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When should antibiotics (and which ones) When should antibiotics (and which ones) be administered to the patient with altered be administered to the patient with altered
mental status?mental status?
J. Stephen Huff, MDJ. Stephen Huff, MD
Department of Emergency Medicine Department of Emergency Medicine
University of VirginiaUniversity of Virginia
Key Clinical QuestionsKey Clinical Questions
• When should a CNS infection be considered When should a CNS infection be considered in the differential diagnosis?in the differential diagnosis?
• What is optimal timing of imaging, What is optimal timing of imaging, procedures, and therapy?procedures, and therapy?
• What empiric therapy should be given?What empiric therapy should be given?
• What adjunctive therapy should be What adjunctive therapy should be administered?administered?
Case PresentationCase Presentation
• 53-year-old clinical psychologist had flu 53-year-old clinical psychologist had flu symptoms and headache for most of daysymptoms and headache for most of day
• Participated in evening meetingParticipated in evening meeting• Went to bed early not feeling wellWent to bed early not feeling well• Awakened confused; could not recognize Awakened confused; could not recognize
partnerpartner• EMS called; transported to EDEMS called; transported to ED
Past Medical History & Social HistoryPast Medical History & Social History
• No details availableNo details available
• School psychologistSchool psychologist
• No chronic medicationsNo chronic medications
• History of “sinus surgery” years agoHistory of “sinus surgery” years ago
• History supplied by partnerHistory supplied by partner
Physical ExamPhysical Exam
• VS: 38.3, 149/palp, 108, 18, sat 97%VS: 38.3, 149/palp, 108, 18, sat 97%• Somnolent / confusedSomnolent / confused• Few words uttered “Far fellow” (?)Few words uttered “Far fellow” (?)• ““Uncooperative” with examinationUncooperative” with examination• Pulmonary, cardiac, abdomen: NormalPulmonary, cardiac, abdomen: Normal• No cutaneous abnormalitiesNo cutaneous abnormalities• Localized painful stimuli, spontaneous eye opening Localized painful stimuli, spontaneous eye opening
and movementsand movements• Context of the moment….Context of the moment….
Your Differential Diagnosis?Your Differential Diagnosis?
Fever, altered mental status?Fever, altered mental status?
Differential DiagnosisDifferential Diagnosis
• NeurologicNeurologic• MeningitisMeningitis• EncephalitisEncephalitis
• Other infectious etiologiesOther infectious etiologies• SepsisSepsis• PneumoniaPneumonia• Urinary tract infectionUrinary tract infection
• MetabolicMetabolic• EndocrineEndocrine• ToxicologicToxicologic
Practical Differential DiagnosisPractical Differential Diagnosis
• Acute Bacterial MeningitisAcute Bacterial Meningitis• Acute Bacterial MeningitisAcute Bacterial Meningitis• Acute Bacterial MeningitisAcute Bacterial Meningitis• Acute Bacterial MeningitisAcute Bacterial Meningitis• Acute Bacterial MeningitisAcute Bacterial Meningitis• Acute Bacterial MeningitisAcute Bacterial Meningitis• Acute Bacterial MeningitisAcute Bacterial Meningitis• Acute Bacterial MeningitisAcute Bacterial Meningitis• Acute Bacterial MeningitisAcute Bacterial Meningitis
ED CourseED Course
What should be done and in what order?What should be done and in what order?
ED Course-what occurredED Course-what occurred
Verify A,B,C’sVerify A,B,C’s
IV access, labs, blood culturesIV access, labs, blood cultures
Empiric antibiotic therapy-ceftriaxoneEmpiric antibiotic therapy-ceftriaxone
Immediate noncontrast cranial CTImmediate noncontrast cranial CT
ED CourseED Course
Lumbar puncture in presence of partnerLumbar puncture in presence of partner
Lumbar punctureLumbar puncture
• Slightly cloudy fluid to inspectionSlightly cloudy fluid to inspection
• Later…Later…• 16,000 WBC (99% segs)16,000 WBC (99% segs)• Glucose <10 Protein 522Glucose <10 Protein 522• Lactic acid 10.9Lactic acid 10.9• Gram stain - no bacteriaGram stain - no bacteria
Lab ResultsLab Results
• WBC = 18.5WBC = 18.5
• Hct =42Hct =42
• Platelets = 203Platelets = 203
• Chemistry = wnlChemistry = wnl
What is the next step in this What is the next step in this patient’s management?patient’s management?
