some clinicians recommend an initial parenteral regimen (e.g., ceftriaxone, penicillin G with or without streptomycin) followed by a long-term regimen of oral co-trimoxazole.

Yaws, Pinta, and Bejel

Treatment of yaws (T. pertenue), pinta (T. carateum), and bejel (T. pallidum var. endemic syphilis) (penicillin G benzathine, penicillin G procaine). Drugs of choice.

Do not use fixed combinations of penicillin G benzathine and penicillin G procaine (Bicillin C-R, Bicillin C-R 900/300) for treatment of yaws, pinta, and bejel.

Prevention of Perinatal Group B Streptococcal Disease

Prevention of early-onset neonatal group B streptococcal (GBS) disease (penicillin G potassium or sodium).

Intrapartum anti-infective prophylaxis to prevent early-onset neonatal GBS disease is indicated in women identified as GBS carriers during routine prenatal GBS screening performed at 35–37 weeks of gestation during the current pregnancy, in women with GBS bacteriuria identified at any time during current pregnancy, and in those with a previous infant diagnosed with invasive GBS disease. In those with unknown GBS status at onset of labor, intrapartum anti-infective prophylaxis indicated in those with delivery at <37 weeks of gestation, amniotic membrane rupture for ≥18 hours, or intrapartum temperature of ≥38°C.

When intrapartum anti-infective prophylaxis indicated in the mother for prevention of GBS in the neonate, initiate at onset of labor or rupture of membranes. If cesarean delivery performed before onset of labor in a woman with intact amniotic membranes, anti-infective prophylaxis not usually indicated, regardless of GBS colonization status of the woman or gestational age.

IV penicillin G is drug of choice and IV ampicillin is preferred alternative. Penicillin G has a narrower spectrum of activity and is less likely to select for antibiotic-resistant organisms.

Regardless of whether the mother received anti-infective prophylaxis, initiate appropriate diagnostic evaluations and anti-infective therapy in the neonate if signs or symptoms of active infection develop.

Consult most recent CDC and AAP guidelines for additional information on prevention of perinatal GBS disease.

Prevention of Rheumatic Fever Recurrence

Prevention of recurrent attacks of rheumatic fever (secondary prophylaxis) in individuals who have had a previous attack of rheumatic fever (penicillin G benzathine).

IM penicillin G benzathine generally considered drug of choice for secondary prophylaxis of rheumatic fever because it ensures compliance; alternatives include oral penicillin V or oral sulfadiazine.

AHA and AAP recommend long-term (continuous) prophylaxis following treatment of documented acute rheumatic fever (even if manifested solely by Sydenham chorea) and in those with evidence of rheumatic heart disease (even after prosthetic valve replacement).

Initiate prophylaxis as soon as rheumatic fever or rheumatic heart disease diagnosed, although patients with acute rheumatic fever should first receive usually recommended anti-infective treatment for S. pyogenes (group A β-hemolytic streptococci; GAS) pharyngitis and tonsillitis (see Pharyngitis and Tonsillitis under Uses).

Penicillin G Dosage and Administration

Administration

Penicillin G benzathine, penicillin G procaine, fixed combinations containing penicillin G benzathine and penicillin G procaine: Administer only by deep IM injection. Do not give IV or admix with IV solutions. Take special precaution to avoid inadvertent intravascular or intra-arterial administration or injection into or near major peripheral nerves or blood vessels since such injections may result in severe and/or permanent neurovascular damage. (See Precautions Related to IM Administration under Cautions.)

Penicillin G potassium, penicillin G sodium: Administer by IM injection or by intermittent IV injection or infusion or continuous IV infusion. Has been administered by intrapleural, intraperitoneal, intra-articular, or other local instillations. Has been administered intrathecally; this route not recommended because of possible neurotoxicity (e.g., seizures).

IM Injection

For IM injection, use penicillin G benzathine, penicillin G procaine, fixed combination of penicillin G benzathine and penicillin G procaine, penicillin G potassium, or penicillin G sodium based on indication.

Penicillin G Benzathine, Penicillin G Procaine, Fixed Combinations of Penicillin G Benzathine and Penicillin G Procaine

Provided in prefilled syringes; administer undiluted according to manufacturer's directions.

In adults, generally give IM injections deeply into gluteus maximus (upper outer quadrant of the buttock) or midlateral thigh. In neonates, infants, and small children, preferably give IM injections into midlateral muscles of the thigh.

To minimize possibility of damage to sciatic nerve, one manufacturer recommends that the periphery of the upper outer quadrant of gluteal region be used in infants and small children only when necessary (e.g., in burn patients) and recommends that the deltoid area be used only if well developed, such as in certain adults and older children, and only with caution to avoid radial nerve injury.

Inject IM at a slow, steady rate to avoid blockage of the needle.

Rotate IM injection sites when repeated doses are given.

Avoid repeated IM injections into anterolateral thigh, especially in neonates and infants, since quadriceps femoris fibrosis and atrophy reported. (See Precautions Related to IM Administration under Cautions.)

Penicillin G benzathine: IM injections may be less painful if warmed to room temperature before administration. One manufacturer suggests dose can be divided and given at 2 separate sites if necessary in children <2 years of age.

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R): Manufacturer states dose usually given at a single session using multiple IM sites; alternatively, total dose can be divided and half given on day 1 and half on day 3 if compliance regarding the return visit is ensured.

Penicillin G Potassium or Sodium

For IM injection, reconstitute vials containing 1 or 5 million penicillin G units (as penicillin G potassium) or vials containing 5 million penicillin G units (as penicillin G sodium) to desired concentration using amount of diluent specified by the manufacturer.

Loosen powder in the vial; hold horizontally and rotate while slowly directing diluent against vial wall. Shake vigorously after diluent added.

Refrigerate reconstituted vials if not used immediately; unstable in solution at room temperature.

Vials containing 20 million penicillin G units (as penicillin G potassium) are intended only for IV administration; do not use to prepare IM injections.

For IM injection, solutions containing up to 100,000 units/mL may be given with a minimum of discomfort; higher concentrations are physically possible and may be used when needed.

If large doses of penicillin G potassium or sodium required, give the drug IV (not IM).

IV Administration

For IV administration, use penicillin G potassium or sodium.

Reconstitute vials containing 1, 5, or 20 million penicillin G units (as penicillin G potassium) or vials containing 5 million penicillin G units (as penicillin G sodium) to desired concentration using amount of diluent specified by manufacturer.

Loosen powder in the vial; hold horizontally and rotate while slowly directing diluent against vial wall. Shake vigorously after diluent added.

Refrigerate reconstituted vials if not used immediately; unstable in solution at room temperature.

Alternatively, thaw commercially available frozen premixed penicillin G potassium injection in dextrose at room temperature (25°C) or in a refrigerator (5°C); do not force thaw by immersion in a water bath or by exposure to microwave radiation. Precipitates that may have formed in the frozen injection usually will dissolve with little or no agitation when the injection reaches room temperature. After thawing, agitate the injection. Discard thawed injection if the solution is cloudy or contains a precipitate or if container seals or outlet ports are not intact. Do not introduce additives into the injection container. Do not use 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.

Intermittent IV administration: Daily dosage usually given in equally divided doses every 4–6 hours; may be given in equally divided doses every 2–3 hours for treatment of severe infections (e.g., meningitis).

Continuous IV infusion: Determine volume of IV fluid and rate of administration required by the patient in a 24-hour period and add the appropriate daily dosage of penicillin G to the fluid. For example, if an adult requires 2 L of fluid in 24 hours and a dosage of 10 million penicillin G units daily, add 5 million units to 1 L of IV solution and adjust administration rate so that the liter of fluid will be infused over 12 hours.

Rate of Administration

Administer large IV doses of penicillin G potassium or sodium (>10 million penicillin G units) slowly because of potential for serious electrolyte disturbances from the potassium and/or sodium content of these preparations. (See Electrolyte Imbalance under Cautions.)

Intermittent IV administration: Has been given by IV infusion over 1–2 hours or by IV infusion over 10–30 minutes. Although doses have been injected IV over 3–5 minutes, large doses should be administered slowly.

Dosage

Dosage of penicillin G benzathine, penicillin G procaine, penicillin G potassium, and penicillin G sodium usually expressed in terms of penicillin G units. Also has been expressed in terms of mg of penicillin G.

Dosage of fixed combinations containing penicillin G benzathine and penicillin G procaine (Bicillin C-R, Bicillin C-R 900/300) usually expressed in terms of the total (sum) of penicillin G units of penicillin G benzathine and penicillin G units of penicillin G procaine.

Pediatric Patients

General Dosage for Neonates
Penicillin G Procaine
IM

Neonates ≤28 days of age: AAP recommends 50,000 units/kg once every 24 hours.

Penicillin G Potassium or Sodium
IV or IM

Neonates ≤7 days of age: AAP recommends 25,000–50,000 units/kg every 12 hours. AAP states higher dosage may be required for treatment of meningitis.

Neonates 8–28 days of age: AAP recommends 25,000–50,000 units/kg every 8 hours. AAP states higher dosage may be required for treatment of meningitis.

General Pediatric Dosage
Penicillin G Benzathine
IM

Pediatric patients beyond neonatal period: AAP recommends a single dose of 300,000–600,000 units in those weighing <27 kg and single dose of 900,000 units in those weighing ≥27 kg for treatment of mild to moderate infections. AAP states inappropriate for severe infections.

Penicillin G Procaine
IM

Pediatric patients beyond neonatal period: AAP recommends 50,000 units/kg daily in 1 or 2 divided doses for treatment of mild to moderate infections. AAP states inappropriate for severe infections.

Fixed Combinations of Penicillin G Benzathine and Penicillin G Procaine
IM

Pediatric patients beyond neonatal period (Bicillin C-R): AAP recommends a single dose of 600,000 units in those weighing <14 kg, single dose of 900,000 to 1.2 million units in those weighing 14–27 kg, and single dose of 2.4 million units in those weighing ≥27 kg.

Penicillin G Potassium or Sodium
IV or IM

Children beyond neonatal period: AAP recommends 100,000–150,000 units/kg daily in 4 divided doses for treatment of mild to moderate infections or 200,000–300,000 units/kg daily in 4–6 divided doses for treatment of severe infections. AAP states use highest recommended dosage for treatment of meningitis.

Endocarditis
Native Valve Endocarditis Caused by S. pyogenes, S. agalactiae†, Streptococci Groups C or G, Viridans Streptococci†, or Nonenterococcal Group D† (S. gallolyticus†, S. equinus†)
IV

Penicillin G potassium or sodium for highly penicillin-susceptible strains (penicillin MIC ≤0.1 mcg/mL): AHA recommends 200,000–300,000 units/kg daily (up to 12–24 million units daily) in divided doses every 4 hours for 4 weeks.

Penicillin G potassium or sodium for relatively resistant strains (penicillin MIC >0.1 but <0.5 mcg/mL): AHA recommends 200,000–300,000 units/kg daily (up to 12–24 million units daily) 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 first 2 weeks of penicillin G treatment).

