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: Bicillin C-R, Bicillin C-R 900/300, Bicillin L-A, Permapen, Pfizerpen
Penicillin G benzathine (Bicillin C-R, Bicillin C-R 900/300),14 15 penicillin G procaine,7 and fixed combination containing penicillin G benzathine and penicillin G procaine (Bicillin L-A)6 are administered by deep IM injection only and should not be injected IV or admixed with other IV solutions.
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.6 7 14 15 16
Inadvertent IV administration of penicillin G benzathine has been associated with cardiorespiratory arrest and death.6 14 15 16
Introduction
Antibacterial; β-lactam antibiotic; natural penicillin. Available as penicillin G benzathine, penicillin G potassium, penicillin G procaine, and penicillin G sodium.1 6 7
Uses for Penicillin G Benzathine/Potassium/Sodium
Endocarditis
Treatment of native valve endocarditis caused by penicillin-susceptible staphylococci. Consider that the majority of staphylococci are resistant to penicillin G and must be treated with a penicillinase-resistant penicillin (e.g., nafcillin, oxacillin).5
Treatment of endocarditis caused by Streptococcus pyogenes (group A β-hemolytic streptococci).7
Treatment of native valve or prosthetic valve endocarditis caused by viridans streptococci (e.g., S. milleri, S. mitis, S. mutans) or S. bovis (nonenterococcal group D streptococcus).5 Used alone or in conjunction with gentamicin.5
Treatment of enterococcal endocarditis;5 9 used in conjunction with an aminoglycoside.5
Meningitis and Other CNS Infections
Treatment of meningitis caused by nonpenicillinase-producing S. aureus or S. epidermidis.1 Consider that the majority of staphylococci are resistant to penicillin G.
Treatment of meningitis caused by susceptible S. pneumoniae.1 Consider that S. pneumoniae with intermediate resistance or complete resistance to penicillin G have been reported with increasing frequency; treatment failures have occurred when penicillin G was used alone in treatment of CNS infections caused by these strains.
Treatment of meningitis caused by susceptible S. agalactiae (group B streptococci). Ampicillin usually the preferred penicillin for empiric treatment of neonatal S. agalactiae meningitis; treatment can be changed to penicillin G after in vitro susceptibility testing is completed.
Treatment of meningitis caused by L. monocytogenes; used alone or in conjunction with an aminoglycoside (e.g., gentamicin).1 Ampicillin in conjunction with an aminoglycoside usually is the regimen of choice for L. monocytogenes meningitis.
Treatment of meningitis caused by Neisseria meningitidis.1 9 Drug of choice.
Pharyngitis and Tonsillitis
Treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A β-hemolytic streptococci).6 8 11 12 13
AAP, IDSA, AHA, and others recommend oral penicillin V or IM penicillin G benzathine as treatments of choice;8 9 11 12 13 oral cephalosporins and oral macrolides are considered alternatives.8 11 12 13 Amoxicillin sometimes used instead of penicillin V, especially for young children.8 13
A second episode can be retreated with the same or other treatment of choice;8 13 other regimens (amoxicillin and clavulanate, clindamycin, penicillin G benzathine with or without rifampin) recommended for symptomatic patients with multiple, recurrent episodes.8 11 13
Consider that multiple, recurrent episodes of symptomatic pharyngitis within several months to years may indicate that a streptococcal carrier experiencing repeated episodes of nonstreptococcal (e.g., viral) pharyngitis;11 13 treatment not usually recommended for streptococcal pharyngeal carriers.8 11 13
Respiratory Tract Infections
Treatment of respiratory tract infections caused by susceptible streptococci, including S. pneumoniae.1 6 7 Consider that S. pneumoniae with intermediate resistance or complete resistance to penicillin G have been reported with increasing frequency.
Septicemia
Treatment of bacteremia caused by susceptible streptococci.1
Has been used for treatment of bacteremia caused by susceptible Acinetobacter faecalis, Enterobacter aerogenes, Escherichia coli, Proteus mirabilis, Salmonella, and Shigella,1 but other more effective anti-infectives (e.g., third generation cephalosporins, aminoglycosides, aminopenicillins, extended-spectrum penicillins) are preferred for these infections.
Skin and Skin Structure Infections
Treatment of skin and skin structure infections caused by susceptible staphylococci or streptococci.7
Drug of choice for treatment of severe S. pyogenes infections, including cellulitis, erysipelas, and necrotizing fasciitis; if presence of staphylococci is suspected, a penicillinase-resistant penicillin (with or without vancomycin) usually is used.
