Outline Infections of the Brain Infections of the Spine Outline - - PDF document

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
• Oriented to person only
• Unable to touch chin to chest
• 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
• Oriented to person only
• Unable to touch chin to chest
• 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?
• CT: antibiotics up front (blood cx 1st)
• No CT: LP and then antibiotics
• What?
• Depends on which bugs….

Thigpen MC. NEJM.2011

Empiric therapy

Risk factor Pathogens Antimicrobials 2-50 yr

• N. meningitidis,
• S. pneumoniae

Vancomycin + Ceftriaxone > 50 yr

• S. pneumoniae,
• N. meningitidis,
• L. monocytogenes

Vancomycin+ Ceftriaxone + Ampicillin

Adapted from Tunkel AR. CID 2004

Vanco?? Pen resistant S. pneumo

1 2 3 4 5 6 5 10 24

Colony forming units/ml CSF Hours post initiation of therapy CFTX RIF VANCO + RIF VANCO CFTX + Vanco

Decision #3: Steroids? Steroids for bacterial meningitis

• When?
• Before first dose of antibiotics
• Not for patients already on antibiotics
• How much?
• Dexamethasone 10mg q6h x 4 days
• For which bugs?
• 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

de Gans J. NEJM 2002

Dex Placebo RR of poor outcome

All

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

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?

20 40 60 80 100 0‐2 2.1‐4 4.1‐6 6.1‐24 24.1‐48 >48

% of CSF sterilized

Time after start of antibiotics (hours)

• N. meningitidis
• S. pneumoniae

Kanegye JT. Pediatrics.

• 2001. 108 (5).

Molecular diagnostics (next negation sequencing) to diagnosis idiopathic CNS infections?

Wilson MR. NEJM. 2019

204 patients with idiopathic meningitis/encephalitis

58/204 had a diagnosis made by any method

13/58 only identified by NGS 32 identified by NGS and

• ther methods

11 identified only by serology 7 diagnosed by non-CSF tissue samples

Case continued

• Rx: Ceftriaxone, Vanco, Amp, Decadron
• CT was normal
• LP:
• WBC: 450 (90% PMNs)
• Glucose: 50 (Serum:170);CSF/serum=0.3
• Protein: 120
• Gm stain: Gram positive diplococci;Culture:NGTD
• Blood cultures: no growth

Definitive antimicrobial therapy

Pathogen Primary Duration

• S. pneumoniae

10-14 days

Pen MIC ≤0.1 µg/ml Penicillin 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

• L. monocytogenes

Ampicillin

≥21 days

Adapted from Tunkel AR. CID 2004

IDSA algorithm for Rx of bacterial meningitis

Indication for head CT

YES NO Blood cx + Lumbar puncture Blood cx Steroids and empiric antimicrobials Steroids and empiric antimicrobials CSF suggestive of bacterial meningitis Head CT w/o mass lesion or herniation Lumbar puncture Refine therapy

Tunkel AR. CID 2004

Tricky scenarios…

Empiric therapy for penicillin allergic?

• What type of reaction?
• Non-IgE mediated: Cephalosporin OK
• IgE-mediated (hives, anaphylaxis)
• Alternate Rx, consider desensitization

If it is IgE mediated…

Empiric: Vanco + (Aztreonam or Meropenem) Directed:

Pathogen Alternative treatment

• S. pneumoniae

Meropenem or fluoroquinolone

• N. meningitidis

Aztreonam, fluoroquinolone

• L. monocytogenes

TMP-SMX, meropenem

Adapted from Tunkel AR. CID 2004

N meningitidis – prophylaxis?

• Who needs prophylaxis?
• Household members
• Direct exposure to oral secretions
• What to give?
• Rifampin 600 mg q12 x 2 days
• Ciprofloxacin 500 mg x 1
• Ceftriaxone 250 mg IM x 1

Preventing spread of

• f 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?
• MRSA
• Resistant Gram negative rods
• Empiric regimen?
• Vancomycin + (Cefepime or Meropenem)

Fever and HA x 5 days; Lymphs in CSF?

• 31 y/o M c/o 5 days of severe HA
• 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

(CSF/serum)

Protein

(mg/dL)

Bacterial meningitis 500- 10K >85 < 0.4 < 200 Aseptic meningitis 10-500 <50 WNL <100 Encephalitis 0-1000 <50 WNL < 100 Chronic meningitis 100-500 <50 < 0.4 > 200 DDx Aseptic Meningitis/Lymphocytic Pleocytosis

• Bacterial
• Bacterial meningitis (10%)
• Partially treated bacterial meningitis
• Listeria (<25%)
• Mycobacteria
• Spirochetes: Syphilis, Lyme, Lepto
• Other: Brucella, RMSF, Q fever
• Para-meningeal focus of infection

(brain/epidural abscess)