Penicillin G potassium or sodium for viridans streptococci with penicillin MIC ≥0.5 mcg/mL: AHA recommends 200,000–300,000 units/kg daily (up to 12–24 million units daily) in divided doses every 4 hours for 4–6 weeks in conjunction with gentamicin (3–6 mg/kg daily IV in divided doses every 8 hours given concomitantly during first 2 weeks of penicillin G treatment).

Native Valve Endocarditis Caused by Abiotrophia† or Granulicatella†
IV

Penicillin G potassium or sodium for strains with penicillin MIC ≥0.5 mcg/mL: AHA recommends 200,000–300,000 units/kg daily (up to 12–24 million units daily) in divided doses every 4 hours for 4–6 weeks in conjunction with gentamicin (3–6 mg/kg daily IV in divided doses every 8 hours given concomitantly during first 2 weeks of penicillin G treatment).

Endocarditis Involving Prosthetic Valves or Other Prosthetic Material Caused by Viridans Streptococci†, Other Streptococci, Abiotrophia†, or Granulicatella†
IV

Penicillin G potassium or sodium for penicillin-susceptible strains (penicillin MIC ≤0.1 mcg/mL): AHA recommends 200,000–300,000 units/kg daily (up to 12–24 million units daily) in divided doses every 4 hours for 6 weeks in conjunction with gentamicin (3–6 mg/kg daily IV in divided doses every 8 hours given concomitantly during first 2 weeks of penicillin G treatment).

Penicillin G potassium or sodium for strains with penicillin MIC ≥0.1 mcg/mL: AHA recommends 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 daily IV in divided doses every 8 hours given concomitantly during entire 6 weeks of penicillin G treatment).

Enterococcal Endocarditis†
IV

Penicillin G potassium or sodium for enterococcal endocarditis involving native valves or prosthetic valves or other prosthetic material: AHA recommends 200,000–300,000 units/kg daily (up to 12–24 million units daily) in divided doses every 4 hours in conjunction with gentamicin (3–6 mg/kg daily IV in divided doses every 8 hours).

Recommended treatment duration of the 2-drug regimen is 4–6 weeks for native valve enterococcal endocarditis; longer duration recommended if prosthetic valve or other prosthetic material involved.

Endocarditis Caused by Staphylococci
IV

Penicillin G potassium or sodium for susceptible S. aureus or coagulase-negative staphylococci (penicillin MIC ≤0.1 mcg/mL): AHA recommends 200,000–300,000 units/kg daily (up to 12–24 million units daily) in divided doses every 4 hours.

Endocarditis Caused by Streptococci
IV or IM

Penicillin G potassium or sodium for susceptible streptococci, including S. pyogenes, streptococci groups C, H, G, L, and M, or S. pneumoniae: Manufacturers recommend 150,000–300,000 units/kg daily in divided doses every 4–6 hours.

Meningitis
Meningitis Caused by L. monocytogenes
IV

Penicillin G potassium or sodium in neonates: IDSA recommends 150,000 units/kg daily in divided doses every 8–12 hours in those ≤7 days of age and 200,000 units/kg daily in divided doses every 6–8 hours in those 8–28 days of age. Continue treatment for 2 weeks beyond first sterile CSF culture or for at least 3 weeks, whichever is longer.

Penicillin G potassium or sodium in infants and children: IDSA recommends 300,000 units/kg daily in divided doses every 4–6 hours for ≥21 days. Consider using an aminoglycoside concomitantly.

Meningitis Caused by N. meningitidis
IV

Penicillin G potassium or sodium in neonates: IDSA recommends 150,000 units/kg daily in divided doses every 8–12 hours in those ≤7 days of age and 200,000 units/kg daily in divided doses every 6–8 hours in those 8–28 days of age. Continue treatment for 2 weeks beyond first sterile CSF culture or for at least 3 weeks, whichever is longer.

Penicillin G potassium or sodium in infants and children: IDSA and AAP recommend 300,000 units/kg daily (up to 12 million units daily) in divided doses every 4–6 hours for 7 days.

Penicillin G potassium or sodium in pediatric patients: Manufacturers recommend 250,000 units/kg daily (up to 12–20 million units daily) in divided doses every 4 hours for 7–14 days.

Meningitis Caused by S. agalactiae† (Group B Streptococci; GBS)
IV

Penicillin G potassium or sodium in neonates: AAP recommends 250,000–450,000 units/kg daily in 3 divided doses in those ≤7 days of age and 450,000–500,000 units/kg daily in 4 divided doses in those >7 days of age. Continue treatment for ≥14 days.

Penicillin G potassium or sodium in neonates: IDSA recommends 150,000 units/kg daily in divided doses every 8–12 hours in those ≤7 days of age and 200,000 units/kg daily in divided doses every 6–8 hours in those 8–28 days of age. Continue treatment for 2 weeks beyond first sterile CSF culture or for at least 3 weeks, whichever is longer.

Penicillin G potassium or sodium in infants and children: IDSA recommends 300,000 units/kg daily in divided doses every 4–6 hours for 14–21 days. Consider using an aminoglycoside concomitantly.

Meningitis Caused by S. pneumoniae
IV

Penicillin G potassium or sodium in neonates: IDSA recommends 150,000 units/kg daily in divided doses every 8–12 hours in those ≤7 days of age and 200,000 units/kg daily in divided doses every 6–8 hours in those 8–28 days of age. Continue treatment for 2 weeks beyond first sterile CSF culture or for at least 3 weeks, whichever is longer.

Penicillin G potassium or sodium in infants and children ≥1 month of age: AAP recommends 250,000–400,000 units/kg daily in divided doses every 4–6 hours. IDSA recommends that infants and children receive 300,000 units/kg daily in divided doses every 4–6 hours for 10–14 days.

Penicillin G potassium or sodium in pediatric patients: Manufacturers recommend 250,000 units/kg daily (up to 12–20 million units daily) in divided doses every 4 hours for 7–14 days.

Healthcare-associated Ventriculitis and Meningitis Caused by C. acnes†
IV

Penicillin G potassium or sodium: IDSA recommends 300,000 units/kg daily in divided doses every 4–6 hours. 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.

Pharyngitis and Tonsillitis
Treatment of S. pyogenes Pharyngitis and Tonsillitis
IM

Penicillin G benzathine: AAP, IDSA, and AHA recommend a single dose of 600,000 units in those weighing <27 kg and single dose of 1.2 million units in those weighing ≥27 kg. Manufacturers recommend a single dose of 300,000–600,000 units in those weighing <27 kg and single dose of 900,000 units in older children.

Penicillin G procaine: Manufacturer recommends 300,000 units daily for at least 10 days in children weighing <27 kg and 600,000 to 1 million units daily for at least 10 days in others. AHA, IDSA, and AAP recommend penicillin G benzathine.

Eradication of Pharyngeal Carriage of S. pyogenes†
IM

Penicillin G benzathine in certain circumstances when eradication of carrier state is desirable (see Pharyngitis and Tonsillitis under Uses): IDSA states a single of 600,000 units in those weighing <27 kg or single dose of 1.2 million units in those weighing ≥27 kg given in conjunction with oral rifampin (20 mg/kg daily [up to 600 mg daily] given in 2 doses for 4 days) is an option.

Respiratory Tract Infections
IM

Penicillin G benzathine for mild to moderate upper respiratory infections caused by susceptible S. pyogenes: Manufacturer recommends a single dose of 300,000–600,000 units in children weighing <27 kg and single dose of 900,000 units in older pediatric patients.

Penicillin G procaine for moderately severe to severe upper respiratory infections caused by susceptible S. pyogenes: Manufacturer recommends 300,000 units daily for ≥10 days in children weighing <27 kg and 600,000 to 1 million units daily for ≥10 days in others.

Penicillin G procaine for moderately severe, uncomplicated respiratory infections (pneumonia) caused by susceptible S. pneumoniae: Manufacturer recommends 300,000 units daily in children weighing <27 kg and 600,000 to 1 million units daily in others.

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R) for moderately severe to severe upper respiratory infections caused by susceptible S. pyogenes: Manufacturer recommends a single dose of 600,000 units in children weighing <13.6 kg, single dose of 900,000 to 1.2 million units in those weighing 13.6–27.2 kg, and single dose of 2.4 million units in those weighing >27.2 kg.

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R) for moderately severe respiratory infections (pneumonia, otitis media) caused by susceptible S. pneumoniae: Manufacturer recommends 600,000 units once every 2 or 3 days until patient is afebrile for 48 hours.

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R 900/300) for moderately severe to severe upper respiratory infections caused by susceptible S. pyogenes: Manufacturer states a single dose of 1.2 million units usually sufficient in pediatric patients.

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R 900/300) for moderately severe respiratory infections (pneumonia, otitis media) caused by susceptible S. pneumoniae: Manufacturer recommends 1.2 million units once every 2 or 3 days until patient has been afebrile for 48 hours.

IV or IM

Penicillin G potassium or sodium for CAP caused by susceptible S pyogenes in infants and children ≥3 months of age: IDSA recommends 100,000–200,000 units/kg daily in 4–6 divided doses; 200,000–250,000 units/kg daily may be used for severe infections.

Penicillin G potassium or sodium for CAP caused by susceptible S. pneumoniae (penicillin MIC ≤2 mcg/mL) in infants and children ≥3 months of age: IDSA recommends 200,000–250,000 units/kg daily in divided doses every 4–6 hours. For nonmeningeal infections caused by susceptible S. pneumoniae in infants and children ≥1 month of age, AAP recommends 250,000–400,000 units/kg daily in divided doses every 4–6 hours.

Penicillin G potassium or sodium for serious infections (e.g., pneumonia) caused by susceptible S. pyogenes, streptococci groups C, H, G, L, and M, or S. pneumoniae in pediatric patients: Manufacturers recommend 150,000–300,000 units/kg daily in divided doses every 4–6 hours.

Skin and Skin Structure Infections
IM

Penicillin G procaine for moderately severe infections (including erysipelas) caused by susceptible staphylococci: Manufacturer recommends 300,000 units daily in children weighing <27 kg and 600,000 to 1 million units daily in others.

Penicillin G procaine for moderately severe to severe infections caused by susceptible S. pyogenes: Manufacturer recommends 300,000 units daily for at least 10 days in children weighing <27 kg and 600,000 to 1 million units daily for at least 10 days in others.

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R) for moderately severe to severe infections (including erysipelas) caused by susceptible S. pyogenes: Manufacturer recommends a single dose of 600,000 units in children weighing <13.6 kg, single dose of 900,000 to 1.2 million units in those weighing 13.6–27.2 kg, and single dose of 2.4 million units in those weighing >27.2 kg.

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R 900/300) for moderately severe infections (including erysipelas) caused by susceptible S. pyogenes: Manufacturer states a single dose of 1.2 million units usually sufficient in pediatric patients.

