Penicillin is absolutely still used, and for certain infections it remains the single best antibiotic available. While newer antibiotics have replaced it for many common conditions, penicillin holds its ground as the gold-standard treatment for syphilis, strep throat, rheumatic fever prevention, and several other serious infections. It’s not a relic of the past. It’s a drug that doctors prescribe every day.
Where Penicillin Is Still the First Choice
Penicillin’s most critical modern role is in treating syphilis. It is the only recommended treatment for pregnant women with syphilis and for babies born with congenital syphilis. The CDC recommends a single injection of benzathine penicillin G for primary and secondary syphilis in adults. No substitute works as reliably for this disease, which is why a current shortage of injectable penicillin in the U.S. has become a serious public health concern.
Strep throat is the other big one. Group A Streptococcus, the bacterium behind strep throat, has never developed resistance to penicillin or amoxicillin. The CDC confirms these remain the first-line antibiotics for the infection. That’s remarkable for a drug discovered nearly a century ago, and it means penicillin is still routinely prescribed for one of the most common bacterial infections people get.
Beyond those two, penicillin G carries FDA-approved indications for a wide range of conditions: bacterial meningitis caused by susceptible organisms, anthrax, tetanus (alongside a vaccine and immune support), certain heart valve infections, and rat bite fever. It’s also recommended during labor for women who carry Group B Streptococcus, protecting newborns from a potentially life-threatening infection.
Preventing Rheumatic Heart Disease
One of penicillin’s most important jobs doesn’t involve curing an active infection at all. People who’ve had rheumatic fever, a complication of untreated strep throat that can damage heart valves, often need regular penicillin injections for years to prevent the disease from coming back. The American Heart Association calls benzathine penicillin injections “the cornerstone of secondary prevention.”
How long someone stays on these injections depends on how severe the damage was. For rheumatic fever without heart involvement, guidelines recommend prophylaxis for at least 5 years or until age 21, whichever is longer. If there was heart damage that resolved, that extends to 10 years or until age 21. For people with severe, lasting heart disease from rheumatic fever, prophylaxis may continue until age 40 or even for life. In many low- and middle-income countries, where rheumatic heart disease is still common, penicillin injections are a lifeline.
Two Forms for Different Jobs
When doctors say “penicillin,” they’re typically talking about one of two forms. Penicillin G is given by injection or IV and is the version used for serious infections like syphilis, meningitis, and endocarditis. Because it’s delivered directly into the bloodstream or muscle, it reaches high concentrations quickly. Penicillin V is the oral tablet form, the one you’d pick up at a pharmacy for something like strep throat. It’s less potent but more convenient, and it works well for infections that don’t require the heavy-hitting injectable version.
Why Penicillin Doesn’t Work for Everything Anymore
Penicillin kills bacteria by breaking apart their cell walls. Specifically, it locks onto proteins that bacteria need to build and maintain that wall, causing the cell to rupture. The problem is that many bacteria have learned to fight back. The most common defense is producing enzymes that chew up penicillin’s core structure before it can do its job, essentially snipping open the ring-shaped molecule that makes the drug work. This is the dominant resistance strategy in many common bacteria.
Some bacteria take a different approach. MRSA, for instance, produces a modified version of the protein penicillin targets, one that the drug can’t latch onto effectively. Other bacteria pump the antibiotic out of their cells before it can accumulate, or reduce the number of entry points in their outer membrane so less drug gets in. Some species use multiple strategies at once, stacking defenses to become highly resistant.
This is why penicillin no longer works for many staph infections, most urinary tract infections, and plenty of respiratory infections. For those, doctors turn to newer antibiotics.
How Modern Derivatives Expanded the Family
Amoxicillin, the most commonly prescribed antibiotic in the world, is a direct descendant of penicillin. It’s chemically modified to be absorbed better when taken by mouth and to work against a slightly broader range of bacteria. For many everyday infections (ear infections, sinus infections, mild pneumonia), amoxicillin has largely replaced original penicillin simply because it’s more practical.
When bacteria produce those penicillin-destroying enzymes, doctors can pair amoxicillin with clavulanic acid, a compound that blocks those enzymes. This combination, sold as Augmentin, essentially restores amoxicillin’s effectiveness against resistant bacteria. In one clinical trial comparing this combination to penicillin V for dental abscesses, both were effective, but patients on the combination reported significantly faster pain relief during the first few days.
These derivatives haven’t replaced penicillin so much as expanded its reach. Original penicillin still gets used where it works best, while its modified cousins handle the infections it can no longer touch.
The Shortage Problem
Despite its importance, injectable penicillin is currently in short supply in the United States. Bicillin L-A, the only FDA-approved formulation of benzathine penicillin G in the country, has been in limited supply, with the manufacturer extending delivery timelines to October 2026 and full recovery not expected until late 2027. This matters enormously because syphilis rates have been climbing, and there is no adequate substitute for pregnant patients.
The CDC has recommended that healthcare systems prioritize their remaining supply for pregnant patients. The FDA has also allowed temporary importation of an alternative product from outside the U.S. to help bridge the gap. The shortage underscores just how essential penicillin remains: when supply runs low, there’s no easy replacement for certain patients.
Most “Penicillin Allergies” Aren’t Real
About 10% of people in the U.S. have a penicillin allergy on their medical record, but the vast majority of them aren’t truly allergic. When tested, fewer than 1 in 20 of those people react to the drug, meaning less than 1% of the general population has a genuine penicillin allergy. Many people were labeled allergic as children after a rash that may have been caused by their illness rather than the antibiotic, or they had a mild reaction decades ago that their immune system no longer remembers.
This matters because a penicillin allergy label often pushes doctors toward broader-spectrum antibiotics that are more expensive, carry more side effects, and contribute to antibiotic resistance. Many hospitals now run allergy “de-labeling” programs, where patients undergo simple skin testing or supervised oral challenges to determine whether they can safely take penicillin. Most can. If you’ve been carrying a penicillin allergy label for years, getting tested could open up better treatment options for you down the road.