2/21/19 Update Outline in CNS Infections • Infections of the Brain • Infections of the Spine Brian Schwartz, MD Division of Infectious Diseases, UCSF Outline • Infections of the Brain • Infections of the Spine 1
2/21/19 Case If you would like…pick a partner • 65 y/o male presents to ED by ambulance • Turn to the person next to you after a seizure. He had progressive lethargy, fever, and stiff neck x 48 hrs • Spend 3 minutes sharing how you • Exam: 39 � C, 110, 110/50, 20, 99% RA would approach the following case o Oriented to person only o Unable to touch chin to chest o No focal neurological abnormalities • 65 y/o male presents to ED by ambulance after a seizure. He Decision #1: CT before LP? had progressive lethargy, fever, and stiff neck x 48 hrs. • Exam: 39 � C, 110, 110/50, 20, 99% RA Yes if… CT -Yes o Oriented to person only • New-onset seizure o Unable to touch chin to chest o No focal neurological abnormalities • Immunocompromised DISCUSS • Focal neurological finding 1. CT scan yes/no? • Papilledema 2. LP when? 3. Empiric antibiotics (when, what)? • Mod-severe impaired consciousness 4. Steroids (yes/no, when)? Hasbun R. NEJM. 2001. Gopal AK. Arch Int Med. 1999. 2
2/21/19 Listeria monocytogenes GBS Haemophilus influenzae Decision #2: Antibiotics? Neisseria meningitidis Streptococcus pneumoniae 100 • When? 90 Percentage of Total Cases 80 o CT: antibiotics up front (blood cx 1st) 70 60 o No CT: LP and then antibiotics 50 40 • What? 30 20 10 o Depends on which bugs…. 0 18–34 35–49 50–64 ≥ 65 All adult Thigpen MC. Yr Yr Yr Yr cases NEJM.2011 Vanco?? Pen resistant S. pneumo Empiric therapy 6 Colony forming units/ml CSF Risk factor Pathogens Antimicrobials 5 2-50 yr N. meningitidis, Vancomycin + 4 S. pneumoniae Ceftriaxone CFTX 3 RIF > 50 yr S. pneumoniae, Vancomycin+ 2 VANCO + RIF N. meningitidis, Ceftriaxone + VANCO L. monocytogenes Ampicillin 1 CFTX + Vanco Adapted from Tunkel AR. CID 2004 0 0 5 10 24 Hours post initiation of therapy 3
2/21/19 Decision #3: Steroids? Steroids for bacterial meningitis • When? o Before first dose of antibiotics o Not for patients already on antibiotics • How much? o Dexamethasone 10mg q6h x 4 days • For which bugs? o S pneumoniae Tunkel et al, CID 2004:39. Dexamethasone for Bacterial Meningitis Summary of plan: • Double-blinded RCT in adults from the Netherlands 1. Blood cultures • Dexamethasone 10 mg q6h vs. placebo x 4d 2. Vanco + Ceftriaxone + Amp + Steroids • 1° outcome: Death or neurological disability 3. CT scan Dex Placebo RR of poor outcome All 4. LP 15% 25% 0.59 (0.37-0.94), p=0.03 S. pneumoniae 26% 52% 0.50 (0.30-0.83), p=0.006 N. meningitidis 8% 11% 0.75 (0.21-2.63), p=0.74 de Gans J. NEJM 2002 4
2/21/19 How quickly does the CSF sterilize after Molecular diagnostics helpful? antibiotic administration? 100 • 451 suspected bacterial meningitis % of CSF sterilized 80 • 98 had antibiotics in CSF sample 60 • Sensitivity 40 o Culture: 78% N. meningitidis 20 o Gram Stain: 99% S. pneumoniae 0 o RT-PCR: 95% 0-2 2.1-4 4.1-6 6.1-24 24.1-48 >48 Time after start of antibiotics (hours) Kanegye JT . Pediatrics. Wu et al. BMC Infectious Diseases. 2013 2001. 108 (5). Case continued Definitive antimicrobial therapy Pathogen Primary Duration • Rx: Ceftriaxone, Vanco, Amp, Decadron S. pneumoniae • CT was normal Pen MIC ≤0.1 µg/ml Penicillin 10-14 days • LP: Pen MIC 0.1-1.0 µg/ml Ceftriaxone o WBC: 450 (90% PMNs) Pen MIC >0.1-1.0 µg/ml Vanco + Ceftriaxone N. meningitidis o Glucose: 50 (Serum:170);CSF/serum=0.3 7 days Pen MIC ≤0.1 µg/ml Penicillin G o Protein: 120 Pen MIC 0.1-1.0 µg/ml Ceftriaxone o Gm stain: Gram positive diplococci;Culture:NGTD Ampicillin L. monocytogenes ≥21 days • Blood cultures: no growth Adapted from Tunkel AR. CID 2004 5
2/21/19 IDSA algorithm for Rx of bacterial meningitis Tricky scenarios… Indication for head CT NO YES Blood cx Blood cx + Lumbar puncture Steroids and empiric antimicrobials Steroids and empiric antimicrobials Head CT w/o mass lesion or herniation CSF suggestive of bacterial meningitis Refine therapy Lumbar puncture Tunkel AR. CID 2004 Empiric therapy for penicillin allergic? If it is IgE mediated… • What type of reaction? Empiric: Vanco + (Aztreonam or Meropenem) o Non-IgE mediated: Cephalosporin OK o IgE-mediated (hives, anaphylaxis) Directed: • Alternate Rx, consider desensitization Pathogen Alternative treatment S. pneumoniae Meropenem or fluoroquinolone N. meningitidis Aztreonam, fluoroquinolone L. monocytogenes TMP-SMX, meropenem Adapted from Tunkel AR. CID 2004 6