IV

Penicillin G potassium or sodium for necrotizing infections of skin, fascia, and muscle caused by susceptible S. pyogenes in pediatric patients: IDSA recommends 60,000–100,000 units/kg every 6 hours in conjunction with clindamycin (10–13 mg/kg IV every 8 hours).

Anthrax
Postexposure Prophylaxis (Inhalational Anthrax)
IM

Penicillin G procaine: 25,000 units/kg (up to 1.2 million units) every 12 hours recommended by manufacturer. AAP and CDC recommend other penicillins (oral amoxicillin or penicillin V) for prophylaxis following exposure to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism when penicillin-susceptible strains involved.

Total duration of anti-infective prophylaxis following aerosol exposure to B. anthracis spores in the context of biologic warfare or bioterrorism should be ≥60 days. Manufacturer states safety data for penicillin G procaine administered at dosage recommended for inhalational anthrax (postexposure) supports a duration ≤2 weeks; consider risks versus benefits of continuing the drug for >2 weeks or switching to an appropriate alternative anti-infective.

Treatment of Mild, Uncomplicated Cutaneous Anthrax (Naturally Occurring or Endemic Exposure)
IM

Penicillin G procaine in children weighing <20 kg: 25,000–50,000 units/kg daily (single or 2 divided doses daily) recommended by some experts.

Although 3–10 days of anti-infective therapy may be adequate if mild, uncomplicated cutaneous anthrax occurred as the result of natural or endemic exposures, some experts recommend duration of 7–14 days. CDC and others recommend 60 days of anti-infective treatment if cutaneous anthrax occurred as the result of exposure to aerosolized B. anthracis spores (e.g., in the context of biologic warfare or bioterrorism).

Treatment of Systemic Anthrax (Naturally Occurring or Endemic Exposure)
IV

Penicillin G potassium or sodium in children with inhalational, GI, or meningeal anthrax: Some clinicians recommend 100,000–150,000 units/kg daily given in divided doses every 4–6 hours.

Penicillin G potassium or sodium in children with severe or life-threatening systemic anthrax (inhalational, GI, meningoencephalitis, sepsis) or cutaneous anthrax with signs of systemic involvement, lesions on head or neck, or extensive edema: Some experts recommend 300,000–400,000 units/kg daily given in divided doses every 4–6 hours.

Concomitant use of other anti-infectives (e.g., streptomycin or other aminoglycoside, clindamycin, clarithromycin, rifampin, vancomycin) may also be indicated. Continue treatment of naturally occurring or endemic anthrax for ≥14 days after symptoms abate.

Treatment of Systemic Anthrax (Biologic Warfare or Bioterrorism Exposure)
IV

Penicillin G potassium or sodium in full-term neonates: AAP recommends 300,000 units/kg daily given in divided doses every 8 hours in those ≤7 days of age and 400,000 units/kg daily given in divided doses every 6 hours in those 1–4 weeks of age.

Penicillin G potassium or sodium in premature neonates (gestational age 32–34 weeks): AAP recommends 200,000 units/kg daily given in divided doses every 12 hours in those ≤7 days of age and 300,000 units/kg daily given in divided doses every 8 hours in those 1–4 weeks of age.

Penicillin G potassium or sodium in premature neonates (gestational age 34–37 weeks): AAP recommends 300,000 units/kg given in divided doses every 8 hours in those ≤7 days of age and 400,000 units/kg daily given in divided doses every 6 hours in those 1–4 weeks of age.

Penicillin G potassium or sodium in infants and children ≥1 month of age: 400,000 units/kg daily in divided doses every 4 hours (up to 4 million units per dose).

Use in 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). Continue parenteral regimen for ≥2–3 weeks until patient is clinically stable; treatment can then be switched to an oral regimen. CDC and other experts state that total duration of anti-infective treatment for anthrax in the context of biologic warfare or bioterrorism should be 60 days.

Clostridium Infections
Myonecrosis and Gas Gangrene
IV

Penicillin G potassium or sodium: IDSA recommends 60,000–100,000 units/kg every 6 hours in conjunction with clindamycin (10–13 mg/kg IV every 8 hours). AAP recommends 250,000–400,000 units/kg daily and states that concomitant use of clindamycin may be more effective than penicillin G alone.

Perform surgical debridement and/or surgery as indicated.

Tetanus
IV

Potassium G potassium or sodium: AAP recommends 100,000 units/kg daily (up to 12 million units daily) given in divided doses every 4–6 hours for 7–10 days.

Adjunct to TIG. (See Clostridium Infections under Uses.)

Diphtheria
Treatment of Diphtheria
IM

Penicillin G procaine: Manufacturer recommends 300,000–600,000 units daily for 14 days. CDC recommends 300,000 units daily in those weighing ≤10 kg or 600,000 units daily in those weighing >10 kg.

Adjunct to diphtheria antitoxin. (See Diphtheria under Uses.)

IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 150,000–250,000 units/kg daily given in divided doses every 6 hours for 7–10 days. CDC recommends penicillin G procaine if a penicillin used.

Adjunct to diphtheria antitoxin. (See Diphtheria under Uses.)

Prevention of Diphtheria in Close Contacts†
IM

Penicillin G benzathine: CDC and AAP recommend a single dose of 600,000 units in children <6 years of age or weighing <30 kg or single dose of 1.2 million units in those ≥6 years of age or weighing ≥30 kg.

Provide anti-infective prophylaxis regardless of immunization status and closely monitor for symptoms of diphtheria for 7 days.

Contacts inadequately immunized against diphtheria or with unknown immunization status: Give immediate dose of age-appropriate preparation containing diphtheria toxoid adsorbed and complete primary series according to recommended schedules.

Contacts fully immunized against diphtheria but received last booster dose ≥5 years previously: Give immediate booster dose of age-appropriate preparation containing diphtheria toxoid adsorbed.

Elimination of Diphtheria Carrier State
IM

Penicillin G benzathine: CDC and AAP recommend a single dose of 600,000 units in children <6 years of age or weighing <30 kg or single dose of 1.2 million units in those ≥6 years of age or weighing ≥30 kg.

Penicillin G procaine: Manufacturer recommends 300,000 units daily for 10 days. CDC and AAP recommend penicillin G benzathine if a penicillin used.

Obtain follow-up cultures ≥2 weeks after treatment of diphtheria carriers; if cultures are positive, give a 10-day course of oral erythromycin and obtain additional follow-up cultures.

Lyme Disease†
Early Lyme Disease with Acute Neurologic Disease†
IV

Penicillin G potassium or sodium: 200,000–400,000 units/kg daily (up to 18–24 million units daily) given in 6 divided doses (every 4 hours) for 10–28 days.

Late Lyme Disease with Recurrent Lyme Arthritis and Evidence of Neurologic Disease†
IV

Penicillin G potassium or sodium: 200,000–400,000 units/kg daily (up to 18–24 million units daily) given in 6 divided doses (every 4 hours) for 14–28 days.

Late Neurologic Lyme Disease†
IV

Penicillin G potassium or sodium: 200,000–400,000 units/kg daily (up to 18–24 million units daily) given in 6 divided doses (every 4 hours) for 14–28 days.

Neisseria meningitidis Infections
Serious Infections
IV or IM

Penicillin G potassium or sodium in pediatric patients: Manufacturers recommend 150,000–300,000 units/kg daily in divided doses every 4–6 hours.

Also see Pediatric Patients: Meningitis Caused by L. monocytogenes, under Dosage and Administration.

Rat-bite Fever
IV or IM

Penicillin G potassium or sodium in pediatric patients: Manufacturers recommend 150,000–250,000 units/kg daily in divided doses every 4 hours for 4 weeks.

Penicillin G potassium or sodium in pediatric patients: Some clinicians recommend 20,000–50,000 units/kg IV 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). For S. moniliformis endocarditis caused by a strain less susceptible to penicillin G (MIC >0.1 mcg/mL), some clinicians recommend 160,000–240,000 units/kg IV daily (up to 20 million units daily) for 6 weeks; concomitant use of an aminoglycoside (streptomycin or gentamicin) may be indicated for initial treatment.

Syphilis
Neonates with Proven or Highly Probable Congenital Syphilis
IM

Penicillin G procaine: CDC and AAP recommend 50,000 units/kg once daily for 10 days. If >1 day of treatment missed, restart entire course of treatment.

IV

Penicillin G potassium or sodium: CDC recommends 50,000 units/kg every 12 hours during first 7 days of life and 50,000 units/kg every 8 hours thereafter for total duration of 10 days. If >1 day of treatment missed, restart entire course of treatment.

Neonates with Possible Congenital Syphilis or When Congenital Syphilis Less Likely
IM

Penicillin G benzathine: CDC and manufacturers recommend a single dose of 50,000 units/kg.

Penicillin G procaine: CDC recommends 50,000 units/kg once daily for 10 days.

IV

Penicillin G potassium or sodium: CDC recommends 50,000 units/kg every 12 hours during first 7 days of life and 50,000 units/kg every 8 hours thereafter for total duration of 10 days.

Infants and Children ≥1 Month of Age with Reactive Serologic Test for Syphilis and Normal CSF Evaluation
IM

Penicillin G benzathine: CDC states 50,000 units/kg (up to 2.4 million units) once weekly for up to 3 weeks can be considered. Alternatively, may consider a single dose of 50,000 units/kg (up to 2.4 million units) after completion of 10-day regimen of IV penicillin G potassium or sodium.

IV

Penicillin G potassium or sodium: CDC recommends 50,000 units/kg every 4–6 hours for 10 days. Some clinicians recommend that this regimen be followed by a single dose of IM penicillin G benzathine (50,000 units/kg).

Congenital Syphilis or Neurosyphilis in Infants and Children >1 Month of Age
IV

Penicillin G potassium or sodium: CDC, AAP, and manufacturers recommend 200,000–300,000 units/kg daily (50,000 units every 4–6 hours) for 10–14 days. 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]).

Primary, Secondary, or Early Latent Syphilis in Infants and Children ≥1 Month of Age
IM

Penicillin G benzathine: CDC, AAP, and others recommend a single dose of 50,000 units/kg (up to 2.4 million units).

When syphilis diagnosed in infants and children ≥1 month of age, CDC states treatment should be managed by a pediatric infectious disease specialist.

Late Latent Syphilis in Infants and Children ≥1 Month of Age
IM

Penicillin G benzathine: CDC, AAP, and others recommend 50,000 units/kg (up to 2.4 million units) once weekly for 3 consecutive weeks (up to a maximum total dosage of 7.2 million units).

When syphilis diagnosed in infants and children ≥1 month of age, CDC states treatment should be managed by a pediatric infectious disease specialist. Examination of CSF indicated in those with latent syphilis.

Primary, Secondary, or Early Latent Syphilis in Adolescents
IM

Penicillin G benzathine in adolescents 10–19 years of age: Some experts recommend a single dose of 2.4 million units.

Penicillin G procaine in adolescents 10–19 years of age: Some experts recommend 1.2 million units once daily for 10–14 days as an alternative to penicillin G benzathine.

