Successful Treatment of Listeria Meningitis in a Pregnant Woman with Ulcerative Colitis Receiving Infliximab

Abstract

Objectives: To report a case of Listeria monocytogen meningitis; a rare complication during Infliximab therapy for
ulcerative colitis during early pregnancy.

Case presentation and intervention: A 28 year old woman was treated with prior immunosuppression and
recent infliximab for ulcerative colitis. Pregnancy was confirmed at second infliximab infusion. Five days after the third dose, she developed signs of acute meningitis with subsequent VI cranial neuropathy. Cerebrospinal fluid Gram-stain suspected listeria monocytogen organisms, which was confirmed by blood and cerebrospinal fluid cultures. Meningitis was successfully treated with Ampicillin and Gentamycin. Spontaneous Intrauterine death of fetus occurred at 15 weeks gestation.

Conclusions: This case highlights the importance of high index of suspicion of opportunistic infections such as
Listeria meningitis with the use of infliximab.

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ISSN: 2327-5146
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General Medicine: Open Access
Lamdhade et al., General Med 2013, 1:3
http://dx.doi.org/10.4172/2327-5146.1000116
Open Access
Case Report
Volume 1 • Issue 3 • 1000116
General Med
ISSN: 2327-5146 GMO, an open access journal
Successful Treatment of Listeria Meningitis in a Pregnant Woman with
Ulcerative Colitis Receiving Infliximab
Lamdhade SJ1, Thussu A1, Al Benwan KO2 and Alroughani R1*
1Division of Neurology, Department of Medicine, Amiri Hospital, Kuwait
2Department of Microbiology, Amiri Hospital, Kuwait
Abstract
Objectives: To report a case of Listeria monocytogen meningitis; a rare complication during Iniximab therapy for
ulcerative colitis during early pregnancy.
Case presentation and intervention: A 28 year old woman was treated with prior immunosuppression and
recent iniximab for ulcerative colitis. Pregnancy was conrmed at second iniximab infusion. Five days after the third
dose, she developed signs of acute meningitis with subsequent VI cranial neuropathy. Cerebrospinal uid Gram-stain
suspected listeria monocytogen organisms, which was conrmed by blood and cerebrospinal uid cultures. Meningitis
was successfully treated with Ampicillin and Gentamycin. Spontaneous Intrauterine death of fetus occurred at 15
weeks gestation.
Conclusions: This case highlights the importance of high index of suspicion of opportunistic infections such as
Listeria meningitis with the use of iniximab.
*Corresponding author: Raed Alroughani, Division of Neurology, Department
of Medicine, Amiri Hospital, PO BOX. 1661, Qurtoba, 73767, Kuwait, Tel: +965
22450005, Fax: +965 22467499; E-mail: alroughani@gmail.com
Received August 26, 2013; Accepted September 06, 2013; Published September
12, 2013
Citation: Lamdhade SJ, Thussu A, Al Benwan KO, Alroughani R1 (2013)
Successful Treatment of Listeria Meningitis in a Pregnant Woman with Ulcerative
Colitis Receiving Iniximab. General Med 1: 116. doi: 10.4172/2327-5146.1000116
Copyright: © 2013 Lamdhade SJ, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.
Introduction
Iniximab (Remicade) is a chimeric IgG1 monoclonal antibody
and has a high specicity and anity to Tumor necrosis factor alpha
(TNF-α). It is frequently used as disease modifying agent in refractory
cases of Inammatory Bowel Disease (IBD) and Rheumatoid Arthritis
(RA) [1,2]. However emergence of opportunistic infections such
as mycobacteria, listeria monocytosis, nocardiosis, and invasive
aspergilosis raised safety concerns.
Listeria monocytogen is gram-positive bacilli commonly isolated
from environmental sources (water and food such as cheese, milk
products, and undercooked meat). It can cause sporadic or epidemic
infections and can be found in feces of 1-5% asymptomatic healthy
adults. Immunosuppression, defective cell mediated immunity and
pregnancies are considered high-risk conditions.Case mortality with
central nervous system (CNS) infection is very high reaching 27% and
many patients are le with neurological sequel [3]. ough listeria
meningitis has been described with the use of iniximab, its occurrence
during pregnancy in ulcerative colitis is rare. We report a case of listeria
meningitis in a woman who received iniximab during pregnancy.
Case Report
A 28-year-old married female was diagnosed with ulcerative
colitis in May 2006. She was given Mesalamine and Azathioprine was
subsequently added in 2008 as disease modifying erapy. However,
both were stopped for seven months since she was planning to get
pregnant. e symptoms of ulcerative colitis reappeared. Hence
Mesalamine, azathioprine and oral prednisolone 40 mg daily were
instituted in December 2009. Iniximab was started due to increased
disease activity manifested by frequent bloody diarrhea in February
2010. Prior to her second iniximab infusion, she noticed amenorrhea
and pregnancy was conrmed by abdominal ultrasound. She continued
to receive iniximab, as there was no absolute contraindication for its use
during pregnancy. On 5th April 2012, she received the third iniximab
infusion. Five days later (11 weeks gestation), she presented with body
ache, fever and severe headache for four days. She looked sick, toxic and
had fever of 39.3°C. e sequence of events occurred in the case was
summarized in Figure 1. Mild diuse abdominal tenderness was noted.
Except for neck stiness, her systemic and neurological examinations
were unremarkable. Her complete blood count showed WBC 11.4×109,
Paent with acve Ulcerave Colis received first dose of
Infliximab
She connued to receive
Infliximab. She received 2nd and
3rd doses.
5 days post 3rd dose of Infliximab:
Fever (39.3o C), body ache and severe headache
Toxic looking, nuchal rigidity, abdominal
tenderness
Serum: elevated WCB, ESR & CRP
Abdominal US: negave
MRI Brain: Negave
Day 0 of hospilizaon: Meniingis was
suspected and empiric Anbiocs were started
CSF Analysis: Turbid,
Lymphocyc pleocytosis,
elevated protein and low
glucose, gram-posive Bacilli
Day 0 of hopsilzaon:: anbiocs
were changed to Ampicillin and
Gentamycin
Day 1: Paent became afebrile
and Headache improved
Day 5: Headache resolved, paent
developed diplopia (Le CN VI Palsy)
Day 21: Paent was discharged aer
compleng 3-week course of
anbiocs
Day 28: Diplopia resolved,
paent became asymptomac
Paent became pregnant prior
to 2nd dose of Infliximab
Figure 1: Sequence of events observed in the patient.