• Viral
• Arboviruses (West Nile Virus)
• Enteroviruses
• Herpesviruses (HSV, VZV, CMV, EBV)
• Acute HIV
• Others (LCMV, Measles, Mumps)
• Fungal
• Crypto
• Endemic fungi (e.g., cocci)
• Parasites
• Toxoplasma gondii
• Helminths (eg neurocystercircosis)
• Amoeba (eg Balamuthia)
• Non-infectious
• Medications (e.g., NSAIDs, Abx)
• Rheumatologic Disease (e.g., SLE,

sarcoid)

• Carcinomatous meningitis

DDx Aseptic Meningitis: Most Common Infections

• Bacterial
• Syphilis
• Lyme
• Viral
• Enteroviruses
• HSV, VZV
• Acute HIV
• West Nile virus

Diagnostics:

• Serum
• RPR
• HIV Ab and VL
• West Nile IgM/IgG
• Lyme Ab (if risk factors)
• CSF
• VDRL
• Enterovirus PCR
• 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

WBCs

PMNs %

Glucose

(CSF/serum)

Protein

(mg/dL)

Bacterial meningitis 500-10K >85 < 0.4 < 200 Aseptic meningitis 10-500 <50 WNL <100 Encephalitis 0-1000 <50 WNL < 100 Chronic meningitis 100-500 <50 < 0.4 > 200

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
• Meds:
• Metoprolol
• Nephrovite
• SH:
• Teacher
• no IVDU

Exam: 37.5, 89, 154/66, 16 Skin: L forearm AVF, no

erythema/TTP

Back: TTP L2-L3 Neuro: normal

• Spend 2 minutes discussing next steps:
• Radiographic testing?
• Laboratory testing?
• 63 year-old male with ESRD on HD has 3

weeks of progressive back pain, tender to palpation over L2-3

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
• Constitutional symptoms
• Recent S aureus infection
• Exam
• TTP over vertebrae
• Fever (low sensitivity)
• Labs
• Elevated CRP/ESR

Next steps?

• Radiographic testing?
• Spine films? Dx compression fracture
• MRI? sensitive for osteo/discitis
• Laboratory testing?
• CRP? Sensitive for osteo/discitis

Next decisions (2 min)

• Urgent surgical therapy?
• How to make micro Dx?
• Empiric antibiotic regimen?

Is surgical therapy indicated?

• Immediate indication
• Progressive neurologic deficits
• Other
• Progressive deformity and/or instability
• Persistent/recurrent infection
• Worsening pain despite appropriate Rx

How to make a micro Dx?

• CT guided biopsy

How to make a micro Dx?

• CT guided biopsy (50% sens)

How to make a micro Dx?

• CT guided biopsy (50% sens)
• Blood cultures

How to make a micro Dx?

• CT guided biopsy (50% sens)
• Blood cultures (50% sens)
• Ok to wait on antibiotics
• If no immediate neuro threat
• If no bacteremia

Empiric therapy: common pathogens?

S aureus 48% GNR 23%

Strep 9% Polymicrobial 8% S epi 7% Other 5%

McHenry et al CID 2002

Directed therapy

• Treatment usually 6 weeks
• Go to the guidelines…

2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults

Oral Rx for S. aureus vertebral osteo?

• Open-label RCT, pts with vert osteo
• Treatment: 6 wks v. 12 wks
• Most common regimen (47%):
• IV Nafcillin x 2 wk  FQ + Rifampin x 4/10 wk

Bernard et al. Lancet. 2015

6 wk (%) 12 wk (%) (n) 176 175 Cure 160 (91) 159 (91)

Other infectious causes?

• Bacteria
• Tuberculosis
• Brucellosis
• Fungi
• Cocci
• Consider work-up if...
• Epi risk factors
• MRI findings
• Anterior body 1st –

disc sparing

• >2 vertebrae

Follow-up?

• Patient completed 6 wks of Rx
• Presents with continued back pain
• CRP: 4 (2-7 normal)
• MRI:
• Persistent BM edema/disc enhancement

consistent with discitis/osteomyelitis

• Unchanged from prior study (7 weeks ago)

What do you do next?

• Extend antibiotics?
• Surgery consult?
• Re-biopsy?
• Reassurance?

Follow-up?

• Back pain may persist
• MRI often not helpful
• Bone changes remain for many months
• CRP correlates with disease
• Recs:
• No follow-up MRI needed if CRP normal and

no constitutional symptoms

Epidural abscess

• Etiology
• Sequela of vertebral osteo/discitis
• Hematogenous to epidural alone
• Clinical
• Fever + Back Pain +/- Neuro Sx
• Diagnosis: MRI > CT
• Treatment
• Neuro deficit  urgent surgery
• Other  antibiotics (4 wks)

Take home discitis/vertebral osteo

• Hard to diagnose: Back pain +
• Vert tender, recent bacteremia, fever, high CRP
• Micro Dx: CT guided biopsy
• Rx: 6 wks, S aureus: FQ/Rifampin
• Routine follow-up MRI not helpful
• Assuming CRP normal