Ampicillin vs. Amoxicillin

Ampicillin and amoxicillin are members of the penicillin class of antibiotics, more specifically classified as aminopenicillins within the larger beta-lactam family. Both work by disrupting bacterial cell wall formation, which ultimately causes the organism to die. They are used to treat numerous types of bacterial infections, though they are not interchangeable in every clinical situation. While these two drugs share structural similarities and belong to the same antibiotic class, important differences exist in how they are absorbed, administered, and used clinically.

Quick comparison: Ampicillin vs. Amoxicillin

Key differences between ampicillin and amoxicillin

Ampicillin is a penicillin-class antibiotic effective against many gram-positive and gram-negative bacterial species. It was originally sold under the brand name Principen, which is no longer available commercially. Today, ampicillin is available only as a generic medication—either as oral capsules or injectable formulations. When combined with sulbactam (a beta-lactamase inhibitor that helps overcome bacterial resistance), ampicillin is marketed as Unasyn for injection; this combination is also available generically as ampicillin/sulbactam.

Amoxicillin is similarly a penicillin antibiotic with a broad spectrum of activity against gram-positive and gram-negative bacteria. It was originally branded as Amoxil, which is no longer sold commercially. Amoxicillin is available only in generic form, typically dispensed as capsules for adults, liquid suspension for children, or—when paired with clavulanic acid (another beta-lactamase inhibitor)—as the combination product Augmentin. Additionally, amoxicillin was previously part of a combination therapy known as Prevpac (amoxicillin, lansoprazole, and clarithromycin) for H. pylori eradication, though this brand is no longer available.

When taking any antibiotic, it is crucial to follow the prescribed instructions carefully and complete the entire course of treatment, even if symptoms resolve early. If your condition does not improve after several days of treatment, or if you feel worse, contact your healthcare provider without delay.

Detailed comparison: Ampicillin vs. Amoxicillin

Infections treated by these antibiotics

According to its FDA-approved labeling, ampicillin is indicated for bacterial infections including:

• Respiratory tract infections caused by non-penicillinase-producing strains of Haemophilus influenzae, Staphylococcus species, and Streptococcus (including Streptococcus pneumoniae)
• Urinary tract infections caused by Escherichia coli and Proteus mirabilis
• Gastrointestinal infections caused by Shigella, Salmonella typhosa, other Salmonella species, E. coli, P. mirabilis, and enterococci
• Meningitis caused by Neisseria meningitidis

Amoxicillin's labeling indicates FDA approval for treating:

• Ear, nose, and throat infections caused by susceptible strains of Streptococcus, S. pneumoniae, Staphylococcus species, or Haemophilus influenzae
• Urinary tract infections caused by E. coli, P. mirabilis, or Enterococcus faecalis
• Skin and soft tissue infections caused by susceptible Streptococcus, Staphylococcus species (including Staphylococcus aureus), or E. coli
• Lower respiratory tract infections caused by Streptococcus, S. pneumoniae, Staphylococcus species, or H. influenzae
• Helicobacter pylori eradication (in combination with lansoprazole and clarithromycin) to prevent duodenal ulcer recurrence

Antibiotics such as these should be reserved strictly for confirmed or suspected bacterial infections, as determined by a healthcare provider. Inappropriate use accelerates the development of antibiotic resistance. The Centers for Disease Control and Prevention actively promotes antibiotic stewardship—a coordinated effort to help clinicians select appropriate agents and minimize unnecessary prescribing—as a key strategy to combat resistance and improve patient outcomes.

Which antibiotic is more effective?

In most outpatient care situations, amoxicillin is the preferred choice because it reaches higher, more stable blood concentrations when taken by mouth compared to oral ampicillin. This superior oral absorption makes amoxicillin ideal for common infections such as middle ear infections, sinusitis, strep throat, community-acquired pneumonia, and dental infections. Ampicillin, by contrast, is poorly absorbed from the gastrointestinal tract and remains in the intestines longer, which actually makes it useful for treating intestinal infections caused by Salmonella and Shigella.

