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MAJOR CHANGES IN EPIDEMIOLOGY OF MENINGITIS SINCE THE 1990’S
mainly due to the introduction of Hib vaccine
Dramatic drop in the number of Dramatic drop in the number of H.influenzae H.influenzae meningitis casesmeningitis cases
Dramatic drop in the overall number of meningitis casesDramatic drop in the overall number of meningitis cases
Shift in age of distribution of bacterial meningitis Shift in age of distribution of bacterial meningitis (median age was 15 months in 1986, but 25 yrs in 1995)(median age was 15 months in 1986, but 25 yrs in 1995)
Before the 1990’s: Before the 1990’s: H. infl> S. pneumoniae> N. meningitidisH. infl> S. pneumoniae> N. meningitidis
Since the 1990’s: Since the 1990’s: S. pneumoniae> N. meningitidis>>>H. infl.S. pneumoniae> N. meningitidis>>>H. infl.
NEJM 1997;337:970-6NEJM 1997;337:970-6
Etiology Of Bacterial Meningitis In The USEtiology Of Bacterial Meningitis In The US
Percentage of Total CasesPercentage of Total Cases
OrganismOrganism ((1978-811978-81) () (19851985) () (19951995))H. InflunezaeH. Influnezae 48 48 45 7 45 7N. meningitidisN. meningitidis 20 14 25 20 14 25S. pneumoniae S. pneumoniae 13 13 18 47 18 47Strep. agalactiaeStrep. agalactiae 3 6 12 3 6 12Listeria m. 2 3 8Listeria m. 2 3 8Other 8 14 -Other 8 14 -Unknown 6 -Unknown 6 - --JAMA.1985;253:1749-1754JAMA.1985;253:1749-1754JID.1990;162:1316-1323JID.1990;162:1316-1323NEJM.1997;337:970-976NEJM.1997;337:970-976
INCIDENCEINCIDENCE OF BACTERIAL OF BACTERIAL MENINGITIS IN THE USA MENINGITIS IN THE USA
Per 100,000 populationPer 100,000 population %% S. pneumoniaeS. pneumoniae 1.1 1.1 47 47 N. meningitidisN. meningitidis 0.6 250.6 25 Group B Strep.Group B Strep. 0.3 120.3 12 L. monocytogenes 0.2 8L. monocytogenes 0.2 8 H. influenzae H. influenzae 0.20.2 7 7
NEJM 1997;337:970-6NEJM 1997;337:970-6
CHANGES IN EPIDEMIOLOGY CHANGES IN EPIDEMIOLOGY (cont’d)
Increase in cases of MDR- Increase in cases of MDR- S. pneumoniaeS. pneumoniae.. [Resulted in changes in empiric Rx][Resulted in changes in empiric Rx]
Clusters of cases of meningococcal meningitis in adolescents Clusters of cases of meningococcal meningitis in adolescents & young adults.& young adults. [Resulted in change in recommendation for meningococcal vaccination][Resulted in change in recommendation for meningococcal vaccination]
Cochlear implants and higher risk for bacterial meningitisCochlear implants and higher risk for bacterial meningitis.. [Change in recommendation for Pneumococcal +/- Hib?][Change in recommendation for Pneumococcal +/- Hib?]
Decrease in pneumococcal invasive disease including Decrease in pneumococcal invasive disease including meningitis after widespread use of of pediatric meningitis after widespread use of of pediatric pneumococcal vaccinepneumococcal vaccine..
<1 month Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, Klebsiella species
1 - 23 mos Streptococcus pneumoniae, Neisseria meningitidis, S. agalactiae, Haemophilus influenzae, E. coli
2 - 50 yrs N . meningitidis, S. pneumoniae
>50 yrs S.pneumoniae, N. meningitidis, L. monocytogenes, aerobic gram-negative bacilli
ETIOLOGY OF BACTERIAL MENINGITIS
BY AGE
ETIOLOGY OF BACTERIAL MENINGITIS
BY PREDISPOSING CONDITIONBY PREDISPOSING CONDITION
Immunocompromised state: S. pneumoniae, N. meningitidis, Listeria, aerobic GNR (including Ps.aeruginosa)
Basilar skull fracture: S. pneumoniae, H. influenzae, beta-hemolytic strep group A.
Head trauma or post-neurosurgery: S. aureus, S. epidermidis, aerobic GNR
CSF shunt: S. epidermidis, S. aureus, aerobic GNR, Propionibacterium acnes
PATHOGENESIS PATHOGENESIS
OF BACTERIAL MENINGITIS
1.1. Nasopharyngeal colonizationNasopharyngeal colonization
2.2. Direct extension of bacteriaDirect extension of bacteria.. Parameningeal foci (sinusitis, mastoiditis, or Parameningeal foci (sinusitis, mastoiditis, or
brain abscess)brain abscess) Across skull defects/fractureAcross skull defects/fracture
3.3. From remote foci of infectionFrom remote foci of infection ((e.g., endocarditis, pneumonia, UTI…)e.g., endocarditis, pneumonia, UTI…)
Cohen & Powderly: Infectious Diseases, 2nd ed., Copyright © 2004 Mosby
Brain with inflammatory exudate covering the cortical hemispheres in purulent meningitis.
