MENINGITISMENINGITISLaurie J Burton, MDLaurie J Burton, MD

PEM Fellows ConferencePEM Fellows Conference

December 6, 2006December 6, 2006

OUTLINEOUTLINE

PathophysiologyPathophysiology CasesCases Neonatal meningitisNeonatal meningitis The bugs, the drugsThe bugs, the drugs HSV, Listeria, EnterovirusHSV, Listeria, Enterovirus Dex for who?Dex for who? CT before LPCT before LP Interpreting CSF / Lab testingInterpreting CSF / Lab testing

PATHOPHYSPATHOPHYS

The blood-brain barrier, which excludes The blood-brain barrier, which excludes most macromolecules and most macromolecules and microorganisms, is due to the cellular microorganisms, is due to the cellular configuration of the cerebral capillaries, configuration of the cerebral capillaries, the choroid plexus, and arachnoid cells the choroid plexus, and arachnoid cells

This barrier excludes not only most This barrier excludes not only most microbes, but also excludes immune microbes, but also excludes immune defenses derived from serum defenses derived from serum

PATHOPHYSPATHOPHYS

Antibodies found in the normal CNS are derived Antibodies found in the normal CNS are derived from the serum. from the serum.

Levels of IgG and IgA in the CSF are Levels of IgG and IgA in the CSF are approximately 0.2 to 0.4 percent of the serum approximately 0.2 to 0.4 percent of the serum levels. levels.

Since diffusion of macromolecules across the Since diffusion of macromolecules across the barrier is largely size dependent, IgM is present barrier is largely size dependent, IgM is present at even lower levels. at even lower levels.

There is also no lymphatic system in the usual There is also no lymphatic system in the usual sense, and few, if any, phagocytic cells. sense, and few, if any, phagocytic cells.

Complement is also largely excluded. Complement is also largely excluded.

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

Therefore, although the barrier deters Therefore, although the barrier deters invasion of infectious agents, it hampers invasion of infectious agents, it hampers their clearance once it is penetrated. their clearance once it is penetrated.

. Therefore, bacteria that enter this space . Therefore, bacteria that enter this space undergo an initial phase of undergo an initial phase of logarithmic logarithmic growthgrowth, accounting for the often explosive , accounting for the often explosive onset of acute bacterial meningitis onset of acute bacterial meningitis

DDX ORGDDX ORG Bacterial infections — Partially treated bacterial meningitis, bacterial Bacterial infections — Partially treated bacterial meningitis, bacterial

infection with a parameningeal focus (brain or epidural abscess), infection with a parameningeal focus (brain or epidural abscess), tuberculosis tuberculosis

Viral infections — Herpes simplex meningoencephalitis, Viral infections — Herpes simplex meningoencephalitis, cytomegalovirus, enteroviruses, rubella, lymphocytic cytomegalovirus, enteroviruses, rubella, lymphocytic choriomeningitis, varicella choriomeningitis, varicella

Spirochetal infections — Syphilis, Lyme disease Spirochetal infections — Syphilis, Lyme disease Parasitic infections — Toxoplasmosis, Chagas' disease Parasitic infections — Toxoplasmosis, Chagas' disease Mycoplasma infections — M. hominis infection, Ureaplasma Mycoplasma infections — M. hominis infection, Ureaplasma

urealyticum infection urealyticum infection Fungal infection — Candidiasis, coccidioidomycosis, cryptococcus Fungal infection — Candidiasis, coccidioidomycosis, cryptococcus Trauma — Subarachnoid hemorrhage, traumatic lumbar puncture Trauma — Subarachnoid hemorrhage, traumatic lumbar puncture Malignancy — Teratoma, medulloblastoma, choroid plexus Malignancy — Teratoma, medulloblastoma, choroid plexus

papilloma and papilloma and

Case 1.Case 1.

5 week old with fever, irritability, poor 5 week old with fever, irritability, poor feeding. History of maternal herpes in first feeding. History of maternal herpes in first trimester.trimester.

FSWU done, CSF only able to obtain FSWU done, CSF only able to obtain enough for culture.enough for culture.

Ampicillin and cefotaxime started. Should Ampicillin and cefotaxime started. Should you also start acyclovir? you also start acyclovir?