Actinomycosis
Treatment of actinomycosis;1 9 drug of choice for all forms of actinomycosis, including thoracic, abdominal, CNS, and cervicofacial infections.9
Anthrax
Treatment of clinically apparent inhalational, GI, or meningeal anthrax or anthrax septicemia caused by susceptible Bacillus anthracis that occurs as the result of natural or endemic exposures to the organism.1 7 9 1 Considered a drug of choice, but B. anthracis with naturally-occurring penicillin resistance have been reported rarely and there are published reports of strains engineered to have penicillin and tetracycline resistance as well as resistance to other anti-infectives (e.g., macrolides, chloramphenicol, rifampin).
Alternative for use in multiple-drug regimens for treatment of anthrax that occurs as the result of exposure to B. anthracis spores in the context of biologic warfare or bioterrorism. Initiate treatment with IV ciprofloxacin or doxycycline and 1 or 2 anti-infectives predicted to be effective (e.g., chloramphenicol, clindamycin, rifampin, vancomycin, clarithromycin, imipenem, penicillin, ampicillin); if meningitis is established or suspected, use IV ciprofloxacin (rather than doxycycline) and chloramphenicol, rifampin, or penicillin. Because of concerns regarding possible penicillin resistance or induction of penicillin resistance during treatment, use of a penicillin alone is not recommended for treatment of inhalational anthrax that occurs as the result of biologic warfare or bioterrorism when high concentrations of the organism are likely to be present, although penicillin can be included in appropriate combination regimens.
Treatment of mild, uncomplicated cutaneous anthrax caused by susceptible B. anthracis that occurs as the result of naturally occurring or endemic exposure to anthrax. If cutaneous anthrax occurs in the context of biologic warfare or bioterrorism, initial drugs of choice are ciprofloxacin or doxycycline. If penicillin susceptibility is confirmed, consideration can be given to changing to a penicillin in infants and children or in pregnant or lactating women; amoxicillin usually is recommended.
Alternative for postexposure prophylaxis of anthrax following exposure to B. anthracis spores (inhalational anthrax). Ciprofloxacin and doxycycline are initial drugs of choice following suspected or confirmed bioterrorism-related anthrax exposure. If penicillin susceptibility is confirmed, consideration can be given to changing prophylaxis to a penicillin (e.g., amoxicillin, penicillin V, penicillin G procaine) in infants and children and in pregnant or lactating women; amoxicillin usually is recommended.
Clostridium Infections
Treatment of infections caused by Clostridium perfringens, including empyema and gas gangrene.1 9 The drug of choice.9 In treatment of gas gangrene, used as an adjunct to debridement and excision of the infected area; hyperbaric oxygen therapy also may be useful in the management of spreading, necrotic types of infections.9
Adjunct to tetanus immune globulin (TIG), tetanus toxoid adsorbed, sedatives, and muscle relaxants in the treatment of active tetanus infection.1 9 Although C. tetani is susceptible to penicillin G, the nature of the infected wound generally makes the organism inaccessible to anti-infectives. Anti-infective agents cannot neutralize toxin already formed and cannot eradicate C. tetani spores which may revert to toxin-producing vegetative forms. Treatment of a tetanus wound consists of surgical debridement and prevention of associated infections that could create an anaerobic environment and help proliferation of C. tetani.
Adjunct to active immunization with tetanus toxoid or, preferably, tetanus toxoid adsorbed and passive immunization with TIG in the prophylactic treatment of individuals with tetanus-prone wounds (e.g., a severe deep puncture wound). ACIP states that chemoprophylaxis against tetanus is neither practical nor useful in managing wounds and proper immunization is the most important measure.
Adjunct in the treatment of wound botulism caused by germination of C. botulinum spores in a contaminated wound with in vivo toxin production. Anti-infective agents have no known direct effects on botulinum toxin and therefore are not usually indicated in the management of most forms of botulism (foodborne botulism, infant botulism, adult or child infectious botulism), except for the treatment of secondary infection (e.g., respiratory or urinary tract infections). If anti-infective therapy is needed for the treatment of secondary infection in a patient with botulism, aminoglycosides, tetracyclines, and clindamycin should not be used since these anti-infective agents may exacerbate neuromuscular blockade.
Treatment strategies for most forms of botulism include intensive supportive care (including aggressive use of respiratory care) and prompt administration of botulinum antitoxin when appropriate. Botulinum antitoxin also may be indicated for botulism that occurs in the context of biologic warfare or bioterrorism. Timely administration of botulinum antitoxin is important since it can minimize subsequent nerve damage but will not reverse existent paralysis. Botulinum antitoxin is not commercially available in the US but is available from the CDC.
