What to Know About Penicillins

Penicillin is an antibiotic used to treat certain types of bacterial infections, such as pneumonia, meningitis, or strep throat.

There are different types of penicillin with different mechanisms of action. All forms are derived, at least in part, from a fungus known as Penicillium chrysogenum.

Penicillin may be administered by mouth or by injection. When given by injection, it may be administered intravenously (IV, into a vein), or intramuscularly (IM, in a large muscle).

What Is Penicillin?

Penicillins are antibiotics that belong to a larger family of drugs known as beta-lactam antibiotics.

Penicillins work by binding to molecules on the walls of bacteria called peptidoglycan. When the bacteria divide, penicillin prevents proteins in the cell wall from reassembling properly, causing the bacterial cell to rupture and quickly die.

Natural penicillins are those directly derived from P. chrysogenum fungi. There are two natural penicillins.

Semisynthetic penicillins are produced in a lab to resemble chemical substances found in P. chrysogenum. There are four classes of semisynthetic penicillins, including commonly prescribed antibiotics like amoxicillin and ampicillin.

Natural
  • Penicillin G (benzylpenicillin)

  • Penicillin V (phenoxymethylpenicillin)

Semisynthetic
  • Aminopenicillins (ampicillin, amoxicillin, and hetacillin)

  • Antistaphylococcal penicillins (cloxacillin, dicloxacillin, nafcillin, and oxacillin)

  • Broad-spectrum penicillins (carbenicillin, mezlocillin, piperacillin, ticarcillin)

  • Beta-lactamase inhibitor (clavulanic acid)

Each of these types has a slightly different molecular structure and may be administered differently than the others.

What Does Penicillin Treat?

Penicillins are used for treating bacterial infections. They don't treat viral, fungal, or parasitic infections. The drugs are generally active against gram-positive bacteria, a group of bacteria that has peptidoglycan on the outside of the cell wall. With gram-negative bacteria, the peptidoglycan layer is buried beneath a layer of lipid cells, making it harder for the drug to access the molecule.

The list of gram-positive bacteria that are treatable by penicillins includes those of the Clostridium, Listeria, Neisseria, Staphylococcal, and Streptococcal genus.

Natural penicillins—penicillin G and penicillin V—are still used today and are appropriate for the treatment of certain common and uncommon bacterial infections.

Drug  Administration Conditions Commonly Treated
Penicillin G Intravenous or intramuscular injection • Anthrax
Bacterial endocarditis
Bacterial meningitis
Cellulitis
Diphtheria
Gangrene
Necrotizing enterocolitis
Pneumococcal pneumonia
Strep throat
Syphilis (advanced disseminated or congenital)
Tetanus
Tonsillitis
Penicillin V By mouth  • Anthrax
• Cellulitis
Dental abscess
Erysipelas
Rheumatic fever
• Strep throat
• Streptococcal skin infections
• Tonsillitis

Semisynthetic antibiotics like amoxicillin—one of the most commonly prescribed antibiotics today—can be used to treat a broad spectrum of respiratory, skin, and bacterial infections like H. pylori, Lyme disease, and acute otitis media.

Off-Label

The off-label use of penicillins is common, albeit more often with drugs like amoxicillin and ampicillin than natural penicillins. Off-label use includes treatment of critical care patients with sepsis or newborns with acute respiratory distress. In neither instance are the drugs indicated for such use, but they are often considered necessary when no other treatment options are available.

Penicillin G is sometimes used off-label to treat prosthetic joint infections, Lyme disease, and leptospirosis. Penicillin V is occasionally used off-label to treat Lyme disease and otitis media, or to prevent infections in people undergoing stem cell transplant.

Penicillin Resistance

Penicillin resistance has been known since the 1960s, when scientists began developing the first semisynthetic penicillin drugs to treat a broader range of bacterial infections. Penicillin resistance occurs when mutant bacterial strains resistant to the antibiotic are passed throughout a population.

