alexa Successful Treatment of Listeria Meningitis in a Pregnant Woman with Ulcerative Colitis Receiving Infliximab | Open Access Journals
ISSN: 2327-5146
General Medicine: Open Access
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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, Kuwai
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: [email protected]
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 Infliximab. Gen Med (Los Angel) 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.
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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.

Introduction
Infliximab (Remicade) is a chimeric IgG1 monoclonal antibody and has a high specificity and affinity to Tumor necrosis factor alpha (TNF-α). It is frequently used as disease modifying agent in refractory cases of Inflammatory 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 left with neurological sequel [3]. Though listeria meningitis has been described with the use of infliximab, its occurrence during pregnancy in ulcerative colitis is rare. We report a case of listeria meningitis in a woman who received infliximab during pregnancy.
Case Report
A 28-year-oldmarried female was diagnosed with ulcerative colitis in May 2006. She was given Mesalamine and Azathioprine was subsequently added in 2008 as disease modifying therapies. However, both were stopped for seven months since she was planning to get pregnant. The symptoms of ulcerative colitis reappeared. Hence Mesalamine, azathioprine and oral prednisolone 40 mg daily were instituted in December 2009. Infliximab was started due to increased disease activity manifested by frequent bloody diarrheain February 2010. Prior to her second infliximab infusion, she noticed amenorrhea and pregnancy was confirmed by abdominal ultrasound. She continued to receive infliximab, as there was no absolute contraindication for its use during pregnancy. On 5th April 2012, she received the third infliximab 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. The sequence of events occurred in the case was summarized in Figure 1. Mild diffuse abdominal tenderness was noted. Exceptfor neck stiffness, her systemic and neurological examinations were unremarkable. Her complete blood count showed WBC 11.4×109, hemoglobin was 132 g/L, platelets 330×109/L. The 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 Ceftriaxone 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 imagingof 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 fluid (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. Therefore, 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. After a 24-h incubation of plates Gram-positive bacilli grew. The 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. The isolate was identified 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). The 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 significant relief from headache. However she noticed diplopia due to left 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 after her discharge, she suffered intrauterine death of fetus. She remained free of neurological symptoms with no residual deficit at 6 months followup period.
Discussion
Infliximab is an effective 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 Infliximab [4]. Two-fold increase in the risk of serious infections was noted in Cohn’s disease (CD) patients who had been prescribed infliximab and prior prednisolone and azathioprine (Hazard Ratio 2.807, 95% CI (1.305-6.038) p<0.008) [5].
Infliximab-associated listeria infections had also been reported in patients with ulcerative colitis, psoriatic arthritis and juvenile rheumatoid arthritis. The rate of infections with listeria monocytogen has doubled after Infliximab was approved for the treatment of rheumatoid arthritis compared to IBD patients; possibly due to different institutions of immune-suppression regimens [2]. TNF-α plays an important role in host defense system. Animal studies have shown that TNF-alpha deficient mice were highly susceptible to listeria infection [6].
In clinical trials, no definite correlations were made between the number of infliximab infusions and the onset of infection by listeria monocytogen. Listeia meningitis was reported as early as after second dose of Infliximab [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 after the initiation of therapy with Infliximab 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.
Though Infliximab is currently rated as Class B medication during pregnancy, approximately 150 exposures during pregnancy were reported. In a report of 96 women exposed to Infliximab, the rate of live birth was 67% while miscarriagesand therapeutic termination were 15% and 19% respectively which were similar to the rates in US general population pregnant women with CD [9]. In another study assessing the intentional use of Infliximab 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 first case-report from Kuwait of Infliximab-associated Listeria meningitis [11].
Conclusion
Infection of listeria monocytogen meningitis during pregnancy is rare with Infliximab use. Clinicians should have a high index of suspicion of uncommon infections while using biologic agents and immunosuppression during pregnancy. Safe food practices arerecommended in all pregnant women.
Acknowledgement
The authors thank Dr. Waleed Al-Azmi for his contribution to the case.
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