Benzathine Penicillin


Article Author:
William Gartlan


Article Editor:
Kaitlyn Reti


Editors In Chief:
Niamh Condon
Terry Tressler


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Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
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Radia Jamil
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Saad Nazir
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Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
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John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
3/4/2019 8:57:29 AM

Indications

Benzathine penicillin is formulated from two penicillin G molecules reacting with diphenylethylene diamine. It is active against gram-positive bacteria including beta-hemolytic streptococci (groups A, B, C, G, H, L, and M) as well as Treponema pallidum and T. carateum. There has been no reported resistance to benzathine penicillin in Streptococcus pyogenes.[1][2][3][4][5]

Benzathine penicillin is FDA-approved to treat the following: 

Adult

1. Upper respiratory infection, group A streptococci

  • Secondary prevention of glomerulonephritis
  • Secondary prevention of rheumatic fever

2. Pharyngitis, group A streptococci (Infectious Diseases Society of America [IDSA] guidelines)

  • Acute and chronic carrier treatment

3. Syphilis (CDC)

  • Primary, secondary, and early latent (less than 1-year duration)
  • Late latent, latent with an unknown duration, or tertiary syphilis (with normal cerebrospinal fluid examination)
  • Neurosyphilis, including ocular syphilis (not indicated for use)

4. Yaws, bejel, and pinta

Pediatric

1. Upper respiratory infection, group A streptococci (e.g., pharyngitis)

2. Primary prevention of rheumatic fever

3. Secondary prevention of rheumatic fever

4. Pharyngitis, group A streptococci (IDSA)

  • Acute and chronic carrier state

5. Syphilis (off-label population) (CDC)

  • Primary, secondary, and early latent (less than 1-year duration)
  • Late latent

 FDA Labeled Indications

  1. Acute glomerulonephritis
  2. Respiratory tract infections
  3. Rheumatic fever and chorea
  4. Rheumatic heart disease
  5. Syphilis and another venereal disease

Mechanism of Action

Benzathine penicillin is in a class of beta-lactam antibiotics. Beta-lactams are bactericidal antibiotics. This type of antibiotic inhibits biosynthesis of the cell wall peptidoglycan during the stage of active multiplication. This results in an osmotically unstable cell wall, leading to lysis of the cell wall, subsequent destruction of the bacterial cell, and death.

Administration

Benzathine Penicillin is available as an injectable suspension that is administered intramuscularly, not intravenous, intra-arterial, or subcutaneous. The medication should be warmed to room temperature before administration to lessen the pain associated with the injection, and it should not be given near an artery or nerve. In adults, administer the injection to the upper outer quadrant of buttocks. In children less than 2 years old, administer the injection to the mid-lateral muscle of the thigh, not the gluteal region, and rotate the injection site on repeat doses.

Benzathine penicillin is opaque and viscous with very low solubility. The antibiotic is, therefore, slowly released from the site of injection and hydrolyzed to penicillin G. Due to the slow absorption and the hydrolysis, the levels of the drug in the blood remain lower but for a prolonged period. After a 1.2 million unit injection, adults have detectable drug levels for 14 days, often longer.

The antibiotic typically is manufactured in 600,000 units/1 mL, 1.2 million units/2 mL, or 2.4 million units/4 mL syringes. The antibiotic is to be stored in a refrigerator from 36 to 46 degrees F (2 to 8 degrees C), never frozen. Dosing recommendations are as follows:

Adult

  • Pharyngitis/tonsillitis, group A streptococci (1.2 million units IM x 1)
  • Upper respiratory infection, group A streptococci that are mild to moderate and are susceptible to low, prolonged concentrations of benzathine penicillin (1.2 million units intramuscularly [IM] x 1)
  • Secondary prevention of glomerulonephritis (prophylaxis for patients with history of acute glomerulonephritis) (1.2 million units IM every 4 weeks or 600,000 units IM twice monthly)
  • Secondary prevention (prophylaxis) of rheumatic fever (1.2 million units IM every 3 to 4 weeks or 600,000 units IM twice monthly)
  • Syphilis: Primary, secondary, or latent less than 1 year (2.4 million units IM x 1, may repeat dose x 1 after 1 week in pregnant patients); latent greater than 1 year (2.4 million units IM weekly for 3 weeks)
  • Yaws, bejel, and pinta (1.2 million units IM x 1)

Pediatric

  • Pharyngitis/tonsillitis, group A streptococci: Acute treatment (less than 27 kg = 600,000 units IM x 1; greater than 27 kg = 1.2 million units IM x 1); Chronic carrier treatment (less than 27 kg = 600,000 units IM x 1 in combination with oral rifampin; greater than 27 kg = 1.2 million units IM x 1 in combination with oral rifampin)
  • Upper respiratory infection, group A streptococci: (less than 27 kg = 300,000 – 600,000 units IM x 1; greater than 27 kg = 900,000 units IM x 1)
  • Secondary prevention of rheumatic fever (less than 27 kg = 600,000 units IM every 3-4 weeks; greater than 27 kg = 1.2 million units IM every 3 to 4 weeks)

Geriatric

  • Refer to adult dosing

Infants and Children

  • Syphilis: Primary, secondary, and early latent less than 1 year duration (50,000 units/kg/dose IM x 1, maximum 2.4 million units/dose); late latent greater than 1 year duration (50,000 units/kg/dose IM weekly for 3 doses, maximum 2.4 million units/dose)

Renal Impairment

The medication is excreted by renal tubular excretion.