HSVHSV

DOL 0 - 4 weeks most common per Red DOL 0 - 4 weeks most common per Red BookBook

11stst week, more often disseminated (sepsis, week, more often disseminated (sepsis, elevated transaminases)elevated transaminases)

22ndnd-3-3rdrd week more often meningitis week more often meningitis

In a neonate (ie < 4 weeks old)In a neonate (ie < 4 weeks old)

Just takes Just takes 1 vesicle1 vesicle

HSVHSV

Significant % of neonates with HSV who Significant % of neonates with HSV who do not manifest skin lesionsdo not manifest skin lesions

Consider in neonates with sepsis Consider in neonates with sepsis syndrome, elevated ALT/AST or PT/PTT, syndrome, elevated ALT/AST or PT/PTT, CSF pleocytosis or even RBCs especially CSF pleocytosis or even RBCs especially with negative bacterial cultureswith negative bacterial cultures

HSVHSV

Neonatal HSV meningitis/encephalitis high Neonatal HSV meningitis/encephalitis high morbidity and mortality regardless of morbidity and mortality regardless of treatmenttreatment

HSVHSV

In neonates, scraping of skin lesions and In neonates, scraping of skin lesions and additional cultures from conjunctivae, additional cultures from conjunctivae, throat, nasopharynx, stool, and urine throat, nasopharynx, stool, and urine specimens can aid in the diagnosis of specimens can aid in the diagnosis of CNS disease for HSVCNS disease for HSV

HSVHSV

In the majority of patients, HSV mucosal In the majority of patients, HSV mucosal lesions precede signs and symptoms of lesions precede signs and symptoms of meningeal inflammation with a mean meningeal inflammation with a mean interval of one week interval of one week

Beyond the neonatal period, the Beyond the neonatal period, the incubation period ranges from two days to incubation period ranges from two days to 12 days, with a mean of four days12 days, with a mean of four days

HSVHSV

Herpes CNS infections (meningitis, Herpes CNS infections (meningitis, encephalitis) require 21 days of acyclovirencephalitis) require 21 days of acyclovir

PCR availablePCR available

MOLLARETSMOLLARETS

Mollaret's meningitis is characterized by Mollaret's meningitis is characterized by recurrent episodes of aseptic meningitis. recurrent episodes of aseptic meningitis. Using polymerase chain reaction (PCR) Using polymerase chain reaction (PCR) based testing, HSV-2 has been strongly based testing, HSV-2 has been strongly associated with Mollaret's meningitis, a associated with Mollaret's meningitis, a form of benign recurrent aseptic meningitis form of benign recurrent aseptic meningitis

Additional few cases have been reported Additional few cases have been reported due to HSV-1 and EBVdue to HSV-1 and EBV

CaseCase

2 week old infant with fever. Infant’s 2 week old infant with fever. Infant’s mother makes her own cheese and mother makes her own cheese and sausagessausages

FSWUFSWU On Gram stain of CSF…On Gram stain of CSF…

LISTERIALISTERIA

Furthermore, when organisms are seen, Furthermore, when organisms are seen, Listeria may resemble pneumococci Listeria may resemble pneumococci (diplococci) or diphtheroids (diplococci) or diphtheroids (Corynebacteria) or be Gram-variable and (Corynebacteria) or be Gram-variable and be confused with Haemophilus species be confused with Haemophilus species Thus, Listeria should always be Thus, Listeria should always be considered when "diphtheroids" are considered when "diphtheroids" are reported to be growing from blood or CSF reported to be growing from blood or CSF cultures cultures

LISTERIALISTERIA

Listeria is the one cause of Listeria is the one cause of bacterialbacterial meningitis in which a substantial number meningitis in which a substantial number of lymphocytes (>25 percent) can be seen of lymphocytes (>25 percent) can be seen in the CSF differential countin the CSF differential count

Tb meningitisTb meningitis

cerebrospinal fluid (CSF) white blood cell cerebrospinal fluid (CSF) white blood cell count of <1000/mm3, clear appearance of count of <1000/mm3, clear appearance of CSF, lymphocyte proportion of >30%, and CSF, lymphocyte proportion of >30%, and protein content of >100 mg/dL. protein content of >100 mg/dL.