Citation: Lamdhade SJ, Thussu A, Al Benwan KO, Alroughani R1 (2013) Successful Treatment of Listeria Meningitis in a Pregnant Woman with
Ulcerative Colitis Receiving Iniximab. General Med 1: 116. doi: 10.4172/2327-5146.1000116
Page 2 of 3
Volume 1 • Issue 3 • 1000116
General Med
ISSN: 2327-5146 GMO, an open access journal
hemoglobin was 132 g/L, platelets 330×109/L. e absolute counts for
neutrophils, lymphocytes, monocytes and basophils/ eosinophils were
9.9×109/L, 0.9 ×109/L, 6×109/L and 0×109/L respectively. ESR was 60
mm at 1st hour, and CRP was 95.4 mg/L. She was given IV Ceriaxone
2 gm as a stat dose. Her abdominal sonography did not show any
infectious mass. Due to her pregnancy, chest radiograph was not done
and further imaging of headwas delayed. Special sequence limited cuts
of MRI brain were done 12hrs later and did not show any intra-cranial
pathology.
A lumbar puncture was performed, and cerebrospinal uid (CSF)
was turbid in appearance. CSF revealed the following results: a WBC
count of 3,600 cells/ml (neutrophils, 86%; lymphocytes, 14%), a protein
level of 984 mg/liter, and a glucose level of 2.6 mmol/liter (blood glucose
7.0 mmol/L). A Gram stain demonstrated Gram-positive bacilli. CSF
was inoculated on 5% sheep blood agar, chocolate agar, and MacConkey
agar, and incubated at 37°C with and without CO2. erefore, Listeria
monocytogen meningitis was suspected and immediate empiric
antibiotic coverage was changed to IV Ampicillin 12 grams/day with
IV Gentamycin 80 mg every 8 hours. Aer a 24-h incubation of plates
Gram-positive bacilli grew. e growth revealed 1-2 mm round, convex,
smooth, translucent colonies with narrow zone of beta haemolysis on
5% sheep blood agar. Growth was also obtained on chocolate agar
whereas no growth was seen on MacConkey agar. e isolate was
identied as L. monocytogenes by colony characters, morphology,
tumbling motility, ability to grow at 4°C, characteristic biochemical
reactions, and by theAPI Listeria system (bioMérieux, Marcy l’Etoile,
France). e isolate was found to be susceptible to ampicillin, ≤0.5 µg/
ml; vancomycin, 1µg/ml; trimethoprim-sulfamethoxazole, ≤0.5 µg/ml,
and gentamicin, ≤4 µg/ml. On the 5th day of hospitalization, she became
afebrile with signicant relief from headache. However she noticed
diplopia due to le 6th nerve paresis, which resolved over in one-week.
On the 12th day, her CRP was reduced to 2.3 mg/L and ESR came down
to 23 mm/1 hour. Antibiotics in meningetic doses were continued for
three weeks along with oral corticosteroids.
Her Echocardiogram did not show any evidence of endocarditis. A
week aer her discharge, she suered intrauterine death of fetus. She
remained free of neurological symptoms with no residual decit at 6
months followup period.
Discussion
Iniximab is an eective alternative treatment option for patients
with moderate to severe ulcerative colitis (UC) with inadequate
response to conventional glucocorticoid treatment [1]. In October
2001, Food & Drug Agency (FDA) issued a warning regarding the
risk of serious infections like tuberculosis, invasive fungal infections
and other opportunistic infections like listeria and pneumocystis
in patients receiving Iniximab [4]. Two-fold increase in the risk of
serious infections was noted in Cohn’s disease (CD) patients who had
been prescribed iniximab and prior prednisolone and azathioprine
(Hazard Ratio 2.807, 95% CI (1.305-6.038) p<0.008) [5].
