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Volume 22, Number 3—March 2016

Methylotroph Infections and Chronic Granulomatous Disease

E. Liana FalconeComments to Author , Jennifer R. Petts, Mary Beth Fasano, Bradley Ford, William M. Nauseef, João Farela Neves, Maria João Simões, Millard L. Tierce, M. Teresa de la Morena, David E. Greenberg, Christa S. Zerbe, Adrian Zelazny, and Steven M. Holland
Author affiliations: National Institutes of Health, Bethesda, Maryland, USA (E.L. Falcone, C.S. Zerbe, A.M. Zelazny, S.M. Holland); University of Iowa Hospital and Clinics, Iowa City, Iowa, USA (J.R. Petts, M.B. Fasano, B. Ford, W.M. Nauseef); Veterans Administration Medical Center, Iowa City (W.M. Nauseef); Centro Hospitalar de Lisboa Central, Lisbon, Portugal (J.F. Neves); Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisbon (M.J. Simões); Detroit Medical Center, Detroit, Michigan, USA (M.L. Tierce IV); University of Texas Southwestern Medical Center, Dallas, Texas, USA (M.T. de la Morena, D.E. Greenberg)

Main Article


Summary of methylotroph infections in patients with chronic granulomatous disease*

Patient no., reference Patient age, y/sex CGD genetics† Clinical findings Microbiological findings Treatment‡ Outcome
1 (this study) 1/F Autosomal recessive (NCF2 c.304C>T; p.R102X) Pneumonia, cervical lymphadenitis Methylobacterium lusitanum (lung),
Serratia marcescens (lymph node) CRO/CLI/ITZ, HSCT Recovered
2 (this study) 19/M X-linked
(CYBB intragenic deletion) Necrotizing cervical lymphadenitis Granulibacter bethesdensis;Staphylococcus epidermidis VAN/CRO, CFD/DOX/RIF Recovered
3 (this study) 16/M X-linked
(CYBB 13-exon deletion) Meningitis G. bethesdensis MEM/CIP/AMK/DOX/TEC/VCZ,
4 (this study) 9/M X-linked
(CYBB point mutation; exon 10) Cervical abscess, lymphadenitis Acidomonas methanolica TZP/VAN/LAMB/CIP, MEM/VAN/LAMB/CIP, CIP/VCZ/TMPSMX/ IFN-γ, HSCT Recovered
5 (this study) 36/M X-linked
(CYBB c.1139 G>A; p.W380X) Multifocal lymphadenitis G. bethesdensis;S. epidermidis VAN/CRO, CRO/DOX/TMPSMX/ITZ Still receiving treatment as of 2015
6 (4) 10/M X-linked
(CYBB p.Arg226X) Necrotizing cervical lymphadenitis A. methanolica TMPSMX/CRO/DOX, TMPSMX/RFB/GEN Recovered
7 (5) 10/M X-linked Bacteremia G. bethesdensis TMPSMX/CAZ/MTZ/LZD/VCZ Died
8 (6) 39/M X-linked Necrotizing cervical, mediastinal, axillary lymphadenitis G. bethesdensis MEM/DOX, CRO/DOX
9 (6) 36/M X-linked Multifocal necrotizing lymphadenitis, splenic lesions,
ascites G. bethesdensis MEM/TMPSMX/ITZ, MEM/TMPSMX/VCZ/TOB, CRO/TMPSMX/IFN-γ, CPD/DOX/TMPSMX/IFN-γ, splenectomy/TGC Recovered
10 (6) 13/M X-linked Necrotizing thoracic lymphadenitis G. bethesdensis,
S. epidermidis,
Candida glabrata,
Streptococcus mitis group MEM/VCZ, CRO/TOB/DOX/VCZ, CRO, DOX, CRO, CFD Recovered
11 (6) 17/M X-linked Necrotizing cervical and mediastinal lymphadenitis G. bethesdensis LVX, DOX, lymph node excision Recovered
12 (6) 37/M X-linked Necrotizing supraclavicular lymphadenitis,
splenic and liver lesions G. bethesdensis CRO/GEN/VAN, CRO/DOX/TMPSMX, CFD/ DOX/TMPSMX, DOX/TMPSMX Recovered