Ampicillin, unlike amoxicillin, has an injectable form and is commonly used in hospital settings, often paired with sulbactam to overcome bacterial resistance mechanisms. This approach mirrors the outpatient use of Augmentin (amoxicillin plus clavulanic acid), which also incorporates a beta-lactamase inhibitor.

Determining which drug is most effective requires a healthcare provider to first confirm that the infection is bacterial rather than viral—a critical distinction, since antibiotics do not treat viral illness and inappropriate use fuels resistance. If a bacterial infection is confirmed, the choice between these agents depends on identifying the specific organism responsible. This is ideally done through culture and sensitivity testing of a sample from the infection site (such as urine, blood, or sputum). More commonly, prescribers rely on established clinical guidelines from organizations like the Infectious Diseases Society of America or on local epidemiologic data regarding bacterial resistance patterns. Your provider will also review your complete medical history, including comorbidities and concurrent medications, to assess potential drug interactions before finalizing a prescription.

Cost and savings

Most commercial insurance plans and Medicare Part D programs cover both ampicillin and amoxicillin.

Without insurance coverage, the typical cash price for a 28-capsule bottle of 500 mg ampicillin is approximately $14.51. A 21-capsule bottle of 500 mg amoxicillin typically costs around $11 or more without coverage.

Cost comparison: Ampicillin vs. Amoxicillin

Discount programs and coupons are available through various channels to help reduce out-of-pocket costs on both medications. Comparing prices across different pharmacies in your area can also yield significant savings.

Common side effects

The most frequently encountered adverse effects of both ampicillin and amoxicillin involve the gastrointestinal tract and allergic responses, particularly in patients with a history of penicillin sensitivity. Typical side effects include nausea, vomiting, diarrhea, and skin rashes or other manifestations of hypersensitivity. Severe anaphylactic reactions, though uncommon, require immediate emergency medical intervention.

Antibiotics can alter the balance of normal bacterial flora in the body, increasing the risk of diarrhea or secondary yeast infections. Consult your healthcare provider about whether a probiotic supplement might be appropriate for you during treatment.

This summary does not cover all possible side effects. Speak with your healthcare provider or pharmacist for a complete list of potential adverse reactions.

Drug interactions

Because ampicillin and amoxicillin share similar chemical structures, they have comparable drug interaction profiles.

Combining either medication with anticoagulants such as warfarin may alter bleeding risk, and patients on this combination require monitoring. Allopurinol, used to treat gout, can increase the likelihood of rash development when combined with ampicillin or amoxicillin.

Current evidence suggests that ampicillin and amoxicillin do not substantially diminish the effectiveness of oral contraceptive medications. However, severe vomiting or diarrhea—whether from the infection itself or as an antibiotic side effect—could interfere with birth control pill absorption. Discuss backup contraceptive measures with your healthcare provider if you experience gastrointestinal symptoms.

Both drugs interact with the live oral typhoid vaccine (Vivotif Berna), as the antibiotic may inactivate the vaccine.

This is not an exhaustive list of interactions. Ask your healthcare provider or pharmacist for complete information on all possible drug interactions.

Warnings and precautions

Clostridium difficile–associated diarrhea has been documented with most antibiotics and can range from mild symptoms to life-threatening colitis. This complication can develop during treatment or emerge months later. Report diarrhea, nausea, abdominal cramping, and fever to your healthcare provider immediately.

A personal or family history of allergic reaction to penicillins is a contraindication to ampicillin or amoxicillin therapy. Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, have occurred with penicillin-class drugs. Cross-reactivity with cephalosporin antibiotics (such as cephalexin) is possible in penicillin-allergic patients. If signs of allergic reaction appear, discontinue the medication at once and seek emergency care.

