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

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 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. • 65 y/o male presents to ED by • Exam: 39 ° C, 110, 110/50, 20, 99% RA ambulance after a seizure. He had o Oriented to person only progressive lethargy, fever, and stiff o Unable to touch chin to chest o No focal neurological abnormalities neck x 48 hrs DISCUSS • Exam: 39 ° C, 110, 110/50, 20, 99% 1. CT scan yes/no? RA 2. LP when? o Oriented to person only 3. Empiric antibiotics (when, what)? o Unable to touch chin to chest 4. Steroids (yes/no, when)? o No focal neurological abnormalities 1

2/7/2017 Decision #2: Antibiotics? Decision #1: CT before LP? • When? Yes if… • New-onset seizure o CT: antibiotics up front (blood cx 1st) • Immunocompromised o No CT: LP and then antibiotics • Focal neurological finding • What? • Papilledema o Depends on which bugs…. • Mod-severe impaired consciousness Hasbun R. NEJM. 2001. Gopal AK. Arch Int Med. 1999. Could molecular diagnostics How quickly does the CSF sterilize after antibiotic administration? be helpful in those cases? 100 • 451 suspected bacterial meningitis 80 % of CSF sterilized • 98 had antibiotics in CSF sample 60 • Sensitivity 40 N. meningitidis o Culture: 78% 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) Wu et al. BMC Infectious Diseases. 2013 Kanegye JT. Pediatrics. 2001. 108 (5). 2

2/7/2017 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 Thigpen MC. NEJM.2011 Why add vanco? Decision #3: Steroids? Answer: 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 Friedland ET. AAC. 1993 3

2/7/2017 Steroids for bacterial Dexamethasone for Bacterial Meningitis meningitis • Double-blinded RCT in adults from the Netherlands • When? • Dexamethasone 10 mg q6h vs. placebo x 4d o Before first dose of antibiotics • 1° outcome: Death or neurological disability o Not for patients who already received antibiotics Dex Placebo RR of poor outcome • How much? 15% 25% 0.59 (0.37-0.94), p=0.03 All o Dexamethasone 10mg q6h x 4 days 26% 52% 0.50 (0.30-0.83), p=0.006 S. pneumoniae • For which bugs? 8% 11% 0.75 (0.21-2.63), p=0.74 N. meningitidis o S pneumoniae de Gans J. NEJM 2002 Tunkel et al, CID 2004:39. Case continued What do you do next and in what order? • Rx: Ceftriaxone, Vanco, Amp, Decadron • CT was normal 1. Blood cultures • LP: 2. Vanco + Ceftriaxone + Amp + o WBC: 450 (90% PMNs) Steroids o Glucose: 50 (Serum:170);CSF/serum=0.3 3. CT scan o Protein: 120 o Gram stain: Gram positive diplococci 4. LP o Culture: negative • Blood cultures: no growth 4

2/7/2017 IDSA algorithm for management of Definitive antimicrobial therapy bacterial meningitis Pathogen Primary Duration of Rx Indication for head CT S. pneumoniae NO YES Pen MIC ≤ 0.1 µg/ml Penicillin 10-14 days Blood cx Blood cx + Lumbar Pen MIC 0.1-1.0 µg/ml Ceftriaxone puncture Pen MIC >0.1-1.0 µg/ml Vanco + Ceftriaxone Steroids and empiric Steroids and empiric antimicrobials N. meningitidis antimicrobials 7 days Pen MIC ≤ 0.1 µg/ml Penicillin G Head CT w/o mass lesion CSF suggestive of bacterial Pen MIC 0.1-1.0 µg/ml Ceftriaxone or herniation meningitis Ampicillin ≥ 21 days L. monocytogenes Refine Lumbar puncture Adapted from Tunkel AR. CID 2004 therapy Tunkel AR. CID 2004 Empiric therapy for penicillin Tricky scenarios… allergic? • What type of reaction? o Non-IgE mediated: Cephalosporin OK o IgE-mediated (hives, anaphylaxis) • Alternate Rx, consider desensitization https://en.wikipedia.org/wiki/Urticaria 5

2/7/2017 If it is IgE mediated… If it is IgE mediated… Empiric: Empiric: Vancomycin + (Aztreonam or Meropenem) Vancomycin + (Aztreonam or Meropenem) Directed: Directed: Pathogen Alternative treatment Pathogen Alternative treatment Meropenem or fluoroquinolone Vancomycin, fluoroquinolone S. pneumoniae S. pneumoniae Aztreonam, fluoroquinolone Aztreonam, fluoroquinolone N. meningitidis N. meningitidis TMP-SMX, meropenem TMP-SMX, meropenem L. monocytogenes L. monocytogenes Adapted from Tunkel AR. CID 2004 Adapted from Tunkel AR. CID 2004 Preventing spread of N meningitidis – prophylaxis? of N meningitidis (inpatient) • Who needs prophylaxis? • Droplet precautions o Household members • DCed after 24h ceftriaxone 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 http://www.cdc.gov/MMWR/preview/mmwrhtml/00046263.htm http://www.cdc.gov/MMWR/preview/mmwrhtml/00046263.htm 6

