Orlynvah, a combination of sulopenem and probenecid, was recently approved to treat uncomplicated female UTIs. Sulopenem is a beta-lactam antibiotic in the penem class that inhibits bacterial cell wall synthesis. Probenecid inhibits renal organic anion transporter 3 (OAT3), reducing sulopenem clearance and increasing its exposure. Orlynvah was compared to ciprofloxacin (250 mg BID for 3 days) in 1671 women with acute uncomplicated UTI. The primary endpoint - resolution of UTI symptoms and a urine culture showing less than 10³ CFU/mL of the culprit bacteria at day 12 - occurred in 65.6% of the sulopenem group and 67.9% of the ciprofloxacin group (diff -2.3%, 95%CI [-7.9 to 3.3]). In the subgroup of patients with ciprofloxacin-resistant bacteria, cure rates were 62.6% and 36%, respectively (p<0.001). [PubMed abstract]

Orlynvah is dosed as one tablet with food twice daily for 5 days. Common side effects include diarrhea (10%) and nausea (4%). Drug interactions, which are related to probenecid's OAT1/3 inhibition, include ketorolac, ketoprofen, indomethacin, naproxen, methotrexate, rifampin, lorazepam, and sulfonylureas.

Orlynvah is considerably more expensive than available therapies, creating issues with insurance coverage and affordability that likely limit its use to cases of multidrug-resistant bacteria. However, sulopenem is not a part of standard urine culture sensitivity reports. Imipenem, a carbapenem related to sulopenem, is often included and may be used as a surrogate marker of sulopenem sensitivity, with the understanding that cross-sensitivity between the drugs has not been validated in a study.

Orlynvah is the second new drug approved for UTIs in 2024. Pivmecillinam (Pivya), a penicillin antibiotic, was approved in April; however, it was discontinued by the manufacturer shortly after its approval for reasons that are unclear.

• Orlynvah prescribing information
• Urinary tract infection treatment recommendations