Download Bacillus cereus, an unusual cause of fulminant liver failure

Journal of Medical Microbiology (2012), 61, 743–745
Case Report
DOI 10.1099/jmm.0.038547-0
Bacillus cereus, an unusual cause of fulminant liver
failure: diagnosis may prevent liver transplantation
Mohamed Saleh,1,23 Malik Al Nakib,2,33 Alexandra Doloy,3
Sébastien Jacqmin,1 Sébastien Ghiglione,1 Nicolas Verroust,1
Claire Poyart2,3 and Yves Ozier1,2
1
Correspondence
Service d’Anesthésie-Réanimation Chirurgicale, Groupe Hospitalier Cochin Hôtel Dieu Broca,
Assistance Publique – Hôpitaux de Paris, Paris, France
Claire Poyart
[email protected]
2
Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
3
Service de Bactériologie, Groupe Hospitalier Cochin Hôtel Dieu Broca, Assistance Publique –
Hôpitaux de Paris, Paris, France
Received 23 September 2011
Accepted 9 January 2012
Bacillus cereus is a well-known cause of foodborne disease usually of benign course. Here, we
present the case of a 15-year-old boy who developed reversible fulminant liver failure associated
with rhabdomyolysis after pasta consumption. Suspecting B. cereus as the aetiological agent may
prevent unnecessary liver transplantation.
Introduction
Bacillus cereus is a soil-dwelling, spore-forming, Grampositive bacterium surviving in a wide variety of environments. It is a known food-poisoning pathogen but is also
responsible for extraintestinal infections. Some strains can
produce exotoxins responsible for two different types of
disease: diarrhoeal syndrome due to enterotoxins, and
emetic syndrome due to cereulide toxin (Stenfors Arnesen
et al., 2008). The illness is generally considered mild and
short-lasting. Rare fatal cases have been reported involving
healthy young persons (Dierick et al., 2005; Mahler et al.,
1997). Up to now, very few cases of fulminant liver failure
(FLF) have been reported. Two of these were lethal, and
one was observed in a child who recovered fully, avoiding
liver transplantation (Dierick et al., 2005; Mahler et al.,
1997; Pósfay-Barbe et al., 2008). Recently, a case of acute
encephalopathy with liver failure mimicking Reye syndrome was reported, with hepatic transplantation not
considered for the patient (Ichikawa et al., 2010). Here we
report a new case of FLF associated with a cereulideproducing B. cereus strain.
Case report
In September 2008, a 15-year-old boy was referred to our
Centre for FLF. He had no past medical history, and did
not take drugs or medications. The first symptoms began
30 h before admission, with acute onset of abdominal pain
and emesis without evidence of a triggering factor. The
following day, blood was noticed in his vomit, and he was
3These authors contributed equally to this work.
Abbreviation: FLF, fulminant liver failure.
038547 G 2012 SGM
brought to the emergency department of the nearest
hospital. Blood tests showed elevated liver enzymes
(alanine aminotransferase .3000 IU l21) and incipient
liver failure (prothrombin ratio 52 %, factor V ratio 35 %).
An upper gastrointestinal endoscopy revealed ulceronecrotic oesophagitis and gastritis. Echocardiography and
Doppler ultrasonography of the liver were unremarkable.
The toxicology screen was negative. The patient was
seronegative for hepatitis A, C and hantavirus. He had
evidence of prior hepatitis B vaccination. He was treated
with intravenous rehydration and acetylcysteine. On the
same day, given the rapid deterioration in the prothrombin and factor V ratios (20 % and 18 %, respectively)
suggesting fulminant hepatic failure, emergency liver
transplantation was considered and he was referred to
our intensive care unit. On arrival, he was found to be
afebrile, with tachycardia (140 b.p.m.). Laboratory results
showed elevated alanine aminotransferase (4823 IU l21),
aspartate aminotransferase (3729 IU l21), serum bilirubin
(42 mmol l21) and creatine kinase (12 592 IU l21) and
lactic acidosis (pH 7.41, bicarbonates 20 mmol l21, lactate
5.4 mmol l21). Haemoglobin was within the normal range,
with a white blood cell count of 14 500 mm23. The
prothrombin ratio was 21 %, with factor V 23 % and factor
II 34 %. Procalcitonin was 14.9 ng l21. Plasma PCR assays
for the family Herpesviridae were negative. Viral serological
testing was negative for herpes simplex virus, cytomegalovirus, human immunodeficiency virus and human T-cell
leukemia virus, and showed past infection for Epstein–Barr
virus, varicella-zoster virus and parvovirus B19. A thoracoabdominal CT scan showed non-specific hepatomegaly. A few hours later, the neurological status deteriorated
with coma and the patient was immediately scheduled
for emergency liver transplantation. A profuse nonbloody
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743
M. Saleh and others
diarrhoea was also noticed, and stools were analysed. Two
days after admission, fever appeared and treatment with
intravenous piperacillin–tazobactam (4/0.5 g every 6 h)
was given for 7 days for positive blood cultures showing
growth of Klebsiella pneumoniae and Enterobacter cloacae,
which was attributed to intestinal translocation. A leukopenia and thrombopenia were investigated by bone marrow
examination, which detected a maturation blockade of the
granulocytic series compatible with toxic injury. Bacterial,
parasitological and mycological bone marrow cultures were
sterile. After 3 days, the hepatic cytolysis started to decrease,
and prothrombin and factor V ratios increased, leading to
reconsideration of the liver transplantation indication.