2/7/2017 Fever and HA x 5 days; Patient with meningitis, 7 days post Lymphs in CSF? meningioma resection • 31 y/o M c/o 5 days of severe HA • Bugs? o Sore throat, malaise, fever, chills o MRSA • PMH: none; Meds: Acetaminophen o Resistant Gram negative rods • SH: Sacramento, 1 female partner • Empiric regimen? o Vancomycin • Exam: T-38.6, pain w/ neck flexion PLUS • LP: WBC 228 (96% L),Gluc 63, Protein 76 o Cefepime or Meropenem Case created by Jen Babik DDx Aseptic Meningitis: Most CSF findings Common Infections PMNs WBCs Glucose Protein Diagnostics : % • Bacterial (CSF/serum) (mg/dL) o Serum o Syphilis Bacterial 500- >85 < 0.4 < 200 • RPR o Lyme meningitis 10K • HIV Ab and VL Aseptic • West Nile IgM/IgG 10-500 <50 WNL <100 • Viral meningitis • Lyme Ab (if risk factors) o Enteroviruses Encephalitis 0-1000 <50 WNL < 100 o CSF o HSV, VZV Chronic • VDRL 100-500 <50 < 0.4 > 200 o Acute HIV meningitis • Enterovirus PCR o West Nile virus • HSV/VZV PCR • West Nile IgM/IgG Case created by Jen Babik 7

2/7/2017 Back to the Case… Progressive headache x 3 weeks • 56 y/o male c/o 3 wks of progressive • CSF HSV, VZV PCR negative HA, fatigue, low grade fevers, confusion • RPR negative • PMH: Diabetes, HTN • HIV Ab negative • SH: Phoenix, AZ; construction worker • HIV VL 120,000 • Exam: T-38.1, pain w/ neck flexion • Diagnosis: Acute HIV Infection • LP: o WBC: 190 (85% lymphs), TP: 420, Gluc 39 Case created by Jen Babik CSF findings Chronic meningitis PMNs WBCs Glucose Protein • Definition: >4 weeks of symptoms % (CSF/serum) (mg/dL) • LP: Lymphs, low glucose, high protein Bacterial 500- >85 < 0.4 < 200 meningitis 10K • History important! Aseptic 10-500 <50 WNL <100 meningitis • DDx: TB, crypto, cocci, histo, etc. Encephalitis 0-1000 <50 WNL < 100 • Work up: Chronic 100-500 <50 < 0.4 > 200 meningitis o LP, CrAg, AFB/fungal Cx, Cocci IgM, HIV • Empiric Rx: RIPE + steroids (+/- fluc) 8

2/7/2017 Take home points: meningitis Case continued • CT scan before LP in patients w/: • Serum and CSF Coccidiodes immitis o Seizure, altered MS, neuro deficits, IS, papilledema titers; 1:256 and 1:8 • Give Abx immediately if going to CT • 2 months ago had pneumonia while working at a new construction site with • Add Ampicillin if >50 yr or IS for Listeria lots of dust • Steroids before Abx, only S pneumo • Started on fluconazole • 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 37.5, 89, 154/66, 16 • Meds: Skin: L forearm AVF, no erythema/TTP o Metoprolol o Nephrovite • SH: o Teacher Back: TTP L2-L3 o no IVDU Neuro: normal http://www.medpagetoday.com/Nephrology/ESRD/52319 9

2/7/2017 Vertebral osetomyelitis/discitis • 63 year-old male with ESRD on HD has is hard to diagnose? 3 weeks of progressive back pain, tender to palpation over L2-3 • Median time to Dx: 48 days • Fever only present in 13% • Spend 2 minutes discussing next steps: o Radiographic testing? o Laboratory testing? Nolla JM. Arthritis and Rheumatisim. 2002 Clues to infectious etiology Next steps? of back/neck pain? • History • Radiographic testing? o Constitutional symptoms o Spine films? Dx compression fracture o Recent S aureus infection o MRI? sensitive for osteo/discitis • Exam • Laboratory testing? o TTP over vertebrae o CRP? Sensitive for osteo/discitis o Fever (low sensitivity) • Labs o Elevated CRP/ESR 10

2/7/2017 Next decisions (2 min) • Urgent surgical therapy? • How to make micro Dx? • Empiric antibiotic regimen? Is surgical therapy How to make a indicated? microbiologic diagnosis? • Immediate indication • CT guided biopsy o Progressive neurologic deficits • Other o Progressive deformity and/or instability o Persistent/recurrent infection o Worsening pain despite appropriate Rx 11