Case courseCase course
• Patient given ceftriaxone (before CT), Patient given ceftriaxone (before CT), vancomycin, and acyclovirvancomycin, and acyclovir
• ICU admission - ICU admission -
• Blood cultures +4 Blood cultures +4 S. pneumoniaeS. pneumoniae
• Continued ceftriaxone and vancomycinContinued ceftriaxone and vancomycin
• Culture- sensitive to ceftriaxoneCulture- sensitive to ceftriaxone
• Discharged day 7 continue outpatient therapyDischarged day 7 continue outpatient therapy
Case courseCase course
• ENT referralENT referral• Pansinusitis on CTPansinusitis on CT• Endoscope-encephalocele from sinus Endoscope-encephalocele from sinus
surgery (FESS) in pastsurgery (FESS) in past• Elective surgical repairElective surgical repair• Return to work - functionalReturn to work - functional
Farfalla
Butterfly---Italian
Risk FactorsRisk Factors
• Bacterial meningitis may occur in any Bacterial meningitis may occur in any adult adult
• Identified risk factors-Identified risk factors-• Diabetes mellitusDiabetes mellitus• Otitis mediaOtitis media• PneumoniaPneumonia• SinusitisSinusitis• Alcohol abuseAlcohol abuse
Pattern of Presentation-TriadPattern of Presentation-Triad
• Fever, neck stiffness, altered mental statusFever, neck stiffness, altered mental status• Fever-high sensitivity, low specificityFever-high sensitivity, low specificity• Sens 85%; spec 45%Sens 85%; spec 45%
• Neck stiffness 70% pooled sensitivityNeck stiffness 70% pooled sensitivity• Altered mental status-67% pooled sensitivityAltered mental status-67% pooled sensitivity
• Triad is imperfect to detect meningitis by this pooled Triad is imperfect to detect meningitis by this pooled retrospective analysisretrospective analysis
• Attia J, Hatala R, Cook DJ, Wong JG: Does this adult patient have meningitis? JAMA Attia J, Hatala R, Cook DJ, Wong JG: Does this adult patient have meningitis? JAMA 1999; 282:175.1999; 282:175.
Neck StiffnessNeck Stiffness
• Kernig’s sign - knee extension / responseKernig’s sign - knee extension / response• Brudzinski’s sign-neck flexion / responseBrudzinski’s sign-neck flexion / response• Nuchal rigidity “stiff neck” on examNuchal rigidity “stiff neck” on exam
• Prospective study, “…these diagnostic tools are too Prospective study, “…these diagnostic tools are too insensitive to identify the majority of patients with insensitive to identify the majority of patients with meningitis in contemporary practice….”meningitis in contemporary practice….”
• Thomas KE, Hasbun R, Jekel J, Quagliarello VJ: The diagnostic accuracy of Kernig’s sign, Thomas KE, Hasbun R, Jekel J, Quagliarello VJ: The diagnostic accuracy of Kernig’s sign, Brudzinski’s sign, and nuchal rigidity in patients in adults with suspected meningitis. Clin Brudzinski’s sign, and nuchal rigidity in patients in adults with suspected meningitis. Clin In Dis 2002;35:46.In Dis 2002;35:46.
A new sign?A new sign?
• Jolt accentuation of headache…Jolt accentuation of headache…
• Patient turns head horizontallyPatient turns head horizontally• 2-3 rotations / second2-3 rotations / second• Does headache get worse?Does headache get worse?
