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What is Pivmecillinam?

Pivmecillinam (brand name Pivya) is a new antibiotic approved by the U.S. Food and Drug Administration (FDA) in April 2024. It is prescribed for the treatment of uncomplicated urinary tract infections (UTIs) in female adults (18 years and older).

Classification 

Pivmecillinam is a penicillin, a beta-lactam antibiotic. 

Mechanism of Action

Pivmecillinam is a prodrug that is converted to the pivaloyloxymethyl ester of mecillinam and pivalic acid. Prodrugs are considered the “forerunner” of an active drug; prodrugs are essentially inactive until it’s converted to their active form after it’s being administered. 

In other words, when you take pivmecillinam by mouth, it is absorbed by your body and converted to mecillinam and pivalic acid. Mecillinam is the active antibacterial agent. It works by preventing susceptible bacteria from forming a cell wall, thus killing the microorganisms that cause UTIs.

Pivmecillinam Uses

Pivmecillinam is used to treat uncomplicated urinary tract infections (UTIs) in females aged 18 and older. 

An uncomplicated UTI is a lower urinary tract infection or acute cystitis (bladder infection) must meet the following criteria:

• No structural abnormalities of the urinary tract

• Not being immunocompromised

• No chronic illness

• Not being pregnant

Pivmecillinam is effective against bacterial infections of the lower urinary tract caused by Escherichia coli, Proteus mirabilis, and Staphylococcus saprophyticus. 

Special Features of Pivmecillinam

• Pivmecillinam is the pro-drug of mecillinam, which has specific and high activity against Gram-negative organisms that cause uncomplicated cystitis (lower urinary tract infections).

• This antibiotic is absorbed orally very well.

• There are low rates of antibiotic resistance against pivmecillinam.

• Although it has been FDA approved in the US only in 2024, pivmecillinam has been used for decades in Nordic countries without any major safety concerns.

Pivmecillinam Efficacy and Treatment Process

Understanding UTI Cure Rates

The clinical efficacy of pivmecillinam therapy in treating acute uncomplicated UTI has been assessed with controlled clinical trials. These trials measured the effectiveness of pivmecillinam antibiotic treatment based on a composite response rate 8-14 days after starting antimicrobial therapy. The composite response rate includes: 

• Clinical cure (resolution of symptoms of uncomplicated UTI and no new symptoms) 

• Microbiological response (demonstrated reduction in bacteria on urine culture) 

How Effective is Pivmecillinam for UTIs?

Pivmecillinam has been found to be superior to placebo (inactive drug) and anti-inflammatory medication for UTI symptom management.

Pivmecillinam (Pivya) vs. placebo 

In a clinical trial that compared pivmecillinam to a placebo, 62% of the 137 participants who took pivmecillinam achieved a composite response compared to 10% of the 134 who received the placebo.

Pivmecillinam (Pivya) vs. ibuprofen

In a clinical trial that compared pivmecillinam to the anti-inflammatory drug ibuprofen, 66% of the 105 participants who took pivmecillinam achieved a composite response compared to 22% of the 119 who took ibuprofen. 

Notably, the composite response rate in these clinical trials, which is the most important measure, includes:

• Clinical cure: resolution of the initial symptoms of the uncomplicated UTIs at trial entry and no new symptoms;

• Microbiological response: reduction of bacteria in urine culture. 

Pivmecillinam vs. Other Antibacterial Agents for UTI

The FDA reports that in a clinical trial that compared pivmecillinam to another oral antibacterial drug, 72% of the 127 participants who took pivmecillinam achieved a composite response compared to 76% of the 132 who took the comparative drug.

Bacteriological efficacy of pivmecillinam is reported as 75% compared to 91% for norfloxacin, an antibiotic that can be used for UTIs. Clinical cure or improvement in symptoms after 4 days of starting antibiotic therapy is similar for pivmecillinam and norfloxacin at 95-96%. In women younger than 50 years, early clinical cure rates are comparable at 84% for pivmecillinam versus 88% for norfloxacin. 

Other comparative studies of pivmecillinam versus norfloxacin have shown that pivmecillinam 200 mg twice daily for 7 days has similar results as norfloxacin 400 mg twice daily for 3 days.

