First Report of Infectious Pericarditis Due to Bordetella holmesii in an
Adult Patient with Malignant Lymphoma
Takahito Nei,aHideya Hyodo,bKazunari Sonobe,cKazuo Dan,band Ryoichi Saitod
Department of Internal Medicine,aDivisions of Respiratory Medicine, Infection and Oncology,bDivisions of Hematology, Gastroenterology and Endocrinology and
Metabolism, Nippon Medical School, and Department of Clinical Laboratory, Nippon Medical School,cTokyo, Japan, and Department of Moleculo-genetic Sciences,
Microbiology and Immunology, Tokyo Medical and Dental University, Tokyo, Japand
Bordetella holmesii is a fastidious Gram-negative rod first identified in 1995. Though rare, it is isolated mainly in immunocom-
Herein, we describe a unique B. holmesii infectious pericarditis patient with malignant lymphoma.
on effort. He had received 8 cycles of chemotherapy for malig-
but complete remission was not achieved. Because of a persistent
lesion, we initiated maintenance therapy, including rituximab ad-
ministration which was continued until the present hospitalization.
pnea on effort and a rising low-grade fever. Follow-up computed
ral change was suspected (Fig. 1B). He was thus admitted under a
diagnosis of possible pericarditis. Clinical examination findings on
notransferase (AST) and alanine aminotransaminase (ALT) to 30
and 59 IU/liter, respectively (normal ranges, 10 to 28 and 5 to 33
IU/liter, respectively), an alkaline phosphatase level of 392 IU/liter
(normal range, 104 to 338 IU/liter), a hemoglobin level of 11.1 g/dl
Serum electrolytes and creatinine were within normal limits. Chest
radiographs showed slight cardiomegaly, whereas abdominal radio-
graphs revealed no abnormalities. HBs antigen and anti-hepatitis C
drainage therapy and empirical antimicrobial administration
sion was bloody and contained neutrophil-rich inflammatory
cells but no malignant cells. Gram staining was negative. With
empirical antimicrobial therapy, his clinical symptoms disap-
peared and pericardial effusion did not reaccumulate after drain
removal. We ultimately removed more than 1,000 ml of pericar-
dial effusion, and culture of approximately 20 ml of this effusion
was started. Forty-eight hours after starting the culture, gray,
smooth, round colonies less than 1 mm in diameter were isolated
from blood agar (Eiken Chemical Co., Tokyo, Japan) (Fig. 2).
onto 5% sheep blood agar plates and incubated in 5% CO2under
agar (Oriental Yeast Co., Tokyo, Japan). Isolates were small
Gram-negative coccobacilli on microscopic observation, and no
motility was seen in sulfide-indole-motility medium. Further-
more, isolates were oxidase test negative and showed neither ni-
trate reduction nor urease production. We finally identified the
strain with 16S rRNA genotyping, as previously described (7), as
being Bordetella holmesii, and a similarity search was conducted
using the BLAST program (DDBJ, Shizuoka, Japan). The results
(1,456 bp) showed 100% similarity to the reference strain
(GenBank accession no. DQ409136) (similarity to Bordetella per-
tussis [GenBank accession no. BX640420], 99.73%; similarity to
Bordetella parapertussis [GenBank accession no. BX640434],
99.52; similarity to Bordetella bronchiseptica [GenBank accession
no. BX640449], 99.52%). Furthermore, the isolates were con-
firmed by PCR detection of bhoE (2), a gene not found in B. per-
tussis but present in B. holmesii, using primers Bh-bhoE-F (TGG
GGAGCAAACAGGATTAG) and Bh-bhoE-R (AGAGTGCCCTT
TCGTAGCAA). Agglutination testing (Denka Seiken, Co., Ltd.,
Tokyo, Japan) for identification of B. pertussis was negative. Sus-
ceptibility to representative antimicrobial agents was determined
to ampicillin (MIC, 1 ?g/ml), ceftriaxone (MIC, 1 ?g/ml), clari-
than 0.12 ?g/ml). The patient’s fever resolved within 2 days of
commencing intravenous ceftriaxone, and the pericardial fluid
did not reaccumulate after beginning antimicrobial therapy. He
felt better, and CRP normalized. Administration of ceftriaxone
was continued for 4 weeks, but myelosuppression associated with
ceftriaxone administration developed. Ceftriaxone was thus
switched to levofloxacin, in response to the ongoing neutropenia.