• One study…One study…• Attia J, Hatala R, Cook DJ, Wong JG: Does this adult patient have meningitis? JAMA Attia J, Hatala R, Cook DJ, Wong JG: Does this adult patient have meningitis? JAMA
1999; 282:175.1999; 282:175.• Uchihara T, Tsukagoshi H. Jolt accentuation of headache: the most sensitive sign of CSF Uchihara T, Tsukagoshi H. Jolt accentuation of headache: the most sensitive sign of CSF
pleocytosis. Headache 1991;31:167.pleocytosis. Headache 1991;31:167.
Anatomy and PathophysiologyAnatomy and Pathophysiology
• Vicious cycle of pathophysiologyVicious cycle of pathophysiology• BacteremiaBacteremia• Meningeal inflammationMeningeal inflammation• Blood-brain barrier breachBlood-brain barrier breach• Inflammatory responses within brain with Inflammatory responses within brain with
neuronal injuryneuronal injury• VasculitisVasculitis
• Cerebral edemaCerebral edema
OrganismsOrganisms
• < 3 months< 3 months
• 3 months - 18 years3 months - 18 years
• 18 years - 50 years18 years - 50 years
• > 50 years> 50 years
• E.coli, Listeria, StreptococciE.coli, Listeria, Streptococci
• N. meningitidis, H. influenzae, S. N. meningitidis, H. influenzae, S. pneumoniaepneumoniae
• N. meningitidis, S. pneumoniaeN. meningitidis, S. pneumoniae
• S. pneumoniae, Listeria, gram-S. pneumoniae, Listeria, gram-negative bacillinegative bacilli
Complications-Complications-S. pneumoniaeS. pneumoniae
• Increased cerebral pressure from edemaIncreased cerebral pressure from edema
• SeizuresSeizures
• Stroke syndromesStroke syndromes
• Intracranial hemorrhageIntracranial hemorrhage
Lab studiesLab studies
• CBC, chemistriesCBC, chemistries
• Coagulation studies?Coagulation studies?
• Blood culturesBlood cultures
• Other cultures as appropriateOther cultures as appropriate
ProceduresProcedures
• Lumbar punctureLumbar puncture• Neutrophilic predominance in bacterial Neutrophilic predominance in bacterial
meningitismeningitis• Low glucose, high proteinLow glucose, high protein
• Alternative diagnoses?Alternative diagnoses?
• Mass lesion?Mass lesion?
• Do not delay therapy in high-suspicion cases Do not delay therapy in high-suspicion cases for imaging….for imaging….
CT before LP?CT before LP?
Emergency Department CareEmergency Department Care
• Prompt recognitionPrompt recognition
• Prompt interventionPrompt intervention• DiagnosticDiagnostic• Therapeutic-do not delay pending diagnostic Therapeutic-do not delay pending diagnostic
interventions in high-suspicion casesinterventions in high-suspicion cases• Antibiotics-multipleAntibiotics-multiple• Anti-inflammatory-steroidsAnti-inflammatory-steroids
AntibioticsAntibiotics
• < 3 months< 3 months
• 3 months - 18 years3 months - 18 years
• 18 years - 50 years18 years - 50 years
• > 50 years> 50 years
• Ampicillin, third-generation Ampicillin, third-generation cephalosporincephalosporin
• Third-generation cephalosporin Third-generation cephalosporin (ceftriaxone) + vancomycin(ceftriaxone) + vancomycin
• Third-generation cephalosporin Third-generation cephalosporin (ceftriaxone) + vancomycin(ceftriaxone) + vancomycin
• Ampicillin, third-generation Ampicillin, third-generation cephalosporin, vancomycincephalosporin, vancomycin
Anti-inflammatory medicationsAnti-inflammatory medications
• Dexamethasone - 10 mg IV at or before (15-20 Dexamethasone - 10 mg IV at or before (15-20 minutes) antibiotics…minutes) antibiotics…
• 10 mg q 6h for 4 days10 mg q 6h for 4 days• Adults…Adults…• Pediatrics?Pediatrics?
