Infections Brian S. Schwartz, MD UCSF, Division of Infectious - PDF document

2/17/16 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 1

2/17/16 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)? 2

2/17/16 Decision #1: CT before LP? s e Yes if … Y - T C • 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 … . 3

2/17/16 How quickly does the CSF sterilize after antibiotic administration? 100 ¡ 80 ¡ % ¡of ¡CSF ¡sterilized ¡ 60 ¡ 40 ¡ N. ¡meningi)dis ¡ 20 ¡ S. ¡pneumoniae ¡ 0 ¡ 0-­‑2 ¡ 2.1-­‑4 ¡ 4.1-­‑6 ¡ 6.1-­‑24 ¡ 24.1-­‑48 ¡ >48 ¡ Time ¡a3er ¡start ¡of ¡an5bio5cs ¡(hours) ¡ 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 o Culture: 78% o Gram Stain: 99% o RT-PCR: 95% Wu et al. BMC Infectious Diseases. 2013 4

2/17/16 Listeria monocytogenes GBS Haemophilus influenzae Neisseria meningitidis Streptococcus pneumoniae 100 90 Percentage of Total Cases 80 70 60 50 40 30 20 10 0 18–34 35–49 50–64 ≥ 65 All adult Yr Yr Yr Yr cases Thigpen MC. NEJM.2011 Empiric therapy Risk factor Pathogens Antimicrobials 2-50 yr N. meningitidis, Vancomycin + S. pneumoniae Ceftriaxone > 50 yr S. pneumoniae, Vancomycin+ N. meningitidis, Ceftriaxone + L. monocytogenes Ampicillin Adapted from Tunkel AR. CID 2004 5

2/17/16 Why add vanco? 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 ¡ini5a5on ¡of ¡therapy ¡ Friedland ET. AAC. 1993 Decision #3: Steroids? 6

2/17/16 Steroids for bacterial meningitis • When? o Before first dose of antibiotics o Not for patients who already received 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 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 de Gans J. NEJM 2002 7

2/17/16 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: o WBC: 450 (90% PMNs) o Glucose: 50 (Serum:170);CSF/serum=0.3 o Protein: 120 o Gram stain: Gram positive diplococci o Culture: negative • Blood cultures: no growth 8

2/17/16 Definitive antimicrobial therapy ¡ Pathogen ¡ Primary ¡ Duration of Rx ¡ S. pneumoniae ¡ Pen MIC ≤ 0.1 µ g/ml ¡ Penicillin ¡ 10-14 days ¡ Pen MIC 0.1-1.0 µ g/ml ¡ Ceftriaxone ¡ ¡ Vanco + Ceftriaxone ¡ Pen MIC >0.1-1.0 µ g/ml N. meningitidis ¡ Pen MIC ≤ 0.1 µ g/ml ¡ 7 days ¡ Penicillin G ¡ Pen MIC 0.1-1.0 µ g/ml ¡ Ceftriaxone ¡ L. monocytogenes ¡ Ampicillin ¡ ≥ 21 days ¡ ¡ Adapted from Tunkel AR. CID 2004 IDSA algorithm for management of bacterial meningitis Indication for head CT NO YES Blood cx Blood cx + Lumbar puncture Steroids and empiric Steroids and empiric antimicrobials antimicrobials Head CT w/o mass lesion CSF suggestive of bacterial or herniation meningitis Refine Lumbar puncture therapy Tunkel AR. CID 2004 9

2/17/16 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 https://en.wikipedia.org/wiki/Urticaria 10

2/17/16 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 11

2/17/16 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 http://www.cdc.gov/MMWR/preview/mmwrhtml/00046263.htm Preventing spread of of N meningitidis (inpatient) • Droplet precautions • DCed after 24h ceftriaxone http://www.cdc.gov/MMWR/preview/mmwrhtml/00046263.htm 12

2/17/16 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 PLUS o 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 created by Jen Babik 13

2/17/16 CSF findings WBCs PMNs 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 DDx Aseptic Meningitis/Lymphocytic Pleocytosis • Bacterial • Fungal o Bacterial meningitis (10%) o Crypto o Partially treated bacterial meningitis o Endemic fungi (e.g., cocci) o Listeria (<25%) • Parasites o Mycobacteria o Toxoplasma gondii o Spirochetes: Syphilis, Lyme, Lepto o Helminths (eg neurocystercircosis) o Other: Brucella, RMSF, Q fever o Amoeba (eg Balamuthia) o Para-meningeal focus of infection (brain/epidural abscess) • Non-infectious • Viral o Medications (e.g., NSAIDs, Abx) o Arboviruses (West Nile Virus) o Rheumatologic Disease (e.g., o Enteroviruses SLE, sarcoid) o Herpesviruses (HSV, VZV, CMV, EBV) o Carcinomatous meningitis o Acute HIV o Others (LCMV, Measles, Mumps) 14

2/17/16 DDx Aseptic Meningitis: Most Common Infections Diagnostics : • Bacterial o Serum o Syphilis • RPR o Lyme • HIV Ab and VL • West Nile IgM/IgG • Viral • Lyme Ab (if risk factors) o Enteroviruses o CSF o HSV, VZV • VDRL o Acute HIV • Enterovirus PCR o West Nile virus • HSV/VZV PCR • West Nile IgM/IgG Case created 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 15

2/17/16 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: o WBC: 190 (85% lymphs), TP: 420, Gluc 39 CSF findings WBCs PMNs 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 meningitis 100-500 <50 < 0.4 > 200 16

2/17/16 Chronic meningitis • Definition: >4 weeks of symptoms • LP: Lymphs, low glucose, high protein • History important! • DDx: TB, crypto, cocci, histo, etc. • Work up: o 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 17

2/17/16 Take home points: meningitis • CT scan before LP in patients w/: o 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 18