Methylotroph Infections and Chronic Granulomatous Disease

E. Liana Falcone; Jennifer R. Petts; Mary Beth Fasano; Bradley Ford; William M. Nauseef; João Farela Neves; Maria João Simões; Millard L. Tierce IV; M. Teresa de la Morena; David E. Greenberg; Christa S. Zerbe; Adrian M. Zelazny; Steven M. Holland


Emerging Infectious Diseases. 2016;22(3):404-409. 

In This Article

Patient 4

In 2013, a 9-year-old multiracial boy from Iowa, USA, who had X-linked CGD was examined for a 1-day history of fever, fatigue, decreased appetite, headache, and neck pain. He had been receiving oral trimethoprim/sulfamethoxazole, voriconazole and interferon-γ for CGD prophylaxis. When he was 1 month of age, he had had disseminated Candida lusitaniae infection with retropharyngeal, parapharyngeal, hepatic, and splenic abscesses. At 6 months of age, he was hospitalized for a progressively enlarging left posterior neck mass. A lymph node biopsy sample showed necrotizing granulomata and rare yeast forms suggestive of Histoplasma, but no specific organism was identified. He also had recurrent otitis media, tonsillitis, and aphthous stomatitis. Two months before the visit reported here, he had had Aspergillus versicolor pneumonia complicated by granulomatous appendicitis.

At the time of this hospital admission, he had 2 enlarged right anterior cervical nodes, which were soft, mobile, and not tender. ESR was 41 mm/h, and CRP concentration was 76 mg/L. CT images showed a 23 × 9 × 18-mm abscess adjacent to the right sternocleidomastoid muscle, extensive left supraclavicular lymphadenopathy, and left-sided pneumonia and pleural effusion.

Excisional biopsy of the right cervical lymph nodes yielded pus but no organisms. After 3 days of culture on chocolate agar, ≈20 tan colonies of an aerobic gram-negative bacillus were seen. The organism was oxidase-positive, catalase-positive, and indole-negative. After 6 days, abundant growth of a morphologically identical organism was seen on potato dextrose agar without antimicrobial agent and on Mycosel agar with chloramphenicol and cycloheximide but not on brain heart infusion agar with chloramphenicol and gentamicin (all media from Remel, Lenexa, KS, USA). Matrix-assisted laser desorption/ionization–time of flight mass spectrometry (Biotyper system version 3.1; Bruker Daltonics Inc., Billerica, MA, USA) from directly smeared colonies with and without formic acid overlay[9] yielded no identification, and growth was insufficient for biochemical identification or susceptibility testing. Species-level identification conducted by 16S rRNA gene sequencing (ABI MicroSeq 500 kit; Thermo Fisher Scientific, Grand Island, NY, USA, and the IDNS SmartGene system, version 3.6.10; SmartGene Inc., Raleigh, NC, USA) was interpreted as A. methanolica (100% identity >388 bp with type strain CGDAM1).[7] No other pathogens were grown or amplified from any specimen.

The patient initially received piperacillin/tazobactam and vancomycin; liposomal amphotericin B was administered in view of his recent A. versicolor pneumonia. After 4 days, the piperacillin/tazobactam was switched to meropenem and ciprofloxacin was added. Levels of inflammatory markers eventually returned to reference values, and the lymphadenopathy improved after 5 weeks of intravenous meropenem and intravenous and oral ciprofloxacin. The patient was discharged with ciprofloxacin, voriconazole for A. versicolor pneumonia, prophylactic trimethoprim/sulfamethoxazole, and interferon-γ. He subsequently underwent successful transplant of matched unrelated hematopoietic stem cells.