The mainstay of treatment of foodborne botulism, infant botulism, and adult and child infectious botulism is use of botulinum antitoxin and supportive care. Anti-infectives are not indicated for the treatment of these forms of botulism since lysis of intraluminal C. botulinum may increase the amount of toxin in the body, but anti-infectives may be used for the treatment of secondary infections if necessary.
Diphtheria
Adjunct to diphtheria antitoxin for treatment of diphtheria caused by Corynebacterium diphtheriae.1 7 9 Diphtheria antitoxin is the most important aspect of treatment of respiratory diphtheria. Anti-infectives may eliminate C. diphtheriae from infected sites, prevent spread of the organism and further toxin production, and prevent or terminate the diphtheria carrier state, but appear to be of no value in neutralizing diphtheria toxin and should not be considered a substitute for antitoxin therapy.
Because diphtheria infection often does not confer immunity, active immunization with a diphtheria toxoid preparation should be initiated or completed during convalescence.
Prevention of diphtheria in close contacts of patients with respiratory or cutaneous diphtheria. Prophylaxis is indicated in all household or other close contacts of individuals with suspected or proven diphtheria, regardless of vaccination status; prophylaxis should be initiated promptly and should not be delayed pending culture results. An age-appropriate diphtheria toxoid preparation also may be indicated.
Elimination of diphtheria carrier state in individuals known to carry toxigenic strains of C. diphtheriae.1
Erysipelothrix rhusiopathiae Infections
Treatment of infections caused by Erysipelothrix rhusiopathiae, including erysipeloid or endocarditis.1 7 9 A drug of choice.9
Leptospirosis
Treatment of leptospirosis†.9 A drug of choice.9 Many leptospiral infections are self-limited, and the effectiveness of anti-infective therapy in the treatment of the disease has been questioned. Anti-infective therapy initiated after the fifth day of illness probably will not alter the course of the disease.
Listeria Infections
Treatment of infections caused by L. monocytogenes (e.g., infections during pregnancy, granulomatosis infantiseptica, sepsis, meningitis, endocarditis, foodborne infections).1 Ampicillin used alone or in conjunction with gentamicin or streptomycin generally is considered the treatment of choice for these infections.
For treatment of foodborne Listeria infections, the CDC recommends use of ampicillin, penicillin G, or co-trimoxazole when there is invasive disease.
Lyme Disease
Treatment of early or late Lyme disease† when a parenteral regimen is indicated.9
Treatment of late Lyme disease when neurologic manifestations affecting the CNS or peripheral nervous system are present.
Alternative to IV ceftriaxone or IV cefotaxime for patients with late neurologic disease affecting the CNS or peripheral nervous system (e.g., encephalopathy, neuropathy). Treatment of neurologic (e.g., radicular pain, motor deficits) abnormalities in patients with Lyme meningitis† or arthritis associated with Lyme disease†. Ceftriaxone may be preferable to penicillin G for serious manifestations of early disseminated or late Lyme disease (i.e., those involving major organs) based on ceftriaxone’s greater in vitro and in vivo activity against B. burgdorferi, excellent CSF penetration, and prolonged serum concentrations achievable with once-daily administration.
Necrotizing Ulcerative Gingivitis
Treatment of acute necrotizing ulcerative gingivitis (Vincent’s infection, trench mouth, Fusobacterium gingivitis or pharyngitis, Leptotrichia buccalis infection).1 7 9
Neisseria Infections
Treatment of upper respiratory tract infections, bacteremia, and meningitis caused by N. meningitidis.1 (See Meningitis and Other CNS Infections under Uses.) The drug of choice for most meningococcal infections.
Does not eliminate the meningococcus carrier state and should not be used for chemoprophylaxis in asymptomatic N. meningitidis carriers. Ceftriaxone, ciprofloxacin, or rifampin usually used to eliminate nasopharyngeal carriage of N. meningitidis.
Should not be used for treatment of gonorrhea.7 14 15 Previously used for treatment of uncomplicated gonorrhea and disseminated gonococcal infections caused by susceptible nonpenicillinase-producing N. gonorrhoeae.1 No longer recommended by CDC or other experts (high incidence of penicillinase-producing strains).
Pasteurella Infections
Treatment of infections caused by Pasteurella multocida; a drug of choice for local infections, septicemia, osteomyelitis, endocarditis, or other serious infections.1 9
Rat-bite Fever
Treatment of rat-bite fever caused by Streptobacillus moniliformis (erythema arthriticum epidemicum, Haverhill fever) or Spirillum minus (sodoku).1 7 9 Drug of choice.9
Relapsing Fever
Alternative to tetracyclines for treatment of tick-borne (endemic) or louse-borne (epidemic) relapsing fever† caused by Borrelia.