Overall, short-term treatment with norfloxacin appears to be superior to pivmecillinam in terms of bacteriological outcomes (bacteria isolated on culture). However, clinical outcomes (reduction in symptoms), especially in young women, are comparable.

Before pivmecillinam (Pivya), many antibiotics were effective for treating UTIs. However, according to a global surveillance report from the World Health Organization, 20% of E. coli in urine samples are found to be resistant to second and even first-line drugs for UTIs. Therefore, even though we have many antibiotics to choose from, we can research new antibiotics or discover ways to use old antibiotics to combat the rise of antibiotic resistance, a global health concern. 

The approval of pivmecillinam (Pivya) is a prime example here, as it becomes FDA-approved on 24th April 2024; however, this antibiotic has been available in Europe for more than 40 years due to the increased antibiotic resistance to the commonly prescribed antibiotics in the U.S. 

Pivmecillinam Dosage and Treatment Duration for Optimal Results

Pivmecillinam tablets (brand name Pivya) are available in 185-milligrams (mg) dosage strength. Pivmecillinam (Pivya) is to be taken by mouth three times a day for three to seven days or as instructed by your doctor. It can be taken with or without food.

Just as with any antibiotics, it is important to finish the whole course, even if you start to feel better before finishing the entire course of medication. Not finishing the whole course of antibiotics is the reason for antibiotic resistance. 

Potential Side Effects, Warnings, and Drug Interactions

Common Side Effects of Pivmecillinam

The most common side effects of pivmecillinam antibiotic treatment are nausea and diarrhea. Tell your doctor if these side effects are severe or persistent.

Important Safety Information and Warnings for Patients

Hypersensitivity Reactions

Serious allergic reactions, including anaphylaxis (throat closing), have been reported in people who took pivmecillinam. Stop taking the antibiotic and seek emergency medical care if you develop swelling of the face, eyes, lips, tongue, or throat, hoarseness, or difficulty breathing or swallowing. 

Severe Cutaneous Adverse Reactions

Rarely, pivmecillinam can cause severe skin reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), toxic epidermal necrolysis (TEN), and Stevens-Johnson syndrome (SJS). Stop taking pivmecillinam and seek emergency medical care if you develop a severe skin rash, itching, peeling, or blistering skin. 

Carnitine Deficiency

Carnitine is a substance that helps the body convert fat into energy. There are reports of clinically significant low carnitine levels in certain high-risk patients who took pivmecillinam. People with significant renal impairment (kidney dysfunction), decreased muscle mass, and prolonged treatment with antimicrobial agents are at an increased risk of carnitine deficiency. Pivmecillinam should not be used when long-term treatment with antibiotics is necessary. 

Clostridioides difficile- Associated Diarrhea (CDAD)

CDAD is a type of severe diarrhea that occurs due to a disruption of the gut microbiome following antibiotic treatment. It is a risk with nearly all antimicrobial agents, including pivmecillinam. Tell your doctor without delay if you develop severe, watery diarrhea with or without abdominal pain and/or fever. This can occur up to 2 months after taking antibiotics. 

Interference with Newborn Screening Test

If a pregnant woman takes pivmecillinam before delivery, it can result in a false positive screening test for isovaleric acidemia on newborn screening.

Drug Interactions 

Taking certain other drugs at the same time as pivmecillinam can affect how each of the medicines works. Drug interactions can also increase the risk of serious adverse effects. The following medications should not be taken with pivmecillinam:

• Certain vaccines, such as the BCG vaccine and live typhoid vaccine

• Other antibiotics such as doxycycline, minocycline, tetracycline, oxytetracycline, and demeclocycline

• Immunosuppressive drugs such as mycophenolate

• Probenecid (gout medication)

The above-list does not contain all the potential interactions of pivmecillinam. Give your doctor and pharmacist a complete list of all your prescription drugs, over-the-counter medications, dietary supplements, and herbal remedies to avoid potentially dangerous interactions.

Contraindications

The following people should not take pivmecillinam:

• Pediatric patients under 18 years of age. 

• People with a history of serious allergic reactions to pivmecillinam or other penicillins.

• Those with medical conditions such as carnitine deficiency, other inborn errors of metabolism (propionic acidemia, methylmalonic aciduria), or acute porphyria.

Who Should Consider Pivmecillinam?

