[PDF] - Outline in CNS Infections Infections of the Brain Infections of PDF Document

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2/21/19 1

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

SLIDE 2

2/21/19 2

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: 39C, 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: 39C, 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.

CT -Yes

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2/21/19 3

Decision #2: Antibiotics?

When?
CT: antibiotics up front (blood cx 1st)
No CT: LP and then antibiotics
What?
Depends on which bugs….

18–34 Yr 35–49 Yr 50–64 Yr ≥65 Yr All adult cases Percentage of Total Cases 100 80 90 70 60 40 30 10 50 20

Thigpen MC. NEJM.2011

Streptococcus pneumoniae Neisseria meningitidis GBS Haemophilus influenzae Listeria monocytogenes

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

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2/21/19 4

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

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2/21/19 5

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 helpful?

451 suspected bacterial meningitis
98 had antibiotics in CSF sample
Sensitivity
Culture: 78%
Gram Stain: 99%
RT-PCR: 95%

Wu et al. BMC Infectious Diseases. 2013

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

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2/21/19 6

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

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2/21/19 7

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

SLIDE 8

2/21/19 8

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

SLIDE 9

2/21/19 9 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

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2/21/19 10

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

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2/21/19 11

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

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2/21/19 12

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

No urgent surgery

How to make a micro Dx?

CT guided biopsy

How to make a micro Dx?

CT guided biopsy (50% sens)

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2/21/19 13

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

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2/21/19 14 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 à 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?

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2/21/19 15

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 à urgent surgery
Other à 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