Clinical improvement ensued, the neurological condition
fully resolved and the liver functions normalized in a few days.
A detailed history of the patient and his relatives revealed
that he had eaten pasta 4 h before the first symptoms. The
pasta had been cooked 4 days before, stored in a refrigerator,
and was found to have an abnormal taste and smell.
Stools were tested for B. cereus on days 3, 4, 5, 7 and 8 after
admission. To isolate B. cereus, a Gram-positive selective
blood agar plate containing colistin and nalidixic acid was
used (Oxoid). Identification of isolates was performed on
the basis of Gram staining, motility, colony appearance and
haemolysis, amylase production (starch hydrolysis test),
API 50 CH and API 20E strips (bioMérieux), and
susceptibility to penicillin. Stool cultures yielded growth
of B. cereus with decreasing counts from 105 c.f.u. g21 on
day 3 to the absence of detection on day 8. To demonstrate
the toxigenic potential of B. cereus isolates, genes encoding
emetic-toxin cereulide (ces) and enterotoxins (nhe, hbl and
cytK) were analysed by multiplex PCR, as previously
described (Ehling-Schulz et al., 2006). Strains isolated from
each stool showed the same toxin gene pattern, ces+ nhe+
hbl2 cytK2, characteristic of cereulide-producing strains
(Ehling-Schulz et al., 2005, 2006; Pósfay-Barbe et al., 2008).
Moreover, these strains were not capable of producing
amylase, a feature highly suggestive of cereulide-producing
strains (Ehling-Schulz et al., 2004).
Discussion
Cereulide is plasmid-encoded (Stenfors Arnesen et al.,
2008), and B. cereus strains producing cereulide are most
frequently reported in starchy foods. Once ingested, it
resists acid conditions and proteolytic enzymes of the
gastrointestinal tract. Mahler et al. (1997) were the first to
demonstrate a link between cereulide-producing B. cereus
strains and FLF. They provided experimental evidence
that cereulide acts as a mitochondrial toxin via fatty-acid
metabolism impairment, in keeping with liver microvesicular steatosis observed in their patient. Furthermore,
the occurrence of FLF with microvesicular steatosis after
cereulide injection has been described in mice. It was
reversible within a few weeks with a rapid decrease of hepatic
enzymes and regeneration of hepatocytes (Yokoyama et al.,
1999). Interestingly, liver microsteatosis was reported in the
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first description of lethal B. cereus food poisoning in Japan
(Takabe & Oya, 1976). Although the presence of cereulide
in the pasta could not be tested in this case, the toxin gene
pattern of strains isolated from the patient’s stools
was characteristic of cereulide-producing strains (EhlingSchulz et al., 2005, 2006; Pósfay-Barbe et al., 2008).
Moreover, our report shares many of the hallmarks of B.
cereus-associated FLF: an extremely acute onset and rapid
progression of the disease in a young person, rhabdomyolysis which is also in keeping with mitochondrial
dysfunction, and severe lactic acidosis (Dierick et al., 2005;
Mahler et al., 1997; Pósfay-Barbe et al., 2008). The connection between the reversible bone marrow suppression
of white cell precursors observed in our case and cereulide
is uncertain, as b-lactam antibiotics were used and are a
possible cause of leukopenia, especially for a patient with
hepatic failure (Singh et al., 1993).
