A 22‑year‑old male developed persistent folliculitis after septoplasty for deviated septum, has low‑grade immune dysfunction, multiple antibiotic‑resistant infections, and has experienced orange‑colored urine during treatment; what is the most likely cause of the orange urine and what is the appropriate diagnostic work‑up and management for his folliculitis?

Management of Persistent Folliculitis with Antibiotic Resistance and Orange Urine

Orange Urine: Most Likely Cause

The orange-colored urine is most likely caused by rifampicin (rifampin), which is a first-line antibiotic used in combination therapy for treatment-resistant folliculitis and commonly causes harmless orange discoloration of body fluids. 1, 2

Key Points About Rifampicin-Induced Orange Urine:

• Rifampicin causes orange discoloration of urine, tears, sweat, and other body fluids as a benign side effect 2
• This is not a sign of toxicity or treatment failure 2
• The combination of clindamycin and rifampicin is commonly used for resistant folliculitis, though it has high relapse rates (80% in one study) 1
• Patient education about this expected side effect is essential to prevent unnecessary alarm and hospital admissions

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Diagnostic Work-Up for Antibiotic-Resistant Folliculitis

Microbiological Assessment:

• Obtain bacterial culture and susceptibility testing from pustular lesions to identify the causative organism and resistance patterns 3
• Screen specifically for Staphylococcus aureus (including MRSA), which colonizes inflamed follicles in approximately 18% of cases 4
• Consider fungal culture if bacterial cultures are negative, as fungal colonization occurs in 8% of folliculitis cases 4
• Test for biofilm-forming organisms, as both Staphylococcus and Propionibacterium acnes can form macrocolonies/biofilms in follicles 4

Immune Function Evaluation:

• Assess HIV status and CD4 count, as immunodeficiency predisposes to resistant follicular infections 2
• Evaluate for diabetes mellitus, which increases susceptibility to gram-negative follicular infections 5
• Consider testing for other immunodeficiency states if no obvious cause is identified 5

Risk Stratification for Multidrug-Resistant Organisms:

• Document prior antibiotic therapy in the past 90 days (major risk factor for MDRO) 3
• Assess for prior hospitalization or healthcare exposure in the past 90 days 3
• Evaluate functional status and any history of hemodialysis 3

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Management Algorithm for Antibiotic-Resistant Folliculitis

First-Line Approach: Oral Isotretinoin

Oral isotretinoin should be considered as the primary treatment for antibiotic-resistant folliculitis, as it achieves stable remission in 90% of patients during treatment and up to two years after cessation. 1

Isotretinoin Protocol:

• Dosing typically ranges from 0.5-1.0 mg/kg/day (standard acne dosing applies) 1
• Treatment duration: minimum 4-6 months, often extended based on clinical response 1
• This approach avoids further antibiotic resistance development 1
• Monitor for standard isotretinoin side effects (teratogenicity, hepatotoxicity, lipid abnormalities) 1

Second-Line Options When Isotretinoin Is Contraindicated:

Option A: Oral Fusidic Acid

• Dosing: 500 mg three times daily for 2-3 months 2
• Highly effective against Staphylococcus aureus with low resistance rates despite years of use 2
• Combine with topical betamethasone dipropionate 0.05% + salicylic acid 3% lotion once daily 2
• Add azelaic acid 5% lotion to affected areas once daily 2
• Maintenance therapy with zinc sulfate after initial treatment may prevent recurrence 2

Option B: Dapsone

• Achieves stable remission in 43% of patients 1
• Requires G6PD screening before initiation 1
• Typical dosing: 50-100 mg daily 1

Option C: Clarithromycin

• Achieves stable remission in 33% of patients 1
• Dosing: 500 mg twice daily 1
• Lower relapse rate than clindamycin/rifampicin combination 1

Third-Line: Combination Antibiotic Therapy (Use Only When Culture-Directed)

Avoid empiric clindamycin/rifampicin combination due to 80% relapse rate after treatment cessation. 1

• Use combination therapy only when cultures confirm susceptible organisms 3
• For MDRO infections, consider risk stratification approach to guide antibiotic selection 3
• If carbapenems or fluoroquinolones were used in past 90 days, risk of MDR Pseudomonas increases 3

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Management of Underlying Immune Dysfunction

Antimicrobial Stewardship Principles:

• Implement an education-based antimicrobial stewardship program to reduce inappropriate antibiotic use and consumption 3
• Avoid treating asymptomatic colonization, which increases risk of symptomatic infection and bacterial resistance 6
• Use procalcitonin (PCT) monitoring with repeat measurements to guide antibiotic duration 3

Infection Prevention:

• Improve hygiene and living conditions as fundamental intervention 7
• Debride crusts from wound surfaces using poloxamer 188 7
• Address any mechanical factors (follicular occlusion, overhydration) 7

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Critical Pitfalls to Avoid

Common Errors in Management:

• Do not continue empiric broad-spectrum antibiotics without culture confirmation of resistant organisms 3
• Avoid repeated courses of clindamycin/rifampicin as first-line therapy given the 80% relapse rate 1
• Do not ignore the development of antibiotic resistance by continuing ineffective antibiotic regimens 3
• Failing to consider isotretinoin early in treatment-resistant cases delays definitive therapy 1

Monitoring and Follow-Up:

• Reassess clinical response at 48-72 hours after initiating any new treatment 8
• Obtain repeat cultures if patient remains symptomatic despite appropriate therapy 8
• Evaluate for structural follicular abnormalities if infection recurs after successful treatment 7
• Monitor for treatment-related adverse effects, particularly with isotretinoin (hepatotoxicity, teratogenicity, lipid abnormalities) 1

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Special Considerations for This Patient

Post-Surgical Context:

• The temporal relationship to septoplasty suggests possible nasal Staphylococcus aureus colonization spreading to facial/scalp follicles 4
• Consider nasal decolonization with mupirocin ointment if nasal carriage is confirmed 7
• Hospital exposure during surgery increases risk of healthcare-associated MDRO colonization 3

Addressing Frequent Hospitalizations:

• Educate patient that orange urine from rifampicin is benign and does not require hospitalization 2
• Establish clear criteria for when hospital admission is truly necessary (systemic signs, hemodynamic instability) 8
• Transition to isotretinoin-based therapy to achieve durable remission and reduce need for repeated antibiotic courses 1