He was given granulocyte-colony stimulating factor, and his neu-
trophil count normalized. On the 63rd hospital day, he was dis-
charged in good condition.
The genus Bordetella belongs to the Alcaligenaceae family,
Received 25 December 2011 Returned for modification 19 January 2012
Accepted 20 February 2012
Published ahead of print 29 February 2012
Address correspondence to Takahito Nei, email@example.com.
Copyright © 2012, American Society for Microbiology. All Rights Reserved.
0095-1137/12/$12.00 Journal of Clinical Microbiologyp. 1815–1817jcm.asm.org
resentative species, B. pertussis is the causative agent of whooping
cough (pertussis), and B. parapertussis and B. bronchiseptica have
present species, B. holmesii, was also recently reported to have
(6, 15). The other species, Bordetella avium, Bordetella hinzii, and
Bordetella petrii, are rarely detected in respiratory samples from
patients with chronic respiratory infectious diseases, including
cystic fibrosis (4, 15, 18). Moreover, Bordetella trematum has also
reportedly been detected in ear and wound infections (1, 19). Im-
munocompromised status is considered to be strongly associated
with the establishment of infection due to these rare Bordetella
B. holmesii was first described in 1995 as a cause of sepsis in 15
patients (20), including at least three asplenic children, but no
specific clinical findings were described. The first detailed clinical
case report was published later that year. A 12-year-old male with
a history of splenectomy for idiopathic thrombocytopenic pur-
pura was diagnosed with sepsis due to B. holmesii. However, he
complained only of low-grade fever, no other symptoms, and his
physical state was essentially normal (8). Since then, B. holmesii
has been reported as a causative microorganism of bacteremia,
(black dashed line). High-density lesions are seen in the pleura and lung parenchyma adjacent to the pericardium while chest CT scan of a normal control
individual without pericarditis shows no such changes (C).
isolates (the upper right panel, original magnification of ?1,000). Colonies
the medium. Isolates were found to be short Gram-negative coccobacilli by
jcm.asm.org Journal of Clinical Microbiology
endocarditis,andcommunity-acquiredpneumonia.Inthesepre- Download full-text
vious reports, it is noteworthy that most patients were in immu-
12, 14, 16). Shepard and colleagues reported 26 patients with B.
asplenic state (14). Moreover, the clinical courses were usually
uneventful and relatively mild. Most patients recovered without
The present case is the first description, to our knowledge, of
infectious pericarditis due to B. holmesii. Bacterial pericarditis ac-
counts for approximately 5% of all pericarditis cases (9, 13, 17)
catheter drainage by spread from an intrathoracic, myocardial, or
subdiaphragmatic focus and by hematogenous dissemination.
The frequent causative organisms are Staphylococcus spp. and
Streptococcus spp., which often cause rheumatic pancarditis, Hae-
mophilus spp., and Mycobacterium tuberculosis. M. tuberculosis is
considered to be the most common microorganism causing bac-
terial pericarditis, because the pericardium can be reached via he-
matogenous spread or extension from adjacent organs, particu-
larly the lungs or pleural space (13). In the present case, chest CT
showed slight changes of the pleura and adjacent lung paren-
chyma (Fig. 1B and C). However, we were not able to obtain
pleura or lung samples from the indicated regions and can only
speculate that B. holmesii had migrated to the pericardium from
the lung or pleural space.
causative microbes of infectious pericarditis. A recent report (15)
showed B. holmesii to be strongly associated with pertussis-like
respiratory syndrome caused by B. pertussis and B. parapertussis.