Syphilis
Treatment of syphilis.1 6 7 Penicillin G is drug of choice for all stages and forms of syphilis, including primary infection (i.e., ulcer or chancre at the infection site), secondary infection (i.e., manifestations that include rash, mucocutaneous lesions, and adenopathy), tertiary infection (i.e., cardiac, ophthalmic, auditory, or gummatous lesions), early latent syphilis (latent syphilis acquired within the preceding year), late latent syphilis or latent syphilis of unknown duration, neurosyphilis, and congenital syphilis.
Penicillin G benzathine is drug of choice for treatment of primary syphilis, secondary syphilis, latent syphilis, and tertiary syphilis in adults, adolescents, and children.
Penicillin G potassium or penicillin G sodium is drug of choice for treatment of neurosyphilis in adults and adolescents; alternatively, penicillin G procaine (with oral probenecid) may be used if compliance can be ensured.
Penicillin G potassium or sodium or penicillin G procaine recommended for congenital syphilis (proven or highly probable). Penicillin G benzathine is not recommended for the treatment of known congenital syphilis, but may be used in infants at lower risk of congenital syphilis.
Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R, Bicillin C-R 900/300) should not be used for treatment of any form of syphilis17 18 since it may not result in the sustained serum concentrations required for syphilis treatment and could increase the risk for treatment failure and neurosyphilis, especially among HIV-infected patients.18
Efficacy of currently recommended syphilis treatment regimens may be reduced in HIV-infected patients; higher doses and/or more prolonged duration of therapy may be necessary in these patients. Careful follow-up is recommended in all patients coinfected with syphilis and HIV to assure adequacy of treatment.
There are no proven alternatives to penicillin G for treatment of congenital syphilis or syphilis during pregnancy in patients with penicillin hypersensitivity. These patients should be desensitized, if necessary, and treated with penicillin G.
Whipple's Disease
Treatment of Whipple’s disease† caused by Tropheryma whippelii.9
Yaws, Pinta, and Bejel
Treatment of yaws (T. pertenue), pinta (T. carateum), and bejel (T. pallidum var. endemic syphilis).6 7 9 Drug of choice.9
Prevention of Perinatal Group B Streptococcal Disease
Prevention of early-onset neonatal group B streptococcal (GBS) disease†.
Intrapartum anti-infective prophylaxis to prevent early-onset neonatal GBS disease is administered to women identified as GBS carriers during routine prenatal GBS screening performed at 35–37 weeks during the current pregnancy and to women who have GBS bacteriuria during the current pregnancy, a previous infant with invasive GBS disease, unknown GBS status with delivery at <37 weeks gestation, amniotic membrane rupture for ≥18 hours, or intrapartum temperature of ≥38°C.
When intrapartum GBS prophylaxis is indicated, IV penicillin G is the drug of choice. Although IV ampicillin can be used, CDC and AAP state that penicillin G is preferred since it has a narrower spectrum of activity and is less likely to select for antibiotic-resistant organisms.
Prevention of Rheumatic Fever Recurrence
Prevention of recurrence of rheumatic fever (secondary prophylaxis).6 Continuous prophylaxis recommended following treatment of documented rheumatic fever (even if manifested solely by Sydenham chorea) and in those with evidence of rheumatic heart disease.
AHA recommends IM penicillin G benzathine, oral penicillin V, or oral sulfadiazine for such prophylaxis.
Penicillin G Benzathine/Potassium/Sodium Dosage and Administration
Administration
Administer penicillin G potassium or sodium by IM injection or IV infusion;1 4 also has been administered intrathecally or by intrapleural, intra-articular, or other local instillations.1 4
Administer penicillin G benzathine,6 16 penicillin G procaine,7 or fixed combination containing penicillin G benzathine and penicillin G procaine14 15 only by deep IM injection. Do not inject these drugs IV or admix with other IV solutions; inadvertent IV administration of penicillin G benzathine has been associated with cardiorespiratory arrest and death.6 7 14 15 16 Also take special precaution to avoid intravascular or intra-arterial administration or injection of these drugs into or near major peripheral nerves or blood vessels since such injections may produce severe and/or permanent neurovascular damage.6 7 14 15 16 (See Administration Precautions under Cautions.)
Vials containing 20 million units of penicillin G potassium are intended for IV administration only and should not be used to prepare IM injections.1 Penicillin G potassium or sodium should generally be given IV when large doses (10 million units or more) are required.