LISTERIALISTERIA

Cephalosporins are inactive in vitro and Cephalosporins are inactive in vitro and ineffective clinically ineffective clinically

Ampicillin with gentamicin for synergyAmpicillin with gentamicin for synergy Imipenem or meropenem excellentImipenem or meropenem excellent

LISTERIALISTERIA

In the newborn, L. monocytogenes can present In the newborn, L. monocytogenes can present as an early onset sepsis in the first week of life, as an early onset sepsis in the first week of life, or more commonly, with a late onset after the or more commonly, with a late onset after the first week of life (usually first week of life (usually << 6 weeks, up to 2 6 weeks, up to 2 months). months).

Early-onset disease primarily is sepsis, with high Early-onset disease primarily is sepsis, with high neonatal mortality in association with maternal neonatal mortality in association with maternal illness and premature delivery. illness and premature delivery.

With late-onset disease, babies generally are With late-onset disease, babies generally are full-term and have no history of perinatal full-term and have no history of perinatal complications; cultures of CSF are more likely to complications; cultures of CSF are more likely to be positive than are blood cultures be positive than are blood cultures

LISTERIALISTERIA

ampicillin is added to the standard ampicillin is added to the standard therapeutic regimen of cefotaxime or therapeutic regimen of cefotaxime or ceftriaxone plus vancomycin when ceftriaxone plus vancomycin when L. L. monocytogenesmonocytogenes is considered and to an is considered and to an aminoglycoside if a gram-negative enteric aminoglycoside if a gram-negative enteric pathogen is of concern. pathogen is of concern.

NEONANEONA

DOL 7 irritable infant discharged DOL 2, DOL 7 irritable infant discharged DOL 2, “Full” fontanelle, poor feeding x 1 day“Full” fontanelle, poor feeding x 1 day

FSWUFSWU Antibiotics? Or wait for CSF Gram stain to Antibiotics? Or wait for CSF Gram stain to

help guide correct coverage?help guide correct coverage?

NEONANEONA

Prolonged hospitalization, add vancoProlonged hospitalization, add vanco Hardware, manipulation, add vancoHardware, manipulation, add vanco Otherwise amp and gent < DOL 7, amp Otherwise amp and gent < DOL 7, amp

and cefotaxime and cefotaxime >> DOL 7 DOL 7 If Gram stain shows Gram + diplococci => If Gram stain shows Gram + diplococci =>

add vancoadd vanco

NEONATNEONAT

DOL 20, former premature infant, DOL 20, former premature infant, T< 36T< 36 Suspect clinical meningitisSuspect clinical meningitis FSWU doneFSWU done Treatment?Treatment?

NEWBORNNEWBORN

if GBS or Listeriosis is suspected (eg, on if GBS or Listeriosis is suspected (eg, on the basis of the Gram stain), add ampicillin the basis of the Gram stain), add ampicillin because vancomycin concentrations in because vancomycin concentrations in the CSF are not bactericidal for these the CSF are not bactericidal for these organismsorganisms

GBS goes out to 3-4 months of ageGBS goes out to 3-4 months of age Listeria can go out to 6-8 weeks of ageListeria can go out to 6-8 weeks of age

NEONATENEONATE

The clinical presentation of neonatal The clinical presentation of neonatal meningitis often is indistinguishable from meningitis often is indistinguishable from that of neonatal sepsis without meningitis. that of neonatal sepsis without meningitis.

The most commonly reported clinical signs The most commonly reported clinical signs are temperature instability (T< 36), are temperature instability (T< 36), irritability, and poor feeding or vomiting irritability, and poor feeding or vomiting

NEONATANEONATA

Findings of neonatal bacterial meningitis, and their Findings of neonatal bacterial meningitis, and their approximate frequencies are listed below:approximate frequencies are listed below:

Fever or hypothermia T< 36: 60%Fever or hypothermia T< 36: 60% Poor feeding/vomiting: 50 percent Poor feeding/vomiting: 50 percent Respiratory distress (tachypnea, grunting, flaring Respiratory distress (tachypnea, grunting, flaring

of the nasal alae, retractions, decreased breath of the nasal alae, retractions, decreased breath sounds): 33 to 50 percent sounds): 33 to 50 percent

Apnea: 10 to 30 percent Apnea: 10 to 30 percent Diarrhea: 20 percent Diarrhea: 20 percent

NEONATENEONATE

GBS and Escherichia coli are the two most GBS and Escherichia coli are the two most common organisms causing neonatal common organisms causing neonatal meningitismeningitis

when E. coli occurs after 6 days of age, when E. coli occurs after 6 days of age, galactosemia should be excluded… galactosemia should be excluded…