Today, there is a growing number of bacterial infections that are either fully or partially resistant to the original penicillin drugs, including Neisseria gonorrhoeae (gonorrhea) and methicillin-resistant Staphylococcal aureus (MRSA).

Streptococcal pneumoniae (a type of bacterial pneumonia) and certain types of Clostridium and Listeria bacteria have become less responsive to these antibiotics as well.

The overuse of antibiotics in livestock to promote growth is known to increase the risk of resistant bacteria, including superbugs, all along the food chain. As a result of this growing global concern, the United States banned the use of antibiotics for growth promotion in animals in 2017.

To help overcome penicillin resistance, penicillins that don't have direct antibacterial activity may be used in combination therapies. For example, clavulanic acid blocks an enzyme secreted by antibiotic-resistant bacteria (beta-lactamase) that inhibits the activity of beta-lactam antibiotics.

Before Taking

Penicillin can be very effective if used appropriately. Even so, there are instances when the drug is not effective in clearing an infection. In such cases, antibiotic susceptibility testing (also known as antibiotic sensitivity testing) may be used to determine if a person's infection is responsive to penicillin.

The test starts by culturing bacteria taken from a swab of body fluid, then directly exposing the bacteria to various penicillin types in a lab. Antibiotic susceptibility testing is often used for people with community-acquired pneumonia who are at high risk of severe illness or death.

Precautions and Contraindications

Penicillins are contraindicated if you've had a prior allergy to any drug in the penicillin family. It should also be used with extreme caution if you have ever had a severe drug hypersensitivity reaction in the past, including anaphylaxis, Stevens-Johnson syndrome (SJS), or toxic epidermal necrosis (TEN).

If you have had an allergic reaction to penicillin G or penicillin V in the past, you may be—but are not necessarily—allergic to semisynthetic penicillins like amoxicillin or ampicillin.

Other beta-lactam antibiotics should be used with caution in people with penicillin allergy as there is a risk, albeit slight, of a cross-reactive allergy. This includes cephalosporin antibiotics like Keflex (cephalexin), Maxipime (cefepime), Rocephin (ceftriaxone), and Suprax (cefixime).

If you are concerned that you may be allergic to penicillin, you can have skin allergy testing to see if you react to a minute amount of the drug placed under the skin.

Penicillin should also be used with extreme caution if you have acute renal (kidney) failure. Penicillin is mainly excreted through the kidneys, and diminished kidney function can cause the drug to accumulate to toxic levels. The ensuing overdose of penicillin can lead to symptoms of agitation, confusion, stupor, abnormal twitches, and, in rare cases, coma.

Dosage

The recommended dosage of penicillin G and penicillin V can vary depending on the disease and the age of the person being treated.

The doses are measured in several different ways depending on the formulation. In adults, the drug is usually measured in units or milligrams (mg). In children, the dose may be calculated by milligrams per kilograms of body weight per day (mg/kg/day) or units per kilogram of body weight per day (units/kg/day).

Drug Indication Recommended Dose
Penicillin G Anthrax Minimum 8 million units per day in four divided doses
  Diphtheria Adults: 2 to 3 million units per day in divided doses for 10 to 12 days
Children: 150,000 to 250,000 units/kg/day in four divided doses for 7 to 14 days
  Endocarditis Adults: 15 to 20 million units per day for 4 weeks
Children: 150,000 to 300,000 units/kg/day in four to six divided doses (duration varies by the severity of the illness)
  Gangrene 20 million units per day
  Meningitis Adults: 14 to 20 million units per day for 2 weeks
Children: 150,000 to 300,000 units/kg/day in four to six divided doses (duration varies by the severity of illness)
  Pneumonia Adults: 5 to 24 million units per day in four to six divided doses (duration varies by the severity of illness)
  Syphilis Adults: 12 to 24 million units per day every four hours for 10 to 14 days
Children: 200,000 to 300,000 units/kg/day in four to six divided doses for 10 to 14 days
Penicillin V Dental abscess 250 to 500 mg every 6 hours for 5 to 7 days
  Erysipelas 500 mg every 6 hours as needed
  Rheumatic fever Adults: 250 mg every 12 hours as needed
Children: 125 to 250 mg every 12 hours as needed
  Strep throat Adults: 500 mg every 12 hour or 250 every 6 hours for 10 day
Children: 250 to 500 mg every 8 to 12 hours for 10 days
  Staphylococcal skin infections 250 to 500 mg every 6 to 8 hours (duration varies by the severity of illness)

