Alemtuzumab Indicated for relapsing forms of multiple sclerosis - PDF document

2/3/2018 ALEMTUZUMAB ASSOCIATED LISTERIA MONOCYTOGENES MENINGITIS DURING THE TREATMENT OF MULTIPLE SCLEROSIS A Case Report CORRIE BLACK , PHARMACY STUDENT, MS ISU/UAA COP RYAN W. STEVENS , PHARMD, BCPS- PAMC THOMAS G. WADSWORTH , PHARMD, BCPS ISU/UAA COP 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 1

2/3/2018 CASE REPORT Prior symptoms worsen with development of nausea and neck stiffness Repeat MRI of brain, and patient presents to Emergency Department for admission shows a decreased 44 y/o female initiated enhancement of the Febrile (39.5°c), WBC: 6.4 10 3 / μ L (95% neutrophils), on alemtuzumab original abnormal Absolute CD4 count: 1 cell/ μ L(0%), regimen for the signal, patient released Absolute CD8 count: 5 cells/ μ L (3%) treatment of multiple to home, and sclerosis (MS) continued on Herpes Brain MRI: a focus of abnormal signal and prophylaxis and enhancement in the left cingulate gyrus initiated on sulfamethoxazole- Patient returned to Lumbar puncture: trimethoprim for PCP baseline and transfers 23 nucleated cells/ μ L, glucose <10 μ g/dL, and protein 181 mg/dL prophylaxis to a rehab facility to Completion of initial complete antibiotic Blood and cerebrospinal fluid (CSF) cultures collected: alemtuzumab therapy CSF gram-stain negative infusion regimen Patient initiated on ampicillin 2 g IV q4h + ceftriaxone 2 g IV q12h + vancomycin (goal trough 15-20 mcg/mL) Development Blood cultures result positive for of fever & gram-positive bacilli in both sets after headache 23 hours of incubation Fever and headache CSF cultures showed 1+ growth of persist; outpatient gram-positive bacilli blood cultures show gram positive bacilli Both the blood and CSF cultures in one of two draws would subsequently be finalized as Listeria monocytogenes 14 Day Day Day Day Day Day Day & 24 37 7 12 18 0 5 15 Day 14: Blood smear Brain MRI: Abnormal heterogeneous signal enhancement of the cingulate gyrus secondary to Listeria monocytogenes encephalitis, Day 14 Day 14: CSF smear 2

2/3/2018 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 or 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 Substantial Alemtuzumab Exposure to drop in CD4 Listeriosis Infusion raw food & CD8 count 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 3