In a 16‑year‑old obese adolescent female with flank pain, urinary‑tract infection, no hematuria, irregular menses, hepatomegaly, and a reactive antistreptolysin O titer, what is the most likely diagnosis and first‑line management?

Polycystic Ovary Syndrome (PCOS) with Acute Pyelonephritis

This 16-year-old obese female with flank pain, UTI, irregular menses, and hepatomegaly most likely has polycystic ovary syndrome (PCOS) complicated by acute pyelonephritis, and should be treated immediately with empiric antibiotics while addressing the underlying metabolic syndrome.

Most Likely Diagnosis

The constellation of obesity, irregular menses, and hepatomegaly in an adolescent female strongly suggests PCOS with associated metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). 1 The reactive ASO titer is likely an incidental finding or reflects a recent streptococcal pharyngitis, but does not explain the current presentation. 2 The absence of hematuria makes post-streptococcal glomerulonephritis unlikely, as that condition typically presents with hematuria, edema, and hypertension—none of which are present here. 2

Key Diagnostic Features Supporting PCOS:

• Irregular menses in an obese adolescent is a hallmark of PCOS, which affects 6-10% of reproductive-age women and commonly presents during adolescence 1
• Hepatomegaly in this context likely represents NAFLD, which occurs in 40-70% of PCOS patients due to insulin resistance 1
• Obesity is present in 50-80% of PCOS patients and drives the metabolic complications 1

Acute Pyelonephritis Diagnosis:

• Flank pain with documented UTI establishes the diagnosis of acute pyelonephritis 1, 3, 4
• Fever ≥38°C with costovertebral angle tenderness is nearly universal in pyelonephritis and distinguishes it from lower tract infection 3, 4
• Urinalysis showing pyuria and/or bacteriuria confirms urinary tract infection 3, 4
• Urine culture with antimicrobial susceptibility testing must be obtained before starting antibiotics 5, 1, 3

Immediate Management of Acute Pyelonephritis

Initial Assessment and Risk Stratification:

• This patient should be classified as having complicated pyelonephritis due to obesity and likely metabolic syndrome, which increases risk of treatment failure 5, 1
• Obtain urine culture before initiating antibiotics to guide subsequent therapy 5, 1, 6
• Blood cultures are recommended if the patient appears systemically ill or has high fever 1

Empiric Antibiotic Therapy:

For outpatient management (if hemodynamically stable and able to tolerate oral intake):

• Ciprofloxacin 500-750 mg orally twice daily for 7 days OR levofloxacin 750 mg orally once daily for 5-7 days 5, 1
• If local fluoroquinolone resistance exceeds 10%, give one dose of ceftriaxone 1-2 g IV or gentamicin before starting oral fluoroquinolone 5, 6
• Avoid trimethoprim-sulfamethoxazole empirically unless susceptibility is confirmed, as resistance frequently exceeds 20% 1, 7

For inpatient management (if septic, unable to tolerate oral intake, or hemodynamically unstable):

• Ceftriaxone 1-2 g IV once daily is the preferred initial parenteral agent 5, 1, 6
• Alternative: Cefotaxime 2 g IV three times daily 5
• For suspected enterococcal infection (if gram-positive cocci on Gram stain): add ampicillin or use piperacillin-tazobactam 8, 9

Treatment Duration:

• Total duration of 7-14 days is recommended for complicated pyelonephritis 5, 1
• Transition to oral therapy once afebrile for 24-48 hours and clinically improving, using culture-directed agents 1, 6

Imaging Strategy

Initial Imaging Recommendations:

• Imaging is NOT indicated for initial evaluation if the patient is clinically stable and responding to antibiotics 5, 1, 3
• 95% of patients with uncomplicated pyelonephritis become afebrile within 48 hours of appropriate antibiotic therapy, and nearly 100% within 72 hours 5, 1, 3

Indications for Imaging:

• Perform renal ultrasound immediately if there is flank swelling, as this may indicate hydronephrosis or obstruction 1
• Obtain contrast-enhanced CT abdomen/pelvis if: 5, 1, 3
  • Fever persists beyond 72 hours despite appropriate antibiotics
  • Clinical deterioration occurs
  • Suspicion of renal or perirenal abscess
  • Concern for urinary obstruction or nephrolithiasis
  • Patient has diabetes or is immunocompromised (lower threshold for imaging)

Ultrasound Findings to Evaluate:

• Hydronephrosis or ureterectasis (sensitivity 100%, specificity 90% for obstruction) 1
• Renal or perinephric abscess 1, 3
• Nephrolithiasis (though direct stone detection sensitivity is only 24-57%, hydronephrosis detection is excellent) 1

Management of Underlying PCOS

After Acute Infection Resolves:

• Confirm PCOS diagnosis with clinical criteria (irregular menses, hyperandrogenism, polycystic ovaries on ultrasound—two of three required)
• Screen for metabolic complications: fasting glucose, lipid panel, liver function tests, and consider oral glucose tolerance test
• Lifestyle modification is first-line therapy: weight loss of 5-10% can restore ovulatory cycles and improve metabolic parameters
• Metformin 500-2000 mg daily improves insulin sensitivity and may restore menstrual regularity
• Combined oral contraceptives regulate menses and reduce androgen levels if pregnancy is not desired

Common Pitfalls to Avoid

• Do not delay antibiotic therapy while awaiting culture results; empiric treatment must begin immediately to prevent renal scarring 4, 8, 6
• Do not obtain imaging in the first 48-72 hours if the patient is clinically improving, as this exposes the patient to unnecessary radiation 5, 1, 3
• Do not attribute all findings to post-streptococcal glomerulonephritis based solely on elevated ASO titer—the absence of hematuria and edema makes this diagnosis unlikely 2
• Do not use empiric beta-lactam oral antibiotics due to high resistance rates and inferior efficacy compared to fluoroquinolones 1
• Do not assume hepatomegaly is infectious—in an obese adolescent with irregular menses, NAFLD secondary to PCOS is far more likely 1
• Do not miss the opportunity to address PCOS after treating the acute infection, as untreated PCOS leads to long-term metabolic and reproductive complications

Expected Clinical Course

• Reassess at 48-72 hours to confirm defervescence and clinical improvement 1, 6
• If fever persists beyond 72 hours, obtain CT imaging immediately to evaluate for abscess, obstruction, or emphysematous pyelonephritis 5, 1, 3
• Follow-up urine culture is not routinely needed if the patient responds clinically, but should be obtained if symptoms recur 6