Penicillin G procaine in children >12 years of age: Manufacturer recommends 600,000 units daily for 8 days (total dosage 4.8 million units). CDC and others recommend penicillin G benzathine.

Tertiary or Late Latent Syphilis in Adolescents
IM

Penicillin G benzathine in adolescents 10–19 years of age: Some experts recommend 2.4 million units once weekly for 3 consecutive weeks for late latent syphilis or syphilis of unknown duration. Interval between doses should not be >14 days.

Penicillin G procaine in adolescents 10–19 years of age: Some experts recommend 1.2 million units once daily for 20 days as an alternative to penicillin G benzathine for late latent syphilis or syphilis of unknown duration.

Penicillin G procaine in children >12 years of age: Manufacturer recommends 600,000 units daily for 10–15 days (total dosage 6–9 million units). CDC and others recommend penicillin G benzathine.

Neurosyphilis and Otic or Ocular Syphilis in Adolescents
IV

Penicillin G potassium or sodium: 18–24 million units daily (by continuous IV infusion or given as 3–4 million units every 4 hours) for 10–14 days. Some clinicians recommend this regimen be followed by IM penicillin G benzathine (2.4 million units once weekly for up to 3 weeks).

Yaws, Pinta, and Bejel
IM

Penicillin G benzathine in children: A single dose of 600,000 units in children <10 years of age or single dose of 1.2 million units in those ≥10 years of age has been used. For treatment of yaws, a single dose of 50,000 units/kg (up to 2.4 million units) has been used.

Penicillin G procaine: Manufacturer states dosage is the same as that recommended for corresponding stage of syphilis.

Prevention of Rheumatic Fever Recurrence
IM

Penicillin G benzathine: AAP and AHA recommend 600,000 units once every 4 weeks in children weighing ≤27 kg and 1.2 million units once every 4 weeks in those weighing >27 kg. Manufacturers recommend 1.2 million units once monthly or 600,000 units once every 2 weeks.

AAP and AHA state that 4-week dosing interval seems adequate and is recommended for most US patients, but 3-week dosing interval may be warranted and is recommended when risk of rheumatic fever is particularly high (e.g., recurrent acute rheumatic fever despite adherence to 4-week regimen). There is some evidence that serum penicillin concentrations may decline to subtherapeutic concentrations before fourth week in some patients.

Initiate prophylaxis as soon as active rheumatic fever or rheumatic heart disease diagnosed; however, patients with acute rheumatic fever should first receive usually recommended anti-infective regimen for treatment of S. pyogenes (group A β-hemolytic streptococci; GAS) pharyngitis and tonsillitis (see Pharyngitis and Tonsillitis under Uses).

Long-term, continuous prophylaxis required. (See Table 1.) Some clinicians use IM penicillin G benzathine initially and change to oral prophylaxis (usually penicillin V) when patient reaches late adolescence or young adulthood and has remained free of rheumatic attacks for ≥5 years.

Table 1. Recommended Duration of Prophylaxis for Prevention of Rheumatic Fever Recurrence292375

Patient Category

Duration

Rheumatic fever without carditis

5 years since last episode or until 21 years of age, whichever is longer

Rheumatic fever with carditis but no residual heart disease (no valvular disease)

10 years since last episode or until 21 years of age, whichever is longer

Rheumatic fever with carditis and residual heart disease (persistent valvular disease)

10 years since last episode or until 40 years of age, whichever is longer; sometimes for life

Adults

Bone and Joint Infections†
Native Vertebral Osteomyelitis or Prosthetic Joint Infections†
IV

Penicillin G potassium or sodium for infections caused by susceptible β-hemolytic streptococci: IDSA recommends 20–24 million units daily (by continuous IV infusion or in 6 divided doses). Recommended treatment duration is 6 weeks in those with native vertebral osteomyelitis or 4–6 weeks in those with prosthetic joint infections.

Penicillin G potassium or sodium for infections caused by susceptible Enterococcus: IDSA recommends 20–24 million units daily (by continuous IV infusion or in 6 divided doses) for 4–6 weeks. Consider concomitant treatment with an aminoglycoside given for 4–6 weeks; concomitant treatment recommended if infective endocarditis also present.

Penicillin G potassium or sodium for infections caused by susceptible C. acnes (formerly P. acnes): IDSA recommends 20 million units daily (by continuous IV infusion or in 6 divided doses). Recommended treatment duration is 6 weeks in those with native vertebral osteomyelitis or 4–6 weeks in those with prosthetic joint infections.

Endocarditis
Native Valve Endocarditis Caused by Viridans Streptococci† or S. gallolyticus†
IV

Penicillin G potassium or sodium for highly penicillin-susceptible strains (penicillin MIC ≤0.12 mcg/mL): AHA recommends 12–18 million units daily (by continuous IV infusion or in 4 or 6 divided doses) given for 4 weeks. Alternatively, 12–18 million units daily (by continuous IV infusion or in 6 divided doses) given for 2 weeks in conjunction with gentamicin (3 mg/kg IM or IV as a single daily dose or as 1 mg/kg every 8 hours given for 2 weeks) can be used in those at low risk for aminoglycoside-associated adverse effects. Do not use 2-week regimen in those with known cardiac or extracardiac abscesses, Clcr <20 mL/minute, impaired eighth cranial nerve function, or infection with Abiotrophia, Granulicatella, or Gemella.

Penicillin G potassium or sodium for strains relatively resistant to penicillin G (penicillin MIC >0.12 mcg/mL but <0.5 mcg/mL): AHA recommends 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 IV or IM daily given as a single daily dose or as 1 mg/kg every 8 hours during first 2 weeks of penicillin G treatment).

Penicillin G potassium or sodium for viridans streptococci with penicillin MIC ≥0.5 mcg/mL: AHA states 18–30 million units daily (by continuous IV infusion or in 6 divided doses) in conjunction with gentamicin (3 mg/kg IV or IM daily in 2 or 3 divided doses) is a reasonable regimen. AHA states consult with an infectious disease expert to determine treatment duration for such infections.

Native Valve Endocarditis Caused by Abiotrophia† or Granulicatella†
IV

Penicillin G potassium or sodium for strains with penicillin MIC ≥0.5 mcg/mL: AHA states 18–30 million units daily (by continuous IV infusion or in 6 divided doses) in conjunction with gentamicin (3 mg/kg IV or IM daily in 2 or 3 divided doses) is a reasonable regimen. AHA states consult with an infectious disease expert to determine treatment duration for such infections.

Endocarditis Involving Prosthetic Valves or Other Prosthetic Material Caused by Viridans Streptococci†, Abiotrophia†, or Granulicatella†
IV

Penicillin G potassium or sodium for highly penicillin-susceptible strains (penicillin MIC ≤0.12 mcg/mL): AHA recommends 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 IV or IM as a single daily dose or as 1 mg/kg every 8 hours given concomitantly during first 2 weeks of penicillin G treatment).

Penicillin G potassium or sodium for strains relatively or highly resistant to penicillin (penicillin MIC >0.12 mcg/mL): Use same regimen recommended for highly penicillin-susceptible strains, but AHA states it is reasonable to extend the duration of concomitant gentamicin to 6 weeks.

Enterococcal Endocarditis†
IV

Penicillin G potassium or sodium for endocarditis involving native valve or prosthetic valve or other prosthetic material caused by enterococci susceptible to penicillin and gentamicin: AHA recommends 18–30 million units daily (by continuous IV infusion or in 6 divided doses) in conjunction with gentamicin (3 mg/kg IV or IM daily in 2 or 3 divided doses; adjust dose to achieve gentamicin peak serum concentrations of 3–4 mcg/mL and trough concentrations <1 mcg/mL).

Enterococcal endocarditis involving native valves: Continue both drugs for 4 weeks if symptoms were present for <3 months prior to treatment or for 6 weeks if symptoms were present for ≥3 months prior to treatment.

Enterococcal endocarditis involving prosthetic heart valves or other prosthetic material: Continuation of both drugs for 6 weeks is reasonable.

Enterococci resistant to gentamicin, but susceptible to penicillin and streptomycin: In above regimen, may substitute streptomycin (15 mg/kg IV or IM daily in 2 divided doses; dose adjusted to achieve streptomycin peak serum concentrations of 20–35 mcg/mL and trough concentrations <10 mcg/mL) instead of gentamicin. Consider alternative regimens (e.g., double β-lactam regimens) in patients with Clcr <50 mL/minute.

Endocarditis Caused by Staphylococci
IV or IM

Penicillin G potassium or sodium for susceptible staphylococci: Manufacturers recommend 5–24 million units daily in divided doses every 4–6 hours. Penicillin G not included in current AHA recommendations for treatment of staphylococcal endocarditis.

Endocarditis Caused by Streptococci
IM

Penicillin G procaine for susceptible S. pyogenes: Manufacturer recommends 600,000 to 1 million units daily. If a penicillin used, AHA recommends IV penicillin G potassium or sodium.

IV or IM

Penicillin G potassium or sodium for susceptible streptococci, including S. pyogenes, streptococci groups C, H, G, L, and M, or S. pneumoniae: Manufacturers recommend 12–24 million units daily in divided doses every 4–6 hours.

Meningitis
Meningitis Caused by L. monocytogenes
IV

Penicillin G potassium or sodium: IDSA and others recommend 24 million units daily (4 million units every 4 hours) for ≥21 days. Consider using an aminoglycoside concomitantly.

Penicillin G potassium or sodium: Manufacturers recommend 15–20 million units daily given in divided doses every 4–6 hours for 2 weeks.

Meningitis Caused by N. meningitidis
IV

Penicillin G potassium or sodium: IDSA recommends 24 million units daily (4 million units every 4 hours) for 7 days.

Penicillin G potassium or sodium: Manufacturers recommend 24 million units daily (2 million units every 2 hours).

Meningitis Caused by S. agalactiae† (Group B Streptococci; GBS)
IV

Penicillin G potassium or sodium: IDSA recommends 24 million units daily (4 million units every 4 hours) for 14–21 days. Consider using an aminoglycoside concomitantly.

Meningitis Caused by S. pneumoniae
IV

Penicillin G potassium or sodium: IDSA and others recommend 24 million units daily (4 million units every 4 hours) for 10–14 days.

Penicillin G potassium or sodium: Manufacturers recommend 12–24 million units daily given in divided doses every 4–6 hours. One manufacturer recommends 5–24 million units daily given in divided doses every 4–6 hours.

Healthcare-associated Ventriculitis and Meningitis Caused by C. acnes†
IV

Penicillin G potassium or sodium: IDSA recommends 24 million units daily given in divided doses every 4 hours. 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.

Pharyngitis and Tonsillitis
Treatment of S. pyogenes Pharyngitis and Tonsillitis
IM

Penicillin G benzathine: A single dose of 1.2 million units.

Eradication of Pharyngeal Carriage of S. pyogenes†
IM

Penicillin G benzathine in certain circumstances when eradication of carrier state is desirable (see Pharyngitis and Tonsillitis under Uses): IDSA states a single dose of 600,000 units in those weighing <27 kg or single dose of 1.2 million units in those weighing ≥27 kg given in conjunction with oral rifampin (20 mg/kg daily [up to 600 mg daily] given in 2 doses for 4 days) is an option.