CLINICAL CLINICAL PRESENTATIONPRESENTATION
Symptom or Sign Relative Frequency (% )
FEVER >90 HEADACHE >90 NUCHAL RIGIDITY >85 ALTERED MENTAL STATUS 80 BRUDZINSKI SIGN 50 KERNIG SIGN 50 VOMITING ~35 SEIZURES 10-30 FOCAL NEURO SIGNS 10-30 PAPILLEDEMA <1 PHOTOPHOBIA SKIN RASH (e.g., petechia/purpura in meningococcemia)
CONFIRMATION OF SUSPECTED CONFIRMATION OF SUSPECTED BACTERIAL MENINGITISBACTERIAL MENINGITIS
Lumbar puncture ASAP.
If LP has to be delayed for any reason, send blood culture and start empiric antibiotics.
Who should undergo CT prior to lumbar puncture?
Who should undergo CT prior to lumbar puncture?Criterion Comment
Immunocompromised state
HIV infection or AIDS, receiving immunosuppressive therapy, or after transplantation
History of CNS disease Mass lesion, stroke, or focal infection
New onset seizure Within 1 week of presentation; some authorities would not perform a lumbar puncture on patients with prolonged seizures or would delay lumbar puncture for 30 min in patients with short, convulsive seizures
Papilledema Presence of venous pulsations suggests absence of increased intracranial pressure
Abnormal level of consciousness
...
Focal neurologic deficit Including dilated nonreactive pupil, abnormalities of ocular motility, abnormal visual fields, gaze palsy, arm or leg drift
DIAGNOSIS - CSF ExaminationDIAGNOSIS - CSF Examination TypicalTypical CSF in Patients with Bacterial Meningitis CSF in Patients with Bacterial Meningitis
Opening pressureOpening pressure 200-500 mmH200-500 mmH22OO White blood cell countWhite blood cell count 1000-5000/mm1000-5000/mm33
NeutrophilsNeutrophils >>80%80% ProteinProtein >100 mg/dl>100 mg/dl GlucoseGlucose <40 mg/dl<40 mg/dl CSF/serum glu ratioCSF/serum glu ratio <<0.40.4 Gram stainGram stain Positive in 50-80%Positive in 50-80% CultureCulture Positive in ~85%Positive in ~85% Bacterial antigen detectionBacterial antigen detection Positive in 50-100%Positive in 50-100%
CSF ANALYSISCSF ANALYSIS
PARAMETEPARAMETERR
BACTERIALBACTERIAL VIRALVIRAL
OPENING OPENING PRESSUREPRESSURE
200-500 200-500 mm mm H20H20
<<250 250 mm H20mm H20
WBCWBC 1000-50001000-5000(mainly (mainly neutrophils)neutrophils)
<1000<1000(mainly (mainly lymphocytes)lymphocytes)
GLUCOSEGLUCOSE <40 <40 mg/dLmg/dL >45 >45 mg/dLmg/dL
PROTEINPROTEIN 100-500 100-500 mg/dLmg/dL
<200 mg/dL<200 mg/dL
CSF PREDICTIVE OF BACTERIAL CSF PREDICTIVE OF BACTERIAL MENINGITIS WITH 99% MENINGITIS WITH 99%
ACCURACY, IF:ACCURACY, IF:
WBC count WBC count >2,000 >2,000 NeutrophilsNeutrophils >1180>1180 ProteinProtein >220 >220 mg/dlmg/dl
Glucose Glucose <34 <34 mg/dlmg/dl
Glu (CSF/serum):Glu (CSF/serum): <0.23 <0.23
Spanos et al. JAMA Spanos et al. JAMA 1989;262(19):2700-71989;262(19):2700-7
What Specific CSF Diagnostic Tests Should Be Used What Specific CSF Diagnostic Tests Should Be Used to Determine the Bacterial Etiology of Meningitis?to Determine the Bacterial Etiology of Meningitis?
Gram Stain Latex Agglutination (the Practice Guideline Committee does not recommend
routine use of this modality): Does not appear to modify the decision to administer antimicrobial therapy False-positive results have been reported Some would recommend it for patients with a negative CSF Gram stain result
and may be most useful for the patient who has been pretreated with antimicrobial therapy and whose Gram stain and CSF culture results are negative.
Polymerase Chain Reaction (PCR) Broad-based PCR may be useful for excluding the diagnosis of bacterial
meningitis, with the potential for influencing decisions to initiate or discontinue antimicrobial therapy.
Although PCR techniques appear to be promising for the etiologic diagnosis of bacterial meningitis, further refinements of the available techniques may lead to their use in patients with bacterial meningitis for whom the CSF Gram stain result is negative.
CID 2004;39:1267-1284
What Laboratory Testing May Be Helpful in What Laboratory Testing May Be Helpful in DistinguishingDistinguishing Bacterial from Viral Bacterial from Viral
Meningitis?Meningitis? CSF LACTATE:
Not recommended in suspected community-acquired bacterial meningitis
May be helpful in the postoperative neurosurgical patient, If CSF lactate concentrations are 4.0 mmol/L, initiation of
empirical antimicrobial therapy should be considered pending results of additional studies.
C-REACTIVE PROTEIN: Normal CRP has a high negative predictive value in the
diagnosis of bacterial meningitis. Measurement of serum CRP concentration may be helpful in
patients with CSF findings consistent with meningitis, but for whom the Gram stain is negative and you’re considering withholding antimicrobial therapy.
PROCALCITONIN: At present, because measurement of serum procalcitonin concentrations is not readily available in clinical laboratories, recommendations on its use cannot be made at this time.
PCR: Enterovirus-PCR (rapid, sensitivity 86-100% specificity 92-100%) CID.2004;39:1267-1284
IS CSF CULTURE IS CSF CULTURE ALWAYS POSITIVE IN ALWAYS POSITIVE IN
BACTERIAL BACTERIAL MENINGITIS?MENINGITIS?
