What is the appropriate management plan now for a 36‑year‑old male kidney transplant recipient on chronic immunosuppression who developed severe odynophagia, was treated with amoxicillin‑clavulanate 1 g twice daily for five days with initial improvement then recurrence of pain?

Management of Recurrent Odynophagia in Kidney Transplant Recipient After Failed Amoxicillin-Clavulanate Course

This patient requires immediate evaluation for esophageal candidiasis or viral esophagitis (HSV/CMV), as these are the most common causes of recurrent odynophagia in immunosuppressed transplant recipients that fail to respond to antibacterial therapy. 1

Immediate Diagnostic Workup

• Perform upper endoscopy with biopsy and culture to definitively diagnose esophageal candidiasis, HSV esophagitis, or CMV esophagitis, which are the most likely diagnoses given immunosuppression and failure of antibacterial therapy 1
• Check CMV viral load by nucleic acid testing (NAT) or pp65 antigenemia to evaluate for CMV disease 1
• Consider HSV PCR testing if vesicular lesions are present or if endoscopy shows characteristic findings 1
• Review current immunosuppression levels (tacrolimus or cyclosporin trough, mycophenolate dose) to assess if overimmunosuppression is contributing 2

Empiric Treatment While Awaiting Endoscopy

• Start empiric fluconazole 200-400 mg daily orally for presumed esophageal candidiasis, as this is the most common cause of odynophagia in transplant recipients 1
• If symptoms are severe or patient cannot swallow, use intravenous fluconazole 400 mg daily 1
• Continue empiric antifungal therapy for at least 14-21 days if candidiasis is confirmed 1

Immunosuppression Adjustment

• Temporarily reduce mycophenolate dose by 50% until the infection resolves, as this is the first-line adjustment for serious infections in transplant recipients 1, 3
• Maintain calcineurin inhibitor (tacrolimus or cyclosporin) at low therapeutic range during active infection 1, 3
• Continue baseline corticosteroids without reduction to prevent adrenal insufficiency 3
• Monitor tacrolimus/cyclosporin levels closely, as fluconazole can increase calcineurin inhibitor levels through CYP3A4 inhibition 1, 3

Alternative Diagnoses if Candidiasis Treatment Fails

• If symptoms persist after 7 days of fluconazole, proceed urgently to endoscopy to evaluate for HSV or CMV esophagitis 1
• For confirmed HSV esophagitis: treat with oral acyclovir 400 mg five times daily or valacyclovir 1 g three times daily for 14-21 days 1
• For systemic or severe HSV disease: use intravenous acyclovir 5-10 mg/kg every 8 hours and reduce immunosuppression further 1
• For confirmed CMV esophagitis: treat with intravenous ganciclovir 5 mg/kg twice daily or oral valganciclovir 900 mg twice daily 1
• Continue CMV treatment until CMV is no longer detectable by plasma NAT 1

Monitoring During Treatment

• Monitor graft function (creatinine, eGFR) closely during infection and immunosuppression adjustment to detect early rejection 2, 3
• Check CMV viral load weekly if CMV disease is diagnosed 1
• Resume full-dose immunosuppression once infection is controlled and symptoms resolve 3

Critical Pitfalls to Avoid

• Do not continue antibacterial therapy beyond the initial failed course, as bacterial pharyngitis would have responded to amoxicillin-clavulanate; recurrence indicates fungal or viral etiology 1
• Avoid excessive immunosuppression reduction that could trigger acute rejection, but recognize that life-threatening infections require temporary reduction 1, 3
• Be aware that amoxicillin-clavulanate can reduce mycophenolate levels by approximately 50% through disruption of enterohepatic recirculation, which may have transiently reduced immunosuppression during the antibiotic course 4
• Do not assume the initial improvement was due to antibacterial effect; it may have been spontaneous or related to the temporary reduction in mycophenolate absorption from the antibiotic 4