Respiratory Tract Infections
IM

Penicillin G benzathine for mild to moderate upper respiratory infections caused by susceptible S. pyogenes: Manufacturers recommend a single dose of 1.2 million units.

Penicillin G procaine for moderately severe to severe upper respiratory infections caused by susceptible S. pyogenes: Manufacturer recommends 600,000 to 1 million units daily for ≥10 days.

Penicillin G procaine for moderately severe, uncomplicated respiratory infections (pneumonia) caused by susceptible S. pneumoniae: Manufacturer recommends 600,000 to 1 million units daily for ≥10 days.

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R) for moderately severe to severe infections caused by susceptible S. pyogenes: Manufacturer recommends a single dose of 2.4 million units.

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R) for moderately severe to severe infections (pneumonia, otitis media) caused by susceptible S. pneumoniae: Manufacturer recommends 1.2 million units once every 2 or 3 days until patients has been afebrile for 48 hours.

IV or IM

Penicillin G potassium or sodium for serious infections (e.g., pneumonia, empyema) caused by susceptible nonpenicillinase-producing staphylococci: Manufacturers recommend 5–24 million units daily in divided doses every 4–6 hours depending on severity.

Penicillin G potassium for serious infections (e.g., pneumonia, empyema) caused by susceptible S. pyogenes, streptococci groups C, H, G, L, and M, or S. pneumoniae: Manufacturers recommend 12–24 million units daily in divided doses every 4–6 hours depending on severity.

Penicillin G sodium for serious infections (e.g., pneumonia, empyema) caused by susceptible streptococci: Manufacturer recommends 5–24 million units daily in divided doses every 4–6 hours depending on severity.

Septicemia
IV or IM

Penicillin G potassium or sodium for susceptible nonpenicillinase-producing staphylococci: Manufacturers recommend 5–24 million units daily in divided doses every 4–6 hours depending on severity.

Penicillin G potassium or sodium for susceptible S. pyogenes, streptococci groups C, H, G, L, and M, or S. pneumoniae: Manufacturers recommend 12–24 million units daily in divided doses every 4–6 hours depending on severity.

Skin and Skin Structure Infections
IM

Penicillin G procaine for moderately severe to severe infections caused by susceptible staphylococci: Manufacturer recommends 600,000 to 1 million units daily.

Penicillin G procaine for moderately severe to severe infections (including erysipelas) caused by susceptible streptococci: Manufacturer recommends 600,000 to 1 million units daily for ≥10 days.

Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R) for moderately severe to severe infections (including erysipelas) caused by susceptible S. pyogenes: Manufacturer recommends a single dose of 2.4 million units.

IV

Penicillin G potassium or sodium for necrotizing infections of skin, fascia, and muscle caused by susceptible S. pyogenes: IDSA recommends 2–4 million units every 4–6 hours in conjunction with clindamycin (600–900 mg IV every 8 hours).

Actinomycosis
IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 1–6 million units daily in divided doses every 4–6 hours for cervicofacial infections or 10–20 million units daily in divided doses every 4–6 hours for thoracic or abdominal infections.

Penicillin G potassium or sodium: Some clinicians recommend 18–24 million units daily IV (3–4 million units every 4 hours) for ≥2–6 weeks followed by 6–12 additional months of an oral regimen (penicillin V or amoxicillin) for pulmonary or other severe infections. Shorter treatment duration may be sufficient for less extensive disease (e.g., cervicofacial region).

Individualize dosage and treatment duration based on severity and response; perform surgical procedures as indicated.

Anthrax
Postexposure Prophylaxis (Inhalational Anthrax)
IM

Penicillin G procaine: Manufacturer recommends 1.2 million units every 12 hours. CDC recommends other penicillins (oral amoxicillin or penicillin V) for prophylaxis following exposure to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism when penicillin-susceptible strains involved.

Total duration of anti-infective prophylaxis following aerosol exposure to B. anthracis spores in the context of biologic warfare or bioterrorism should be ≥60 days. Manufacturer states safety data for penicillin G procaine administered at dosage recommended for inhalational anthrax (postexposure) supports a duration ≤2 weeks; consider risks versus benefits of continuing the drug for >2 weeks or switching to an appropriate alternative anti-infective.

Treatment of Mild, Uncomplicated Cutaneous Anthrax (Naturally Occurring or Endemic Exposure)
IM

Penicillin G procaine: Manufacturer recommends 600,000 to 1 million units daily. Some experts recommend 600,000 to 1.2 million units every 12–24 hours.

Although 3–10 days of anti-infective therapy may be adequate for treatment if mild, uncomplicated cutaneous anthrax occurred as the result of natural or endemic exposures, some experts recommend duration of 7–14 days. CDC and others recommend 60 days of anti-infective treatment if cutaneous anthrax occurred as the result of exposure to aerosolized B. anthracis spores (e.g., in the context of biologic warfare or bioterrorism).

Treatment of Systemic Anthrax (Naturally Occurring or Endemic Exposure)
IV or IM

Penicillin G potassium or sodium: Manufacturers recommend minimum dosage of 8 million units daily given in divided doses every 6 hours; higher dosage may be required depending on susceptibility.

Penicillin G potassium or sodium in adults with inhalational, GI, or meningeal anthrax: Some clinicians recommend 8–12 million units IV daily given in divided doses every 4–6 hours.

Penicillin G potassium or sodium in adults with severe or life-threatening systemic anthrax (inhalational, GI, meningoencephalitis, sepsis) or cutaneous anthrax with signs of systemic involvement or extensive edema: Some clinicians recommend 16–24 million units IV daily (4 million units every 4–6 hours).

Concomitant use of other anti-infectives (e.g., streptomycin or other aminoglycoside, clindamycin, clarithromycin, rifampin, vancomycin) may also be indicated. Continue treatment of naturally occurring or endemic anthrax for ≥14 days after symptoms abate.

Treatment of Systemic Anthrax (Biologic Warfare or Bioterrorism Exposure)
IV

Penicillin G potassium or sodium in adults (including pregnant and postpartum women): 4 million units every 4 hours if penicillin-susceptible B. anthracis involved.

Use in multiple-drug parenteral regimen for initial treatment of systemic anthrax (inhalational, GI, meningitis, cutaneous anthrax with systemic involvement or extensive edema). Continue parenteral regimen for ≥2–3 weeks until patient is clinically stable; treatment can then be switched to an oral regimen. CDC and other experts state that total duration of anti-infective treatment in the context of biologic warfare or bioterrorism should be 60 days.

Clostridium Infections
Botulism
IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 20 million units daily given in divided doses every 4–6 hours. Some clinicians recommend 10–20 million units daily for wound botulism.

Adjunct to botulinum antitoxin. (See Clostridium Infections under Uses.)

Myonecrosis and Gas Gangrene
IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 20 million units daily given in divided doses every 4–6 hours. IDSA recommends 2–4 million units every 4–6 hours in conjunction with clindamycin (600–900 mg IV every 8 hours).

Perform surgical debridement and/or surgery as indicated.

Tetanus
IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 20 million units daily given in divided doses every 4–6 hours.

Adjunct to TIG. (See Clostridium Infections under Uses.)

Diphtheria
Treatment of Diphtheria
IM

Penicillin G procaine: Manufacturer recommends 300,000–600,000 units daily for 14 days. CDC recommends 600,000 units daily in those weighing >10 kg.

Adjunct to diphtheria antitoxin. (See Diphtheria under Uses.)

IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 2–3 million units daily given in divided doses every 4–6 hours for 10–12 days. CDC recommends penicillin G procaine if a penicillin used.

Adjunct to diphtheria antitoxin. (See Diphtheria under Uses.)

Prevention of Diphtheria in Close Contacts†
IM

Penicillin G benzathine: CDC recommends a single dose of 1.2 million units.

Provide anti-infective prophylaxis regardless of immunization status and closely monitor for symptoms of diphtheria for 7 days.

Contacts inadequately immunized against diphtheria or with unknown immunization status: Give immediate dose of age-appropriate preparation containing diphtheria toxoid adsorbed and complete primary series according to recommended schedules.

Contacts fully immunized against diphtheria but received last booster dose ≥5 years previously: Give immediate booster dose of age-appropriate preparation containing diphtheria toxoid adsorbed.

Elimination of Diphtheria Carrier State
IM

Penicillin G benzathine: CDC recommends a single dose of 1.2 million units.

Penicillin G procaine: Manufacturer recommends 300,000 units daily for 10 days. CDC recommends penicillin G benzathine if a penicillin used.

Obtain follow-up cultures ≥2 weeks after treatment of diphtheria carriers; if cultures are positive, give a 10-day course of oral erythromycin and obtain additional follow-up cultures.

Erysipelothrix rhusiopathiae Infections
Uncomplicated Infections (e.g., Erysipeloid)
IM

Penicillin G procaine: Manufacturer recommends 600,000 to 1 million units daily.

Severe Infections (e.g., Endocarditis)
IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 12–20 million units daily given in divided doses every 4–6 hours for 4–6 weeks.

Fusobacterium Infections
Oropharyngeal, Lower Respiratory Tract, or Genital Infections
IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 5–10 million units daily in divided doses every 4–6 hours.

Necrotizing Ulcerative Gingivitis
IM

Penicillin G procaine: Manufacturer recommends 600,000 to 1 million units daily.

Leptospirosis
IV

Penicillin G potassium or sodium: Has been given in a dosage of 6 million units daily (1.5 million units every 6 hours) for 7 days. Initiate anti-infective treatment as soon as possible after symptom onset.

Listeria Infections
Serious Infections
IV

Penicillin G potassium or sodium: Manufacturers recommend 15–20 million units daily in divided doses every 4–6 hours.

Also see Adults: Meningitis Caused by L. monocytogenes, under Dosage and Administration.

Lyme Disease†
Early Lyme Disease with Acute Neurologic Symptoms†
IV

Penicillin G potassium or sodium: 18–24 million units daily given in 6 divided doses (every 4 hours) for 10–28 days.

Late Lyme Disease with Recurrent Lyme Arthritis Symptoms†
IV

Penicillin G potassium or sodium: 18–24 million units daily given in 6 divided doses (every 4 hours) for 14–28 days.

Late Neurologic Lyme Disease†
IV

Penicillin G potassium or sodium: 18–24 million units daily given in 6 divided doses (every 4 hours) for 14–28 days.

Neisseria meningitidis Infections
Serious Infections
IV

Penicillin G potassium or sodium: Manufacturers recommend 24 million units daily (2 million units every 2 hours).

Also see Adults: Meningitis Caused by N. meningitidis, under Dosage and Administration.

Pasteurella multocida Infections
Serious Infections
IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 4–6 million units daily given in divided doses every 4–6 hours for 2 weeks for serious infections, including bacteremia and meningitis.

