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 3

In 2012, a 16-year-old boy from Portugal who had X-linked CGD was examined for fever, cervical lymphadenopathy, and elevated inflammatory markers. CT images showed a deep cervical abscess, from which nothing grew on culture but which completely resolved after 5 weeks of intravenous ceftriaxone, doxycycline, and ciprofloxacin and 6 weeks of oral amoxicillin/clavulanate, ciprofloxacin, and doxycycline, along with prophylactic itraconazole and interferon-γ.

Immediately after completion of that course of antimicrobial drugs, pneumonia with pleural effusions developed. Results of all cultures (blood, lymph node, broncheoalveolar lavage, and pleural fluid) were negative, but full 16S rRNA gene sequencing (≈1,500 bp) of pleural fluid showed a >99% match to Cupriavidus spp. The patient received meropenem, ciprofloxacin, amikacin, doxycycline, teicoplanin, and voriconazole. Two weeks later, fever with splenomegaly, pancytopenia, low fibrinogen levels, and elevated ferritin and soluble CD25 levels were noted. Interferon-γ prophylaxis was discontinued and the patient was administered dexamethasone and intravenous immunoglobulin, after which the presumed exuberant inflammatory response quickly resolved. CT images of the neck and lung were unremarkable, as were positron emission tomography images.

A month later, the boy was examined for fever, cough, and altered mental status; he required intubation and transfer to the intensive care unit. Magnetic resonance imaging revealed bilateral pneumonia and multiple intraparenchymal brain abscesses. Cerebrospinal fluid (CSF) was unremarkable. A lung biopsy sample, collected while the patient was receiving meropenem, ciprofloxacin, amikacin, doxycycline, teicoplanin, and voriconazole, was sterile. Voriconazole was switched to caspofungin and liposomal amphotericin B, and teicoplanin was switched to linezolid. The patient eventually recovered and was transferred out of the intensive care unit.

One month later, fever with focal neurologic deficits developed. CSF examination confirmed persistent pleocytosis with low glucose and elevated protein levels, and CT images indicated leptomeningitis. A 4-day culture of CSF on chocolate agar showed brownish colonies 1–2 mm in diameter. Full 16S rRNA gene sequencing (≈1,500 bp) performed on the isolate from CSF showed a 99.7% match to the G. bethesdensis type strain. Etest showed the following MICs (in μg/mL): tobramycin (MIC = 12), ceftriaxone (MIC >32), doxycycline (MIC = 24), and trimethoprim/sulfamethoxazole (MIC = 0.25). Isoniazid, clarithromycin, and rifampin had already been added to the patient's treatment regimen. Despite the above interventions, the patient died of obstructive hydrocephalus and multiorgan failure.