A Study to Investigate Pivmecillinam Versus Nitrofurantoin in Female Adolescents 12 to Less Than 18 Years of Age With Uncomplicated Urinary Tract Infection

1. Female adolescents 12 years to less than 18 years of age at the time of consent and a body weight ≥ 40 kg (≥ 88 lbs).
2. Written informed consent from parent(s) or legally acceptable representative(s), and informed assent from participant (according to the local regulations) before initiation of any trial-related procedures.
3. Able to supply a urine specimen from clean-catch midstream urine sample.
4. Have 2 or more of the following clinical signs and symptoms of acute cystitis with onset ≤ 96 hours prior to trial entry: dysuria, urinary frequency, urinary urgency, or suprapubic pain (lower abdominal pain).

5. A urine specimen* that is positive for nitrite, pyuria, or the presence of 3 plus (+)/large leukocyte esterase. Evidence of pyuria is to be confirmed by either a urine specimen that is positive for leukocyte esterase via urine dipstick or urinalysis, or a urine specimen with either > 10 white blood cells (WBCs) per microliter from an unspun urine or > 5 WBCs per high power field from a centrifuged specimen.

   *Note: Sample obtained from clean-catch midstream urine sample.

6. Participants of childbearing potential (who have reached menarche) will be advised to avoid conception and not to attempt pregnancy from the time of screening until 7 days after the end of trial treatment and will be provided guidelines regarding the continuation of abstinence, initiation of abstinence, or about allowed contraception. Participants of childbearing potential must meet the following criteria:

   1. Report use of at least 1 of the acceptable methods of contraception, including an intrauterine device (with copper banded coil), levonorgestrel intrauterine system, or regular medroxyprogesterone injections (Depo Provera®); or
   2. Agree to initiate sexual abstinence from the time of screening until 7 days after the end of trial treatment.

7. Participants of childbearing potential (who have reached menarche) must have a negative pregnancy test result from a validated assay* with a sensitivity of ≤ 25 IU/L human chorionic gonadotropin (hCG).

   • Note: Local urine testing will be standard for the protocol unless serum testing is required by local regulation or IRB

Exclusion Criteria:

Participants are excluded from the trial if any of the following criteria apply:

1. Signs or symptoms of systemic illness such as fever (temperature ≥ 38.0 °C [100.4 °F]), shaking chills, or other clinical manifestations suggestive of cUTI such as acute flank pain or costovertebral angle tenderness.
2. Presence of risk factors for cUTI, including urinary tract instrumentation, nephrostomy, ureter stent or other foreign material (including catheter), nephrolithiasis, current known functional or anatomical abnormality of the urogenital tract (including kidneys), complete or partial obstructive uropathy, urinary retention, or known underlying renal disease with blood urea nitrogen (BUN) > 20 mg/dL, or serum creatinine > 1.4 mg/dL.
3. Multi-recurrent UTI (defined as 3 or more previous UTIs within a 6-month period).
4. Receipt of systemic antibacterials within the 7 days prior to first dose of trial drug. Note: Topical antimicrobial for skin or otic or ophthalmic infection is allowed.
5. Receipt of immunotherapy treatment through an autovaccine for UTI recurrence prevention within 72 hours prior to the first dose of trial drug and for the duration of the trial.
6. Treatment with valproic acid, valproate, or other medication liberating pivalic acid (such as corticosteroid pivalates or hormonal pivalate esters due to increased risk of carnitine depletion) within 72 hours prior to the first dose of trial drug and for the duration of the trial.
7. Known hypersensitivity to beta-lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems, and monobactams), or to nitrofurantoin, as well as known allergy/hypersensitivity to any component of the trial drug, including excipients.
8. Genetic metabolism anomalies known to lead to severe carnitine deficiency, such as carnitine transporter defect, methylmalonic aciduria or propionic acidemia.
9. Known underlying kidney disease.
10. Pre-existing polyneuropathy and/or optic neuritis.
11. Known or suspected renal impairment.
12. Known or suspected severe hepatic impairment including clinical signs of cirrhosis or end stage hepatic disease (e.g., ascites, hepatic encephalopathy), excluding isolated hyperbilirubinemia consistent with suspected or known Gilbert's syndrome.
13. Medical history of porphyria.
14. Known glucose-6 phosphate dehydrogenase deficiency.
15. Previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin.
16. Infection at another site, excluding skin, mucous, or ocular infections that can be treated with topical antimicrobials.
17. Any potentially immune compromising condition (e.g. uncontrolled diabetes, renal transplant recipients, patients with clinically significant persistent granulocytopenia [absolute neutrophil count \< 1000/μL], and patients receiving systemic immunosuppressive therapy, including systemic corticosteroid therapy [> 40 mg/day prednisolone or equivalent for > 1 week, ≥ 20 mg/day prednisolone or equivalent for > 2 weeks, or prednisolone or equivalent ≥ 10 mg/day for > 6 weeks]), or known CD4 count of \< 200 cells/mm3.
18. Poorly controlled asthma or chronic obstructive pulmonary disease at screening and, in the opinion of the Investigator, not stable on current therapy.
19. Vomiting or not able to tolerate oral medication.
20. Pregnancy or lactation or considering becoming pregnant.
21. Unable or unwilling, in the judgment of the Investigator, to comply with the protocol or complete the clinical trial.
22. Receipt of any investigational medication or investigational device during the 30 days prior to enrollment.
23. Any acute or chronic illness/condition or evidence of an unstable clinical condition that, in the opinion of the Investigator, would place the participant at increased risk if participating in the study.