Furthermore, B. holmesii was identified as a causative microbe of
only a cause of sepsis or septicemia in immunocompromised or
asplenic individuals but also a common cause of infectious respi-
ratory system diseases associated with involvement of adjacent
major diagnostic impact.
carditis. In view of the possibility of this microbe causing respira-
tory system disease, awareness of B. holmesii is warranted.
We thank Bierta Barfod for editing the manuscript and Toshie Sekine for
We do not have financial relationships with any commercial entity
with an interest in the subject of the manuscript.
1. Daxboeck F, Goerzer E, Apfalter P, Nehr M, Krause R. 2004. Isolation
of Bordetella trematum from a diabetic leg ulcer. Diabet. Med. 21:1247–
2. Diavatopoulos DA, et al. 2006. Characterization of a highly conserved
island in the otherwise divergent Bordetella holmesii and Bordetella per-
tussis genomes. J. Bacteriol. 188:8385–8394.
3. Dörbecker C, et al. 2007. Community-acquired pneumonia due to Bor-
detella holmesii in a patient with frequently relapsing nephrotic syn-
drome. J. Infect. 54:e203–e205.
4. Fry NK, et al. 2007. A UK clinical isolate of Bordetella hinzii from a
patient with myelodysplastic syndrome. J. Med. Microbiol. 56:1700–
5. Greig JR, Gunda SS, Kwan JTC. 2001. Bordetella holmesii bacteraemia in
an individual on haemodialysis. Scand. J. Infect. Dis. 33:716–717.
6. Harrington AT, Castellanos JA, Ziedalski TM, Clarridge JE, III, Cook-
son BT. 2009. Isolation of Bordetella avium and novel Bordetella strain
from patients with respiratory disease. Emerg. Infect. Dis. 15:72–74.
7. Kageyama A, et al. 2004. Nocardia arthritidis sp. nov., a new pathogen
isolated from a patient with rheumatoid arthritis in Japan. J. Clin. Micro-
8. Lindquist SW, Weber DJ, Mangum ME, Hollis DG, Jordan J. 1995.
9. Maisch B, Ristic ´ AD. 2002. The classification of pericardial disease in the
age of modern medicine. Curr. Cardiol. Rep. 4:13–21.
10. McCavit TL, Grube S, Revell P, Quinn CT. 2008. Bordetella holmesii
bacteremia in sickle cell disease. Pediatr. Blood Cancer 51:814–816.
11. Morris JT, Myers M. 1998. Bacteremia due to Bordetella holmesii. Clin.
Infect. Dis. 27:912–913.
12. Njamkepo E, Delisle F, Hagege I, Gerbaud G, Guiso N. 2000. Bordetella
parison with other Bordetella holmesii isolates. Clin. Microbiol. Infect.
13. Sagrista `-Sauleda J, Barrabés JA, Permanyer-Miralda G, Soler-Soler J.
1993. Purulent pericarditis: review of a 20-year experience in a general
hospital. J. Am. Coll. Cardiol. 22:1661–1665.
14. Shepard CW, et al. 2004. Bordetella holmesii bacteremia: a newly recog-
nized clinical entity among asplenic patients. Clin. Infect. Dis. 38:799–
15. Spilker T, Liwienski AA, LiPuma JJ. 2008. Identification of Bordetella
spp. in respiratory specimens from individuals with cystic fibrosis. Clin.
Microbiol. Infect. 14:504–506.
16. Tang YW, et al. 1998. Bordetella holmesii-like organisms associated with
17. Troughton RW, Asher CR, Klein AL. 2004. Pericarditis. Lancet 363:717–
and humans. Int. J. Syst. Bacteriol. 45:37–45.
19. Vandamme P, et al. 1996. Bordetella trematum sp. nov., isolated from
wounds and ear infections in humans, and reassessment of Alcaligenes
denitrificans Ruger and Tan 1983. Int. J. Syst. Bacteriol. 46:849–858.
species associated with septicemia. J. Clin. Microbiol. 33:1–7.
May 2012 Volume 50 Number 5jcm.asm.org 1817