Rotavirus gastroenteritis was complicated by Klebsiella Pneumoniae bacteraemia in two infants with glucocorticoid deficient conditions who were treated with 'stress dose' hydrocortisone during their illness. Delayed healing in the context of glucocorticoid administration combined with damage from rotavirus infection may result in increased risk of mucosal invasion by gastrointestinal bacteria and subsequent enteric gram-negative bacteraemia

Adler A

Carneiro NB

Carpani de Kaski M

Cicchetti R

Di Biase AM

Gonzalez-Carretero P

Kashiwagi Y

Lowenthal A

Luo JC

Mel E

Parashar UD

Superti F

Vesikari T

Longmore, DK

Batch, JA

McMahon, SK

Conwell, LS

University of Queensland eSpace

© Freund Publishing House Ltd., London Journal of Pediatric Endocrinology & Metabolism, 23,293-295 (2010)
Klebsiella pneumoniae Bacteraemia Complicating Rotavirus
Gastroenteritis in Two Infants with Glucocorticoid Deficiency
Danielle K. Longmore1, Jennifer A. Batch1'2, Sarah K. McMahon1·2 and Louise S. Conwell1·2
'Department of Endocrinology and Diabetes, Royal Children 's Hospital, Brisbane and
Discipline of Paediatrics and Child Health, School of Medicine, University of Queensland, Australia
ABSTRACT
Rotavirus gastroenteritis was complicated
by Klebsiella Pneumoniae bacteraemia in two
infants with glucocorticoid deficient conditions
who were treated with 'stress dose' hydro-
cortisone during their illness. Delayed healing
in the context of glucocorticoid administration
combined with damage from rotavirus infec-
tion may result in increased risk of mucosal
invasion by gastrointestinal bacteria and sub-
sequent enteric gram-negative bacteraemia.
KEY WORDS
glucocorticoid deficiency, rotavirus, gastro-
enteritis, enteric gram-negative bacteraemia,
corticosteroids, congenital adrenal hyperplasia
INTRODUCTION
Klebsiella pneumoniae bacteraemia complica-
ted rotavirus gastroenteritis in two infants with
glucocorticoid deficiency being treated with
stress-dose hydrocortisone during their illness.
Enteric gram-negative (EGN) bacteraemia is an
infrequently recognised complication of rotavirus
infection. Rotavirus has not been shown to cause
significant gastrointestinal mucosal changes;
however, it has been shown to increase epithelial
permeability and enhance the ability of bacteria to
invade enterocytes1. Glucocorticoids are thought
to cause delay in gastroduodenal healing, most
likely due to inhibition of prostaglandin syn-
Reprint address:
Danielle Longmore
Department of Endocrinology and Diabetes
Royal Children's Hospital
Brisbane, Herston, 4006, Australia
e-mail: daniellelongmore@yahoo.com.au
thesis2. There have been no reports of secondary
EGN bacteraemia in infants or children with
rotavirus infection on corticosteroids. It is
hypothesised that high dose glucocorticoids may
increase the risk of EGN bacteraemia in rotavirus
gastroenteritis.
PATIENT I
An 8 month-old male infant with congenital
adrenal hyperplasia secondary to 21-hydroxylase
deficiency was admitted with rotavirus gastro-
enteritis. His regular medication included oral
hydrocortisone (10.5 mg/m2/day) and oral fludro-
cortisone (100 μg twice daily). He presented
with a one-day history of vomiting and watery
diarrhoea with no history of fever. Rotavirus
infection was confirmed via immunoassay antigen
detection (VIKIA® Rota-Adeno by bioMerieux).
He was commenced on hydrocortisone at a dose
of 2 mg/kg intravenously every 6 hours on
admission, in addition to intravenous fluids. On
admission his C-reactive protein (CRP) was <1.0
mg/L, white blood cell count 19.3 χ 103/mm3
with a neutrophil count of 7.3 χ 103/mm3. His
gastroenteritis was complicated by concurrent
Norovirus enteric infection. He was hospitalised
for six days and then discharged on oral
hydrocortisone (triple his oral maintenance dose)
after his symptoms settled. However, he required
readmission due to recurrence of vomiting and
large volume diarrhoea. Previously afebrile, his
temperature increased to 39°C 11 days after
readmission. Blood cultures revealed a pure
growth of Klebsiella pneumoniae after 5.9 hours.
Haematological testing revealed anaemia, lympho-
penia and thrombocytopenia. He was commenced
on ceftriaxone and gentamicin, continuing on
gentamicin (7.5 mg/kg daily) for seven days after
sensitivities were available. Resolution of fever
VOLUME 23, NO. 3,2010 293
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294 O.K. LONGMORE ET AL.
occurred within 48 hours of antibiotic commence-
ment with subsequent decline of inflammatory
markers, improvement in haematological markers
and ultimately full recovery.
PATIENT 2
A male infant aged 8 months with bilateral
optic nerve hypoplasia and panhypopituitarism
(including ACTII deficiency) was admitted with
gastroenteritis. His regular medication included
oral hydrocortisone (10.1 mg/m2/day), oral des-
mopressin (20 μg three times daily) and oral
thyroxine (50 [ig daily). He had a two-day history
of vomiting with no history of diarrhoea. His
temperature was 37.8°C on admission. He was
commenced on intravenous hydrocortisone at a
dose of 2 mg/kg six hourly. An initial blood
culture collected at the time of admission was
negative. His white cell count on admission was
9.2 χ 103/mm3. He was managed with oral fluids