NEONATNEONAT

Gram negative rods (esp E coli) in blood Gram negative rods (esp E coli) in blood or CSF in infant > DOL 6, suspicion for or CSF in infant > DOL 6, suspicion for galactosemia (vomiting, jaundice, HSM)galactosemia (vomiting, jaundice, HSM)

Send urine for reducing substancesSend urine for reducing substances

Neonate-N. MeningNeonate-N. Mening

Neisseria meningitidis also can rarely Neisseria meningitidis also can rarely cause meningitis in newborn infants. cause meningitis in newborn infants.

73 percent of neonates that had N. mening 73 percent of neonates that had N. mening disease had meningitisdisease had meningitis

NEONATAL BACTNEONATAL BACT

In a Canadian review of 101 infants with gestational age In a Canadian review of 101 infants with gestational age 35 weeks admitted to a tertiary care center with a 35 weeks admitted to a tertiary care center with a diagnosis of neonatal meningitis between 1979 and diagnosis of neonatal meningitis between 1979 and 1998, the following organisms were cultured:1998, the following organisms were cultured:

Group B Streptococcus — 50 percent of cases Group B Streptococcus — 50 percent of cases E. coli — 25 percent E. coli — 25 percent Other gram-negative rods — 8 percent Other gram-negative rods — 8 percent Listeria monocytogenes — 6 percent Listeria monocytogenes — 6 percent Streptococcus pneumoniae — 5 percent Streptococcus pneumoniae — 5 percent Group A Streptococcus — 4 percent Group A Streptococcus — 4 percent Haemophilus influenzae — 3 percent Haemophilus influenzae — 3 percent

NEON / LABNEON / LAB

Isolation of a bacterial pathogen from the Isolation of a bacterial pathogen from the CSF by culture or visualization by Gram CSF by culture or visualization by Gram stain stain

Increased CSF white blood cell (WBC) Increased CSF white blood cell (WBC) count (typically >1000 WBC/microL, but count (typically >1000 WBC/microL, but may be lower, especially with gram-may be lower, especially with gram-positive organisms), with a predominance positive organisms), with a predominance of neutrophils of neutrophils

NEONATE LABNEONATE LAB

Neonates can have normal CSF Neonates can have normal CSF parameters and yet meningitisparameters and yet meningitis

If clinical suspicion for meningitis is high, If clinical suspicion for meningitis is high, empirically treat and “ignore” normal empirically treat and “ignore” normal resultsresults

NEONATNEONAT

Neonates < DOL 7, mothers treated Neonates < DOL 7, mothers treated antenatally for Group B strep, 75% antenatally for Group B strep, 75% successfulsuccessful

ie 25% can still get Group B strep sepsis ie 25% can still get Group B strep sepsis or meningitisor meningitis

NEONATENEONATE

>1 month of age vancomycin + cefotaxime >1 month of age vancomycin + cefotaxime or ceftriaxoneor ceftriaxone

Gram stain may modify eg ADD ampicillin Gram stain may modify eg ADD ampicillin for the presence of gram-positive cocci or for the presence of gram-positive cocci or bacilli (rods)bacilli (rods)

Proven enteroviral meningitisProven enteroviral meningitis

The odds of a CSF white blood cell being The odds of a CSF white blood cell being mononuclear increased by 15.7% (95% mononuclear increased by 15.7% (95% confidence interval: -3.8% to 38.0%; P confidence interval: -3.8% to 38.0%; P = .11) for each day of symptoms. Fifty = .11) for each day of symptoms. Fifty percent of patients with symptoms of 1 day percent of patients with symptoms of 1 day or less had predominance of mononuclear or less had predominance of mononuclear cells among CSF white blood cells cells among CSF white blood cells

Soft correlation though, other factors such Soft correlation though, other factors such as amount of meningeal irritationas amount of meningeal irritation

EV -LABEV -LAB

White blood cells (WBC) — Pleocytosis usually ranges White blood cells (WBC) — Pleocytosis usually ranges from 10 to 500 cells/microL (higher values can be seen from 10 to 500 cells/microL (higher values can be seen with some viruses); mononuclear leukocytes with some viruses); mononuclear leukocytes predominate in most cases, although polymorphonuclear predominate in most cases, although polymorphonuclear (PMN) leukocytes have been described early and late in (PMN) leukocytes have been described early and late in the course of EV meningitis. the course of EV meningitis.

