bacterial meningitis gebre k. tseggay, md november 21, 2005

BACTERIAL MENINGITIS

Gebre K. Tseggay, MD

November 21, 2005

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

ARE NEUTROPHILIC PLEOCYTOSIS & LOW CSF

GLUCOSE UNIQUE FOR BACTERIAL MENINGITIS?

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


>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


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


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


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


>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?

MANAGEMENT

DO YOU WANT MORE SLIDES ON BACTERIAL MENINGITIS??

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...

Hasbun et al. NEJM 2001: 345 (24): 1727

Hasbun et al. NEJM 2001: 345 (24): 1727-33

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

JAMA. Vol. 294 No. 16, October 26, 2005

bacterial meningitis gebre k. tseggay, md november 21, 2005

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