BACTERIAL MENINGITIS CAN BE BACTERIAL MENINGITIS CAN BE “CULTURE-NEGATIVE”“CULTURE-NEGATIVE”
10-15% of bacterial meningitidis are culture-neg.
Pre-LP use of even oral antibiotics may lower
Gram stain positivity by 20% & Culture positivity by 30%
In children (S.pneumo, H.flu, N. mening.) in 90-100% of pts within 24-36h of “appropriate” antibiotic Rx:
CSF became culture-negative No sig change in cell count/chemistry.
Ped.ID J.1992 11 423-32Ped.ID J.1992 11 423-32
NEUTROPHILIC PLEOCYTOSIS & LOW CSF GLUCOSENEUTROPHILIC PLEOCYTOSIS & LOW CSF GLUCOSE
May Not Always Mean Bacterial MeningitisMay Not Always Mean Bacterial Meningitis
INFECTIONS:INFECTIONS: Viral meningitis (early Viral meningitis (early
phase only)phase only) Some parameningeal Some parameningeal
foci/ cerebritisfoci/ cerebritis Leakage of brain abscess Leakage of brain abscess
into ventricleinto ventricle Amebic Amebic
meningoencephalitismeningoencephalitis TB meningitis (rarely, & TB meningitis (rarely, &
usu. only early)usu. only early)
NON-INFECTIOUSNON-INFECTIOUS:: Chemical-meningitis Chemical-meningitis
(contrast…)(contrast…) Behcet syndromeBehcet syndrome Drug –induced Drug –induced ( NSAIDs, ( NSAIDs,
Sulfa, INH, IVIG, OKT3…)Sulfa, INH, IVIG, OKT3…)
BACTERIAL MENINGITIS BACTERIAL MENINGITIS MAY NOT MAY NOT ALWAYSALWAYS HAVEHAVE NEUTROPHILIC NEUTROPHILIC
PLEOCYTOSISPLEOCYTOSIS??
Partially Rx’d bacterialPartially Rx’d bacterial ListeriaListeria some GNR...some GNR...
PRINCIPLES OF TREATMENTPRINCIPLES OF TREATMENT Suspected Bacterial meningitisSuspected Bacterial meningitis
Prompt initiation of treatment. Prompt initiation of treatment. BactericidalBactericidal agents, with agents, with adequate adequate
CSF levelsCSF levels.. Empiric Rx Empiric Rx (based on age and (based on age and
predisposing factors)predisposing factors) Specific Rx Specific Rx (based on Gram-stain or (based on Gram-stain or
antigen).antigen). Include steroids where indicatedInclude steroids where indicated
EMPIRIC THERAPY
Patient’s AgeCommon pathogens Antimicrobial therapy
<1 month Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, Klebsiella species
Ampicillin plus cefotaxime or ampicillin plus an aminoglycoside
1 - 23 mos Streptococcus pneumoniae, Neisseria meningitidis, S. agalactiae, Haemophilus influenzae, E. coli
Vancomycin plus a third-generation cephalosporin
2 - 50 yrs N . meningitidis, S. pneumoniae
Vancomycin plus a third-generation cephalosporin
>50 yrs S.pneumoniae, N. meningitidisL. monocytogenes, aerobic gram-negative bacilli
Vancomycin plus ampicillin plus a third-generation cephalosporin
EMPIRIC THERAPY
Predisposing factor
Common pathogens Antimicrobial therapy
Basilar skull fracture
S. pneumoniae, H. influenzae, group A -hemolytic streptococci
Vancomycin plus a third-generation cephalosporin
Penetrating trauma
Staphylococcus aureus, coagulase-negative staphylococci (especially Staphylococcus epidermidis), aerobic gram-negative bacilli (including Pseudomonas aeruginosa)
Vancomycin plus cefepime, vancomycin plus ceftazidime, or vancomycin plus meropenem
Post- neurosurgery
Aerobic gram-negative bacilli (including P. aeruginosa), S . aureus, coagulase-negative staphylococci (especially S. epidermidis)
Vancomycin plus cefepime, vancomycin plus ceftazidime, or vancomycin plus meropenem
CSF shunt Coagulase-negative staphylococci (especially S. epidermidis), S. aureus, aerobic gram-negative bacilli (including P. aeruginosa), Propionibacterium acnes
Vancomycin plus cefepime,c vancomycin plus ceftazidime,c or vancomycin plus meropenemc
MicroorganismSPECIFIC-RXRecommended Rx Alternative therapies
Streptococcus pneumoniae
Vancomycin plus a third-generation cephalosporina,b
Meropenem (C-III), fluoroquinolonec (B-II)
Neisseria meningitidis
Third-generation cephalosporina
Penicillin G, ampicillin, chloramphenicol, fluoroquinolone, aztreonam
Listeria monocytogenes
Ampicillind or penicillin Gd
Trimethoprim-sulfamethoxazole, meropenem (B-III)
Streptococcus agalactiae
Ampicillind or penicillin Gd
Third-generation cephalosporina (B-III)
Haemophilus influenzae
Third-generation cephalosporina (A-I)
Chloramphenicol, cefepime (A-I), meropenem (A-I), fluoroquinolone
Escherichia coli Third-generation cephalosporina (A-II)
Cefepime, meropenem, aztreonam, fluoroquinolone, trimethoprim-sulfamethoxazole.
a Ceftriaxone or cefotaxime. b Some experts would add rifampin if dexamethasone is also given (B-III). c Gatifloxaxin or moxifloxacin. d Addition of an aminoglycoside should be considered.