Normal WBC counts can be seen in EV and more rarely Normal WBC counts can be seen in EV and more rarely with HSV meningoencephalitiswith HSV meningoencephalitis

Glucose — Normal or slightly reduced, usually 40 Glucose — Normal or slightly reduced, usually 40 percent or more of the serum value. percent or more of the serum value.

Protein — Normal to slightly elevated protein, usually Protein — Normal to slightly elevated protein, usually less than 150 mg/dL. less than 150 mg/dL.

N. MENINGN. MENING

w/ meningococcemia, most children (72 w/ meningococcemia, most children (72 percent) had one of the three sepsis percent) had one of the three sepsis symptoms (eg, leg pain, abnormal skin symptoms (eg, leg pain, abnormal skin color, or cold hands and feet) at a median color, or cold hands and feet) at a median time of 8 hours after onset of illness, 11 time of 8 hours after onset of illness, 11 hours sooner than the median time of hours sooner than the median time of hospital admission (19 hours). hospital admission (19 hours).

N. meningN. mening

Inotropic support—dopamine, dobutamine, Inotropic support—dopamine, dobutamine, adrenaline (epinephrine)—may be started adrenaline (epinephrine)—may be started and then given in combination if response and then given in combination if response is suboptimal. is suboptimal.

Eventual infusion of fluid up to several Eventual infusion of fluid up to several times the circulating blood volume may be times the circulating blood volume may be needed. needed.

N. MENING-Archiv 9/02N. MENING-Archiv 9/02

N. mening notorious (8%)for normal CSF N. mening notorious (8%)for normal CSF and + culture- tx all cases of suspected N. and + culture- tx all cases of suspected N. mening for meningitismening for meningitis

Gram stain + in 70-80% of meningitis, Gram stain + in 70-80% of meningitis, could miss 30%could miss 30%

Immunodeficient child, add fungal and Immunodeficient child, add fungal and mycobacterial analysesmycobacterial analyses

N. MENINGN. MENING

The vital signs often show a low blood The vital signs often show a low blood pressure with an elevated pulse rate. The pressure with an elevated pulse rate. The patient should be examined for postural patient should be examined for postural hypotension as a sign of early vascular hypotension as a sign of early vascular instability. instability.

N. MENINN. MENIN

The mucous membranes of the soft The mucous membranes of the soft palate, ocular and palpebral conjunctiva palate, ocular and palpebral conjunctiva must be carefully examined for signs of must be carefully examined for signs of hemorrhage. Over 50 percent of patients hemorrhage. Over 50 percent of patients will have petechiae upon presentationwill have petechiae upon presentation

Fever and petechiae “below the nipple Fever and petechiae “below the nipple line” – just takes 1 petechiaeline” – just takes 1 petechiae

““Tumbler test”Tumbler test”

Duration of Antimicrobial Therapy Duration of Antimicrobial Therapy for Meningitis Based on Isolated for Meningitis Based on Isolated

PathogenPathogen

MicroorganismMicroorganism Duration of therapy, daysDuration of therapy, daysNeisseria meningitidisNeisseria meningitidis 77Haemophilus influenzaeHaemophilus influenzae 77Streptococcus pneumoniaeStreptococcus pneumoniae 10-1410-14Streptococcus agalactiaeStreptococcus agalactiae 14-2114-21Aerobic gram-negative bacilli Aerobic gram-negative bacilli 2121Listeria monocytogenesListeria monocytogenes 2121Neonatal HSV Neonatal HSV 2121

LATEX AGGLATEX AGG

Latex AgglutinationLatex Agglutination false-positive resultsfalse-positive results Practice Guideline Committee does not Practice Guideline Committee does not

recommend routine use recommend routine use most useful for the patient who has been most useful for the patient who has been

pretreated with antimicrobial therapypretreated with antimicrobial therapy

Latex AgglutinationLatex Agglutination

Organisms available:Organisms available:

Neisseria MeningitisNeisseria Meningitis HIBHIB S. pneumoS. pneumo Group B strepGroup B strep Cryptococcal (HIV, immunocompromised)Cryptococcal (HIV, immunocompromised)

PCRPCR

Organisms available:Organisms available: HSVHSV EnterovirusEnterovirus

? Faster PCR assay for Enterovirus?? Faster PCR assay for Enterovirus? Turn around < 4 hoursTurn around < 4 hours Avoid hospitalizationAvoid hospitalization ? 2007? (Reimbursement issue)? 2007? (Reimbursement issue)

CaseCase

3 month old fever, persistent irritability, 3 month old fever, persistent irritability, bulging fontanellebulging fontanelle

FSWUFSWU

In addition to empiric antibiotics, should In addition to empiric antibiotics, should you use dexamethasone?you use dexamethasone?