IV Infusion
For IV infusions, use penicillin G potassium or penicillin G sodium.1 Do not administer penicillin G benzathine, penicillin G procaine, or fixed combination of penicillin G benzathine and penicillin G procaine IV.6 7 14 15 16
Reconstitution and Dilution (Penicillin G Potassium or Penicillin G Sodium)
Reconstitute penicillin G potassium or sodium powders with the amount of diluent specified by the manufacturer.1
For continuous IV infusion, reconstituted solutions of penicillin G potassium or sodium generally should be added to 1–2 L of a compatible IV solution. The volume of IV fluid and rate of administration required by the patient in a 24-hour period should be determined and the appropriate daily dosage of penicillin G added to the fluid.4 For example, if an adult patient requires 2 L of fluid in 24 hours and a dosage of 10 million units of penicillin G daily, 5 million units can be added to 1 L of IV solution and the rate of administration adjusted so that the liter of fluid will be infused over 12 hours.4
Thaw the commercially available injection (frozen) at room temperature or in a refrigerator; do not force thaw by immersion in a water bath or by exposure to microwave radiation. A precipitate may have formed in the frozen injection, but should dissolve with little or no agitation after reaching room temperature. Discard thawed injection if an insoluble precipitate is present or if container seals or outlet ports are not intact. The injection should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.
Rate of Administration (Penicillin G Potassium or Penicillin G Sodium)
For intermittent IV infusion, penicillin G potassium or sodium generally should be infused over 1–2 hours. One suggested method for adults is to administer (1/6) or ¼ of the total daily dose as a 1- to 2-hour infusion every 4 or 6 hours, respectively. Divided doses of the drug have also been infused intermittently IV over 15–30 minutes in neonates and children.
IM Injection
For IM injection, use penicillin G potassium, penicillin G sodium, penicillin G benzathine, penicillin G procaine, or fixed combination of penicillin G benzathine and penicillin G procaine based on the indication.1 6 7 14 15 16
Penicillin G potassium or sodium solutions containing up to 100,000 units/mL may be administered IM with a minimum of discomfort; higher concentrations are physically possible and may be used when needed.1
When penicillin G benzathine, penicillin G procaine, or fixed combination of penicillin G benzathine and penicillin G procaine is given IM, inject deeply into the gluteus maximus or into the midlateral thigh (may be preferred for neonates and small children).6 7 14 15 16 Avoid injection or injection into the fat layer since such injections may cause pain and induration.6 In addition, avoid injection into or near a nerve since permanent neurologic damage may result.6 7 14 15 16 Repeated IM injections into the anterolateral thigh, especially in neonates and infants, also should be avoided since quadriceps femoris fibrosis and atrophy may occur.6 (See Administration Precautions under Cautions.)
IM injections should be made at a slow, steady rate to avoid blockage of the needle.6 7 14 15 16 Rotate IM injection sites when repeated doses are given.6 7 14 15 16
Discontinue IM injection of the dose if patient complains of severe, immediate pain at the injection site or if (especially in neonates, infants, and young children) symptoms occur suggesting onset of severe pain.6 7 14 15 16
Reconstitution and Dilution
Penicillin G benzathine and penicillin G procaine are provided in prefilled syringes or Tubex injectors and should be administered undiluted according to manufacturer's directions.6 7
Prepare IM injections of penicillin G potassium or penicillin G sodium according to manufacturer's directions.
Dosage
Dosage of penicillin G potassium, penicillin G sodium, penicillin G benzathine, penicillin G procaine, and fixed combination of penicillin G benzathine and penicillin G procaine is expressed in terms of USP penicillin G units.1 6 7 14 15 16
Pediatric Patients
General Dosage for Neonates
Penicillin G Potassium or Penicillin G Sodium
IV or IM
Neonates <1 week of age: AAP recommends 25,000–50,000 units/kg every 12 hours in those weighing ≤2 kg and 25,000–50,000 units/kg every 8 hours for those weighing >2 kg.
Neonates 1–4 weeks of age: AAP recommends 25,000–50,000 units/kg every 12 hours in those weighing <1.2 kg, 25,000–50,000 units every 8 hours for those weighing 1.2–2 kg, and 25,000–50,000 units every 6 hours for those weighing >2 kg.
Penicillin G Procaine
IM
Neonates <1 week of age: AAP recommends 50,000 units/kg every 24 hours in those weighing ≥1.2 kg.
Neonates 1–4 weeks of age: AAP recommends 50,000 units/kg every 24 hours in those weighing ≥1.2 kg.
General Pediatric Dosage
Penicillin G Benzathine
IM
Children ≥1 month of age: AAP recommends 600,000 units/kg daily in children weighing <27.3 kg or 1.2 million units/kg daily for those weighing ≥27.3 kg for treatment of mild to moderate infections. Inappropriate for severe infections according to AAP.
