meningitis agents of infant-->elderly Flashcards
Streptococcus pneumoniae
Gram-positive, lancet-shaped diplococcus
Not fastidious, grows on blod agar – alpha hemolytic.
aerotolerant anaerobe - catalse negative
S. pneumo virulence factors
Encapsulated (90 serotypes):
antiphagocytic.
little or no crossreactivity among capsular types relates to possibility of multiple infections.
coagulase negative
S. pneumo Incidence and Prevalence:
Most common infectious agent associated with patients with RECURRENT meningeal infections.
Of the 7 major agents of bacterial meningitis, the HIGHEST CASE FATALITY RATE occurs with pneumococcal meningitis
S. pneumo peaks in what age groups ??
young (infants and children
S. pneumo Risk Factors
Patients may have:
antecedent RT infections → pneumonoccal pulmonary infections.
CSF leaks → recurrent meningeal infections
consistent with the presence of CSF
Invasive Pneumococcal Disease (IPD
CSF leaks occur in patients with:
history of head trauma.
congenital defect
*it is not uncommon to observe CSF leakage through ear or nose; If the fluid contains β2-transferrin, that finding consistent with the presence of CSF
a common complication of pneumococcal pneumonia that occurs in many (@25→ 30% of all) cases ??
meningitis?
Invasive Pneumococcal Disease (IPD)
Disease in which agent has been isolated from a normally sterile site:
blood
CSF
synovial fluid
S. pneumo pathogenesis
Primary site of damage is the hippocampus due to neuronal injury/loss via induced apoptosis
If pneumococcal bacteremia occurs, may produce petechial-purpuric skin lesions (AKA symmetrical peripheral gangrene (SPG) but no organisms are present in the lesion. (Indistinguishable in appearance from purpura fulminans caused by N. meningitidis, except that the pneumococcus is not in the lesion)
S. pneumo tx
IV cefotaxime (an extended-spectrum cephalosporin, 200 mg/kg/d) and continuous infusion vancomycin (60mg/kg/d after a loading dose of 15mg/kg) with adjunctive therapy with dexamethasone (10 mg every 6 hours) until strain is proven penicillin-sensitive (penicillins)
Adjunctive therapy with dexamethasone
Penicillin susceptible (PenicillinS) S. pneumo is treated with penicillin
Penicillin nonsusceptible S. pneumoniae (PNSP) include both
intermediately resistance to penicillin
full resistance to penicillin.
Resistance to other antibiotics also appeared along with penicillin resistance:
Trimethoprim-Sulfamethoxazole,
Macrolides; Erythromycin resistance is common (@ 20%) in USA
Fluoroquinolones
Drug-resistance S. pneumoniae (DRSP)
present and increasing in US
due to mutations in PBPs (AKA transpeptidases).
(Resistance to cephalosporins is also increasing, but may be effective)
Strains resistant to penicillin are often resistant to at least one other antibiotic, thus penicillin (the drug) resistance is a marker for resistance to several drugs
Multiply drug resistant (MDR) S. pneumoniae (MDRSP)
are resistant to >3 classes of antibiotics.
Vancomycin tolerance
(antibiotic is now static, no longer tidal):
First step in acquisition of vancomycin resistance is occurring in a small percentage of community-circulating strains.
Vancomycin tolerance occurs with penicillin, aminoglycoside and quinolone tolerance.
Clinically Important, related to relapses, esp. in pediatric cases of pneumococcal meningitis.
Prophylaxis to prevent S. pneumoniae disease:
23 valent polysaccharide vaccines (PPV23; Type II, T-cell independent antigen; Pneumovax or Pnu-immune) (pneumonia in elderly)
conjugated vaccine (T-dependent antigen; PCV-7 AKA Prevenar [7 valent vaccine]) is FDA approved and has resulted in a significant decreases in pneumococcal meningitis (kiddos)
Neisseria meningitidis – Meningococcal Meningitis spp.
Two pathogenic species:
N. meningitidis (the meningococcus).
N. gonorrhoeae (the gonococcus).
Nonpathogenic species:
NF of URT and other mucosal surfaces in the human body.
Many nonpathogenic species are non-encapsulated variants of the encapsulated/disease-causing strains of N. meningitidis
Characteristics of Neisseria meningitidis (the meningococcus):
Gram-negative diplococcus - kidney-bean shaped
oxidase positive
fastidious.
N. meningitidis Virulence factors and surface antigens
Group specific polysaccharide capsule (lipid moiety integrated into O.M.)
All infectious meningococcus are encapsulated and are grouped, based largely on the serological differences in capsular types.
Numerous groups exist; important groups:
A, B, C, Y, W-135, X
Capsular polysaccharide is antiphagocytic.
Group-specific antibodies do not significantly cross-react.
Type B capsule and E. coli K1 capsule have the same chemical composition (sialic acid); sialic acid is a human self antigen, hence are poorly immunogenic.