Case (continued)Case (continued)

What if you pushed cefotaxime alone and What if you pushed cefotaxime alone and the Gram stain looked liked this?the Gram stain looked liked this?

Would you now add dexamethasone?Would you now add dexamethasone?

DEXDEX

What Is the Role of Adjunctive What Is the Role of Adjunctive Dexamethasone Therapy in Patients Dexamethasone Therapy in Patients with Bacterial Meningitis?with Bacterial Meningitis?

NeonatesNeonates ““At present, there are insufficient data to At present, there are insufficient data to

make a recommendation on the use of make a recommendation on the use of adjunctive dexamethasone in neonates adjunctive dexamethasone in neonates with bacterial meningitis”with bacterial meningitis”

DEXDEX

The 2003 statement by the Committee on The 2003 statement by the Committee on Infectious Diseases of the American Infectious Diseases of the American Academy of Pediatrics on the use of Academy of Pediatrics on the use of steroids for steroids for pneumococcalpneumococcal meningitis is as meningitis is as follows: "For infants and children 6 weeks follows: "For infants and children 6 weeks of age and older, adjunctive therapy with of age and older, adjunctive therapy with dexamethasone may be considered after dexamethasone may be considered after weighing the potential benefits and weighing the potential benefits and possible risks.."possible risks.."

DexDex

Is there a downside to Dex?Is there a downside to Dex?

? Unclear if it affects CSF penetration by ? Unclear if it affects CSF penetration by antimicrobials, since reduce inflammation.antimicrobials, since reduce inflammation.

Could be most true for vancomycin, which Could be most true for vancomycin, which well known to have poor CSF penetrationwell known to have poor CSF penetration

DEXDEX

Dexamethasone should be initiated 10-20 min Dexamethasone should be initiated 10-20 min prior to, or at least concomitant with, the first prior to, or at least concomitant with, the first antimicrobial dose, at 0.15 mg/kg every 6 h for antimicrobial dose, at 0.15 mg/kg every 6 h for 2-4 days. 2-4 days.

Adjunctive dexamethasone should not be given Adjunctive dexamethasone should not be given to infants and children who have already to infants and children who have already received antimicrobial therapy, because received antimicrobial therapy, because administration of dexamethasone in this administration of dexamethasone in this circumstance is unlikely to improve patient circumstance is unlikely to improve patient outcome outcome

DEXDEX

Meningococcal meningitis appears to have Meningococcal meningitis appears to have the lowest risk of major neurological the lowest risk of major neurological sequelae compared with pneumococcal sequelae compared with pneumococcal and H. influenzae meningitisand H. influenzae meningitis

HIB >> S. pneumo >> N. Mening (in terms HIB >> S. pneumo >> N. Mening (in terms of neurologic sequelae.) Dexamethasone of neurologic sequelae.) Dexamethasone efficacy seems to be in that order as well.efficacy seems to be in that order as well.

DexDex

Bottom line:Bottom line:

Fairly good evidence to use in the Fairly good evidence to use in the pediatric population older than 1 month old pediatric population older than 1 month old age, especially if suspect HIB or S. age, especially if suspect HIB or S. pneumo meningitis as potential pathogenpneumo meningitis as potential pathogen