Modifications

If you have kidney disease, you may need a lower penicillin dose to prevent drug toxicity. A dose reduction is typically recommended when the creatinine clearance (a measure of kidney function) is less than 10 milliliters per minute (mL/min).

On the other hand, if you are treated with hemodialysis, you may need a higher dose because hemodialysis can speed the clearance of penicillin from the blood.

How to Take and Store

Penicillin G

Penicillin G is available as either a premixed solution or a powder that is reconstituted with sterile water for injection. The premixed solution can be stored in the refrigerator or freezer, while the powder formulation can be kept safely at room temperature.

Penicillin G injections are not self-administered.

Penicillin V

Penicillin V is available as an oral tablet or a cherry-flavored powder mixed with water. Both can be safely stored at room temperature. Once the powder is reconstituted, it should be stored in the refrigerator and discarded after 14 days.

Penicillin V should be taken on an empty stomach to ensure maximum absorption. It should be taken at least one hour before a meal or at least two hours after a meal.

If you miss a dose of penicillin V, take it as soon as you remember. If it is near the time of your next dose, skip the dose and continue as normal. Never double up on doses.

Use As Directed

Always take penicillin as directed and to completion. Do not stop because you feel well. You need to take the entire course so that all bacteria are eradicated. Small amounts of remaining bacteria can proliferate once treatment is stopped.

Side Effects

Most penicillin side effects are mild and transient and will resolve on their own without treatment. But sometimes side effects can be severe—and even life-threatening—and require emergency care.

Common

The most common side effects of penicillins (affecting at least 1% of users) are:

Fever and angioedema (tissue swelling) can also occur but are less common.

Severe

One of the most serious concerns associated with the use of penicillin is the risk of a potentially life-threatening, whole-body allergy known as anaphylaxis. True penicillin-induced anaphylaxis is rare, affecting about .02% to .04% of those taking penicillin.

Anaphylaxis can reap serious harm if it is left untreated. It can lead to shock, coma, respiratory or cardiac failure, and even death.

When to Call 911

Seek emergency care if you experience some or all of the symptoms of anaphylaxis after receiving a dose of penicillin:

  • Shortness of breath
  • Wheezing
  • Dizziness, lightheadedness, or fainting
  • Severe rash or hives
  • Rapid or irregular heartbeat
  • Swelling of the face, tongue, or throat
  • A feeling of impending doom

On rare occasions, penicillins can cause acute interstitial nephritis, an inflammatory kidney condition most often caused by an abnormal immune reaction to medications. Symptoms include nausea, rash, fever, drowsiness, diminished urine output, fluid retention, and vomiting. Most cases are mild, but some can turn serious and cause an acute kidney injury.

Penicillins, like all antibiotics, are associated with an increased risk of Clostridium difficile diarrhea. This is caused when bacteria that are normally present in the gut are obliterated by antibiotics, allowing C. difficile bacteria to proliferate. Most cases are mild and readily treatable, but C. difficile has been known on rare occasions to cause severe fulminant colitis, toxic megacolon, and death.

Warnings and Interactions

Penicillins are generally considered safe during pregnancy and breastfeeding. Evidence in humans is lacking, but animal studies have shown no risk of fetal harm.

If you are pregnant, planning to get pregnant, or breastfeeding, speak with your healthcare provider to fully understand the benefits and risks of using penicillin.

