Alemtuzumab Indicated for relapsing forms of multiple sclerosis - - PDF document

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ALEMTUZUMAB ASSOCIATED LISTERIA MONOCYTOGENES MENINGITIS DURING THE TREATMENT OF MULTIPLE SCLEROSIS

CORRIE BLACK, PHARMACY STUDENT, MS ISU/UAA COP RYAN W. STEVENS, PHARMD, BCPS- PAMC THOMAS G. WADSWORTH, PHARMD, BCPS ISU/UAA COP

A Case Report

BACKGROUND

Alemtuzumab

Indicated for relapsing forms of multiple sclerosis

(MS) and B-cell chronic lymphocytic leukemia

Binds CD52 antigens Destroys

T & B cells

Serious infections occurred in 3% of patients during

clinical trials

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Fever and headache persist; outpatient blood cultures show gram positive bacilli in one of two draws Development

• f fever &

headache 44 y/o female initiated

• n alemtuzumab

regimen for the treatment of multiple sclerosis (MS) Blood cultures result positive for gram-positive bacilli in both sets after 23 hours of incubation CSF cultures showed 1+ growth of gram-positive bacilli Both the blood and CSF cultures would subsequently be finalized as Listeria monocytogenes Day Patient returned to baseline and transfers to a rehab facility to complete antibiotic therapy Repeat MRI of brain, shows a decreased enhancement of the

• riginal abnormal

signal, patient released to home, and continued on Herpes prophylaxis and initiated on sulfamethoxazole- trimethoprim for PCP prophylaxis Completion of initial alemtuzumab infusion regimen Day 5 Day 7 Day 12 14 & 15 Day 18 Day 24 Day 37 Prior symptoms worsen with development of nausea and neck stiffness and patient presents to Emergency Department for admission Febrile (39.5°c), WBC: 6.4 103/μL (95% neutrophils), Absolute CD4 count: 1 cell/μL(0%), Absolute CD8 count: 5 cells/μL (3%) Brain MRI: a focus of abnormal signal and enhancement in the left cingulate gyrus Lumbar puncture: 23 nucleated cells/μL, glucose <10 μg/dL, and protein 181 mg/dL Blood and cerebrospinal fluid (CSF) cultures collected: CSF gram-stain negative Patient initiated on ampicillin 2 g IV q4h + ceftriaxone 2 g IV q12h + vancomycin (goal trough 15-20 mcg/mL)

CASE REPORT

Day 14: Blood smear Day 14: CSF smear

Brain MRI: Abnormal heterogeneous signal enhancement of the cingulate gyrus secondary to Listeria monocytogenes encephalitis, Day 14

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DISCUSSION

 First reported case of alemtuzumab associated listeriosis in the United States

 21 cases described in the literature  16 occurred in patients with MS (9 involved meningitis)

 CD4 and CD8 cells are known to respond to L. Monocytogenes antigens

 Integral in combating listeriosis via cell-mediated cytolysis

 Many of the cases describe a similar temporal relationship with exposure to raw

• r undercooked foods prior to therapy

 L. Monocytogenes incubation period can be as long as 70 days

 Plausible that prior colonization could result in serious infection  Especially during periods of profound immunosuppression caused by alemtuzumab

Exposure to raw food Alemtuzumab Infusion Substantial drop in CD4 & CD8 count Listeriosis

CONCLUSIONS

 Greater dietary precautions are warranted  Greater consideration for prophylactic antibiotics is

warranted

 Greater awareness of the severity of immunosuppression

associated with alemtuzumab is also warranted