DEXDEX Clinical scenarioClinical scenario

An 18 year old student is brought to the Emergency Department An 18 year old student is brought to the Emergency Department having been found collapsed in her room. She had been seen by having been found collapsed in her room. She had been seen by her friends earlier in the day, when she reported that she had a her friends earlier in the day, when she reported that she had a severe headache. On examination, she is found to have a severe headache. On examination, she is found to have a temperature of 38.40C, a GCS of 12 (E3 M6 V3) and slight neck temperature of 38.40C, a GCS of 12 (E3 M6 V3) and slight neck stiffness. She is noted to be more settled with the lights out. There is stiffness. She is noted to be more settled with the lights out. There is no papilloedema and no focal neurological signs. You make an no papilloedema and no focal neurological signs. You make an initial diagnosis of bacterial meningitis, but in view of the depressed initial diagnosis of bacterial meningitis, but in view of the depressed level of consciousness request a CT Brain before lumbar puncture level of consciousness request a CT Brain before lumbar puncture is carried out. This will take at least one hour to be organised, and in is carried out. This will take at least one hour to be organised, and in the meantime, you decide to proceed with intravenous ceftriaxone. the meantime, you decide to proceed with intravenous ceftriaxone. You are unsure whether she would benefit from the administration You are unsure whether she would benefit from the administration of dexamethasone prior to her antibiotics.of dexamethasone prior to her antibiotics.

DexDex

European Dexamethasone in Adulthood Bacterial European Dexamethasone in Adulthood Bacterial Meningitis TrialMeningitis Trial

In this prospective, randomised, double-blind, In this prospective, randomised, double-blind, multicenter trial, which included 301 adults with bacterial multicenter trial, which included 301 adults with bacterial meningitis, treatment with dexamethasone was meningitis, treatment with dexamethasone was associated with a reduction in mortality (relative risk of associated with a reduction in mortality (relative risk of death, 0.48; 95 CI 0.24 to 0.96; p = 0.04). death, 0.48; 95 CI 0.24 to 0.96; p = 0.04).

Therefore, dexamethasone should be given to all adults Therefore, dexamethasone should be given to all adults with bacterial meningitis and should be initiated before or with bacterial meningitis and should be initiated before or with the first dose of antibiotics.with the first dose of antibiotics.

DEXDEX

Currently there is not sufficient published Currently there is not sufficient published evidence to recommend early use of evidence to recommend early use of dexamethasone in order to improve dexamethasone in order to improve neurological outcome in children with neurological outcome in children with meningococcalmeningococcal meningitis. meningitis.

One study showed possibly One study showed possibly disadvantageous as far as hearing is disadvantageous as far as hearing is concernedconcerned

PROGNOSISPROGNOSIS

In one meta-analysis of bacterial meningitis, 83.6 In one meta-analysis of bacterial meningitis, 83.6 percent of the surviving children in developed countries percent of the surviving children in developed countries and 73.9 percent in developing countries had apparently and 73.9 percent in developing countries had apparently complete recovery. The most common sequelae present complete recovery. The most common sequelae present after hospital discharge in the remaining children were:after hospital discharge in the remaining children were:

Deafness — 10.5 percent, including bilateral severe or Deafness — 10.5 percent, including bilateral severe or profound deafness in 5.1 percent profound deafness in 5.1 percent

Mental retardation — 4.2 percent Mental retardation — 4.2 percent Spasticity and/or paresis — 3.5 percent Spasticity and/or paresis — 3.5 percent Seizures — 4.2 percent Seizures — 4.2 percent

PROGNOSIS/ EARLY TXPROGNOSIS/ EARLY TX

The factors contributing to the time required to The factors contributing to the time required to institute therapy were illustrated by a survey of institute therapy were illustrated by a survey of 93 children presenting to the emergency 93 children presenting to the emergency department of two university-affiliated hospitals [ department of two university-affiliated hospitals [ The mean time to initiation of antibiotic therapy The mean time to initiation of antibiotic therapy was two hours. The median time from triage to was two hours. The median time from triage to contact with a physician was 45 minutes, and contact with a physician was 45 minutes, and the time from lumbar puncture until the the time from lumbar puncture until the administration of antibiotics was 30 minutes. administration of antibiotics was 30 minutes. Only one child was treated within 30 minutes Only one child was treated within 30 minutes

What if antibiotics are given before LP What if antibiotics are given before LP is done?is done?

STERLIZ OF CSFSTERLIZ OF CSF

Among children with meningococcal meningitis Among children with meningococcal meningitis who were treated with a parenteral dose of an who were treated with a parenteral dose of an extended-spectrum cephalosporin, three of nine extended-spectrum cephalosporin, three of nine LPs were sterile within one hour (occurring as LPs were sterile within one hour (occurring as early as 15 minutes) and all were sterile by two early as 15 minutes) and all were sterile by two hours. hours.