PATHOGEN susceptibility Standard therapy Alternative therapies
Streptococcus pneumoniae
Penicillin MIC
<0.1 g/mL Penicillin G or ampicillin Third-generation cephalosporin, chloramphenicol
0.1- 1.0 g/mL Third-generation cephalosporin
Cefepime (B-II), meropenem
> 2.0 g/mL Vancomycin plus a third-generation cephalosporin
Fluoroquinolone
Cefotaxime or ceftriaxone MIC >1.0
g/mL
Vancomycin plus a third-generation cephalosporin
Fluoroquinolone
Neisseria meningitidis
Penicillin MIC
<0.1 g/mL Penicillin G or ampicillin Third-generation cephalosporin, chloramphenicol
0.1 1.0 g/mL Third-generation cephalosporin
Chloramphenicol, fluoroquinolone, meropenem
PATHOGEN STANDARD RX ALTERNATIVE RX
Listeria monocytogenes
Ampicillin or penicillin G Trimethoprim-sulfamethoxazole, meropenem
Strep. agalactiae Ampicillin or penicillin G Third-generation cephalosporin
E. coli and other Enterobacteriaceae
Third-generation cephalosporin
Aztreonam, fluoroquinolone, meropenem, trimethoprim-sulfamethoxazole, ampicillin
Pseudomonas aeruginosa
Cefepime or ceftazidime (consider plus aminoglycoside)
Aztreonam ciprofloxacin, meropenem (consider plus aminoglycoside)
Haemophilus influenzae
B -Lactamase . negative
Ampicillin Third-generation cephalosporin, cefepime, chloramphenicol, fluoroquinolone
B -Lactamase positive
Third-generation cephalosporin
Cefepime, chloramphenicol, fluoroquinolone
PATHOGEN STANDARD RX ALTERNATIVE RX
Staphylococcus aureus
Methicillin susceptible
Nafcillin or oxacillin Vancomycin, meropenem
Methicillin resistant Vancomycin (consider adding rifampin)
Trimethoprim-sulfamethoxazole, linezolid (consider adding rifampin)
Staphylococcus epidermidis
Vancomycin Linezolid
Enterococcus species
Ampicillin susceptible
Ampicillin + gentamicin ...
Ampicillin resistant Vanc + gentamicin ...
Ampicillin and vancomycin resistant
Linezolid ...
Antimicrobial agent
In adultsTotal daily dose (dosing interval in hours)
Amikacin 15 mg/kg (8)
Ampicillin 12 g (4)
Aztreonam 6-8g (6-8)
Cefepime 6 g (8)
Cefotaxime 8-12g(4-6)
Ceftazidime 6 g (8)
Ceftriaxone 4g (12-24)
Chloramphenicol 4-6 g (6)
Ciprofloxacin 800-1200mg (8-12)
Gatifloxacin 400 mg (24) CID.2004;39:1267-1284
9
Gentamicin 5 mg/kg (8)
Meropenem 6 g (8)
Moxifloxacin 400 mg (24)
Nafcillin 12 g (4)
Oxacillin 12 g (4)
Penicillin G 24 mU (4)
Rifampin 600 mg (24)
Tobramycin 5 mg/kg (8)
TMP-SMZ 10-20 mg/kg (6-12)
Vancomycin 30-45 mg/kg (8-12)
Antimicrobial agent Total daily dose (dosing interval in hours)
CID 2004;39:1267-1284
MicroorganismDuration of
therapy (days)
Neisseria meningitidis 7
Haemophilus influenzae 7
Streptococcus pneumoniae 10-14
Streptococcus agalactiae 14-21
Aerobic gram-negative bacilli 21
Listeria monocytogenes
>21
Clinical Infectious Diseases 2004;39:1267-1284
BACTERIAL MENINGITISBACTERIAL MENINGITIS CASE FATALITYCASE FATALITY
(%)(%) S. pneumoniaeS. pneumoniae 2121 L. monocytogenesL. monocytogenes 1515 Group B Strep.Group B Strep. 77 H. influenzae H. influenzae 66 N. meningitidisN. meningitidis 3 3
NEJM 1997;337:970-6 NEJM 1997;337:970-6
(based on 248 cases from 4 states, in 1995)(based on 248 cases from 4 states, in 1995)
ROLE OF STEROIDSROLE OF STEROIDS Decrease subarachnoid space inflammatory
response to abx-induced bacterial lysis
Significant reduction in deafness in pediatric H. influenzae & pneumococcal meningitis (JAMA 1997; 278:925).
In adults, reasonable to use steroids: for pts with evidence of cerebral edema. for adult with pneumococcal meningitis
(Nov 14, 2002 issue of NEJM)
Give immediately before or with the 1st dose of antibiotic. Dexamethasone dose: 0.15 mg/kg q6 x 2-4 days
Dexamethasone in Adults with Bacterial Meningitis
Jan de Gans, et.al., for the European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators
NEJM 2002. 347:1549-1556. (Nov. 14, 2002)
Use of Adjunctive Dexamethasone Therapy in Adults with Bacterial Meningitis
In suspected or proven pneumococcal meningitis cases.• Dexamethasone should only be continued if the CSF Gram stain
reveals gram-positive diplococci, or if blood or CSF cultures are positive for S. pneumoniae.
• Adjunctive dexamethasone should not be given to adult patients who have already received antimicrobial therapy, because administration of dexamethasone in this circumstance is unlikely to improve patient outcome.