Pósfay-Barbe et al. (2008) recently highlighted that, given
the incidence of B. cereus food-poisoning outbreaks, it is
surprising that so few cases of B. cereus toxin-mediated FLF
have been reported so far. They suggested that a dosedependent effect and/or a host genetic susceptibility might
explain this rarity, but it could also be an under-recognized
aetiology. However, early diagnosis may not lead to
efficient specific therapeutic measures that could improve
outcome as disease is mainly due to preformed toxin
ingestion. On the other hand, we detected B. cereus in the
patient’s stools, and in previously described cases B. cereus
was found in vomit and intestinal contents (Dierick et al.,
2005; Mahler et al., 1997) so antibiotic treatment could
help to eradicate the bacteria and stop further toxin
production. Charcoal has been suggested for detoxification
(Mahler et al., 1997). The hepatoprotective effect of
acetylcysteine is based on its ability to replenish glutathione
stores, and it could also improve mitochondrial energy
metabolism (Zwingmann & Bilodeau, 2006). However, one
of the reported fatal cases occurred despite high-dose
acetylcysteine administration (Dierick et al., 2005). Close
monitoring of hepatic function allowed our patient to
avoid liver transplantation with a rapid full recovery, as
described in another patient (Pósfay-Barbe et al., 2008) and
in agreement with the reversible pathological effect
observed in mice (Yokoyama et al., 1999). In conclusion,
this case stresses the role of toxigenic B. cereus as a food
pathogen and the importance of suspecting this bacterial
agent as a cause of FLF of unknown pathogenesis in order
to defer hepatic transplantation.
References
Dierick, K., Van Coillie, E., Swiecicka, I., Meyfroidt, G., Devlieger, H.,
Meulemans, A., Hoedemaekers, G., Fourie, L., Heyndrickx, M. &
Mahillon, J. (2005). Fatal family outbreak of Bacillus cereus-associated
food poisoning. J Clin Microbiol 43, 4277–4279.
Ehling-Schulz, M., Fricker, M. & Scherer, S. (2004). Bacillus cereus,
the causative agent of an emetic type of food-borne illness. Mol Nutr
Food Res 48, 479–487.
Downloaded from www.microbiologyresearch.org by
IP: 88.99.165.207
On: Wed, 10 May 2017 15:07:46
Journal of Medical Microbiology 61
Fulminant liver failure due to Bacillus cereus
Ehling-Schulz, M., Svensson, B., Guinebretiere, M. H., Lindbäck, T.,
Andersson, M., Schulz, A., Fricker, M., Christiansson, A., Granum,
P. E. & other authors (2005). Emetic toxin formation of Bacillus
poisoning as a cause of acute liver failure. Pediatr Infect Dis J 27, 846–
847.
cereus is restricted to a single evolutionary lineage of closely related
strains. Microbiology 151, 183–197.
antibiotic-induced leukopenia in severe hepatic dysfunction: risk
factors and implications for dosing in patients with liver disease. Am J
Med 94, 251–256.
Ehling-Schulz, M., Guinebretiere, M. H., Monthán, A., Berge, O.,
Fricker, M. & Svensson, B. (2006). Toxin gene profiling of
enterotoxic and emetic Bacillus cereus. FEMS Microbiol Lett 260,
232–240.
Ichikawa, K., Gakumazawa, M., Inaba, A., Shiga, K., Takeshita, S.,
Mori, M. & Kikuchi, N. (2010). Acute encephalopathy of Bacillus cereus
mimicking Reye syndrome. Brain Dev 32, 688–690.
Mahler, H., Pasi, A., Kramer, J. M., Schulte, P., Scoging, A. C.,
Bär, W. & Krähenbühl, S. (1997). Fulminant liver failure in asso-
ciation with the emetic toxin of Bacillus cereus. N Engl J Med 336,
1142–1148.
Pósfay-Barbe, K. M., Schrenzel, J., Frey, J., Studer, R., Korff, C., Belli,
D. C., Parvex, P., Rimensberger, P. C. & Schäppi, M. G. (2008). Food
http://jmm.sgmjournals.org
Singh, N., Yu, V. L., Mieles, L. A. & Wagener, M. M. (1993). b-Lactam
Stenfors Arnesen, L. P., Fagerlund, A. & Granum, P. E. (2008). From
soil to gut: Bacillus cereus and its food poisoning toxins. FEMS
Microbiol Rev 32, 579–606.
Takabe, F. & Oya, M. (1976). An autopsy case of food poisoning
associated with Bacillus cereus. Forensic Sci 7, 97–101.
Yokoyama, K., Ito, M., Agata, N., Isobe, M., Shibayama, K., Horii, T. &
Ohta, M. (1999). Pathological effect of synthetic cereulide, an emetic
toxin of Bacillus cereus, is reversible in mice. FEMS Immunol Med
Microbiol 24, 115–120.
Zwingmann, C. & Bilodeau, M. (2006). Metabolic insights into the
hepatoprotective role of N-acetylcysteine in mouse liver. Hepatology
43, 454–463.
Downloaded from www.microbiologyresearch.org by
IP: 88.99.165.207
On: Wed, 10 May 2017 15:07:46
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