*AMK, amikacin; CAZ, ceftazidime; CFD, cefdinir; CGD, chronic granulomatous disease; CLI, clindamycin; CLR, clarithromycin; CIP, ciprofloxacin; CPD, cefpodoxime; CRO, ceftriaxone; CSP, caspofungin; CYBB, cytochrome b-245, β polypeptide; DOX, doxycycline; GEN, gentamicin; HSCT, hematopoietic stem cell transplant; IFN-γ, interferon- γ; INH, isoniazid; ITZ, itraconazole; LAMB, liposomal amphotericin B; LVX, levofloxacin; LZD, linezolid; MEM, meropenem; MTZ, metronidazole; NCF2, neutrophil cytosolic factor 2; RFB, rifabutin; RIF, rifampin; TEC, teicoplanin; TGC, tigecycline; TMPSMX, trimethoprim/sulfamethoxazole; TOB, tobramycin; VAN, vancomycin; VRZ, voriconazole.
†Information in parentheses indicates, when known, the mutation that led to CGD.
‡Slashes separate drugs in the same regimen; commas separate regimens.

Main Article

  1. Segal  BH, Leto  TL, Gallin  JI, Malech  HL, Holland  SM. Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore). 2000;79:170200 . DOIPubMedGoogle Scholar
  2. Matute  JD, Arias  AA, Wright  NA, Wrobel  I, Waterhouse  CC, Li  XJ, A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40 phox and selective defects in neutrophil NADPH oxidase activity. Blood. 2009;114:330915. DOIPubMedGoogle Scholar
  3. Anthony  C. The biochemistry of methylotrophs. New York, Academic Press; 1982. p. 2–3.
  4. Chase  JM, Holland  SM, Greenberg  DE, Marshall-Batty  K, Zelazny  AM, Church  JA. Acidomonas methanolica–associated necrotizing lymphadenitis in a patient with chronic granulomatous disease. J Clin Immunol. 2012;32:11936. DOIPubMedGoogle Scholar
  5. López  FC, de Luna  FF, Delgado  MC, de la Rosa  II, Valdezate  S, Nieto  JA, Granulibacter bethesdensis isolated in a child patient with chronic granulomatous disease. J Infect. 2008;57:2757. DOIPubMedGoogle Scholar
  6. Greenberg  DE, Shoffner  AR, Zelazny  AM, Fenster  ME, Zarember  KA, Stock  F, Recurrent Granulibacter bethesdensis infections and chronic granulomatous disease. Emerg Infect Dis. 2010;16:13418. DOIPubMedGoogle Scholar
  7. Clinical and Laboratory Standards Institute. Interpretive criteria for identification of bacteria and fungi by DNA target sequencing. Approved guideline. Document no. MM18-A. Wayne (PA): The Institute; 2008.
  8. Falcone  EL, Zelazny  AM, Holland  SM. Rothia aeria neck abscess in a patient with chronic granulomatous disease: case report and brief review of the literature. J Clin Immunol. 2012;32:14003. DOIPubMedGoogle Scholar
  9. Ford  BA, Burnham  CA. Optimization of routine identification of clinically relevant gram-negative bacteria by use of matrix-assisted laser desorption ionization–time of flight mass spectrometry and the Bruker Biotyper. J Clin Microbiol. 2013;51:141220. DOIPubMedGoogle Scholar
  10. Lai  CC, Cheng  A, Liu  WL, Tan  CK, Huang  YT, Chung  KP, Infections caused by unusual Methylobacterium species. J Clin Microbiol. 2011;49:332931. DOIPubMedGoogle Scholar
  11. Chu  J, Song  HH, Zarember  KA, Mills  TA, Gallin  JI. Persistence of the bacterial pathogen Granulibacter bethesdensis in chronic granulomatous disease monocytes and macrophages lacking a functional NADPH oxidase. J Immunol. 2013;191:3297307. DOIPubMedGoogle Scholar
  12. Zarember  KA, Marshall-Batty  KR, Cruz  AR, Chu  J, Fenster  ME, Shoffner  AR, Innate immunity against Granulibacter bethesdensis: an emerging gram-negative bacterial pathogen. Infect Immun. 2012;80:97581. DOIPubMedGoogle Scholar
  13. Yamashita  S, Uchimura  T, Komagata  K. Emendation of the genus Acidomonas Urakami, Tamaoka, Suzuki and Komagata 1989. Int J Syst Evol Microbiol. 2004;54:86570. DOIPubMedGoogle Scholar
  14. Greenberg  DE, Shoffner  AR, Marshall-Batty  KR, Arora  K, Zhao  M, Martin  R, Serologic reactivity to the emerging pathogen Granulibacter bethesdensis. J Infect Dis. 2012;206:94351. DOIPubMedGoogle Scholar

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Page created: February 18, 2016
Page updated: February 18, 2016
Page reviewed: February 18, 2016
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