• Addition of rifampin to the empirical combination of vancomycin plus a third-generation cephalosporin may be reasonable pending culture results and in vitro susceptibility testing , in patients with suspected pneumococcal meningitis who receive adjunctive dexamethasone.
Some authorities would initiate dexamethasone in all adults because the etiology of meningitis is not always ascertained at initial evaluation, although the data are inadequate to recommend adjunctive dexamethasone to adults with meningitis caused by other bacterial pathogens
Infants and Children•Use in H. influenzae type b meningitis .
•For pneumococcal meningitis, controversial.
NeonatesInsufficient data to make a recommendation on the use of adjunctive dexamethasone.
Use of Adjunctive Dexamethasone Therapy in Pediatric Patients with Bacterial Meningitis
CID 2004;39:1267-1284
•Not indicated routinely in patients with bacterial meningitis who have responded appropriately to antimicrobial therapy, • Repeated CSF analysis should be performed in:
• Any patient who has not responded clinically after 48h of appropriate antimicrobials This is especially true for the patient with pneumococcal meningitis caused by penicillin-or cephalosporin-resistant strains, especially for those who have also received adjunctive dexamethasone therapy.
• Neonate with meningitis due to gram-negative bacilli should have repeated LPs
•To document CSF sterilization, because the duration of antimicrobial therapy is determined, in part, by the result.
• In patients with CSF shunt infections •The presence of a drainage catheter after shunt removal allows for monitoring of CSF parameters to ensure that the infection is responding to appropriate antimicrobial therapy and drainage).
What Are the Indications for Repeated Lumbar Puncture in Patients with Bacterial
Meningitis?
CID 2004;39:1267-1284
PREVENTION OF BACTERIA PREVENTION OF BACTERIA MENINGITISMENINGITIS
Isolation of index patientIsolation of index patient Droplet precautions Droplet precautions For 24 hrs after 1For 24 hrs after 1stst dose of appropriate abx) dose of appropriate abx)
Post-exposure prophylaxisPost-exposure prophylaxis VaccinationVaccination
POST-EXPOSURE POST-EXPOSURE PROPHYLAXISPROPHYLAXIS
Candidates:Candidates: Household membersHousehold members Day care center contactsDay care center contacts Direct exposure to pt’s oral secretion ( as Direct exposure to pt’s oral secretion ( as
in kissing, mouth-to-mouth , in kissing, mouth-to-mouth , intubation/ET tube management)intubation/ET tube management)
Index patient (if not treated w 3Index patient (if not treated w 3rdrd gen gen cephalosporins)cephalosporins)
Regimen:Regimen: Meningococcus: Rifampin, ciprofloxacin, Meningococcus: Rifampin, ciprofloxacin,
or ceftriaxoneor ceftriaxone Hempohilus influenzae serotype b: Hempohilus influenzae serotype b:
Rifampin.Rifampin.
VaccinationVaccination Hib vaccine. Hib vaccine.
Has had major impact in incidence of pediatric Hib meningitis Has had major impact in incidence of pediatric Hib meningitis Pneumococcal vaccinePneumococcal vaccine. .
For chronically ill and elderly, & now universal use in children. For chronically ill and elderly, & now universal use in children. PCV-7PCV-7.. Use of PCV-7 for children has been an effective means Use of PCV-7 for children has been an effective means
of preventing disease in older adults of preventing disease in older adults (JAMA. Vol. 294 No. 16, (JAMA. Vol. 294 No. 16, October 26, 2005 )October 26, 2005 )
Meningococcal vaccineMeningococcal vaccine Effective vs serotype A, C, Y, W135Effective vs serotype A, C, Y, W135 Major reduction of disease in military recruitsMajor reduction of disease in military recruits Recommended for travelers to endemic areas.Recommended for travelers to endemic areas. Offered to college students, specially those residing in Offered to college students, specially those residing in
dormitorydormitory A new quadrivalent vaccine (Menactra) was recently A new quadrivalent vaccine (Menactra) was recently
approved.approved.
•Children aged 11-12 years
•Previously unvaccinated adolescents before entering high school or at age 15 (whichever comes first)
•All first-year college students living in dormitories
•Other high-risk groups, such as those with underlying medical conditions or travelers to areas with high rates of meningococcal disease, such as Africa and India.
•Other adolescents who choose to get the vaccine to reduce their risk
"As the vaccine supply increases, CDC hopes, within three years, to recommend routine vaccination [for] all adolescents beginning at 11 years of age," per CDC's news release
Who Should Be Vaccinated with the NEW MENINGOCOCCAL VACCINE
(Menactra))
FDA and CDC Issue Alert on Menactra Meningococcal Vaccineand Guillain Barre Syndrome
• FDA and CDC alerted consumers and health care providers to five reports of Guillain Barre Syndrome (GBS) following administration of Meningococcal Conjugate Vaccine (trade name Menactra).
• It is not known yet whether these cases were caused by the vaccine or are coincidental.
• Prelicensure studies conducted by Sanofi Pasteur of more than 7000 recipients of Menactra showed no GBS cases.
• CDC conducted a rapid study using available health care organization databases and found that no cases of GBS have been reported to date among 110,000 Menactra recipients.