Rat-bite Fever
IM

Penicillin G procaine: Manufacturer recommends 600,000 to 1 million units daily. Has been given in a dosage of 600,000 units every 12 hours for 10–14 days. Some clinicians state that IV penicillin G potassium or sodium preferred.

IV or IM

Penicillin G potassium or sodium: Manufacturers recommend 12–20 million units daily given in divided doses every 4–6 hours for 3–4 weeks.

Penicillin G potassium or sodium: CDC recommends 1.2 million units IV daily for 5–7 days; if improvement occurs, treatment can be switched to oral penicillin V or oral ampicillin. Some clinicians suggest 400,000–600,000 units IV daily for at least 7 days; if no response occurs within 2 days, increase dosage to 1.2 million units IV daily.

Penicillin G potassium or sodium: Some clinicians suggest 20 million units IV daily given for 4 weeks may be necessary for S. moniliformis endocarditis caused by strain less susceptible to penicillin G (MIC >0.1 mcg/mL); concomitant use of an aminoglycoside (streptomycin or gentamicin) may be indicated for initial treatment.

Syphilis
Primary, Secondary, or Early Latent Syphilis
IM

Penicillin G benzathine: CDC, manufacturers, and others recommend a single dose of 2.4 million units. For pregnant women, some clinicians recommend that a second penicillin G benzathine dose of 2.4 million units be given 1 week after the initial dose.

Penicillin G benzathine for retreatment (no evidence of neurosyphilis): CDC and others recommend 2.4 million units once weekly for 3 successive weeks.

Penicillin G procaine: Manufacturer recommends 600,000 units daily for 8 days (total dosage 4.8 million units). CDC and others recommend penicillin G benzathine for primary, secondary, or early latent syphilis.

Tertiary or Late Latent Syphilis
IM

Penicillin G benzathine: CDC and others recommend 2.4 million units once weekly for 3 successive weeks (total dosage 7.2 million units). Interval between doses should not be >14 days.

Penicillin G procaine: Manufacturer recommends 600,000 units daily for 10–15 days (total dosage 6–9 million units). CDC and others recommend penicillin G benzathine for late latent or tertiary syphilis.

Neurosyphilis and Otic or Ocular Syphilis
IM

Penicillin G benzathine: Manufacturers recommend 2.4 or 3 million units once weekly for 3 weeks; treatment failures reported. CDC and others recommend IV penicillin G potassium or sodium or, alternatively, IM penicillin G procaine (with oral probenecid) for neurosyphilis.

Penicillin G procaine: CDC recommends 2.4 million units once daily for 10–14 days in conjunction with oral probenecid (500 mg every 6 hours for 10–14 days); use only if compliance can be ensured. Some clinicians recommend that this regimen be followed by IM penicillin G benzathine (2.4 million units once weekly for up to 3 weeks).

IV

Penicillin G potassium or sodium: CDC and others recommend 18–24 million units daily (given as 3–4 million units every 4 hours or by continuous IV infusion) for 10–14 days. Some clinicians recommend that this regimen be followed by IM penicillin G benzathine (2.4 million units once weekly for up to 3 weeks).

Penicillin G potassium or sodium: Manufacturers recommend 12–24 million units daily (2–4 million units every 4 hours) for 10–14 days; this may be followed by IM penicillin G benzathine (2.4 million units once weekly for up to 3 weeks).

Whipple's Disease†
IV

Penicillin G potassium or sodium: Some clinicians recommend 10 million units daily for initial treatment. Others recommend 12–24 million units daily (2–4 million units every 4 hours). Regimen of 1.2 million units daily in conjunction with parenteral streptomycin (1 g daily) also recommended. Continue initial parenteral treatment for 2–4 weeks followed by 1–2 years of treatment with an oral regimen (e.g., co-trimoxazole).

Yaws, Pinta, and Bejel
IM

Penicillin G benzathine: Single dose of 1.2 million units recommended by manufacturers and others. For treatment of yaws, a single dose of 2.4 million units has been used.

Penicillin G procaine: Manufacturer states dosage is the same as that recommended for corresponding stage of syphilis.

Prevention of Perinatal Group B Streptococcal (GBS) Disease†
IV

Penicillin G potassium or sodium: Initial dose of 5 million units given at onset of labor or membrane rupture followed by 2.5–3 million units every 4 hours until delivery.

Regardless of whether anti-infective prophylaxis was administered to the mother, initiate appropriate diagnostic evaluations and empiric anti-infective therapy in the neonate if signs or symptoms of active infection develop.

Prevention of Rheumatic Fever Recurrence
IM

Penicillin G benzathine: AHA recommends 1.2 million units once every 4 weeks. Manufacturers recommend 1.2 million units once monthly or 600,000 units once every 2 weeks.

AHA states that 4-week dosing interval seems adequate and is recommended for most US patients, but 3-week dosing interval may be warranted and is recommended when risk of rheumatic fever is particularly high (e.g., recurrent acute rheumatic fever despite adherence to a 4-week regimen). There is some evidence that serum penicillin concentrations may decline to subtherapeutic concentrations before fourth week in some patients

Initiate prophylaxis as soon as rheumatic fever or rheumatic heart disease diagnosed; however, patients with acute rheumatic fever should first receive usually recommended anti-infective regimen for treatment of S. pyogenes (group A β-hemolytic streptococci; GAS) pharyngitis and tonsillitis (see Pharyngitis and Tonsillitis under Uses).

Long-term, continuous prophylaxis required. (See Table 2.)

Table 2. Recommended Duration of Prophylaxis for Prevention of Rheumatic Fever Recurrence292375

Patient Category

Duration

Rheumatic fever without carditis

5 years since last episode or until 21 years of age, whichever is longer

Rheumatic fever with carditis but no residual heart disease (no valvular disease)

10 years since last episode or until 21 years of age, whichever is longer

Rheumatic fever with carditis and residual heart disease (persistent valvular disease)

10 years since last episode or until 40 years of age, whichever is longer; sometimes for life

Special Populations

Renal Impairment

Doses and/or frequency of administration of penicillin G may need modification in response to degree of impairment.

IM or IV penicillin G potassium or sodium: Manufacturers state adjust dosage in patients with severe renal impairment. In patients with Clcr <10 mL/minute per 1.73 m2, manufacturers and others recommend a loading dose using usually recommended dose followed by 50% of usually recommended dose given every 8–10 hours. In uremic patients with Clcr >10 mL/minute per 1.73 m2, manufacturers and others recommend a loading dose using usually recommended dose followed by 50% of usually recommended dose given every 4–5 hours.

Alternatively, some clinicians suggest that if the usual dosing interval for penicillin G potassium or sodium in patients with normal renal function (Clcr >50 mL/minute) is every 6 or 8 hours, then give usual dose every 8–12 hours in those with Clcr 10–50 mL/minute or every 12–18 hours in those with Clcr <10 mL/minute.

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

In patients with impaired hepatic function in addition to impaired renal function, further dosage reductions may be advisable.

Cautions for Penicillin G

Contraindications

  • Penicillin G benzathine, penicillin G procaine, fixed combinations of penicillin G benzathine and penicillin G procaine, penicillin G potassium or sodium: Hypersensitivity to any penicillin.

  • Penicillin G procaine and fixed combinations of penicillin G benzathine and penicillin G procaine: Hypersensitivity to procaine.

  • Commercially available frozen premixed penicillin G potassium injection in dextrose: May be contraindicated in patients with known allergy to corn or corn products.

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Diarrhea and Colitis

Possible emergence and overgrowth of nonsusceptible bacteria or fungi. Monitor carefully; discontinue and institute appropriate therapy if superinfection occurs.

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile. C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including penicillin G, and may range in severity from mild diarrhea to fatal colitis. C. difficile produces toxins A and B which contribute to development of CDAD; hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.

Consider CDAD if diarrhea develops during or after therapy and manage accordingly. Obtain careful medical history since CDAD may occur as late as ≥2 months after anti-infective therapy is discontinued.

If CDAD suspected or confirmed, discontinue anti-infectives not directed against C. difficile as soon as possible. Initiate appropriate anti-infective therapy directed against C. difficile (e.g., vancomycin, fidaxomicin, metronidazole), appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), and surgical evaluation as clinically indicated.

Procaine Toxicity

Immediate toxic reactions to procaine reported rarely with IM penicillin G procaine, especially with large single doses (4.8 million penicillin G units). These reactions may be manifested by mental disturbances (anxiety, confusion, agitation, depression, weakness, seizures, hallucinations, combativeness, fear of impending death) and usually are transient (lasting about 15–30 minutes).

A small percentage of the population is hypersensitive to procaine; sensitivity reactions to IM penicillin G procaine reported. (See Procaine Sensitivity under Cautions.)

Precautions Related to IM Administration

IM penicillin G benzathine, penicillin G procaine, fixed combinations of penicillin G benzathine and penicillin G procaine, penicillin G potassium or sodium: Take special precaution to avoid IV, intravascular, or intra-arterial administration or injection into or near major peripheral nerves or blood vessels.

Inadvertent IV administration of penicillin G benzathine has been associated with cardiorespiratory arrest and death.

Inadvertent intravascular or intra-arterial injection of penicillin G benzathine and/or penicillin G procaine may produce severe and/or permanent neurovascular damage. Transverse myelitis with permanent paralysis, gangrene requiring amputation of digits and more proximal portions of extremities, and necrosis and sloughing at and surrounding injection site reported following inadvertent intravascular administration, including buttock, thigh, and deltoid areas.

Other serious complications of suspected intravascular administration (especially in infants and small children) include immediate pallor, mottling, or cyanosis of the extremity (both distal and proximal to injection site), followed by bleb formation. Severe edema requiring anterior and/or posterior compartment fasciotomy in the lower extremity also reported.

Repeated IM injection of penicillin preparations into the anterolateral thigh has resulted in quadriceps femoris fibrosis and atrophy.

If evidence of compromise of the blood supply occurs at or proximal or distal to administration site, consult appropriate specialist immediately.

Precautions Related to IV Administration

IV penicillin G potassium or sodium: Use caution; possibility of phlebitis and thrombophlebitis.

Administer large IV doses slowly because of potential for serious electrolyte disturbances. (See Electrolyte Imbalance under Cautions.)

Neurotoxic reactions (e.g., hyperreflexia, myoclonic twitches, seizures, coma) reported with massive IV doses of penicillin G. Renal tubular damage and interstitial nephritis (e.g., fever, rash, eosinophilia, proteinuria, esophinophiluria, hematuria, increased BUN concentrations) reported with large IV doses of penicillin G. These reactions most likely to occur in patients with impaired renal function.

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, reported with penicillins. Hypersensitivity reactions are the most frequent adverse effects of penicillins.

Hypersensitivity reactions to penicillins may be immediate (usually occurring within 20 minutes of administration) and range in severity from urticaria and pruritus to angioedema, laryngospasm, bronchospasm, hypotension, vascular collapse, and death. Accelerated reactions (usually occurring between 20 minutes to 48 hours after administration) may include urticaria, pruritus, fever and, occasionally, laryngeal edema. Delayed reactions (usually occurring within 1–2 weeks after initiation of penicillin therapy) may include serum sickness-like symptoms (i.e., fever, malaise, urticaria, myalgia, arthralgia, abdominal pain) and rash ranging from maculopapular eruptions to exfoliative dermatitis.