Iniximab-associated listeria infections had also been reported
in patients with ulcerative colitis, psoriatic arthritis and juvenile
rheumatoid arthritis. e rate of infections with listeria monocytogen
has doubled aer Iniximab was approved for the treatment of
rheumatoid arthritis compared to IBD patients; possibly due to
dierent institutions of immune-suppression regimens [2]. TNF-α
plays an important role in host defense system. Animal studies have
shown that TNF-alpha decient mice were highly susceptible to listeria
infection [6].
In clinical trials, no denite correlations were made between the
number of iniximab infusions and the onset of infection by listeria
monocytogen. Listeia meningitis was reported as early as aer second
dose of Iniximab [7]. Our patient had dual predisposing factors. One
due to immune suppression and second was pregnancy. Timing of her
symptoms suggests that the combination of factors culminated in the
development of listeria meningitis. Indeed, the occurrence of infection
shortly aer the initiation of therapy with Iniximab could be consistent
with reactivation of latent infection [8]. Treating Listeria meningitis
is always challenging due to delayed diagnosis and high mortality.
Standard regimen includes intravenous Ampicillin and Gentamycin.
Our patient responded well to this combination. Meropenem is a
good alternative choice for those patients allergic to Ampicillin or
Amoxycillin.
ough Iniximab is currently rated as Class B medication during
pregnancy, approximately 150 exposures during pregnancy were
reported. In a report of 96 women exposed to Iniximab, the rate of
live birth was 67% while miscarriages and therapeutic termination were
15% and 19% respectively which were similar to the rates in US general
population pregnant women with Crohn’s Disease (CD) [9]. In another
study assessing the intentional use of Iniximab during pregnancy,
three out of ten pregnant women with Crohn’s Disease developed
non-serious infections. All pregnancies ended in live births with no
congenital malformations [10]. Despite these observations, continuous
surveillance for opportunistic infections is warranted especially during
pregnancy. We feel that this is the rst case-report from Kuwait of
Iniximab-associated Listeria meningitis.
Conclusion
Infection of listeria monocytogen meningitis during pregnancy
is rare with Iniximab use. Clinicians should have a high index
of suspicion of uncommon infections while using biologic agents
and immunosuppression during pregnancy. Safe food practices are
recommended in all pregnant women.
Acknowledgement
The authors thank Dr. Waleed Al-Azmi for his contribution to the case.
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Citation: Lamdhade SJ, Thussu A, Al Benwan KO, Alroughani R1 (2013) Successful Treatment of Listeria Meningitis in a Pregnant Woman with
Ulcerative Colitis Receiving Iniximab. General Med 1: 116. doi: 10.4172/2327-5146.1000116
Page 3 of 3
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General Med
ISSN: 2327-5146 GMO, an open access journal
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pregnancy in women receiving iniximab for the treatment of Crohn’s disease
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Citation: Lamdhade SJ, Thussu A, Al Benwan KO, Alroughani R1 (2013)
Successful Treatment of Listeria Meningitis in a Pregnant Woman with
Ulcerative Colitis Receiving Iniximab. General Med 1: 116. doi: 10.4172/2327-
5146.1000116