To the Editors: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency of neutrophil oxidative burst, leading to bacterial and fungal infection with formation of granulomata.1 The X linked form frequently presents with staphylococcal liver abscesses.2 Treatment of liver abscesses usually requires several months of intravenous therapy through a central venous catheter with or without augmentation with gamma interferon and nutritional support.3 This can lead to lengthy stays in hospital, frequent complications from central venous access, and disruption to family life. Here we present a case where a systemic drug reaction to flucloxacillin and teicoplanin, and the failure of daptomycin, prompted the use of linezolid, an oral oxazolidinone antibiotic used in the treatment of patients with multidrug-resistant, gram-positive bacterial infections.4 This is the first described use of linezolid in this condition, which resulted in complete resolution using an oral home therapy regimen. CASE REPORT A 9-year-old boy was referred with a 6-week history of fever, night sweats, and abdominal pain. He was found to have hepatomegaly, and an abdominal ultrasound demonstrated a 6.5-cm diameter liver abscess. The lesion was aspirated and treated with intravenous flucloxacillin (floxacillin). Aspirated pus grew methicillin-susceptible Staphylococcus aureus on blood agar culture susceptible to flucloxacillin and glycopeptides. X-linked CGD was confirmed using assessment of oxidation of dihydrorhodamine 123 by flow cytometry, confirmed by absence of gp91 protein. He did not respond to initial therapy and became increasingly unwell with unremitting fever, generalized maculopapular rash, vomiting, diarrhea, liver dysfunction with alanine transaminase peaking at 121 IU/L, coagulopathy, and eosinophilia of 3.2 × 109 L−1. A diagnosis of drug reaction with eosinophilia and systemic symptoms was made based on these findings and he was treated with 1 g/kg intravenous immunoglobulin.5 In the week before the onset of the drug reaction, he was clinically unstable and was treated with intravenous flucloxacillin, teicoplanin, and piperacillin-tazobactam, all of which were then discontinued. His liver abscess was subsequently treated with intravenous daptomycin 4 mg/kg through a peripherally inserted central venous catheter line. After 57 days he developed a tender, warm to touch palpable mass on his right flank demonstrated by ultrasound to be a 10-cm retroperitoneal extension of the liver abscess. Drainage was not possible by CT-guided needle aspiration and the abscess was assessed as too solid for further intervention. The following week he became unwell with fever and rigors. Blood cultures grew Pseudomonas aeruginosa, the peripherally inserted central venous catheter line was removed and daptomycin therapy discontinued. Due to the failure of daptomycin he was given oral linezolid in a dosage of 10 mg/kg/dose t.d.s.6 There were clinical and radiologic signs of improvement within 4 weeks and a repeat ultrasound 2 months later showed the liver abscess and its retroperitoneal extension had macroscopically resolved. He completed a further month of treatment then stopped after a 98-day course of linezolid. His family were counseled to report paresthesia and visual disturbance, which did not occur.7 His lowest platelet count was 193 × 1012/L and hemoglobin value was stable at 110 g/L, neither required discontinuation of therapy. Six months later he remains well. DISCUSSION This is the first report of the use of oral linezolid for the successful treatment of staphylococcal liver abscess in CGD. Linezolid is an oxazolidinone antibiotic that has a bacteriostatic action by inhibition of the 70s ribosomal initiation complex.8 Linezolid is rapidly and completely absorbed after oral administration.6 It is used in complex or resistant gram-positive infections, and is an oral option where intravenous therapy would be the normal route of administration. In this case it was used with caution and as a last resort because of reports of serious adverse events related to mitochondrial toxicity in treatment courses beyond 28 days.9 Short courses of linezolid are well tolerated in children.10 Common adverse events include nausea, vomiting, and diarrhea.4 Teeth and tongue discoloration with taste disturbance has also been reported.11 Anemia and thrombocytopenia are frequently seen but are reversible and often do not require discontinuation of therapy.12,13 The more serious adverse events relate to its mitochondrial toxicity.14 The main risk of long-course therapy is irreversible peripheral neuropathy; optic neuropathy can also occur but rapidly improves after discontinuation of therapy.15,16 Michel Erlewyn-Lajeunesse, MRCPCH, DM Woolf Walker, BM, MRCPCH Adriana Basarab, MRCP, FRCPath Efrem Eren, FRCPath, PhD Nadeem Afzal, MRCPCH, MRCP(UK) Southampton University Hospitals NHS Trust Southampton, United Kingdom Keith Godfrey, BM, FRCP, PhD Saul N. Faust, MRCPCH, PhD Southampton University Hospitals NHS Trust and University of Southampton Southampton, United Kingdom
Read full abstract
Jun 7, 2018
Hsin-Yun Sun + 8
Open Access
