Picture of pivmecillinam (Pivya) pending
The FDA-approved product’s package insert (Pivya) is pending release
KEY POINTS
- Pivmecillinam (Pivya, Selexid) is a penicillin class (and beta-lactam) antibiotic pro-drug that is hydrolyzed by non-specific esterases to mecillinam (the active antibacterial agent)
- Mecillinam interferes with bacterial cell wall synthesis via interacting with penicillin binding protein 2 (PBP-2)
- Considered narrow-spectrum
- Generally considered to have activity against Citrobacter species, Enterobacter species, E. coli, Klebsiella species, Proteus mirabilis, Salmonella species, Shigella species, and Yersenia species
- Has been shown to be effective versus ESBL-producing E. coli
- Expected to have low levels of cross-resistance with other beta-lactams (i.e., penicillins, cephalosporins)
- Resistance may develop by beta-lactamases or modifications to PBPs
- Has shown clinical benefit against Staphylococcus saprophyticus, attributed to high concentrations in the urinary tract
- Lacks activity against Pseudomonas aeruginosa, Enterococcus faecalis, and Staphylococcus aureus
- Generally considered to have activity against Citrobacter species, Enterobacter species, E. coli, Klebsiella species, Proteus mirabilis, Salmonella species, Shigella species, and Yersenia species
- FDA approved 24 April 2024 for treatment of female adults with uncomplicated urinary tract infections (UTIs) caused by susceptible isolates of Escherichia coli, Proteus mirabilis and Staphylococcus saprophyticus.
- Uncomplicated UTIs are bacterial infections of the bladder in females with no structural abnormalities of their urinary tract. Approximately one-half of all women experience at least one UTI in their lifetime.
- Has been used outside the United States prior to the FDA approval
- FDA approval is with UTILITY therapeutics Ltd.
- Has been placed next to nitrofurantoin by many experts as a go-to drug for consideration when treating uncomplicated cystitis, due to good efficacy and tolerability
- Dose is 185 mg oral TID for 3 to 7 days as clinically indicated
- May be given with or without food
- Generally give at least 3 days, for 48 hours after symptoms resolve, and for up to 7 days
- Each film coated tablet includes 185 mg of pivmecillinam which is equivalent to 200 mg of pivmecillinam hydrochloride
- Table contains simethicone
- Pivmecillinam achieves very high urinary concentration of mecillinam >200 mg/L after intake of one 400 mg tablet
- Primary elimination pathway is urine, where 80% is excreted as mecillinam
- Contraindicated in:
- Serious hypersensitivity reaction
- Not recommended for use in patients who have had severe hypersensitivity to other beta-lactams
- Primary or secondary carnitine deficiency resulting from inherited disorders of mitochondrial fatty acid oxidation and carnitine metabolism, and other inborn errors of metabolism (e.g., methylmalonic aciduria, or propionic acidemia)
- Acute porphyria
- Serious hypersensitivity reaction
- Holds a precaution for:
- Hypersensitivity reactions
- Severe cutaneous adverse reactions
- Carnitine depletion (not recommended to use if primary or secondary carnitine deficiency)
- Clostridioides difficile-associated diarrhea
- Interference with a newborn screening test for isovaleric acidemia, a rare metabolic disorder
- Most common side effects are nausea and diarrhea
- May reduce clearance of methotrexate
RESOURCES
- Pevmecillinam (Pivya) Package Insert
- FDA Release: FDA Approves New Treatment for Uncomplicated Urinary Tract Infections
- Selexid Package Insert
- Treating urinary tract infections in the era of antibiotic resistance (Expert Review Anti-Infective Therapy 2023)
- Ibuprofen Versus Mecillinam for Uncomplicated Cystitis (IMUTI)
- Pivmecillinam in the treatment of urinary tract infections (JAC 2000)
- Pivmecillinam is more effective than ibuprofen in symptom resolution in women with uncomplicated urinary tract infection: antibiotic treatment for UTI is important (BMJ EBM 2019)
- Optimal dosage and duration of pivmecillinam treatment for uncomplicated lower urinary tract infections: a systematic review and meta-analysis (IJID 2017)
- Pivmecillinam compared to other antimicrobials for community-acquired urinary tract infections with Escherichia coli, ESBL-producing or not – a retrospective cohort study (IDR 2019)
- The efficacy of pivmecillinam in oral step-down treatment in hospitalised patients with E. coli bacteremic urinary tract infection; a single-arm, uncontrolled treatment study (BMC ID)
- Pivmecillinam versus sulfamethizole for short-term treatment of uncomplicated acute cystitis in general practice: a randomized controlled trial (2009)
- Pivmecillinam in treatment of Staphylococcus saprophyticus urinary tract infections (1983)