Ideal Candidates for Pivmecillinam Treatment

Ideal candidates for pivmecillinam treatment are adult women over 18 years of age with uncomplicated urinary tract infections caused by mecillinam-sensitive organisms. 

Precautions for Specific Populations (e.g., Pregnancy, Elderly)

Pregnant Women

Pivmecillinam is generally safe for use during pregnancy. However, it can interfere with newborn screening tests if it is used before delivery.

Kidney Disease

Pivmecillinam is eliminated from the body by the kidneys. A dosage adjustment may be necessary in people with impaired renal function (reduced kidney function). 

Liver Disease

Dosage adjustments are not needed for people with impaired hepatic function (liver disease).

Older Adults

Clinical trials have not revealed any differences in the safety or effectiveness of pivmecillinam between elderly individuals (age 65 years and older) and younger adult patients. Notably, older adults frequently have reduced kidney function. However, significant accumulation of pivmecillinam due to reduced elimination by the kidneys is not anticipated when the drug is taken at the recommended dosage.

Frequently Asked Questions

What infections does pivmecillinam treat?

Pivmecillinam is used for the treatment of uncomplicated infections of the lower urinary tract caused by susceptible bacteria including E. coli.

How effective is pivmecillinam for UTI?

Around 7 out of 10 people who take pivmecillinam achieve resolution of UTI symptoms and reduction in bacteria on urine culture.

How long does it take for pivmecillinam to work?

Most patients notice an improvement in their symptoms within 3 days of starting antibiotic treatment. Your doctor will prescribe pivmecillinam for 3-7 days depending on the severity of your urinary tract infection.

Is pivmecillinam better than nitrofurantoin?

There are no head-to-head comparative studies of pivmecillinam vs nitrofurantoin in adults with urinary tract infections. However, small studies in children have shown that while drugs have similar clinical efficacy, pivmecillinam is significantly better tolerated than nitrofurantoin.

Making an Informed Decision

Consult Healthcare Professionals Before Starting Pivmecillinam

It is important to consult a healthcare professional to get a proper diagnosis and treatment for a urinary tract infection. Several other conditions can mimic UTI symptoms, such as vaginitis, kidney stones, overactive bladder, sexually transmitted infections (STIs), and bladder cancer. 

Your doctor may prescribe pivmecillinam if you are an adult female and have clinical and/or laboratory evidence of an uncomplicated UTI caused by susceptible isolates.

Choosing Between Pivmecillinam and Alternative Treatments

Your healthcare provider will use urine culture and susceptibility information (when available) to make the appropriate choice of antibiotic to treat your urinary tract infection. 

Appropriate Use of Antibiotics

Due to widespread use, there is increasing resistance among bacteria to commonly prescribed antibiotics. To reduce the development of antimicrobial resistance, antibiotics should only be used to treat or prevent infections that are known or strongly suspected to be caused by bacteria. Antibiotics are not effective against infectious diseases caused by other microorganisms, such as viruses. Bacterial vs Viral Infection: What’s the Difference?

Do not share your pivmecillinam with others or use someone else’s antibiotics even if you have the same symptoms.

Final Thoughts on Pivmecillinam: Therapy of Choice in UTI Management?

While there are several first-line agents that are highly effective for uncomplicated lower urinary tract infections, the rise of antibiotic resistance makes it more challenging to treat uncomplicated UTIs. Notably, no major differences are reported in the clinical efficacy of pivmecillinam versus other antibiotics used for the treatment of uncomplicated urinary tract infections. 

Therefore, even though pivmecillinam (Pivya) may not automatically become the most preferred antibiotic for uncomplicated UTIs, this antibiotic serves a critical role for those whose urine cultures show resistance to other commonly prescribed antibiotics. 

Once your urine sample is collected, your healthcare provider will follow the urine culture results to monitor for the type of bacteria growing in the urine and whether or not these bacteria are resistant to certain antibiotics. Using these data, your doctor will decide which antibiotic is best for you. 

Regardless of the antibiotic used, symptoms usually improve about 3 days after treatment is started. The important thing is to seek care from a healthcare professional for proper diagnosis. It’s also important to take the recommended antimicrobial therapy as advised. Stopping treatment too soon can cause your urinary tract infection to come back and be more challenging to treat in the future, which is the cause of antibiotic resistance, a global health threat.