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Challenges in Managing Post-Neurosurgical Meningitis & Ventriculitis and CSF Shunt Infections

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Challenges in Managing Post-Neurosurgical Meningitis & Ventriculitis and CSF Shunt Infections Challenges in managing post-neurosurgical meningitis & ventriculitis and CSF shunt infections Adarsh Bhimraj Section of Neurologic Infectious Diseases Cleveland Clinic Foundation, Cleveland, Ohio, US ECCMID 2018 Update on CNS infections ESCMIDApril 24 th 2018eLibrary 13;30-15;30 © by author Conflict of interests • No financial COI”s ESCMID eLibrary © by author ESCMID eLibrary © by author Burden of Healthcare associated meningitis & ventriculitis • 493 episodes of acute bacterial meningitis, of which 197 (40 percent) were postneurosurgical. Durand et al. N Engl J Med 1993; 328:21-28 • 157 patients with acute bacterial meningits 68.2% (107/157) postneurosurgical meningitis Incidence in 2008 was 49% and 2000 was 25% - Lien CY et al. J Clin Neurosci. 2017 Aug;42:59-65 • Decreasing incidence of CABM pathogens, but no significant decrease in post-neurosurgical meningitis pathogens - Castelblanco R.L. et al. Lancet Infect Dis 2014; 14: pp. 813-819 Epidemiology of bacterial meningitis in the USA from 1997 to 2010: a population-based observational study ESCMID eLibrary © by author A Tale of Two Patients Senora Acabm and Senor Haivam ESCMID eLibrary © by author Senora Acabm’s story… 42 Year-old woman with no prior medical problems presents in December with fever, chills, headache, and lethargy that developed over two days. Vital signs: Temp 101° F/ 38.3 C, P 110, RR 24, BP 80/50 mmHg On exam patient is obtunded and has neck stiffness CSF analysis: WBC 2000 cells/µl (200 x 10 6) 90% neutrophils Glucose 10 mg/dl (0.56 mmol/L) Protein 400 mg/dL (6000 mg/L) CSF gram stain: Many Gram-positive diplococci ESCMID eLibrary © by author Does senora ACABM have… …Acute community acquired bacterial meningitis? Does she have inflammation in the meninges? Yes… Menigeal symptoms, signs and CSF with an elevated WBC count and low glucose Is the cause an infectious organism? Yes…The CSF gram stain had Gram positive diplococci Cultures eventually grew Streptococcus pneumoniae ESCMID eLibrary © by author Usual pathogens for CABM S. pneumonia, N. meningitidis, H. influenza, Listeria & other Strep species • Virulent pathogens • Evoke a profuse inflammatory response • Not usually contaminants in the CSF ESCMID eLibrary © by author Compare and contrast that to Senor HAIVM’s story ESCMID eLibrary © by author Senor HAIVM’s story… 54 YO male S/p craniotomy & right hemispherectomy • External Ventricular Drain x 4 days • Temp 101° F/ 38.3 C but no leukocytosis • CSF parameters are as follows: CSF SI RBC, CSF (µL) 14400 1440 x 106 /L WBC, CSF (µL) 123 12.3 x 106 /L Neut%, CSF 90 Protein, CSF mg/dl 545 5450/L Glucose, CSF mg/dl 21 1.17 mmol/L CSF culture No growth ESCMID eLibrary © by author Deos Senor HAIVM have… …Healthcare associated infectious ventriculitis or meningitis? Does he have Inflammation in meninges or cerebral ventricles? Yes… CSF with an elevated WBC count and low glucose Is the cause an infectious organism? Not sure… as there are other causes for elevated CSF inflammatory markers ESCMID eLibrary © by author “Other” or non infectious causes of CSF inflammation in the neurosurgical patient –”Chemical meningitis” • Subarachnoid, intraparenchymal or intraventricular bleeds cause fever, meningeal signs and CSF pleocytosis/ leukocytosis • Craniotomies, especially posterior fossa surgeries cause CSF pleocytosis & low CSF glucose ESCMID eLibrary © by author CSF profiles after neurosurgery “Chemical” meningitis – from the neurosurgery itself. Can also be caused by hemorrhage & rarely tumors CSF WBC count CSF glucose CSF protein ForgacsESCMIDP, Geyer CA, Freidberg SR. Characterization of chemical meningitiseLibrary after neurological surgery. Clin Infect Dis 2001; 32:179 -85. © by author How do we differentiate chemical meningo-ventriculitis from infectious meningo-ventriculitis? Cut-off Chemical Infectious meningoventriculitis meningoventriculitis CSF parameter (WBC, lactate, procalcitonin) ESCMID eLibrary © by author Diagnostic accuracy for CSF parameters in EVD ventriculitis-ROC curves Routine CSF studies can’t easily differentiate chemical from infectious ventriculitis ROC curves a good diagnostic test ROC curves 0f a bad diagnostic test ESCMID eLibrary © by author Can a CSF cell Index predict HAIVAM? ESCMID eLibrary © by author Rising CSF WBC: RBC ratio is predictive of an “infectious ventriculitis” ESCMID eLibrary © by author Back to Senor HAIVM: Does he have an “infectious” ventriculitis ? 