A number of drugs can also interact with penicillin, oftentimes by competing for clearance in the kidneys. This can increase penicillin concentrations in the blood as well as the risk of side effects and drug toxicity. Other medications can speed the clearance of penicillin from the body and reduce the drug's effectiveness.

Among the drugs that are likely to interact with penicillin are:

To avoid interactions, always let your healthcare provider know about any drugs you are taking, whether they are prescription, over-the-counter, nutritional, herbal, or recreational.

22 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Pandey N, Cascella M. Beta lactam antibiotics. In: StatPearls.

  2. Blum JK, Deaguero AL, Perez CV, Bommarius AS. Ampicillin synthesis using a two-enzyme cascade with both α-amino ester hydrolase and penicillin G acylase. ChemCatChem. 2010;2(8):987-91. doi:10.1002/cctc.201000135

  3. Sizar O, Unakal CG. Gram positive bacteria. In: StatPearls.

  4. Evans J, Hannoodee M, Wittler M. Amoxicillin clavulanate. In: StatPearls.

  5. Mukattash TL, Hayajneh WA, Ibrahim SM, et al. Prevalence and nature of off-label antibiotic prescribing for children in a tertiary setting: A descriptive study from Jordan. Pharm Pract (Granada). 2016;14(3):725. doi:10.18549/PharmPract.2016.03.725

  6. Gartlan WA, Rahman S, Reti K. Benzathine penicillin. In: StatPearls.

  7. Rashidi A, Wangjam T, Bhatt AS, Weisdorf DJ, Holtan SG. Antibiotic practice patterns in hematopoietic cell transplantation: A survey of blood and marrow transplant clinical trials network centers. Am J Hematol. 2018;93(11):E348-50. doi:10.1002/ajh.25236

  8. Ventola CL. The antibiotic resistance crisis: Part 1: Causes and threats. P T. 2015;40(4):277-83.

  9. Founou LL, Founou RC, Essack SY. Antibiotic resistance in the food chain: A developing country-perspective. Front Microbiol. 2016;7:1881. doi:10.3389/fmicb.2016.01881

  10. Centers for Disease Control and Prevention. Food and food animals.

  11. Zafar A, Hasan R, Nizamuddin S, et al. Antibiotic susceptibility in Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes in Pakistan: A review of results from the Survey of Antibiotic Resistance (SOAR) 2002-15. J Antimicrob Chemother. 2016;71:i103-9. doi:10.1093/jac/dkw076

  12. Patterson RA, Stankewicz HA. Penicillin allergy. In: StatPearls.

  13. Yuson CL, Katelaris CH, Smith WB. ‘Cephalosporin allergy’ label is misleading. Aust Prescr. 2018;41(2):37-41. doi:10.18773/austprescr.2018.008

  14. Bayer Healthcare LLC. Penicillin G potassium injection, USP.

  15. Smyth B, Jones C, Saunders J. Prescribing for patients on dialysis. Aust Prescr. 2016;39(1):21-4. doi:10.18773/austprescr.2016.008

  16. Cleveland Clinic. Penicillin V powder for oral solution.

  17. Sandoz Pharmaceuticals. Penicillin VK USP tablets.

  18. Yip DW, Gerriets V. Penicillin. In: StatPearls.

  19. Patterson RA, Stankewicz HA. Penicillin allergy. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022.

  20. Finnigan NA, Bashir K. Allergic interstitial nephritis (AIN). In: StatPearls.

  21. Mada PK, Alam MU. Clostridium difficile. In: StatPearls.

  22. Kuscu F, Ulu A, Inal AS, et al. Potential drug-drug interactions with antimicrobials in hospitalized patients: A multicenter point-prevalence study. Med Sci Monit. 2018;24:4240-7. doi:10.12659/MSM.908589

By Naveed Saleh, MD, MS
Naveed Saleh, MD, MS, is a medical writer and editor covering new treatments and trending health news.