These antibiotics are suitable only for treating bacterial infections. Using them for viral illnesses will not resolve the viral illness and contributes to the development of antibiotic resistance.

Prolonged antibiotic use may lead to fungal overgrowth infections, which will require separate treatment.

Are these medications identical?

Although ampicillin and amoxicillin are structurally related and belong to the same antibiotic class, they are not identical medications. Both share similar side effect profiles and drug interaction patterns, but they differ significantly in oral bioavailability, clinical indications, and dosing schedules. Refer to the detailed comparisons earlier in this article for a full breakdown of their differences.

If I'm allergic to one, am I allergic to the other?

Yes. Anyone with a documented allergic reaction to either ampicillin or amoxicillin should be considered allergic to both. In practice, such patients are typically labeled as having a penicillin-class allergy, meaning the entire penicillin family of antibiotics should be avoided.

Do they treat the same types of infections?

In office-based and outpatient practice, oral antibiotics dominate, and amoxicillin is chosen far more often than ampicillin due to its superior intestinal absorption. This preference holds for infections such as ear, sinus, and pulmonary infections. Oral ampicillin is reserved for specific circumstances—notably intestinal infections caused by Shigella or Salmonella—where its poor absorption and prolonged gut residence time become therapeutic advantages. In hospital settings, intravenous ampicillin remains standard for serious infections.

Is amoxicillin a newer drug than ampicillin?

Both drugs were discovered during the 1950s, so neither is substantially newer than the other. Amoxicillin's dominant clinical use today stems not from being a more recent discovery but rather from its superior absorption through the gastrointestinal tract following oral administration. Conversely, ampicillin remains the standard choice in hospitals, where injectable formulations are readily available and preferred.

Which is better: ampicillin or amoxicillin?

Each drug can be effective when used alone for appropriate infections; however, ampicillin's poor oral absorption limits its utility in outpatient settings, which explains why amoxicillin sees much broader use. When either agent is paired with a beta-lactamase inhibitor—ampicillin with sulbactam (Unasyn, given intravenously) or amoxicillin with clavulanic acid (Augmentin, given orally)—the spectrum of antimicrobial coverage expands, and the likelihood of encountering resistant organisms decreases.

Pregnancy use of ampicillin and amoxicillin

Both medications are routinely prescribed during pregnancy. The drug labels note that adequate, well-controlled safety studies in pregnant women are not available. Your healthcare provider will conduct a careful risk-benefit analysis to determine whether antibiotic therapy is necessary and, if so, which agent is most appropriate for your situation.

Alcohol and these antibiotics

Ampicillin and amoxicillin do not have an absolute contraindication to alcohol use. However, alcohol consumption can suppress immune function and reduce your body's ability to fight infection. Additionally, alcohol may worsen gastrointestinal side effects such as nausea and diarrhea. It is advisable to limit or avoid alcohol until your infection has resolved and you feel well.

Are they considered strong antibiotics?

Ampicillin and amoxicillin are classified as broad-spectrum antibiotics, but this designation does not equate to being "strong." The term "strong" is not a standard medical classification for antibiotics. Your healthcare provider selects an antibiotic based on the identity of the bacterial pathogen causing your infection and that organism's susceptibility to available treatments, not on informal notions of drug "strength."

Duration of antibiotic therapy

The appropriate duration of treatment depends on the type and severity of the infection and will be determined individually by your healthcare provider. Most infections are treated for 7 to 14 days. Completing the full prescribed course is important—do not stop treatment early even if symptoms disappear, as incomplete therapy can allow bacteria to rebound and cause relapse.

Bacterial spectrum of ampicillin and amoxicillin

Ampicillin and amoxicillin are active against various bacterial pathogens responsible for urinary tract, respiratory tract, and gastrointestinal tract infections, as well as meningitis. For detailed information on the specific bacterial species targeted by each drug in each infection type, refer to the earlier section titled "Conditions treated by ampicillin and amoxicillin."