Prior to administration, make careful inquiry regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. There is clinical and laboratory evidence of partial cross-allergenicity among penicillins and other β-lactam antibiotics including cephalosporins and cephamycins.

Hypersensitivity reactions to penicillins more likely to occur in individuals with a history of penicillin hypersensitivity and/or history of sensitivity to multiple allergens. Use with caution in patients with history of clinically important allergies and/or asthma.

If hypersensitivity reaction occurs, discontinue immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).

Desensitization to penicillins 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). Usually performed in a hospital setting; expert consultation may be indicated. Consult specialized references for specific information on sensitivity testing and desensitization protocols.

Procaine Sensitivity

A small percentage of patients are sensitive to procaine. If considering use of penicillin G procaine or fixed combinations of penicillin G benzathine and penicillin G procaine in patient with history of procaine sensitivity, give a test dose of procaine (0.1 mL of a 1–2% procaine solution) intradermally prior to IM administration of full doses of penicillin G procaine or fixed combination containing penicillin G procaine. Development of erythema, wheal, flare, or eruption at intradermal test site indicates procaine sensitivity and patient should not receive any preparation containing penicillin G procaine.

If a hypersensitivity reaction to procaine occurs, treat with usual methods; antihistamines may be beneficial and barbiturates should be used if seizures occur.

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of penicillin G and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

Because penicillin susceptibility can no longer be assumed, routinely test staphylococci or S. pneumoniae isolates for in vitro susceptibility.

IM or IV penicillin potassium or sodium: Use for treatment of severe infections caused by susceptible organisms when rapid and high concentrations of penicillin G required.

IM penicillin G benzathine or IM penicillin G procaine: Use only for treatment of mild to moderately severe infections caused by organisms susceptible to low concentrations of penicillin G. IM penicillin G benzathine also can be used for prophylaxis of infections caused by organisms susceptible to low concentrations of penicillin G or as follow-up therapy to IM or IV penicillin G potassium or sodium.

Fixed combinations of penicillin G benzathine and penicillin G procaine (Bicillin C-R, Bicillin C-R 900/300): Use only for labeled indications, including treatment of moderately severe to severe infections caused by susceptible organisms. Do not use for treatment of any venereal diseases, including syphilis, yaws, bejel, or pinta.

Jarisch-Herxheimer Reactions

Jarisch-Herxheimer reactions may occur in patients receiving penicillin G for treatment of syphilis or other spirochetal infections (e.g., leptospirosis, Lyme disease, relapsing fever).

These reactions usually begin 1–2 hours after initiation of the drug, resolve within 12–24 hours, and are characterized by fever, chills, myalgias, headache, exacerbation of cutaneous lesions, tachycardia, hyperventilation, vasodilation with flushing, and mild hypotension.

Laboratory Monitoring

Periodically assess renal, hepatic, and hematologic systems during prolonged therapy, especially if high dosage is used.

Electrolyte Imbalance

Penicillin G potassium or sodium: Serious and potentially fatal electrolyte disturbances may occur, particularly if high IV dosage used.

Massive IV dosages of penicillin G sodium has resulted in a syndrome of hypokalemia, metabolic alkalosis, and hypernatremia. Although it has been suggested that hypokalemia during penicillin G potassium therapy may result from redistribution of potassium within the body, the effect appears to be related to the fact that penicillins act as nonabsorbable anions in the distal renal tubules and therefore promote urinary loss of potassium.

Assess electrolyte balance and cardiac and vascular status in patients receiving penicillin G potassium or sodium, especially if high doses are given IV.

Administer large IV doses of penicillin G potassium (>10 million penicillin G units) slowly because of potential effects on electrolyte balance.

Potassium and Sodium Content

Penicillin G potassium powder for injection: Each 1 million penicillin G units contains approximately 66 mg (1.7 mEq) of potassium and approximately 7 mg (0.3 mEq) of sodium.

Frozen premixed penicillin G potassium injection in dextrose: Each 1 million penicillin G units contains approximately 1.7 mEq of potassium and approximately 1 mEq of sodium.

Penicillin G sodium powder for injection: Each 1 million penicillin G units contains approximately 1.7 mEq of sodium.

Specific Populations

Pregnancy

Reproduction studies evaluating penicillin G in mice, rats, and rabbits have not revealed evidence of impaired fertility or harm to the fetus.

Although experience using 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.

Some clinicians state penicillin G is considered low risk and safe for use during pregnancy. Penicillin G is included in CDC recommendations for treatment of syphilis during pregnancy.

Manufacturers state use penicillin G during pregnancy only when clearly needed.

Lactation

Distributed into milk. Some clinicians state penicillin G usually considered compatible with breast-feeding. The manufacturers and others state use with caution in nursing women.

Pediatric Use

Renal clearance of penicillin G may be delayed in neonates and premature or young infants because of incompletely developed renal function.

Penicillin G potassium or sodium: Make appropriate reductions in dosage and frequency of administration. When used in neonates, monitor closely for clinical and laboratory evidence of toxic or adverse effects.

Geriatric Use

Clinical studies of penicillin G benzathine, penicillin G procaine, and penicillin G potassium did not include sufficient numbers of patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients. Other clinical experience has not identified differences in responses between geriatric and younger patients.

Penicillin G is substantially eliminated by the kidneys and risk of adverse effects may be greater in those with impaired renal function. Because geriatric patients more likely to have reduced renal function, select dosage with caution, usually starting at low end of dosage range, and consider monitoring renal function.

Penicillin G potassium or sodium: Consider potassium and/or sodium content and potential for electrolyte imbalance; geriatric patients may respond with a blunted natriuresis to salt loading that may be clinically important in those with certain conditions (e.g., CHF).

Renal Impairment

Dosage adjustments may be needed based on degree of renal impairment. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Hypersensitivity reactions (rash, urticaria, serum sickness); local effects.

Interactions for Penicillin G

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Aminoglycosides

In vitro evidence of synergistic antibacterial effects against enterococci or viridans streptococci used to therapeutic advantage in treatment of certain infections (e.g., enterococcal endocarditis)

Physical and/or chemical incompatibility between penicillins and aminoglycosides; potential in vitro or in vivo inactivation of aminoglycoside

If concomitant use indicated, administer separately

Chloramphenicol

Possible in vitro antagonism; clinical importance unclear

Avoid concomitant use

Erythromycins

Possible in vitro antagonism; clinical importance unclear

Avoid concomitant use

Ethacrynic acid

Possible decreased renal tubular secretion of penicillin G resulting in increased half-life and prolonged serum concentrations of the penicillin

Furosemide

Possible decreased renal tubular secretion of penicillin G resulting in increased half-life and prolonged serum concentrations of the penicillin

Methotrexate

Penicillins may decrease renal clearance of methotrexate; possible increased methotrexate concentrations and hematologic and GI toxicity

Monitor closely if used concomitantly

NSAIAs

Aspirin, indomethacin: Possible decreased renal tubular secretion of penicillin G resulting in increased half-life and prolonged serum concentrations of the penicillin

Probenecid

Decreased renal tubular secretion of penicillin G; increased and prolonged penicillin G serum concentrations may occur; CSF concentrations also may be increased

Sulfonamides

Possible in vitro antagonism; clinical importance unclear

Avoid concomitant use

Thiazide diuretics

Possible decreased renal tubular secretion of penicillin G resulting in increased half-life and prolonged serum concentrations of the penicillin

Tests for glucose

Possible false-positive reactions in urine glucose tests using Clinitest, Benedict’s solution, or Fehling’s solution

Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix, Tes-Tape)

Tests for uric acid

Possible falsely increased serum uric acid concentrations when copper-chelate method is used; phosphotungstate and uricase methods appear to be unaffected

Tetracyclines

Possible in vitro antagonism; clinical importance unclear

Avoid concomitant use

Penicillin G Pharmacokinetics

Absorption

Bioavailability

Penicillin G benzathine, penicillin G procaine: Relatively insoluble; IM administration provides a tissue depot from which the drugs are slowly absorbed and hydrolyzed to penicillin G. IM administration results in serum concentrations of penicillin G that are more prolonged, but lower, than those attained with an equivalent IM dose of penicillin G potassium or sodium.

Penicillin G benzathine: IM administration of a single dose in adults, children, or neonates results in peak serum concentrations of penicillin G that are attained in 13–24 hours and usually detectable for 1–4 weeks (depending on the dose).

Penicillin G procaine: IM administration of a single dose in adults or neonates results in peak serum concentrations of penicillin G that are attained in 1–4 hours and usually detectable for 1–2 days; may be detectable in serum for up to 5 days (depending on the dose). In general, increasing the dose to >600,000 units tends to prolong duration of penicillin G serum concentrations rather than increase peak serum concentrations.

Fixed combination of penicillin G benzathine and penicillin G procaine containing 1.2 million penicillin G units (i.e., 600,000 units as penicillin G benzathine with 600,000 units as penicillin G procaine; Bicillin C-R): Single IM dose of 1.2 million penicillin G units in adults usually produces peak blood penicillin G concentrations of 2.1–2.6 units/mL within 3 hours and concentrations average 0.75 units/mL at 12 hours, 0.28 units/mL at 24 hours, and 0.04 units/mL at 7 days.

Fixed combination of penicillin G benzathine and penicillin G procaine containing 1.2 million penicillin G units (i.e., 900,000 units as penicillin G benzathine with 300,000 units as penicillin G procaine; Bicillin C-R 900/300): Single IM dose of 1.2 million penicillin G units in patients weighing 45–64 kg resulted in average blood penicillin G concentrations of 0.24 units/mL at 24 hours, 0.039 units/mL at 7 days, and 0.024 units/mL at 10 days after the dose.

Penicillin G potassium or sodium: Rapidly absorbed followed IM administration; peak serum concentrations of penicillin G generally similar with equivalent IM doses of either salt and attained within 15–30 minutes.

Penicillin G potassium or sodium: Following IV infusion, peak serum concentrations attained immediately after infusion completed. In 10 patients who received 5 million penicillin G units 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. In 5 healthy adults who received 1 million penicillin G units given IV over 4 minutes or IV over 60 minutes, mean serum concentrations 8 minutes after administration were 45 or 14.4 mcg/mL, respectively.

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

Penicillin G potassium or sodium: Absorbed from peritoneal cavity following local instillation; also absorbed from pleural surfaces, pericardium, and joint cavities.

Distribution

Extent

Penicillin G widely distributed following absorption from IM or IV administration sites. Highest concentrations generally attained in the kidneys, with lower amounts in the liver, lungs, skin, intestines, and muscle. Also distributed into ascitic, synovial, pleural, pericardial, peritoneal, and interstitial fluids and tonsils, maxillary sinus secretions, and saliva.