September 30, 2005
CRITERIA FOR OUTPATIENT ANTIMICROBIAL THERAPY IN PATIENTS WITH BACTERIAL MENINGITIS
• Inpatient antimicrobial therapy for > 6 days
• Absence of fever for at least 24- 48 h prior to initiation of outpatient therapy
• No significant neurologic dysfunction, focal findings, or seizure activity
• Clinical stability or improving condition
• Ability to take fluids by mouth
• Access to home health nursing for antimicrobial administration
• Reliable intravenous line and infusion device (if needed)
• Daily availability of a physician
• Established plan for physician visits, nurse visits, laboratory monitoring, and emergencies
• Patient and/or family compliance with the program
• Safe environment with access to a telephone, utilities, food, and refrigerator
CID 2004;39:1267-1284
REVIEWREVIEW Most common cause overall….Most common cause overall…. CT?CT? Duration of Rx…Duration of Rx… Steroids for…Steroids for… Most deadly…Most deadly… Isolation for…. How long?Isolation for…. How long? ChemoprophylaxisChemoprophylaxis
For which pathogens?For which pathogens? Which contacts?Which contacts? What Regimen?What Regimen?
Vaccination?Vaccination?
SHUNT INFECTION Removal of all components of the infected shunt, external
drainage, +abxCOAG-NEGATIVE STAPH.:
1. If normal CSF findings, and a negative CSF culture results after externalization, the patient can be reshunted on the 3rd day after removal.
2. If CSF abnormalities are present and a coagulase-negative staphylococcus is isolated, 7 days of antimicrobial therapy are recommended prior to reshunting as long as additional CSF culture results are negative and the ventricular protein concentration is appropriate (<200 mg/dL);
3. If additional culture results are positive, abx are continued until CSF culture results remain negative for 10 consecutive days before a new CSF shunt is placed.
STAPH. AUREUS :10 days of negative culture results are recommended prior to
reshunting .
GRAM-NEGATIVE BACILLI: 10-14 day course of antimicrobial therapy should be used,
although longer durations may be needed depending on the clinical response.
[Some experts also suggest that consideration be given to a 3-day period off antimicrobial therapy to verify clearing of the infection prior to shunt reimplantation; although this approach is optional, it may not be necessary for all patients].
Neisseria Meningitidis 5-15% asymptomatic nasopharyngeal colonization.
Transmission by air-droplets, kissing, sharing saliva…
Most common cause of meningitis in children and young adults , with overall mortality rate of 3- 13%.
Causes epidemics in the “meningitis belt.”
Predisposing Factors :
Deficiencies in the terminal complement components (C5-C9)
Splenectomy
Crowding (military recruits, college dormitory, Hajj…). Tarvel.
College freshmen in dormitory>>dormitory >> freshman>>college students overall.
Rates of meningococcal disease, Rates of meningococcal disease, by risk group--United States, Sept. by risk group--United States, Sept.
1998--Aug. 19991998--Aug. 1999
Risk group Rate per 100,000
Children aged 2-5 years 1.7
Persons aged 18-23 years 1.4
Non-college students aged 18-23 years 1.5
College students 0.6
Undergraduates 0.7
Freshmen 1.8
Dormitory residents 2.2
Freshmen living in dormitories 4.6
MMWR 2000,49(RR-7)1-20
Meningococcal MeningitisMeningococcal Meningitis
Penicillin (or 3Penicillin (or 3rdrd gen cephalosporin) gen cephalosporin) Resistance to penicillin still very rareResistance to penicillin still very rare If penicillin used for Rx, eradication of If penicillin used for Rx, eradication of
pharyngeal colonization of index case pharyngeal colonization of index case advisable advisable
Duration of Rx, 7 daysDuration of Rx, 7 days Chemoprophylaxis for close contactsChemoprophylaxis for close contacts Droplet isolation (for 24h after 1Droplet isolation (for 24h after 1stst dose dose
of abx)of abx)
Most common cause of bacterial Most common cause of bacterial meningitis in the US, with mortality rate of meningitis in the US, with mortality rate of 19 to 26%.19 to 26%. Often from contiguous or distant foci of Often from contiguous or distant foci of
infection (e.g., pneumonia, otitis media, infection (e.g., pneumonia, otitis media,
mastoiditis, sinusitis, endocarditis, ormastoiditis, sinusitis, endocarditis, or after after head trauma w CSF leak).head trauma w CSF leak).
Predisposing factors: Predisposing factors: Anatomic or functional asplenia, multiple Anatomic or functional asplenia, multiple
myeloma, hypogammaglobulinemia, alcoholism, myeloma, hypogammaglobulinemia, alcoholism, malnutrition, chronic liver or renal disease, malnutrition, chronic liver or renal disease,
malignancy, and diabetes mellitusmalignancy, and diabetes mellitus..
Streptococcus PneumoniaeStreptococcus Pneumoniae
Pneumococcal MeningitisPneumococcal Meningitis
Before MICsBefore MICs:: Vancomycin + 3rd gen cephalosporin Vancomycin + 3rd gen cephalosporin If PSSPIf PSSP:: Penicillin (or 3rd gen cephalosporin) alone Penicillin (or 3rd gen cephalosporin) alone If PRSP(CTX-S)If PRSP(CTX-S):: 3rd gen cephalosporin 3rd gen cephalosporin If PRSP&CTX-RIf PRSP&CTX-R:: Vancomycin +3 Vancomycin +3rdrd gen cephalosp gen cephalosp
Steroids in children & adultsSteroids in children & adults If on vanc, and steroids have to be used, add If on vanc, and steroids have to be used, add
rifampin?rifampin? For PRSP: re-LP in few days for response.For PRSP: re-LP in few days for response. Duration of Rx 10-14 daysDuration of Rx 10-14 days
Haemophilus InfluenzaeHaemophilus Influenzae
Meningitis usually seen in children Meningitis usually seen in children <6 years<6 years (peak 6-12mo). (peak 6-12mo).
Capsular type b causes >90% of invasive Capsular type b causes >90% of invasive disease.disease.