Penicillin G Potassium or Penicillin G Sodium
IV or IM
Children ≥1 month of age: AAP recommends 25,000–50,000 units/kg daily given in 4 divided doses for treatment of mild to moderate infections and 250,000–400,000 units/kg daily given in 4–6 divided doses for treatment of severe infections.
Penicillin G Procaine
IM
Children ≥1 month of age: AAP recommends 25,000–50,000 units/kg daily given in 1 or 2 divided doses for treatment of mild to moderate infections. Inappropriate for severe infections according to AAP.
Fixed Combination of Penicillin G Benzathine and Penicillin G Procaine
IM
Treatment of S. pyogenes infections (upper respiratory tract, skin and soft-tissue, scarlet fever, erysipelas): A single dose containing 1.2 million units (2 mL of Bicillin C-R 900/300) usually sufficient.14 Alternatively, if Bicillin C-R is used, children weighing <13.6 kg may receive 600,000 units, those weighing 13.6–27.2 kg may receive 0.9–1.2 million units, and those weighing >27.2 kg may receive 2.4 million units.15 When Bicillin C-R is used, the dose usually is given at a single session using multiple IM sites; alternatively, if compliance regarding the return visit is assured, the total dose can be divided and half given on day 1 and half on day 3.15
Treatment of S. pneumoniae infections (except meningitis): 1.2 units (2 mL of Bicillin C-R 900/300) as a single dose repeated every 2 or 3 days until temperature is normal for 48 hours.14 Alternatively, if Bicillin C-R is used, 600,000 units as a single dose repeated every 2 or 3 days until temperature is normal for 48 hours.15 Other penicillin formulations (penicillin G potassium or penicillin G sodium) may be necessary for severe infections.14 15
Endocarditis
Treatment of Native Valve Endocarditis Caused by Viridans Streptococci or S. bovis
IV
Penicillin G potassium or penicillin G sodium (for penicillin-susceptible strains; MIC≤0.1 mcg/mL): 200,000 units daily given in 4–6 equally divided doses for 4 weeks.5 Alternatively, 200,000 units daily given in 4–6 divided doses for 2 weeks in conjunction with IM or IV gentamicin (3 mg/kg daily in 3 divided doses for 2 weeks; dosage adjusted to achieve peak serum gentamicin concentrations approximately 3 mcg/mL and trough concentrations <1 mcg/mL).5
Penicillin G potassium or penicillin G sodium (for relatively resistant strains; MIC >0.1–0.5 mcg/mL): 300,000 units daily given in 4–6 equally divided doses for 4 weeks; used in conjunction with IM or IV gentamicin (3 mg/kg daily in 3 divided doses for 4 weeks; dosage adjusted to achieve peak serum gentamicin concentrations approximately 3 mcg/mL and trough concentrations <1 mcg/mL).5
Penicillin G potassium or penicillin G sodium (for nutritionally variant or strains with high-level resistance; MIC >0.5 mcg/mL): 300,000 units daily given in 4–6 equally divided doses for 4–6 weeks; used in conjunction with IM or IV gentamicin (3 mg/kg daily in 3 divided doses for 4–6 weeks; dosage adjusted to achieve peak serum gentamicin concentrations approximately 3 mcg/mL and trough concentrations <1 mcg/mL).5
Treatment of Enterococcal Endocarditis
IV
Penicillin G potassium or penicillin G sodium: 300,000 units daily given in 4–6 equally divided doses for 4–6 weeks; used in conjunction with IM or IV gentamicin (3 mg/kg daily in 3 divided doses for 4–6 weeks; dosage adjusted to achieve peak serum gentamicin concentrations approximately 3 mcg/mL and trough concentrations <1 mcg/mL).5
Meningitis
Meningitis Caused by S. pneumoniae
IV
Penicillin G potassium or penicillin G sodium: AAP recommends 250,000–400,000 units/kg daily given in 4–6 divided doses in those ≥1 month of age. A dosage of 250,000 units/kg daily given in 6 divided doses generally results in mean CSF concentrations of 0.8 mcg/mL sustained throughout the 4 hours between infusions.
Meningitis Caused by S. agalactiae (Group B Streptococci)
IV
Penicillin G potassium or penicillin G sodium: AAP recommends 250,000–450,000 units/kg daily IV in 3 divided doses in neonates ≤7 days of age or 450,000 units/kg daily IV in 4 divided doses in neonates >7 days of age.