54 YO male S/p right hemispherectomy, with an EVD. CSF parameters: Post-OP day Day 1 Day 2 Day 3 Day 4 RBC, CSF 14400 4450 6600 510 WBC, CSF 123 110 98 10 Neut%, CSF 90 88 90 92 Protein, CSF 545 1584 1826 858 Glucose, CSF 21 62 56 68 CSF culture No growth No growth No growth No growth ESCMID eLibrary © by author Other diagnostic tests: Healthcare associated ventriculitis and meningitis Serum CSF Procalcitonin Procalcitonin CRP Lactate • Elevated in ventriculomenigitis, but also in other neurologic conditions and other infections • Studies are supportive, but are small and need further validation • Elevated CSF lactate or CSF procalcitonin or serum procalcitonin may be useful in diagnosis ESCMID eLibrary © by author CSF cultures in HAIVM ESCMID eLibrary © by author Etiologic agents Skin colonizers and organisms in the healthcare environment Organism % in Literature Staphylococci (Staph epi & Staph aureus) 65–85 Gram-negative bacteria 6–20 Corynebacteria (mostly Cutibacterium acnes) 1–14 ESCMID eLibrary © by author Pathogenesis of health care associated meningitis & ventriculitis Image modified ESCMIDfrom Van De Beek et al. N Engl J Med 2010; 362:146-154 eLibrary © by author False negative & False positive CSF cultures • Some are indolent pathogens ( can take 10 days and may need anaerobic cx)-False negative if only aerobic cx are done & held for 2-3 days • Skin commensals and can be contaminants in the CSF, so can be “false positive” if improperly collected ESCMID eLibrary © by author Cultures and PCR’s identify an organism, but it is up to the clinician to determine if they are pathogens in the specific instance ESCMID eLibrary © by author Challenges in diagnosis of “Infectious” ventriculitis or meningitis Establishing causality is not easy (unlike community acquired bacterial meningitis) Non-Infectious mimics • Neurosurgery • Neuro comorbidities (SAH) Low virulence pathogens (Minimal inflammation) • Staph epidermidis • P acnes Difficult to detect in the lab CSF aerobic and anaerobic cultures for 10 days (Slow growing) Or CSF PCR • Staph epidermidis ESCMID eLibrary• P acnes © by author A practical approach to diagnosis of Healthcare associated meningitis or ventriculitis Contamination: • An isolated positive CSF culture or Gram stain for non-virulent organisms (espl.if just in enrichment broth) • Normal CSF cell count, glucose, lactate & protein concentrations Exceptions to contamination-virulent organisms: Isolated CSF culture for S. aures, Aerobic GNB’s & fungi ( clinical judgment needed, but often treated) Infectious meningitis or ventriculitis: • Single culture for a virulent organism or multiple positive CSF cultures • With CSF pleocytosis and/or hypoglycorrhachia, • Or a progressively increasing CSF cell count/CSF cell index, or decreasing CSF glucose even with negative CSF cultures ESCMID eLibrary © by author CSF Drain ventriculitis & Craniotomy related ventriculo-meningits Treatment ESCMID eLibrary © by author “Evidence” in Healthcare-associated meningitis and ventriculits? ESCMID eLibrary © by author ESCMID eLibrary © by author 24 YO man with a craniopharyngioma s/p total resection • with severe headache, lethargy, fever and blurred vision • CT brain shows larger ventricles s/p emergent EVD placement • CSF parameters: SI units RBC, CSF (µL) 200 WBC, CSF (µL) 20,076 2007 x 106 /L Neut%, CSF 90 Protein, CSF 1386 mg/dl 13860 mg/L Glucose, CSF <2 mg/dl <0.11 mmol/L CSF gram stain Many gram negative bacilli CSF cultures In process ESCMIDWhat antimicrobial would eLibrary you tell the Neuro ICU to start? © by author How to chose an antimicrobials for meningitis (type, dose & route) • Not just “good CSF penetration” (% of the serum concentration that gets in to CSF) • Achieve target pharmacodynamics in CSF: • Time above MIC for betalactams • C max or AUC above MIC for most other antimicrobials ESCMID eLibrary © by author Vancomycin level in the CSF & serum with IV vancomycin (7 studies, 12 data points) Is this “good CSF penetration”? 15mg/kg load+60 Depends on the mg/kg/day organism and MIC! Open circles: clinical studies that used dexamethasone Open square,: experimental studies with dexamethasone Solid circles: clinical studies in which treatment did not include use of dexamethasone ESCMIDRicard et al. CID 2007:44 eLibrarySolid squares: experimental studies without dexamethasone © by author Goal of treatment: Optimizing CSF pharmacokineticspharmacokinetics & pharmacodynamics Cmax (Peak) Does not reach target AUC: MIC S. aureus vancomycin MIC >1 AUC Acheives target AUC: MIC Concentration MIC S. aureus vancomycin MIC 0.5 Time (hours) ESCMID eLibrary © by author Probability of target (AUC:MIC) attainment in the CSF Vs MIC PK/PD monto carloESCMIDsimulation courtesy Andras Farkas, Pharm D, Mt. Sinai NY eLibraryLi X et al J Pharm Sci 2016 Nov;105(11):3425 - 3431, Ricard et al. CID 2007:44 © by author Intravenous antimicrobials for healthcare acquired ventriculo-meningitis Gram-positive bacteria (Staph epi, Staph aureus, & P acnes) • Vancomycin – goal troughs 15-20 • Linezolid 600 mg IV/PO q 12 hrs • Oxacillin 2 g IV q 4 hrs /Nafcillin /Flucloxacillin for MSSA or
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