Update in CNS Infections Brian Schwartz, MD Division of Infectious Diseases, UCSF Outline • Infections of the Brain • Infections of the Spine
Outline • Infections of the Brain • Infections of the Spine
If you would like…pick a partner • Turn to the person next to you • Spend 3 minutes sharing how you would approach the following case Case • 65 y/o male presents to ED by ambulance after a seizure. He had progressive lethargy, fever, and stiff neck x 48 hrs • Exam: 39 ° C, 110, 110/50, 20, 99% RA 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 had progressive lethargy, fever, and stiff neck x 48 hrs. • Exam: 39 ° C, 110, 110/50, 20, 99% RA o Oriented to person only o Unable to touch chin to chest o No focal neurological abnormalities DISCUSS 1. CT scan yes/no? 2. LP when? 3. Empiric antibiotics (when, what)? 4. Steroids (yes/no, when)? Decision #1: CT before LP? Yes if… • New-onset seizure • Immunocompromised • Focal neurological finding • Papilledema • Mod-severe impaired consciousness Hasbun R. NEJM. 2001. Gopal AK. Arch Int Med. 1999.
Decision #2: Antibiotics? • When? o CT: antibiotics up front (blood cx 1st) o No CT: LP and then antibiotics • What? o Depends on which bugs…. Thigpen MC. NEJM.2011
Empiric therapy Risk factor Pathogens Antimicrobials Vancomycin + 2-50 yr N. meningitidis, Ceftriaxone S. pneumoniae Vancomycin+ > 50 yr S. pneumoniae, Ceftriaxone + N. meningitidis, Ampicillin L. monocytogenes Adapted from Tunkel AR. CID 2004 Vanco?? Pen resistant S. pneumo 6 Colony forming units/ml CSF 5 4 CFTX 3 RIF 2 VANCO + RIF VANCO 1 CFTX + Vanco 0 0 5 10 24 Hours post initiation of therapy
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 • Double-blinded RCT in adults from the Netherlands • Dexamethasone 10 mg q6h vs. placebo x 4d • 1° outcome: Death or neurological disability Dex Placebo RR of poor outcome 15% 25% 0.59 (0.37-0.94), p=0.03 All 26% 52% 0.50 (0.30-0.83), p=0.006 S. pneumoniae 8% 11% 0.75 (0.21-2.63), p=0.74 N. meningitidis de Gans J. NEJM 2002 Summary of plan: 1. Blood cultures 2. Vanco + Ceftriaxone + Amp + Steroids 3. CT scan 4. LP
How quickly does the CSF sterilize after antibiotic administration? 100 % of CSF sterilized 80 60 40 N. meningitidis 20 S. pneumoniae 0 0 ‐ 2 2.1 ‐ 4 4.1 ‐ 6 6.1 ‐ 24 24.1 ‐ 48 >48 Kanegye JT. Pediatrics. Time after start of antibiotics (hours) 2001. 108 (5). Molecular diagnostics (next negation sequencing) to diagnosis idiopathic CNS infections? 204 patients with idiopathic meningitis/encephalitis 58/204 had a diagnosis made by any method 32 identified by NGS and other methods 13/58 only identified by NGS 11 identified only by serology 7 diagnosed by non-CSF tissue samples Wilson MR. NEJM. 2019
Case continued • Rx: Ceftriaxone, Vanco, Amp, Decadron • CT was normal • LP: o WBC: 450 (90% PMNs) o Glucose: 50 (Serum:170);CSF/serum=0.3 o Protein: 120 o Gm stain: Gram positive diplococci;Culture:NGTD • Blood cultures: no growth Definitive antimicrobial therapy Pathogen Primary Duration S. pneumoniae Pen MIC ≤ 0.1 µg/ml Penicillin 10-14 days Pen MIC 0.1-1.0 µg/ml Ceftriaxone Pen MIC >0.1-1.0 µg/ml Vanco + Ceftriaxone N. meningitidis 7 days Pen MIC ≤ 0.1 µg/ml Penicillin G Pen MIC 0.1-1.0 µg/ml Ceftriaxone Ampicillin ≥ 21 days L. monocytogenes Adapted from Tunkel AR. CID 2004
IDSA algorithm for Rx of bacterial meningitis 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 Tricky scenarios…
Empiric therapy for penicillin allergic? • What type of reaction? o Non-IgE mediated: Cephalosporin OK o IgE-mediated (hives, anaphylaxis) • Alternate Rx, consider desensitization If it is IgE mediated… Empiric: Vanco + (Aztreonam or Meropenem) Directed: Pathogen Alternative treatment Meropenem or fluoroquinolone S. pneumoniae Aztreonam, fluoroquinolone N. meningitidis TMP-SMX, meropenem L. monocytogenes Adapted from Tunkel AR. CID 2004
N meningitidis – prophylaxis? • Who needs prophylaxis? o Household members o Direct exposure to oral secretions • What to give? o Rifampin 600 mg q12 x 2 days o Ciprofloxacin 500 mg x 1 o Ceftriaxone 250 mg IM x 1 Preventing spread of of N meningitidis (inpatient) • Droplet precautions • DCed after 24h ceftriaxone http://www.cdc.gov/MMWR/preview/mmwrhtml/00046263.htm