Sterilization of the CSF was slower with Sterilization of the CSF was slower with pneumococcl meningitis. The first negative pneumococcl meningitis. The first negative culture was obtained four hours and five of culture was obtained four hours and five of seven were negative by ten hours. seven were negative by ten hours.

LPLP

Lumbar puncture should be deferred:Lumbar puncture should be deferred: signs of cerebral herniationsigns of cerebral herniation focal neurological signs / papilledemafocal neurological signs / papilledema cardiorespiratory compromisecardiorespiratory compromise risk for brain abscess risk for brain abscess

ImmunocompromisedImmunocompromised Congenital heart with right to left shuntCongenital heart with right to left shunt

? Skin/soft tissue infection at LP site &? Skin/soft tissue infection at LP site & ? bleeding disorder ? bleeding disorder

(? = based on single case reports)(? = based on single case reports)

LPLP

Signs of cerebral herniation:Signs of cerebral herniation: Check pupils before you LPCheck pupils before you LP Irregular respirationsIrregular respirations Abnormal toneAbnormal tone GCS < 8GCS < 8 Focal signsFocal signs Contraindications to LP, Contraindications to LP, even if CT normaleven if CT normal

What about the patient with fever and What about the patient with fever and seizure? ie who do you need to LP?seizure? ie who do you need to LP?

FEBR SZFEBR SZ

A recently published guideline (Arch Dis A recently published guideline (Arch Dis Child ’05) for the management of a child Child ’05) for the management of a child with a with a febrilefebrile seizure recommends seizure recommends antibiotic treatment for children who:antibiotic treatment for children who:

have meningismushave meningismus were drowsy before the seizurewere drowsy before the seizure have altered consciousness > 1hour after have altered consciousness > 1hour after

seizureseizure

FEBR SZFEBR SZ

Duration of febrile seizure > 15 minutes, Duration of febrile seizure > 15 minutes, significantly higher rate of bacterial significantly higher rate of bacterial meningitis (1% vs 18% range in literature)meningitis (1% vs 18% range in literature)

What about Gram stains?What about Gram stains?

GRAM STAINS ORGGRAM STAINS ORG

Gram positive diplococci suggest pneumococcal Gram positive diplococci suggest pneumococcal infection infection

Gram positive cocci or coccobacilli suggest Gram positive cocci or coccobacilli suggest group B streptococcusgroup B streptococcus

Gram positive rods and coccobacilli suggest Gram positive rods and coccobacilli suggest listerial infectionlisterial infection

Gram negative (intracellular) diplococci suggest Gram negative (intracellular) diplococci suggest meningococcal infectionmeningococcal infection

Small pleomorphic Gram negative coccobacilli Small pleomorphic Gram negative coccobacilli suggest Haemophilus influenzae suggest Haemophilus influenzae

CSF LABCSF LAB

CSF parameters in Harriet Lane (cells, CSF parameters in Harriet Lane (cells, protein, glucose)protein, glucose)

Preterm (neonate)Preterm (neonate) Term (neonate)Term (neonate) Child (> neonate)Child (> neonate)

SUMMARYSUMMARY

Dex:Dex:

Neonates - NoNeonates - No Everyone else - Yes Everyone else - Yes Not HIB or S.pneumo – NoNot HIB or S.pneumo – No

NO if antibiotics are already givenNO if antibiotics are already given

SUMMARYSUMMARY

Neonates- subtle clinical signs or none, Neonates- subtle clinical signs or none, normal initial labs possiblenormal initial labs possible

No vancomycin unless Gram positive No vancomycin unless Gram positive cocci in pairs/chains (Pneumococcus)cocci in pairs/chains (Pneumococcus)

Amp/gent < DOL 7 Amp/gent < DOL 7 Amp/cefotax > DOL7Amp/cefotax > DOL7

SUMMARYSUMMARY

RememberRemember

1 vesicle in the neonate1 vesicle in the neonate 1 petechiae, especially below the nipple line1 petechiae, especially below the nipple line

SUMMARY- What’s the Bug?SUMMARY- What’s the Bug?

Gram + diplococciGram + diplococci Gram + cocciGram + cocci Gram + rodsGram + rods Gram – diplococciGram – diplococci Gram - rodsGram - rods