2/21/19 Preventing spread of N meningitidis – prophylaxis? of N meningitidis (inpatient) • Who needs prophylaxis? o Household members • Droplet precautions o Direct exposure to oral secretions • DCed after 24h ceftriaxone • What to give? o Rifampin 600 mg q12 x 2 days o Ciprofloxacin 500 mg x 1 o Ceftriaxone 250 mg IM x 1 http://www.cdc.gov/MMWR/preview/mmwrhtml/00046263.htm Patient with meningitis, 7 days Fever and HA x 5 days; Lymphs in CSF? post meningioma resection • 31 y/o M c/o 5 days of severe HA o Sore throat, malaise, fever, chills • What bugs are your worried about? • PMH: none; Meds: Acetaminophen o MRSA • SH: Sacramento, 1 female partner o Resistant Gram negative rods • Exam: T-38.6, pain w/ neck flexion • Empiric regimen? • LP: WBC 228 (96% L),Gluc 63, Protein 76 o Vancomycin + (Cefepime or Meropenem) Case by Jen Babik 7
2/21/19 CSF findings DDx Aseptic Meningitis/Lymphocytic Pleocytosis • Bacterial WBCs PMNs Glucose Protein o Bacterial meningitis (10%) • Fungal (CSF/serum) (mg/dL) o Partially treated bacterial meningitis o Crypto o Listeria (<25%) Bacterial 500- o Endemic fungi (e.g., cocci) o Mycobacteria >85 < 0.4 < 200 • Parasites meningitis 10K o Spirochetes: Syphilis, Lyme, Lepto o Toxoplasma gondii o Other: Brucella, RMSF, Q fever Aseptic o Helminths (eg neurocystercircosis) o Para-meningeal focus of infection 10-500 <50 WNL <100 (brain/epidural abscess) meningitis o Amoeba (eg Balamuthia) • Viral • Non-infectious Encephalitis 0-1000 <50 WNL < 100 o Arboviruses (West Nile Virus) o Medications (e.g., NSAIDs, Abx) o Enteroviruses o Rheumatologic Disease (e.g., SLE, Chronic o Herpesviruses (HSV, VZV, CMV, EBV) 100-500 <50 < 0.4 > 200 sarcoid) o Acute HIV meningitis o Carcinomatous meningitis o Others (LCMV, Measles, Mumps) Back to the Case… DDx Aseptic Meningitis: Most Common Infections Diagnostics : • Bacterial o Syphilis • CSF HSV, VZV PCR negative o Serum o Lyme • RPR • RPR negative • HIV Ab and VL • Viral • West Nile IgM/IgG • HIV Ab negative o Enteroviruses • Lyme Ab (if risk factors) o CSF o HSV, VZV • HIV VL 120,000 • VDRL o Acute HIV • Enterovirus PCR o West Nile virus • Diagnosis: Acute HIV Infection • HSV/VZV PCR • West Nile IgM/IgG Case by Jen Babik Case created by Jen Babik 8
2/21/19 CSF findings Progressive headache x 3 weeks WBCs PMNs Glucose Protein • 56 y/o M c/o 3 wks of progressive HA, % (CSF/serum) (mg/dL) fatigue, low grade fevers, confusion Bacterial 500- >85 < 0.4 < 200 • PMH: Diabetes, HTN meningitis 10K Aseptic • SH: Phoenix, AZ; construction worker 10-500 <50 WNL <100 meningitis • Exam: T-38.1, pain w/ neck flexion Encephalitis 0-1000 <50 WNL < 100 • LP: WBC: 190 (85% L), TP: 420, Gluc 39 Chronic 100-500 <50 < 0.4 > 200 meningitis Case continued Chronic meningitis • Definition: >4 weeks of symptoms • Serum and CSF Coccidiodes immitis • LP: Lymphs, low glucose, high protein titers; 1:256 and 1:8 • History important! • 2 months ago had pneumonia while working at a new construction site with • DDx: TB, crypto, cocci, histo, etc. lots of dust • Work up: LP, CrAg, AFB/fungal Cx, Cocci IgM, HIV • Started on fluconazole • Empiric Rx: RIPE + steroids (+/- fluc) 9
2/21/19 Take home points: meningitis Outline • CT scan before LP in patients w/… • Give Abx immediately if going to CT • Infections of the Brain • Add Ampicillin if >50 yr or IS for Listeria • Infections of the Spine • Steroids before Abx, only S pneumo • Aseptic: WNV, HSV, entero…syphilis, acute HIV • Chronic: TB, cocci, consider empiric Rx Case: 63 y/o F with ESRD on HD c/o 3 • 63 year-old male with ESRD on HD has 3 wks of lower back pain weeks of progressive back pain, tender to • PMH: ESRD on HD Exam: palpation over L2-3 • Meds: 37.5, 89, 154/66, 16 o Metoprolol Skin: L forearm AVF, no • Spend 2 minutes discussing next steps: o Nephrovite erythema/TTP o Radiographic testing? • SH: Back: TTP L2-L3 o Teacher Neuro: normal o Laboratory testing? o no IVDU 10
2/21/19 Clues to infectious etiology? Vertebral osetomyelitis/discitis is hard to diagnose? • History o Constitutional symptoms o Recent S aureus infection • Median time to Dx: 48 days • Exam • Fever only present in 13% o TTP over vertebrae o Fever (low sensitivity) • Labs o Elevated CRP/ESR Nolla JM. Arthritis and Rheumatisim. 2002 Next steps? • Radiographic testing? o Spine films? Dx compression fracture o MRI? sensitive for osteo/discitis • Laboratory testing? o CRP? Sensitive for osteo/discitis 11
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