N. meningitidis Possess ??? instead of LPS
Lipooligosaccharide (LOS):
consists of Lipid A (endotoxin) + extended core (no antigenic side chain).
is antiphagocytic by molecular mimicry
causes Disseminated Intravascular Coagulopathies (DIC) because contains lipid A.
N. meningitidis Endemic patterns (in the US):
Case rate is low (0.5 → 1.1/100,000 population).
Major serogroups are B, C, Y
Serogroup B causes ½ of all infection in the US.
Serogroup Y infected patients are more likely to be older, manifest with pneumonia.
N. meningitidis Epidemic patterns:
countries where meningococcal disease is hyperendemic or epidemic – Africa and Middle Eastern countries.
in North America vs the rest of the world: Specific serogroups of meningococci are associated with epidemics, which occur in cycles.
N. meningitidis transmission
via aerosols, respiratory droplets
POE and initial site of colonization is the nasopharynx
N. meningitidis Host and source:
humans are the only reservoir for all Neisseria sp.
Non-immune and short-term, group-specific immune carriers exist.
Carrier state duration is highly variable (days → 10 m); chronic carriers do occur.
Carriers are common in epidemics, but few develop disease (1case/1,000 carriers).
Non-immune and immune carriers are largely responsible for spread of disease via aerosols because their numbers are so great vs. diseased patient
N. meningitidis age groups
infants and children (1 month → 24 months-o-age)
older children/adolescents (6 → 19 y-o-age).
young adults (19 → 22 y-o-age): military recruits. college students living in dorms.
N. menigitidis seasonality
Late fall → winter → early spring
crowding
N. meningitidis risk factors
Close contact, crowding → increased risk of exposure and infection.
Susceptibility (lack of group-specific antibodies):
living in a college dormitory or basic training in the military increases a susceptible persons’ increased risk of exposure to new groups of meningococci
N. meningitidis Undefined predisposing conditions: (FYI?)
antecedent RT may predispose host to infection,
intimate kissing.
tobacco smoke exposure (direct or pasive),
bar patronage,
household crowding,
binge drinking,
low socioeconomic status,
N. meningitidis: Susceptible populations in which disease predominates:
Infants → Young adults (1 month → 22 y-of-age).
Families (familial spread) and close contacts.
Genetic predisposition to infection and more severe disease is documented, i.e., some (20% of all) patients with meningococcal meningitis also possess properdin, complement (C3, homozygous C4b, C5, C6, C7, C8), or other deficiencies.
(esp. C5-C9-terminal)
N. meningitidis pathogenesis
After colonization of nasopharynx, the organism invades the blood (meningococcemia) and then from the blood, invades the meninges:
Thrombosis→DIC results from loss of thrombomodulin & protein C receptor (these are down-regulated by inflammatory cytokines). Thus activated protein C and not unactivated protein C is required to decrease DIC in your patient.
Immunity to N. meningitides is provided by several components of the immune system:
Humoral anticapsular antibodies are protective. Most adults have protective antibody to at least some groups.
Complement system is also necessary for protection.
Clinical Manifestations of Neisseria meningitidis
aged 16 years or younger:
Early symptoms of sepsis occurred in 72% of children at a median time of 8 hour:
leg pains.
cold hands and feet.
abnormal skin color.
Late symptoms: meningism and impaired consciousness occur about 13 to 22 hours after onset of early symptoms.
Clinical Manifestations of Neisseria meningitides: adults
Early symptoms may occur and consist of only mild pharyngitis without exudate, slight fever, and headache at onset
OR several days of flu-like symptoms with emesis
then the classic symptoms of meningitis occur
OR classic symptoms without early symptoms occur
Besides the classic clinical manifestations of meningitis, petechial (non-blanching, hemorrhagic) rash on ankles and wrist (first) then trunk, thigh, forearms may appear if ?? also present
septicemia
Patients may survive disease without or with significant sequelae from N. meningitidis, which include:
nerve deafness
CNS damage
necrosis of large areas of skin or tissues often results in amputation
Waterhouse-Friderichsen syndrome
fulminant meningococcemia characterized by:
circulatory shock due to SIRS → severe sepsis or septic shock.
bilateral hemorrhagic necrosis of adrenals → low cortisol leves → hypotension
disseminated intravascular coagulation
*not limited to N. meningitidis; this disease is seen in certain other fulminant bacterial diseases
Purpura fulminans AKA symmetrical peripheral gangrene (SPG): meningococcemia +/- meningitis: complications
hypothermia. seizures. shock. thrombocytopenia. leukocytosis. purpura - meningococcus is in the lesions.
highest mortality rate (15→50%) occurs with Group C disease, esp. in persons with purpura fulminans, even with appropriate treatment
*not limited to N. meningitidis; this disease is seen in certain other fulminant bacterial diseases