  • Creatinine clearance 10 to 50 = decrease dose 25%
  • Creatinine clearance less than 10% = decrease dose 50% to 80%
  • Hemodialysis = give dose after dialysis
  • Peritoneal dialysis = decreased dose 50% to 80%

Hepatic Impairment

There are no dose adjustments for patients with hepatic impairment.

Seizure Disorders

Use with caution in patients with seizure disorder, especially in patients with renal impairment, due to a potential increase in the risk of seizures.

Pregnancy (Category B)

Reproduction studies performed in mice, rats, and rabbits have revealed no evidence of harm to the fetus. Human experience with penicillin during pregnancy have not shown to have any adverse effects on the fetus. However, studies with women who are pregnant are inadequate or not well-controlled and cannot conclusively report harmful effects of penicillin medications on the fetus.

Nursing Mothers

Soluble penicillin G is excreted in breast milk. Caution should be used.

Adverse Effects

Patients generally tolerate benzathine penicillin well, with pain from the injection being the most common complaint. Other adverse events include hypersensitivity reactions. Patients with previous history of hypersensitivity to penicillins or those with a history of asthma, hay fever, allergies, or urticaria, are at higher risk of hypersensitivity reactions. Hypersensitivity reactions can be serious and/or fatal and include the type-I, IgE-mediated reaction, also known as anaphylaxis. This type-I hypersensitivity reaction typically includes urticarial skin rash, itching, wheezing, dyspnea, nausea, vomiting, diarrhea and can progress to hemodynamic instability and death. Any previous anaphylactic reaction or serious skin reaction (for example, Steven-Johnson or Toxic Epidermal Necrosis) to any penicillin is a contraindication for use. There have been previous reports that patients with anaphylactic or serious skin reactions from cephalosporins or carbapenems will have a type of cross-reactivity reaction that will also have such serious adverse events when administered any penicillin medication, but these reports are believed to be much lower than previously suspected. 

The other adverse effect is known as a superinfection that can result from prolonged use. A superinfection can occur up to 2 months post-antibiotic treatment. These potentially fatal infections include C. difficile-associated diarrhea and pseudomembranous colitis.[6][7][8]

Contraindications

Benzathine penicillin is contraindicated in patients who have had a previous anaphylactic reaction or serious skin reaction to any penicillin; for example, Steven-Johnson or toxic epidermal necrosis. There have been reports of patients with anaphylactic or serious skin reactions from cephalosporins or carbapenems having a type of cross-reactivity reaction that also results in serious adverse events when they are administered any penicillin antibiotic, including benzathine penicillin, but these reports are believed to be much lower than previously suspected.

Monitoring

Observe for signs and symptoms of hypersensitivity reactions, including anaphylaxis, or opportunistic infection.

Toxicity

Since a healthcare practitioner administers the medication by injection, overdoses are rare. An overdose has the potential to cause neuromuscular irritability or convulsive seizures.

Enhancing Healthcare Team Outcomes

Benzathine penicillin is often administered by a number of healthcare workers including the nurse practitioner, primary care provider, internist and the infectious disease expert. While the drug is relatively safe it is important to observe the patient for an allergic reaction. Empirical use of this drug can lead to opportunistic infections.


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Benzathine Penicillin - Questions

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Where is benzathine penicillin administered to an adult with primary syphilis?



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A 29-year-old G4P3 female at 30 weeks of gestation presents to the emergency department for evaluation of a nontender lesion about the size of a dime that is located on her labia majora. She reports having sexual intercourse throughout pregnancy with only one man and never uses barrier protection. After treating for gonorrhea and chlamydia, which of the following is the next medication that should be given to the patient?



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Benzathine Penicillin - References

References

Walker GJ,Walker D,Molano Franco D,Grillo-Ardila CF, Antibiotic treatment for newborns with congenital syphilis. The Cochrane database of systematic reviews. 2019 Feb 15;     [PubMed]
Ndeikoundam Ngangro N,Viriot D,Fournet N,Pioche C,De Barbeyrac B,Goubard A,Dupin N,Berçot B,Fouéré S,Alcaraz I,Ohayon M,Spenatto N,Vernay-Vaisse C,Referents For The Regional Offices Of The French National Public Health Agency,Pillonel J,Lot F, Bacterial sexually transmitted infections in France: recent trends and patients' characteristics in 2016. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. 2019 Jan;     [PubMed]
Webber BJ,Kieffer JW,White BK,Hawksworth AW,Graf PCF,Yun HC, Chemoprophylaxis against group A streptococcus during military training. Preventive medicine. 2019 Jan;     [PubMed]
Struyve M,Meersseman W,Van Moerkercke W, Primary syphilitic proctitis : case report and literature review. Acta gastro-enterologica Belgica. 2018 Jul-Sep;     [PubMed]
Khan A,Sutcliffe N,Jawad AS, An old disease re-emerging: acute rheumatic fever. Clinical medicine (London, England). 2018 Oct;     [PubMed]
Benzathine Penicillin G 2006;     [PubMed]
Holland JV,Hardie K,de Dassel J,Ralph AP, Rheumatic Heart Disease Prophylaxis in Older Patients: A Register-Based Audit of Adherence to Guidelines. Open forum infectious diseases. 2018 Jun 1;     [PubMed]
Montagnat OD,Webster GR,Bulitta JB,Landersdorfer C,Wyber R,Sheel M,Carapetis JR,Boyd BJ, Lessons learned in the development of sustained release penicillin drug delivery systems for the prophylactic treatment of rheumatic heart disease (RHD). Drug delivery and translational research. 2018 Jun;     [PubMed]

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