Van: CNS Infections

Van: CNS Infections Tuesday, October 29, 2024 11:41 PM • • • • Meningitis: Inflammation of subarachnoid space or spinal fluid Ventriculitis: Inflammation of the ependymal lining of cerebral ventricles Encephalitis: Inflammation of the brain tissue itself “Aseptic meningitis”: culture negative inflammatory process ○ Viral pathogen → tx is supportive care Bacterial Etiology • Streptococcus pneumoniae ○ Leading cause of acute community-acquired bacterial meningitis in US • Group B Streptococcus • Neisseria meningitidis • Haemophilus influenzae type b • Listeria monocytogenes Clinical Presentation • Classic s/sx (Classic Triad) ○ Fever ○ Neck stiffness (nuchal rigidity) ○ Altered mental status • Kernig’s sign ○ Slowly attempt to straighten the leg: pain or resistance (+) • Brudzinski’s neck and leg signs ○ Severe neck stiffness causes a patient's hips and knees to flex when the neck is flexed Diagnosis • Lumbar Puncture (LP) ○ Needle placed between 3rd and 4th lumbar vertebrae ○ CSF Gram stain ○ CSF culture: gold standard ○ CSF testing ▪ Procalcitonin, lactate, PCR, latex agglutination • Limitations ○ Up to 50% of patients may receive antimicrobials prior to diagnosis of meningitis ▪ Gram stain and culture negative CSF ▪ CSF protein and glucose abnormalities STILL present Treatment • Goals of Therapy ○ Eradication of infection ○ Amelioration of signs and symptoms ○ Prevention of the development of neurologic sequelae: Seizure, Deafness, Coma, Death • Supportive Care ○ Fluids, electrolytes ○ Antipyretics, analgesics ○ Others: ▪ VTE prophylaxis ▪ Antiepileptic therapy ▪ ICP monitoring ▪ Respiratory and circulatory supports, gastrointestinal care • Approach to Treatment ○ Appropriate antibiotic therapy must be started ASAP (time period of suspected diagnosis to initiation of ABx should not exceed 1 hour) ▪ Should not be withheld ○ Until pathogen identified → empiric therapy necessary ▪ Duration: at least 48-72 hours or until diagnosis of bacterial meningitis ruled out ○ Penetration of ABx agents into CSF Therapeutic levels w/wo inflammation Therapeutic levels in CSF with inflammation of meninges Non-therapeutic levels in CSF with/without inflammation ▪ • • • • • • • • • • • • • Penicillins Aztreonam Carbapenems Cefuroxime • 3-4th generation cephalosporins • Vancomycin • Aminoglycosides • B-lactamase inhibitors • Clavulanic acid • Sulbactam • Tazobactam • 1-2nd generation cephalosporins • EXCEPT: cefuroxime • Doxycycline Empiric Therapy by Age Group Age • Acyclovir FQs Fluconazole Flucytosine Metronidazole Rifampin SMX/TMP Voriconazole Most likely Organisms Empiric Treatment Neonate (< 1 month) S. agalactiae GNB (E. coli) Listeria • Ampicillin + cefotaxime • (ampicillin + ceftazidime: if there is cefotaxime shortage) • Ampicillin + aminoglycoside* • *gentamicin for synergy 1 – 23 months S. pneumoniae S. agalactiae, E. coli H. influenzae N. meningitidis • Cefotaxime + vancomycin • Ceftriaxone + vancomycin 2 – 50 years S. pneumoniae N. meningitidis • Cefotaxime + vancomycin • Ceftriaxone + vancomycin > 50 years S. pneumoniae • Vancomycin + ampicillin + ceftriaxone (or cefotaxime) GNB (E. coli) N. meningitidis, Listeria Additional Populations Population Most likely Organisms Immunocompromised state (due to HIV infection or immunosuppressive therapies, etc.) S. pneumoniae N. meningitidis L. monocytogenes Staphylococcus aureus Salmonella spp. Aerobic Gram-negative (including P. aeruginosa) Empiric Treatment • Vancomycin + ampicillin + cefepime • Vancomycin + meropenem • (meropenem covers Listeria and Pseudomonas) PCN allergy (anaphylaxis) Original Regimen Alternative Regimen Vancomycin + 3rd Ceph Vanco + Moxi Vanco + ampicillin + 3rd Ceph Vanco + Bactrim + Moxi Vanco + ampicillin + cefepime Vanco + Bactrim + aztreonam Vanco + meropenem • Presumptive Pathogen Identified by Gram Positive Stain Microorganism Recommended Tx Alternative Tx S. pneumoniae (gram + cocci) Vanco + 3rd Ceph N. meningitidis (gram – cocci) 3rd Ceph • • • • • L. monocytogenes (gram + bacilli) • Ampicillin • Pen G • TMP/SMX • Meropenem S. agalactiae (gram + cocci) • Ampicillin • Pen G 3rd Ceph H. influenzae (gram – bacilli) 3rd Ceph • • • • Chloramphenicol Cefepime Meropenem FQ E. coli (gram – bacilli) 3rd Ceph • • • • • Cefepime Meropenem Aztreonam FQ TMP/SMX (ceftriaxone or cefotaxime) • Meropenem • FQs • Linezolid or Daptomycin? Pen G Ampicillin Chloramphenicol FQ Aztreonam • Bacterial Meningitis – Dosing ○ Adults ▪ Ceftriaxone 2 g IV Q 12 hrs ▪ Vancomycin 15-20 mg/kg IV Q 8-12 hrs • Target serum trough concentration: 15-20 mg/L • AUC/MIC: 400-600 (mg x hr/L)? ▪ If > 50 years old, alcoholic, or immunocompromised: Listeria suspected → add ampicillin 2 g IV Q 4 hrs • Duration of therapy ○ 7 days: N. meningitidis, H. influenzae ○ 10-14 days: S. pneumoniae ○ 14-21 days: S. agalactiae ○ 21 days: GNB ▪ duration in neonate is 2 weeks beyond first sterile CSF culture or ≥ 3 weeks, whichever is longer ○ 21 days or more: Listeria S. pneumoniae (Pneumococcal) Prophylaxis • Vaccinations Population (without any prior vaccinations) • Adults ≥ 50 • Adults 19-49 y/o w/ chronic health conditions ○ Vaccine • Either: • PCV20 • PCV21 • If PCV15 given, then after ≥ 1 year, give PPSV23 • Adults 19-49 y/o with: • Either: • Specified immunocompromising conditions • PCV20 • Cochlear implant or cerebrospinal fluid leak • PCV21 • If PCV15 given, then after ≥ 8 weeks, give PPSV23 N. Meningitidis (Meningococcal) Prophylaxis • Close contacts → increased risk for infection • Should receive antimicrobial chemoprophylaxis ○ ideally < 24 hours after identification of index patient, regardless of immunization status ○ Recommended chemoprophylaxis for high-risk contacts of persons w/ invasive meningococcal disease ▪ Rifampin (PO) ▪ Ceftriaxone (IM – dilute w/ 1% lidocaine to ↓ pain at injection site) ▪ Ciprofloxacin (not recommended for pregnant women) ▪ Azithromycin (alternative, not recommended routinely) • Meningococcal Vaccination ○ Special populations: MenACWY ○ Immunocompromised patients, microbiologists routinely exposed to Neisseria meningitidis, travel to outbreak region, military recruits, first year college students living in residential housing (if not previously vaccinated at age 16 years or older) H. Influenzae Prophylaxis • Chemoprophylaxis recommended: rifampin Role of Dexamethasone • Adults ○ Only ↓ mortality in meningitis due to S. pneumoniae ○ Suspected or proven pneumococcal meningitis ▪ 0.15 mg/kg (10 mg max) IV q 6 hours for 2-4 days ▪ Administered 10-20 min prior to or with the first antibiotic dose ▪ Prior or concurrent, but NOT to be administered after ABX started ▪ Monitor GI bleed, hyperglycemia, mask fever • Pediatrics ○ Dexamethasone recommended for infants and children 6 weeks of age and older with H. influenzae meningitis ○ Pneumococcal meningitis: Risk vs. Benefit Other Pathogens • Viral Encephalitis ○ Herpes simplex virus (HSV) ▪ DOC: Acyclovir 14-21 days ○ Supportive care important (fluid, antipyretics, analgesics, etc.) ○ Ensure adequate hydration to ↓ risk of acyclovir- and foscarnet-induced nephrotoxicity Healthcare-Associated Ventriculitis and Meningitis • Diagnosis: cultures, CFS, symptoms • Empiric ABx Tx ○ Vancomycin + anti-pseudomonal beta-lactams ▪ Cefepime, ceftazidime, or meropenem (2 G IV Q 8 hrs) ▪ No Pip/Taz (no penetration) ○ In seriously ill adult patients ▪ Vancomycin target trough: 15-20 ug/mL; AUC/MIC 400-600 ○ Penicillin allergy (anaphylaxis) ▪ Vancomycin + aztreonam or vancomycin + ciprofloxacin ○ Highly antimicrobial-resistant pathogens in other sites ▪ Adjusting the empiric regimen to cover them ○ Add rifampin for prosthetic material (CSF shunt or drain) ○ For MRSA Infections ▪ Vancomycin is recommended as first-line therapy • with consideration for alternative antimicrobial agent if the vancomycin MIC is > 1 ug/mL ○ Duration of antimicrobial therapy: 10-14 days ▪ in patients with repeatedly positive CSF cultures, continue for 10-14 days after the last positive culture • Monitoring Parameters ○ In patients with no definitive clinical improvement, additional CSF analysis is recommended to ensure that the CSF parameters have improved, and the cultures become negative