Penicillin G potassium or penicillin G sodium: AAP recommends 250,000–400,000 units/kg daily given IV in 4–6 divided doses in those ≥1 month of age. A dosage of 250,000 units/kg daily given in 6 divided doses generally results in mean CSF concentrations of 0.8 mcg/mL sustained throughout the 4 hours between infusions.
Pharyngitis and Tonsillitis
IM
Penicillin G benzathine: AAP, AHA, and IDSA recommend a single dose of 600,000 units for those weighing ≤27 kg and a single dose of 1.2 million units for those weighing >27 kg.8 11 13
Penicillin G benzathine: Manufacturer recommends a single dose of 300,000–600,000 units in those weighing <27 kg and a single dose of 900,000 units in older children.6
Anthrax
Treatment of Naturally Occurring or Endemic Anthrax
IV
Penicillin G potassium or penicillin G sodium: 100,000–150,000 units/kg daily given in divided doses every 4–6 hours.
Continue for ≥14 days after symptoms abate.
Treatment of Inhalational, GI, or Oropharyngeal Anthrax
IV
Penicillin G potassium or penicillin G sodium: 50,000 units/kg IV every 6 hours in children <12 years of age.
Postexposure Prophylaxis Following Exposure in the Context of Biologic Warfare or Bioterrorism
IM
Penicillin G procaine: 25,000 units/kg (maximum 1.2 million units) every 12 hours; use only if penicillin susceptibility is confirmed.7
Total duration of postexposure prophylaxis usually is 60 days.7 Safety data for penicillin G procaine administered at the dosage recommended for prophylaxis of anthrax supports a duration of therapy of ≤2 weeks, and clinicians must consider the risks versus benefits of administering penicillin G procaine for >2 weeks or switching to an appropriate alternative anti-infective (e.g., oral amoxicillin or penicillin V).7
Diphtheria
Treatment of Diphtheria
IV
Penicillin G potassium or penicillin G sodium: 100,000–150,000 units/kg daily given IV in 4 divided doses daily for 14 days; used as an adjunct to diphtheria antitoxin.
IM
Penicillin G procaine: CDC recommends 300,000 units daily in those weighing ≤10 kg or 600,000 units daily in those weighing >10 kg as an adjunct to diphtheria antitoxin. AAP recommends 25,000–50,000 units/kg daily (maximum 1.2 million units daily) given in 2 divided doses for 14 days.
Prevention of Diphtheria in Close Contacts
IM
Penicillin G benzathine: A single dose of 600,000 units in children <6 years of age or weighing <30 kg or 1.2 million units in those ≥6 years of age or weighing ≥30 kg.
Provide prophylaxis regardless of immunization status and closely monitor for symptoms of diphtheria for 7 days.
In addition, contacts who are inadequately immunized against diphtheria (i.e., have previously received <3 doses of diphtheria toxoid) or whose immunization status is unknown should receive an immediate dose of an age-appropriate diphtheria toxoid preparation and the primary series should be completed according to the recommended schedule.
Contacts who are fully immunized should receive an immediate booster dose of an age-appropriate diphtheria toxoid preparation if it has been ≥5 years since their last booster dose.
Elimination of Diphtheria Carrier State
IM
Penicillin G potassium or penicillin G sodium: 300,000–400,000 units daily given in divided doses for 10–12 days.1
Penicillin G benzathine: A single dose of 600,000 units in children <6 years of age or weighing <30 kg or 1.2 million units in those ≥6 years of age or weighing ≥30 kg.
Obtain follow-up cultures ≥2 weeks after treatment of diphtheria carriers; if cultures are positive, a 10-day course of oral erythromycin should be given and additional follow-up cultures obtained.
Listeria Infections
Serious Listeria Infections in Neonates
IV
Penicillin G potassium or penicillin G sodium: 500,000 to 1 million units daily.1
Lyme Disease†
Early or Late Lyme Disease with Serious Neurologic, Cardiac, and/or Arthritic Manifestations†
IV
Penicillin G potassium or penicillin G sodium: 200,000–400,000 units/kg daily (maximum 18–24 million units daily) given in 4 or 6 divided doses (every 4 or 6 hours) for 14–28 days.
Severe Lyme Carditis†
IV
Penicillin G potassium or penicillin G sodium: 200,000–400,000 units/kg daily (maximum 18–24 million units daily) given in 4 or 6 divided doses (every 4–6 hours) for 14–21 days.
