What is the next step in managing a patient with persistent sore throat and cervical lymph node swelling, who completed a round of antibiotics and tested negative for strep, with worsening symptoms and a swollen tonsil with a white patch?

Management of Persistent Pharyngitis with Unilateral Tonsillar Swelling and Cervical Lymphadenopathy

This patient requires immediate evaluation for infectious mononucleosis (EBV) with a monospot test or EBV serology, and you must exclude peritonsillar abscess through careful examination for uvular deviation, trismus, and fluctuance—if any of these are present or if symptoms worsen, obtain urgent CT imaging of the neck. 1, 2

Immediate Clinical Assessment

Red Flags to Exclude Life-Threatening Complications

You must actively rule out the following urgent conditions:

• Peritonsillar abscess: Look specifically for uvular deviation away from the affected side, trismus (inability to open mouth fully), and a fluctuant mass on palpation—the absence of "hot potato voice" and drooling makes this less likely but does not exclude it 1, 2
• Parapharyngeal abscess: Assess for neck stiffness, torticollis, or lateral neck swelling 2
• Lemierre syndrome: Check for persistent high fever, neck pain along the sternocleidomastoid, and signs of septic emboli (respiratory symptoms, joint pain)—this is a thrombophlebitis of the internal jugular vein that can follow pharyngitis 1, 2

Most Likely Diagnosis: Infectious Mononucleosis

The clinical picture strongly suggests EBV infection (infectious mononucleosis):

• Classic presentation: Pharyngitis with unilateral tonsillar exudate, cervical lymphadenopathy (especially posterior cervical nodes), and symptoms persisting beyond typical viral pharyngitis duration 1
• Key distinguishing features: Look for posterior cervical adenopathy (not just anterior), splenomegaly on abdominal exam, and generalized lymphadenopathy 1
• Testing required: Order monospot test (heterophile antibody) or EBV-specific serology (VCA-IgM and VCA-IgG) if monospot is negative but suspicion remains high 1

Diagnostic Algorithm

Step 1: Repeat Strep Testing (Despite Previous Negative Result)

• Perform rapid antigen detection test (RADT) again: The patient has 3-4 Centor criteria (fever implied by "worsening," tonsillar exudate, cervical lymphadenopathy, no mention of cough), which indicates 32-56% probability of Group A streptococcal infection 3
• Consider throat culture if RADT negative: A negative RADT does not exclude Group C or G streptococci, which can cause severe pharyngitis with similar presentation and require antibiotic treatment 1, 4
• Important caveat: The patient may be a chronic GAS carrier (10.9% prevalence in children, 2.3% in adults) experiencing an intercurrent viral infection—carriers show extremely low risk of complications and do not require treatment 1

Step 2: Order EBV Testing

• Monospot test: First-line for suspected infectious mononucleosis 1
• If monospot negative but clinical suspicion high: Order EBV-specific serology (VCA-IgM positive indicates acute infection) 1

Step 3: Consider Imaging if Examination Concerning

• CT neck with contrast: Obtain urgently if you detect uvular deviation, trismus, fluctuance, severe unilateral swelling, or if patient has difficulty swallowing/breathing 2, 5
• Ultrasound: Can be used as initial imaging for suspected suppurative lymphadenitis if CT unavailable 5

Management Based on Findings

If EBV Positive (Infectious Mononucleosis)

• Symptomatic treatment only: Prescribe ibuprofen 400-600 mg every 6-8 hours or acetaminophen 650-1000 mg every 6 hours for pain and fever 3
• Avoid amoxicillin/ampicillin: These cause a characteristic maculopapular rash in 80-100% of patients with EBV 1
• Activity restriction: No contact sports or heavy lifting for 3-4 weeks due to splenomegaly and risk of splenic rupture 1
• Expected course: Symptoms typically improve over 2-4 weeks 1

If Strep Test Positive (Group A, C, or G Streptococcus)

• Penicillin V 500 mg orally twice daily for 10 days: First-line treatment 3
• Alternative for penicillin allergy: Cephalexin 500 mg twice daily for 10 days, or clindamycin 300 mg three times daily for 10 days 6
• Counsel on modest benefit: Antibiotics shorten symptom duration by only 1-2 days but prevent rare complications 3

If Imaging Shows Abscess

• Urgent ENT consultation: Peritonsillar or parapharyngeal abscess requires drainage (needle aspiration or incision and drainage) plus IV antibiotics 5
• Empiric antibiotics: Ampicillin-sulbactam 3g IV every 6 hours or clindamycin 600-900 mg IV every 8 hours pending culture 5
• Send tissue for culture and pathology: This ensures accurate pathogen identification and excludes atypical infections like mycobacterial disease or actinomycosis 5

If All Testing Negative

• Continue symptomatic management: Ibuprofen or acetaminophen, adequate hydration with cool liquids, throat lozenges 3
• Consider alternative diagnoses: GERD, allergic rhinitis with postnasal drip, or chronic irritant exposure 1
• Reassess in 3-5 days: If symptoms persist beyond 2 weeks total or worsen, consider referral to ENT for direct laryngoscopy and possible biopsy to exclude malignancy (though unlikely given acute presentation) 1

Critical Pitfalls to Avoid

• Do not assume previous negative strep test excludes bacterial infection: Group C and G streptococci may not be detected by all RADTs, and the patient's clinical picture has worsened since initial testing 4
• Do not prescribe antibiotics empirically without testing: This patient has already completed one course of antibiotics—adding more without microbiologic confirmation risks masking serious diagnoses and promoting resistance 1, 3
• Do not miss peritonsillar abscess: Unilateral tonsillar swelling with white exudate can represent either severe tonsillitis or early abscess formation—examine carefully for fluctuance and uvular deviation 2
• Do not give amoxicillin if EBV suspected: Wait for monospot results before prescribing any penicillin-based antibiotic 1

Predictors for Surgical Drainage (If Suppurative Lymphadenitis Develops)

Risk factors that increase likelihood of requiring drainage include:

• Male sex 5
• Immunocompromised status 5
• Prior inadequate antibiotic treatment (which this patient has received) 5
• Singular, painful, fluctuant lymph node 5