De Gans J, van de Beek D, et al: Dexamethasone in adults with bacterial meningitis. De Gans J, van de Beek D, et al: Dexamethasone in adults with bacterial meningitis. NEJM 2002;347:1549.NEJM 2002;347:1549.
ConsultationsConsultations
• Will depend upon institutionWill depend upon institution
• Ill patients - ICU admissionIll patients - ICU admission
• Infectious disease, neurology, or others might Infectious disease, neurology, or others might be helpfulbe helpful
SummarySummary
• Acute bacterial meningitis may be a life or Acute bacterial meningitis may be a life or function-limiting eventfunction-limiting event
• Acute intervention may limit morbidity and Acute intervention may limit morbidity and mortalitymortality
• Antibiotics-broad, multipleAntibiotics-broad, multiple
• Anti-inflammatory agent-dexamethasone Anti-inflammatory agent-dexamethasone recommended at this timerecommended at this time
Key Learning PointsKey Learning Points
• When should a CNS infection be considered When should a CNS infection be considered in the differential diagnosis?in the differential diagnosis?
• What is optimal timing of imaging, What is optimal timing of imaging, procedures, and therapy?procedures, and therapy?
• What empiric therapy should be given?What empiric therapy should be given?
• What adjunctive therapy should be What adjunctive therapy should be administered?administered?
Key Learning PointsKey Learning Points
• When should a CNS infection be considered When should a CNS infection be considered in the differential diagnosis?in the differential diagnosis?
• Altered behavior, altered consciousness, Altered behavior, altered consciousness, fever, or seizures may suggest presence of a fever, or seizures may suggest presence of a CNS infectionCNS infection
Key Learning PointsKey Learning Points
• When should a CNS infection be considered When should a CNS infection be considered in the differential diagnosis?in the differential diagnosis?
• What is optimal timing of imaging, What is optimal timing of imaging, procedures, and therapy?procedures, and therapy?
• What empiric therapy should be given?What empiric therapy should be given?
• What adjunctive therapy should be What adjunctive therapy should be administered?administered?
Key Learning PointsKey Learning Points
• What is optimal timing of imaging, What is optimal timing of imaging, procedures, and therapy?procedures, and therapy?
• Do not delay therapy-antibiotics-for imaging Do not delay therapy-antibiotics-for imaging or procedures in patients with high or procedures in patients with high probability of bacterial meningitisprobability of bacterial meningitis
Key Learning PointsKey Learning Points
• When should a CNS infection be considered When should a CNS infection be considered in the differential diagnosis?in the differential diagnosis?
• What is optimal timing of imaging, What is optimal timing of imaging, procedures, and therapy?procedures, and therapy?
• What empiric therapy should be given?What empiric therapy should be given?
• What adjunctive therapy should be What adjunctive therapy should be administered?administered?
Key Learning PointsKey Learning Points
• What empiric therapy should be given?What empiric therapy should be given?
• Empiric therapy should include antibiotics Empiric therapy should include antibiotics for likely organisms based on age….in adults, for likely organisms based on age….in adults, third generation cephalosporin and third generation cephalosporin and vancomycin should constitute initial therapyvancomycin should constitute initial therapy
Key Learning PointsKey Learning Points
• When should a CNS infection be considered When should a CNS infection be considered in the differential diagnosis?in the differential diagnosis?
• What is optimal timing of imaging, What is optimal timing of imaging, procedures, and therapy?procedures, and therapy?
• What empiric therapy should be given?What empiric therapy should be given?
• What adjunctive therapy should be What adjunctive therapy should be administered?administered?
Key Learning PointsKey Learning Points
• What adjunctive therapy should be What adjunctive therapy should be administered?administered?
• Return of steroids….Return of steroids….