Minimal concentrations of penicillin G generally attained in CSF following IM or IV administration of penicillin G potassium or sodium or IM administration of penicillin G benzathine or penicillin G procaine in patients with uninflamed meninges; higher CSF concentrations attained when meninges are inflamed or when oral probenecid administered concomitantly.

Crosses the placenta and is distributed into milk.

Plasma Protein Binding

45–68%.

Elimination

Metabolism

Penicillin G benzathine, penicillin G procaine: Slowly absorbed following IM administration and hydrolyzed to penicillin G.

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

Elimination Route

Penicillin G and its metabolites excreted in urine mainly by tubular secretion. Small amounts of the drug also are excreted in bile.

Penicillin G benzathine, penicillin G procaine: Following IM administration, slowly absorbed and excretion of penicillin G in urine continues over a prolonged period of time. Penicillin G has been detected in urine for up to 12 weeks after a single IM dose of 1.2 million units given as penicillin G benzathine.

Penicillin G sodium or potassium: Following single IM or IV dose in adults with normal renal function, 58–85% of the dose excreted in urine as unchanged drug and active metabolites within 6 hours.

Removed by hemodialysis and, to a lesser extent, by peritoneal dialysis.

Half-life

Adults with normal renal function: 0.4–0.9 hours.

Neonates: Serum half-life varies inversely with age and appears to be independent of birthweight. Serum half-life reported to be 3.2–3.4 hours in neonates ≤6 days of age, 1.2–2.2 hours in neonates 7–13 days of age, and 0.9–1.9 hours in neonates ≥14 days of age.

Special Populations

Renal impairment: Serum concentrations of penicillin G may be higher and the serum half-life prolonged. Serum half-life is 1–2 hours in azotemic patients with serum creatinine concentrations <3 mg/dL and ranges from 6–20 hours in anuric patients.

Anuric patients with hepatic impairment: Serum half-life of penicillin G may be 2–3 times more prolonged compared with anuric patients with normal hepatic function.

Neonates and premature or young infants: Renal clearance of penicillin G may be delayed.

Geriatric patients: Renal clearance of penicillin G may be delayed because of diminished tubular secretion ability.

Pregnant women: Renal clearance of penicillin G may be increased during second and third trimesters.

Stability

Storage

Parenteral

Powder for IM or IV Use

Penicillin G potassium: <30°C. Following reconstitution, store at 2–8°C for up to 7 days.

Penicillin G sodium: 20–25°C. Following reconstitution, store at 2–8°C for up to 3 days.

Suspension for IM Injection

Penicillin G benzathine: 2–8°C; do not freeze.

Penicillin G procaine: 2–8°C; do not freeze.

Fixed combinations of penicillin G benzathine and penicillin G procaine: 2–8°C; do not freeze.

Injection (Frozen)

Penicillin G potassium: −20°C or lower. Thawed solutions are stable for 24 hours at room temperature (25°C) or 14 days when refrigerated at 5°C.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility (Penicillin G Potassium)HID

Compatible

Amino acids 4.25%, dextrose 25%

Dextrose 2.5 or 5% in half-strength Ringer’s injection

Dextrose 5% in Ringer’s injection

Dextrose 2.5, 5, or 10% in Ringer’s injection, lactated

Dextrose 2.5% in sodium chloride 0.45 or 0.9%

Dextrose 5% in sodium chloride 0.225, 0.45, or 0.9%

Dextrose 2.5, 5, or 10% in water

Ionosol B or MB in dextrose 5%

Isolyte M or P in dextrose 5%

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Drug Compatibility
Admixture Compatibility (Penicillin G Potassium)HID

Compatible

Amikacin sulfate

Ascorbic acid

Calcium chloride

Calcium gluconate

Chloramphenicol sodium succinate

Colistimethate sodium

Dimenhydrinate

Diphenhydramine HCl

Ephedrine sulfate

Erythromycin lactobionate

Furosemide

Hydrocortisone sodium succinate

Kanamycin sulfate

Lidocaine HCl

Lincomycin HCl

Magnesium sulfate

Methylprednisolone sodium succinate

Metronidazole

Polymyxin B sulfate

Potassium chloride

Ranitidine HCl

Verapamil HCl

Incompatible

Aminophylline

Amphotericin B

Chlorpromazine HCl

Dopamine HCl

Hydroxyzine HCl

Pentobarbital sodium

Prochlorperazine mesylate

Tranexamic acid

Variable

Heparin sodium

Promethazine HCl

Sodium bicarbonate

Y-site Compatibility (Penicillin G Potassium)HID

Compatible

Acyclovir sodium

Amiodarone HCl

Ceftolozane sulfate-tazobactam sodium

Cyclophosphamide

Diltiazem HCl

Enalaprilat

Esmolol HCl

Fluconazole

Foscarnet sodium

Heparin sodium

Hydrocortisone sodium succinate

Hydromorphone HCl

Labetalol HCl

Magnesium sulfate

Meperidine HCl

Morphine sulfate

Nicardipine HCl

Potassium chloride

Tacrolimus

Theophylline

Verapamil HCl

Incompatible

Tedizolid

Variable

Isavuconazonium sulfate

Solution Compatibility (Penicillin G Sodium)HID

Variable

Dextrose 5% in water

Sodium chloride 0.9%

Drug Compatibility (Penicillin G Sodium)
Admixture CompatibilityHID

Compatible

Calcium chloride

Calcium gluconate

Chloramphenicol sodium succinate

Colistimethate sodium

Dextran 40

Diphenhydramine HCl

Erythromycin lactobionate

Gentamicin sulfate

Hydrocortisone sodium succinate

Lincomycin HCl

Polymyxin B sulfate

Ranitidine HCl

Verapamil HCl

Incompatible

Amphotericin B

Bleomycin sulfate

Chlorpromazine HCl

Cytarabine

Hydroxyzine HCl

Methylprednisolone sodium succinate

Prochlorperazine mesylate

Promethazine HCl

Variable

Heparin sodium

Potassium chloride

Y-Site Compatibility (Penicillin G Sodium)HID

Compatible

Clarithromycin

Levofloxacin

Actions and Spectrum

  • Penicillin G is a β-lactam antibacterial classified as a natural penicillin.

  • Available as penicillin G benzathine, penicillin G procaine, and fixed combinations of penicillin G benzathine and penicillin G procaine; these preparations are referred to as long-acting, depot, or repository forms of penicillin G.

  • Available as penicillin G potassium and penicillin G sodium; these preparations are referred to as aqueous, crystalline forms of penicillin G.

  • Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis. Usually bactericidal against susceptible organisms. Induces a postantibiotic effect (PAE) in some susceptible bacteria.

  • Spectrum of activity of penicillin G includes some non-β-lactamase-producing gram-positive and -negative aerobes, some gram-positive anaerobes, and most spirochetes. Generally inactive against mycobacteria, Chlamydia, Mycoplasma, Rickettsia, and fungi.

  • Gram-positive aerobes: Active in vitro against streptococci, including S. pyogenes (group A β-hemolytic streptococci; GAS), other β-hemolytic streptococci (e.g., groups C, G, H, L, M, R), S. agalactiae (group B streptococci; GBS), and some strains of S. pneumoniae, α-hemolytic streptococci (including viridans streptococci), and nonenterococcal group D streptococci. Active against some non-penicillinase-producing Staphylococcus. Also active against some strains of Bacillus anthracis, Corynebacterium diphtheriae, Erysipelothrix rhusiopathiae, and Listeria monocytogenes. Some strains of enterococci are susceptible to penicillin G, but many strains are resistant and penicillin tolerance reported.

  • Gram-negative aerobes: Active in vitro against Neisseria meningitidis, non-β-lactamase-producing H. influenzae, Bordetella pertussis, Eikenella corrodens, Kingella kingae, Legionella, and Pasteurella multocida. Generally inactive against Enterobacteriaceae and Pseudomonas.

  • Anaerobes: Active in vitro against Actinomyces, Clostridium (including C. botulinum, C. perfringens, and C. tetani), Cutibacterium acnes (formerly Propionibacterium acnes), Eubacterium, Lactobacillus, Peptococcus, Peptostreptococcus, and Veillonella. C. botulinum resistant to penicillin reported. Although Fusobacterium and some strains of Bacteroides melaninogenicus or B. oralis may be susceptible, B. fragilis usually resistant.

  • Spirochetes: Active against Treponema pallidum, Leptospira, Streptobacillus moniliformis, Spirillum minus, and Borrelia hemsii. Also active against B. burgdorferi.

  • Penicillinase-producing bacteria, including penicillinase-producing S. aureus, S. epidermidis, and Neisseria, are resistant. S. pneumoniae resistant to penicillin G, including strains that are relatively or highly resistant, reported with increasing frequency.

Advice to Patients

  • Advise patients that antibacterials (including penicillin G) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).

  • Importance of completing full course of therapy, even if feeling better after a few days.

  • Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with penicillin G or other antibacterials in the future.

  • Importance of discontinuing therapy if an allergic reaction occurs.

  • Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued. Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.

  • Importance of informing clinician of existing or contemplated therapy, including prescription and OTC drugs, and any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of advising patients of other important precautionary information. (See Cautions.)

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.

Penicillin G Benzathine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Suspension, for IM Injection

600,000 units (of penicillin G) per mL

Bicillin L-A

Pfizer

Permapen

Casper

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

Penicillin G Potassium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

1 million units (of penicillin G)*

Penicillin G Potassium for Injection

5 million units (of penicillin G)*

Penicillin G Potassium for Injection

Pfizerpen

Pfizer

20 million units (of penicillin G)*

Penicillin G Potassium for Injection

Pfizerpen

Pfizer

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

Penicillin G Potassium in Dextrose

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection (frozen), for IV infusion

20,000 units (of penicillin G) per mL (1 million units) in 4% Dextrose*

Penicillin G Potassium in Iso-osmotic Dextrose Injection Galaxy

40,000 units (of penicillin G) per mL (2 million units) in 2.4% Dextrose*

Penicillin G Potassium in Iso-osmotic Dextrose Injection Galaxy

60,000 units (of penicillin G) per mL (3 million units) in 0.7% Dextrose*

Penicillin G Potassium in Iso-osmotic Dextrose Injection Galaxy

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

Penicillin G Procaine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Suspension, for IM Injection

600,000 units (of penicillin G) per mL*

Penicillin G Procaine Suspension

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

Penicillin G Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

5 million units (of penicillin G)*

Penicillin G Sodium for Injection

Penicillin G Benzathine and Penicillin G Procaine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Suspension, for IM Injection

1.2 million units of penicillin G per 2 mL (600,000 units as penicillin G benzathine and 600,000 units as penicillin G procaine)

Bicillin C-R

Pfizer

1.2 million units of penicillin G per 2 mL (900,000 units as penicillin G benzathine and 300,000 units as penicillin G procaine)

Bicillin C-R 900/300

Pfizer

AHFS DI Essentials™. © Copyright 2022, Selected Revisions October 1, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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