Syphilis
Fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin C-R, Bicillin C-R 900/300) should not be used for treatment of any form of syphilis.17 18
Neonates with Proven or Presumed Congenital Syphilis
IV
Penicillin G potassium or penicillin G sodium: CDC and AAP recommend 100,000–150,000 units/kg daily (administered as 50,000 units/kg IV every 12 hours during the first 7 days of life and every 8 hours thereafter) for a total duration of 10 days. CDC and AAP state that if >1 day of therapy is missed, the entire course of therapy should be readministered.
IM
Penicillin G benzathine: Manufacturer recommends a single dose of 50,000 units/kg.6 CDC and AAP state that penicillin G benzathine is not recommended for treatment of known congenital syphilis; these experts recommend IV penicillin G potassium or sodium or IM penicillin G procaine for neonates with proven or highly probable congenital syphilis.
Penicillin G procaine: CDC and AAP recommend 50,000 units/kg once daily for 10 days; if >1 day of therapy is missed, the entire course should be readministered.
Children ≥1 Month of Age with Suspected Congenital Syphilis or Late and Previously Untreated Congenital Syphilis
IV
Penicillin G potassium or penicillin G sodium: 200,000–300,000 units/kg daily (given as 50,000 units/kg every 4–6 hours) for 10 days. Some clinicians recommend that this regimen be followed by a regimen of IM penicillin G benzathine (50,000 units/kg once weekly for 1–3 weeks).
IM
Penicillin G benzathine: 50,000 units/kg once weekly for 3 weeks.
Primary or Secondary Syphilis in Children ≥1 Month of Age
IM
Penicillin G benzathine: A single dose of 50,000 units/kg (up to 2.4 million units).
Primary or Secondary Syphilis in Adolescents
IM
Penicillin G benzathine: A single dose of 2.4 million units.6 For HIV-infected adolescents, some clinicians suggest that additional doses of 2.4 million units be given once weekly for a total of 3 weeks of therapy.
Penicillin G procaine: Manufacturer recommends 600,000 units daily for 8 days.7 CDC recommends use of penicillin G benzathine for primary or secondary syphilis.
Latent Syphilis or Tertiary Syphilis in Children ≥1 Month of Age
IM
Penicillin G benzathine: CDC and AAP recommend that early latent syphilis be treated with a single dose of 50,000 units/kg (up to 2.4 million units) and that those with late latent syphilis or latent syphilis of unknown duration receive 50,000 units/kg (up to 2.4 million units) once weekly for 3 successive weeks (up to a maximum total dosage of 7.2 million units).
Latent Syphilis or Tertiary Syphilis in Adolescents
IM
Penicillin G benzathine: For early latent syphilis (syphilis of <1-year duration), CDC recommends a single dose of 2.4 million units. For late latent syphilis, latent syphilis of unknown duration, and tertiary syphilis, CDC recommends 2.4 million units once weekly for 3 successive weeks (7.2 million units total). These regimens also can be used to treat early latent syphilis, late latent syphilis, or syphilis of unknown duration in HIV-infected adolescents, provided they have a normal CSF examination.
Penicillin G procaine: Manufacturer recommends 600,000 units daily for 10–15 days.7 CDC recommends use of penicillin G benzathine for latent or tertiary syphilis.
Neurosyphilis in Children
IV
Penicillin G potassium or penicillin G sodium: AAP recommends 200,000–300,000 units/kg daily for 10–14 days; some clinicians recommend that this regimen be followed by a single IM dose of 50,000 units/kg of penicillin G benzathine (up to 2.4 million units).
IM
Penicillin G benzathine: Manufacturer recommends 2.4 million units once weekly for 3 weeks.6 CDC recommends use of penicillin G potassium or sodium or penicillin G procaine for treatment of neurosyphilis.
Neurosyphilis in Adolescents
IV
Penicillin G potassium or penicillin G sodium: 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 a regimen of IM penicillin G benzathine (2.4 million units once weekly for up to 3 weeks).
IM
Penicillin G benzathine: Manufacturer recommends 2.4 million units once weekly for 3 weeks.6 CDC recommends use of penicillin G potassium or sodium or penicillin G procaine for treatment of neurosyphilis.
Penicillin G procaine: CDC states that 2.4 million units may be given once daily for 10–14 days in conjunction with oral probenecid (500 mg every 6 hours) if compliance can be ensured; some clinicians recommend that this regimen be followed by a regimen of IM penicillin G benzathine (2.4 million units once weekly for up to 3 weeks).
Yaws, Pinta, and Bejel
IM
Penicillin G benzathine: A single dose of 300,000 units in children <6 years of age or a single dose of 1.2 million units in children 6–15 years of age.
Prevention of Rheumatic Fever Recurrence
IM
Penicillin G benzathine: 1.2 million units once every 3–4 weeks.6 11 The 4-week regimen reco
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