Actinomyces in chronic granulomatous disease: an emerging and unanticipated pathogen.
BACKGROUND
Chronic granulomatous disease (CGD) is a rare inherited disease of the phagocyte NADPH oxidase system that causes defective production of toxic oxygen metabolites, impaired bacterial and fungal killing, and recurrent life-threatening infections, mostly by catalase-producing organisms. We report for the first time, to our knowledge, chronic infections with Actinomyces species in 10 patients with CGD. Actinomycosis is a chronic granulomatous condition that commonly manifests as cervicofacial, pulmonary, or abdominal disease, caused by slowly progressive infection with oral and gastrointestinal commensal Actinomyces species. Treatment of actinomycosis is usually simple in immunocompetent individuals, requiring long-term, high-dose intravenous penicillin, but is more complicated in those with CGD because of delayed diagnosis and an increased risk of chronic invasive or debilitating disease.


METHODS
Actinomyces was identified by culture, staining, 16S ribosomal DNA polymerase chain reaction, and/or a complement fixation test in 10 patients with CGD.


RESULTS
All 10 patients presented with a history of fever and elevated inflammatory signs without evident focus. Diagnosis was delayed and clinical course severe and protracted despite high-dose intravenous antibiotic therapy and/or surgery. These results suggest an unrecognized and unanticipated susceptibility to weakly pathogenic Actinomyces species in patients with CGD because these are catalase-negative organisms previously thought to be nonpathogenic in CGD.


CONCLUSIONS
Actinomycosis should be vigorously sought and promptly treated in patients with CGD presenting with uncommon and prolonged clinical signs of infection. Actinomycosis is a catalase-negative infection important to consider in CGD.
Reichenbach
Janine
J
Division of Immunology, University Children's Hospital, Zurich, Switzerland. janine.reichenbach@kispi.uzh.ch
Lopatin
Uri
U
Mahlaoui
Nizar
N
Beovic
Bojana
B
Siler
Ulrich
U
Zbinden
Reinhard
R
Seger
Reinhard A
RA
Galmiche
Louise
L
Brousse
Nicole
N
Kayal
Samer
S
Güngör
Tayfun
T
Blanche
Stéphane
S
Holland
Steven M
SM
D000190:Actinomyces / Q000235:genetics / Q000472:pathogenicity*; D000196:Actinomycosis / Q000175:diagnosis* / Q000188:drug therapy* / Q000601:surgery / Q000628:therapy; D000293:Adolescent; D000328:Adult; D000658:Amoxicillin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D017963:Azithromycin / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002443:Ceftriaxone / Q000627:therapeutic use; D002648:Child; D002981:Clindamycin / Q000627:therapeutic use; D021821:Communicable Diseases, Emerging / Q000382:microbiology* / Q000473:pathology*; D004275:DNA, Ribosomal / Q000235:genetics; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000382:microbiology*; D006801:Humans; D008297:Male; D000077731:Meropenem; D010400:Penicillin G / Q000627:therapeutic use; D010404:Penicillin V / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D013420:Sulfamethoxazole / Q000627:therapeutic use; D013845:Thienamycins / Q000627:therapeutic use; D014295:Trimethoprim / Q000627:therapeutic use; D055815:Young Adult
D000900:Anti-Bacterial Agents; D004275:DNA, Ribosomal; D013845:Thienamycins; D002981:Clindamycin; D002443:Ceftriaxone; D000658:Amoxicillin; D017963:Azithromycin; D014295:Trimethoprim; D000077731:Meropenem; D013420:Sulfamethoxazole; D010400:Penicillin G; D010404:Penicillin V