Meningitis in Meningitis in above 6 yrsabove 6 yrs usually associated usually associated with: sinusitis, otitis, pneumonia, sickle cell with: sinusitis, otitis, pneumonia, sickle cell disease, splenectomy, DM, alcoholism, disease, splenectomy, DM, alcoholism, immuno-deficiency, or head trauma w csf leak.immuno-deficiency, or head trauma w csf leak.
Causes 7% of meningitis cases in USCauses 7% of meningitis cases in US Mortality Mortality 3-63-6%.%.
H. influenzae meningitisH. influenzae meningitis
Ceftriaxone or cefotaxime Ceftriaxone or cefotaxime Steroids in chldrenSteroids in chldren Duration of Rx: 5-7 daysDuration of Rx: 5-7 days Chemoprophylaxis of close contacts.Chemoprophylaxis of close contacts. Droplet precaution Droplet precaution (in pediatric cases, (in pediatric cases,
x 24h of abx)x 24h of abx)
May be isolated from dust, soil, water, sewage, and May be isolated from dust, soil, water, sewage, and
decaying vegetable matter. Usually decaying vegetable matter. Usually foodborne foodborne infections infections (contaminated cole slaw, raw vegetables, milk, cheese...)(contaminated cole slaw, raw vegetables, milk, cheese...)
Causes 8% of cases of bacterial meningitis in the US, Causes 8% of cases of bacterial meningitis in the US,
mortalitymortality rate of rate of 15-2915-29%. (Seizures, focal signs, %. (Seizures, focal signs,
rhomboencephalitis common)rhomboencephalitis common)
Meningitis most commonMeningitis most common in neonates/elderly, alcoholics, in neonates/elderly, alcoholics,
malignancy, corticosteroid Rx.malignancy, corticosteroid Rx.
Other predisposing factorsOther predisposing factors: DM, liver disease, chronic : DM, liver disease, chronic
renal disease, collagen-vascular diseases, & conditions renal disease, collagen-vascular diseases, & conditions
with Fe overloadwith Fe overload. .
Listeria monocytogenesListeria monocytogenes
Asymptomatic vaginal or rectal Asymptomatic vaginal or rectal colonization colonization in 15 to 35% in 15 to 35% of pregnant women .of pregnant women .
Most common cause of meningitis in Most common cause of meningitis in newbornsnewborns
Mostly vertical transmission (but some horizontal Mostly vertical transmission (but some horizontal transmission from the hands of nursery personnel)transmission from the hands of nursery personnel)
Can also cause meningitis in Can also cause meningitis in ADULTS. ADULTS. Risk factors in Risk factors in adultsadults include: age> include: age>60 years, diabetes mellitus, 60 years, diabetes mellitus, pregnancy/the postpartum state, cardiac disease, pregnancy/the postpartum state, cardiac disease, collagen-vascular diseases, malignancy, alcoholism, collagen-vascular diseases, malignancy, alcoholism, hepatic failure, renal failure, previous stroke, neurogenic hepatic failure, renal failure, previous stroke, neurogenic bladder, decubitus ulcers, and corticosteroid therapy.bladder, decubitus ulcers, and corticosteroid therapy.
Streptococcus agalactiaeStreptococcus agalactiae
Staphylococcus aureus Staphylococcus aureus (&/or coag-neg Staph(&/or coag-neg Staph) meningitis is ) meningitis is mainly postneurosurgical, CSF shunts, or post-trauma.mainly postneurosurgical, CSF shunts, or post-trauma.
Community-acquiredCommunity-acquired S. aureusS. aureus meningitis can be seen in meningitis can be seen in
patients with sinusitis, endocarditis, osteomyelitis, and patients with sinusitis, endocarditis, osteomyelitis, and
pneumonia. pneumonia. Other underlying conditions include diabetes mellitus, Other underlying conditions include diabetes mellitus,
alcoholism, hemodialysis, injection drug use, and alcoholism, hemodialysis, injection drug use, and malignanciesmalignancies
StaphylococciStaphylococci
Increasingly important cause of bacterial Increasingly important cause of bacterial
meningitis (e.g., meningitis (e.g., KlebsiellaKlebsiella spp., spp., E. coliE. coli, ,
Serratia marcescensSerratia marcescens, , Pseudomonas Pseudomonas
aeruginosaaeruginosa, , SalmonellaSalmonella spp.) spp.)
Usually after head trauma or neurosurgery. Usually after head trauma or neurosurgery.
May be seen in neonates, the elderly, May be seen in neonates, the elderly,
immuno-suppressed patients, and pts with immuno-suppressed patients, and pts with
gram-negative sepsis. gram-negative sepsis.
Seen w the hyperinfection syndrome of Seen w the hyperinfection syndrome of
disseminated strongyloidiasisdisseminated strongyloidiasis
Aerobic Gram-Negative BacilliAerobic Gram-Negative Bacilli
Garm negative meningitisGarm negative meningitis
Ceftazidime Ceftazidime (or Cefepime or (or Cefepime or meropenemmeropenem) + an aminoglycoside) + an aminoglycoside
Re-LP for proof of response, in 2-4 Re-LP for proof of response, in 2-4 days?days?