initially. Rotavirus testing on stool (VIKIA®
Rota-Adeno by bioMerieux) was positive on day
two of admission and culture of stool from the
day of admission was negative. He deteriorated
clinically on day 3 of his admission with fever up
to 39.4°C and signs consistent with sepsis. A
blood culture subsequently grew Klebsiella
pneumoniae after 10 hours. His white cell count
was initially normal; however, it became elevated
to 24.1 χ lOVmm3 and his CRP peaked at 213
mg/L 32 hours after the initial fever. He also
developed anaemia, neutrophilia and thrombo-
cytopenia during the illness. I le completed an 11
day course of intravenous antibiotics. He had
resolution of fever and improvement in clinical
state within 48 hours of starting antibiotics. He
subsequently made a complete recovery.
DISCUSSION
Rotavirus is the commonest cause of gastro-
enteritis worldwide and it has been recognised as
the cause of 20% of diarrhoeal deaths in children
aged less than 5 years3. Rotavirus infects the
enterocytes and it has been demonstrated that
rotavirus infection increased enterocyte interna-
lisation and replication of bacteria, including
Listeria monocytogenes, Yersinia enterocolilica
and Y. pseudotuberculosis4'5. These mechanisms
are thought to contribute to the pathogenesis of
EGN bacteraemia, a recognised complication of
rotavirus infection. Secondary EGN bacteraemia
complicating rotavirus infection has been de-
scribed in 12 cases in children ranging in age
from two weeks to 18 months6"12. Recrudescence
of fever in infants with rotavirus infection has
been identified as the clinical sign that should
raise suspicion of secondary EGN bacteraemia
and prompt further assessment and investiga-
tion6·9·11.
Unlike other reported cases the patients
discussed here both received 'stress dose' gluco-
corticoid steroids after admission to hospital.
Patients with adrenal insufficiency require
maintenance glucocorticoid replacement when
well. It is recognised that circulating levels of
cortisol normally increase during stress, such as
illness or surgery; therefore increased doses of
glucocorticoids are required in these states and in
some cases may need to be administered
parenterally13. The nature of the effect of high
dose corticosteroids on the gastrointestinal tract is
controversial and the pathophysiology is not
clearly understood. However, studies have shown
delayed epithelial healing is most likely due to
inhibition of prostaglandin synthesis2. Experi-
mental studies have shown that dexamethasone
inhibits epidermal growth factor (EGF)-stimu-
lated gastric epithelial cell proliferation and basic
fibroblast growth factor14'15, which are essential
for mucosal healing via the prostaglandin path-
way. These research findings suggest a patho-
physiological basis for impaired healing of
'damaged' gastrointestinal mucosa in the setting
of glucocorticoid administration. Damage to the
gastrointestinal mucosa due to rotavirus infection
combined with delayed healing in the context of
glucocorticoid administration may increase the
risk of invasion of the mucosa by gastrointestinal
bacteria. Other potential sources of EGN infection
need to be considered, including intravenous
catheter infections; however, in both cases discus-
sed here there was no clinical evidence of venous
catheter infection.
The first infection with rotavirus is often
between 3 and 36 months of age and is more
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BACTERAEMIA COMPLICATING ROTA VIRUS GASTROENTERITIS 295
diarrhoea16. From 1 July 2007, rotavirus vaccina-
tion has been included in the National
Immunisation Program in Australia. The two
infants described here did not receive the rota-
virus vaccine. The impact of rotavirus vaccination
on complications such as EGN bacteraemia
remains uncertain. There remains a significant
population of unvaccinated children within the
higher risk age group. Studies have demonstrated
that the rotavirus vaccination program provides
protection for two years17. The impact of
vaccination after this period for those on high
dose glucocorticoids, who are hypothesised to be
at increased risk, remains uncertain.
These two cases of ENG bacteraemia com-
plicating rotavirus infection in infants on high
dose glucocorticoids for glucocorticoid deficient
states raise concern about a potential increased
risk for these children. Further research would be
beneficial to clarify this possible association and
the relevant pathophysiology. The impact of
rotavirus vaccination on EGN bacteraemia has yet
to be evaluated.
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Klebsiella pneumoniae bacteraemia complicating rotavirus gastroenteritis in two infants with glucocorticoid deficiency

D K. Longmore

J.A. Batch

S K.. McMahon

L.S. Conwell

Crossref

Journal of Pediatric Endocrinology and Metabolism

Bacteraemia Complicating Rotavirus Gastroenteritis Klebsiella pneumoniae Bacteraemia Complicating Rotavirus Gastroenteritis in Two Infants with Glucocorticoid Deficiency

http://espace.library.uq.edu.au/view/UQ:205232/UQ205232_OA.pdf

Klebsiella pneumoniae bacteraemia complicating rotavirus gastroenteritis in two infants with glucocorticoid deficiency

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