Pick a partner Management of CNS Infections Turn to the person - - PDF document

▶
pick a partner
SMART_READER_LITE
LIVE PREVIEW

Pick a partner Management of CNS Infections Turn to the person - - PDF document

Nov 16, 2022 210 likes •376 views

2/7/2017 Update in Diagnosis and Pick a partner Management of CNS Infections Turn to the person next to you Brian S. Schwartz, MD UCSF, Division of Infectious Diseases Say, Hi, my name is your name here . Spend 3 minutes

slide-1
SLIDE 1

2/7/2017 1

Update in Diagnosis and Management of CNS Infections

Brian S. Schwartz, MD UCSF, Division of Infectious Diseases

Pick a partner

  • Turn to the person next to you
  • Say, “Hi, my name is your name here.”
  • 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

DISCUSS

  • 1. CT scan yes/no?
  • 2. LP when?
  • 3. Empiric antibiotics (when, what)?
  • 4. Steroids (yes/no, when)?
  • 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
slide-2
SLIDE 2

2/7/2017 2

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….

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).

Could molecular diagnostics be helpful in those cases?

  • 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

slide-3
SLIDE 3

2/7/2017 3

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

Why add vanco?

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

Friedland ET. AAC. 1993

Answer: Pen resistant S pneumo

Decision #3: Steroids?

slide-4
SLIDE 4

2/7/2017 4

Steroids for bacterial meningitis

  • When?
  • Before first dose of antibiotics
  • Not for patients who already received

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

What do you do next and in what order?

1. Blood cultures

2. Vanco + Ceftriaxone + Amp + Steroids

3. CT scan 4. LP

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
  • Gram stain: Gram positive diplococci
  • Culture: negative
  • Blood cultures: no growth
slide-5
SLIDE 5

2/7/2017 5 Definitive antimicrobial therapy

Pathogen Primary Duration of Rx

  • 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 management 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

  • r 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

https://en.wikipedia.org/wiki/Urticaria

slide-6
SLIDE 6

2/7/2017 6

If it is IgE mediated…

Empiric:

Vancomycin + (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

If it is IgE mediated…

Empiric:

Vancomycin + (Aztreonam or Meropenem)

Directed:

Pathogen Alternative treatment

  • S. pneumoniae

Vancomycin, 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

http://www.cdc.gov/MMWR/preview/mmwrhtml/00046263.htm

Preventing spread of

  • f N meningitidis (inpatient)
  • Droplet precautions
  • DCed after 24h ceftriaxone

http://www.cdc.gov/MMWR/preview/mmwrhtml/00046263.htm

slide-7
SLIDE 7

2/7/2017 7

Patient with meningitis, 7 days post meningioma resection

  • Bugs?
  • MRSA
  • Resistant Gram negative rods
  • Empiric regimen?
  • Vancomycin

PLUS

  • 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 created 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: 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 created by Jen Babik

slide-8
SLIDE 8

2/7/2017 8

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 male 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% lymphs), 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)
slide-9
SLIDE 9

2/7/2017 9

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/:
  • Seizure, altered MS, neuro deficits, IS, papilledema
  • 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

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

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

erythema/TTP

Back: TTP L2-L3 Neuro: normal

http://www.medpagetoday.com/Nephrology/ESRD/52319

slide-10
SLIDE 10

2/7/2017 10

  • 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

  • f back/neck pain?
  • 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
slide-11
SLIDE 11

2/7/2017 11

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 microbiologic diagnosis?

  • CT guided biopsy
slide-12
SLIDE 12

2/7/2017 12

How to make a microbiologic diagnosis?

  • CT guided biopsy (50% sens)

How to make a micro diagnosis?

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

How to make a micro diagnosis?

  • 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

slide-13
SLIDE 13

2/7/2017 13

Empiric therapy: common pathogens?

S aureus 48%

GNR 23%

Strep 9%

Polymicrobial 8% S epi 7% Other 5%

McHenry et al CID 2002

Ceftriaxone Vanco Vanco Vanco

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 (Berbari E Clinical Infectious Diseases 2015

  • r IDSA website)

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
slide-14
SLIDE 14

2/7/2017 14

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)
slide-15
SLIDE 15

2/7/2017 15

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