Patient with meningitis, 7 days post meningioma resection • What bugs are your worried about? o MRSA o Resistant Gram negative rods • Empiric regimen? o Vancomycin + (Cefepime or Meropenem) Fever and HA x 5 days; Lymphs in CSF? • 31 y/o M c/o 5 days of severe HA o Sore throat, malaise, fever, chills • PMH: none; Meds: Acetaminophen • SH: Sacramento, 1 female partner • Exam: T-38.6, pain w/ neck flexion • LP: WBC 228 (96% L),Gluc 63, Protein 76 Case by Jen Babik
CSF findings WBCs PMNs Glucose Protein (CSF/serum) (mg/dL) Bacterial 500- >85 < 0.4 < 200 meningitis 10K Aseptic 10-500 <50 WNL <100 meningitis Encephalitis 0-1000 <50 WNL < 100 Chronic 100-500 <50 < 0.4 > 200 meningitis DDx Aseptic Meningitis/Lymphocytic Pleocytosis • Bacterial o Bacterial meningitis (10%) • Fungal o Partially treated bacterial meningitis o Crypto o Listeria (<25%) o Endemic fungi (e.g., cocci) o Mycobacteria • Parasites o Spirochetes: Syphilis, Lyme, Lepto o Toxoplasma gondii o Other: Brucella, RMSF, Q fever o Helminths (eg neurocystercircosis) o Para-meningeal focus of infection (brain/epidural abscess) o Amoeba (eg Balamuthia) • Viral • Non-infectious o Arboviruses (West Nile Virus) o Medications (e.g., NSAIDs, Abx) o Enteroviruses o Rheumatologic Disease (e.g., SLE, o Herpesviruses (HSV, VZV, CMV, EBV) sarcoid) o Acute HIV o Carcinomatous meningitis o Others (LCMV, Measles, Mumps)
DDx Aseptic Meningitis: Most Common Infections • Bacterial Diagnostics : o Syphilis o Serum o Lyme • RPR • HIV Ab and VL • Viral • West Nile IgM/IgG o Enteroviruses • Lyme Ab (if risk factors) o CSF o HSV, VZV • VDRL o Acute HIV • Enterovirus PCR o West Nile virus • HSV/VZV PCR • West Nile IgM/IgG Case by Jen Babik Back to the Case… • CSF HSV, VZV PCR negative • RPR negative • HIV Ab negative • HIV VL 120,000 • Diagnosis: Acute HIV Infection Case created by Jen Babik
Progressive headache x 3 weeks • 56 y/o M c/o 3 wks of progressive HA, fatigue, low grade fevers, confusion • PMH: Diabetes, HTN • SH: Phoenix, AZ; construction worker • Exam: T-38.1, pain w/ neck flexion • LP: WBC: 190 (85% L), TP: 420, Gluc 39 CSF findings PMNs WBCs Glucose Protein % (CSF/serum) (mg/dL) Bacterial 500-10K >85 < 0.4 < 200 meningitis Aseptic 10-500 <50 WNL <100 meningitis Encephalitis 0-1000 <50 WNL < 100 Chronic 100-500 <50 < 0.4 > 200 meningitis
Chronic meningitis • Definition: >4 weeks of symptoms • LP: Lymphs, low glucose, high protein • History important! • DDx: TB, crypto, cocci, histo, etc. • Work up: LP, CrAg, AFB/fungal Cx, Cocci IgM, HIV • Empiric Rx: RIPE + steroids (+/- fluc) Case continued • Serum and CSF Coccidiodes immitis titers; 1:256 and 1:8 • 2 months ago had pneumonia while working at a new construction site with lots of dust • Started on fluconazole
Take home points: meningitis • CT scan before LP in patients w/… • Give Abx immediately if going to CT • Add Ampicillin if >50 yr or IS for Listeria • Steroids before Abx, only S pneumo • Aseptic: WNV, HSV, entero…syphilis, acute HIV • Chronic: TB, cocci, consider empiric Rx Outline • Infections of the Brain • Infections of the Spine
Case: 63 y/o F with ESRD on HD c/o 3 wks of lower back pain • PMH: ESRD on HD Exam: • Meds: 37.5, 89, 154/66, 16 o Metoprolol Skin: L forearm AVF, no o Nephrovite erythema/TTP • SH: Back: TTP L2-L3 o Teacher Neuro: normal o no IVDU • 63 year-old male with ESRD on HD has 3 weeks of progressive back pain, tender to palpation over L2-3 • Spend 2 minutes discussing next steps: o Radiographic testing? o Laboratory testing?
Vertebral osetomyelitis/discitis is hard to diagnose? • Median time to Dx: 48 days • Fever only present in 13% Nolla JM. Arthritis and Rheumatisim. 2002 Clues to infectious etiology? • History o Constitutional symptoms o Recent S aureus infection • Exam o TTP over vertebrae o Fever (low sensitivity) • Labs o Elevated CRP/ESR
Next steps? • Radiographic testing? o Spine films? Dx compression fracture o MRI? sensitive for osteo/discitis • Laboratory testing? o CRP? Sensitive for osteo/discitis
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