Duration of Rx: 21 daysDuration of Rx: 21 days
BACTERIAL MENINGITISBACTERIAL MENINGITISCOMPLICATIONSCOMPLICATIONS
Death Death ( Pneumococcal> Listeria> Meningococcal)( Pneumococcal> Listeria> Meningococcal) Deafness (5-10%)Deafness (5-10%) Mental retardation (4.2%)Mental retardation (4.2%) Seizures( 4.2%)Seizures( 4.2%) Paresis/spasticity (3.5%)Paresis/spasticity (3.5%)
Poorest prognosisPoorest prognosis: >60, seizure `24h, : >60, seizure `24h, obtunded/comaobtunded/coma
COMPLICATIONSCOMPLICATIONS OFOF BACTERIALBACTERIAL MENINGITISMENINGITIS
Immediate Immediate ComaComa
Loss of airway reflexesLoss of airway reflexesSeizuresSeizuresCerebral edemaCerebral edemaVasomotor collapseVasomotor collapseDisseminated intravascular coagulation (DIC)Disseminated intravascular coagulation (DIC)Respiratory arrestRespiratory arrestDehydrationDehydrationPericardial effusionPericardial effusionDeathDeath
Delayed Delayed Seizure disorderSeizure disorder
Focal paralysisFocal paralysisSubdural effusionSubdural effusionHydrocephalusHydrocephalusIntellectual deficitsIntellectual deficitsSensorineural hearing lossSensorineural hearing lossAtaxiaAtaxiaBlindnessBlindnessBilateral adrenal hemorrhageBilateral adrenal hemorrhageDeathDeath
COMPLICATIONS of COMPLICATIONS of BACTERIAL MENINGITISBACTERIAL MENINGITIS
Cerebral infarctionCerebral infarction from occlusion of from occlusion of inflammed vessels (inflammed vessels (focal neurologic focal neurologic signs, seizures, AMSsigns, seizures, AMS..)..)
Brain edemaBrain edema from disturbance of from disturbance of cerebrovascular autoregulation, leakage cerebrovascular autoregulation, leakage of fluid from damaged vessels, cytotoxic of fluid from damaged vessels, cytotoxic edema from damaged barin cells, or edema from damaged barin cells, or dural sinus thrombosis which impede dural sinus thrombosis which impede blood drainage from brain)blood drainage from brain)
Obstruction of flowObstruction of flow of CSF of CSF (hydrocephalus)(hydrocephalus)
Recommended dosages of antimicrobial agents administered by the intraventricular route (A-
III).
Antimicrobial agent
Daily
intraventricular
dose, mg
Vancomycin 5 20
Gentamicin 1 8
Tobramycin 5 20
Amikacin 5 50
Polymyxin B 5
Colistin 10
Quinupristin/dalfopristin 2 5
Teicoplanin 5 40
NOTE. There are no specific data that define the exact dose of an antimicrobial agent that should be
administered by the intraventricular route. a Most studies have used a 10-mg or 20-mg dose. b Usual daily dose is 1 2 mg for infants and children and 4 8 mg for adults. c The usual daily intraventricular dose is 30 mg. d Dosage in children is 2 mg daily. e Dosage of 5 10 mg every 48 72 h in one study [112].
RECURRENT RECURRENT MENINGITISMENINGITIS
Bacterial:Bacterial: Anatomic Anatomic
defect/CSF leak defect/CSF leak Parameningeal Parameningeal
infectioninfection Immunologic (Ig Immunologic (Ig
def, asplenia, def, asplenia, complement def...)complement def...)
ChemicalChemical: :
Endogenous: cranio-Endogenous: cranio-pharyngioma, pharyngioma, epidermid cyst. epidermid cyst.
Drugs, Behcet, SLE, Drugs, Behcet, SLE, Mollaret...Mollaret...
What Laboratory Testing May Be Helpful in Distinguishing Bacterial from Viral Meningitis?
CSF Lactate •Not recommended for patients with suspected community-acquired bacterial meningitis •However, measurement of CSF lactate concentrations was found to be superior to use of the ratio of CSF to blood glucose for the diagnosis of bacterial meningitis in postoperative neurosurgical patients, in which a CSF concentration of 4.0 mmol/ L was used as a cutoff value for the diagnosis… Therefore, in the postoperative neurosurgical patient, initiation of empirical antimicrobial therapy should be considered if CSF lactate concentrations are > 4.0 mmol/L, pending results of additional studies.
C-reactive ProteinMeasurement of serum CRP concentration may be helpful in patients with CSF findings consistent with meningitis, but for whom the Gram stain result is negative and the physician is considering withholding antimicrobial therapy, on the basis of the data showing that a normal CRP has a high negative predictive value in the diagnosis of bacterial meningitis.ProcalcitoninAt present, because measurement of serum procalcitonin concentrations is not readily available in clinical laboratories, recommendations on its use cannot be made at this time (C-II).Polymerase Chain ReactionIn patients who present with acute meningitis, an important diagnostic consideration is whether the patient has enteroviral meningitis. Rapid detection of enteroviruses by PCR has emerged as a valuable technique that may be helpful in establishing the diagnosis of enteroviral meningitis.
Annual Incidence of Invasive Pneumococcal Disease by Age Group for Adults >50 Years—Active Bacterial Core Surveillance, 1998-2003
Percentage reductions from 1998-1999 to 2002-2003: for persons aged 85 years, –28% (95% confidence interval [CI], –36% to –19%); 75-84 years, –35% (95% CI, –41% to –28%); 65-74 years, –29% (95% CI, –36% to –21%); and 50-64 years, –17% (95% CI, –24% to –11%). Percentage reductions were significant (P<.001) in each age group. PCV-7 indicates 7-valent pneumococcal conjugate vaccine.
JAMA. Vol. 294 No. 16, October 26, 2005
IMPACT OF PCV-7IMPACT OF PCV-7
Recommended