Meningitis/ C. diff Flashcards
causes of meningitis
infection (bacteria/ virus/ fungi/ parasite/ TB/ syphilis)
Drugs (bactrim, ibuprofen)
Autoimmune disease
Which populations are more susceptible to bacterial meningitis?
Men (> female)
More common in children
Pathogenesis of meningitis
immune deficiency/ prolonged close contact/ travel to endemic areas
-> predisposes infection & colonisation by bacteria that can cause meningitis
*strep pneumo, N. meningitidis, H. influenzae, L. monocytogenes etc
-> Bacteria gain entry into the body via various mechanisms:
1. invasion of mucosal surface
2. spread from para-meningeal focus (otitis media, sinusitis etc)
3. penetrating head trauma
4. anatomic defects in meninges
5. previous neurological procedures
-> in a susceptible host: bacteria enter CSF & colonise meninges *esp arachnoids -> bacterial meningitis
Risk factors/ predisposing factors for bacterial meningitis
head trauma
CNS shunts
neurosurgical patients
CSF fistula/ leak
local infections (otitis media, sinusitis)
immunosuppression
splenectomised pts
congenital defects
symptoms of bacterial meningitis
fever
chills
*(classic triad) headache/ backache/ nuchal (neck) rigidity
nausea, vomiting, anorexia, poor feeding habits in infants
petechiae/ purpura (specific for neisseria meningitis)
physical signs:
Kernig sign (while supine, 1 leg raised 90degrees -> pain)
Brudzinski sign ( while supine, legs bend as neck is lifted from ground)
Bulging fontane: ‘soft’ spot @ centre of infant’s skull (natural)
diagnosis for bacterial meningitis (lab measures etc)
History & physical examination (any headache/backache/neck rigidity, Kernig/Brudzinski sign)
Blood cultures (>50%: +ve)
Lumbar puncture:
Opening pressure - elevated
CSF composition - elevated WBCs (>100/mm3) & protein (>1.5g/L), lowered glucose (<0.4)
CSF gram stain & culture
CSF PCR
General lab findings (WBC, CRP, calcitonin) *non-specific for bact. meningitis
Radiology (brain imaging) *for differential diagnosis
Empiric therapy for bacterial meningitis in NEONATES
Likely pathogen: Group B Strep (S. agalactiae) // E.coli // Listeria monocytogenes
Abx: IV ceftriaxone (2g q12h(?)) + IV ampicillin (2g q4h(?))
*ampi - covers listeria
Duration of therapy:
Group B strep - 14-21d
Listeria - =/>21d
Empiric therapy for bacterial meningitis for INFANTS (1-23mths)
Likely pathogen: Strep pneumo // N. meningitidis // E.coli // Group B Strep (S. agalactiae)
Abx: IV Ceftriaxone (2g q12h(?)) + IV Vancomycin (25-30mg/kg LD, 15mg/kg q8-12h until AUC/MIC 400-600(?))
*vanco: covers strep pneumo
Duration of therapy
Strep pneumo - 10-14d
N. meningitidis - 5-7d
Group B Strep - 14-21d
Empiric therapy for bacterial meningitis in children & adult (2-50y/o)
Likely pathogen: strep pneumo // n. meningitidis
Abx: IV Ceftriaxone (2g q12h) + IV vancomycin (25-30mg/kg LD, 15mg/kg q8-12h until AUC/MIC 400-600)
*vanco covers strep pneumo
Duration of therapy:
Strep pneumo - 10-14
N. meningitidis - 5-7
Empiric therapy for bacterial meningitis in adults (>50y/o)
Likely pathogen: Strep pneumo // N. meningitidis // Listeria monocytogenes // aerobic GN bacilli (E.coli/Klebsiella)
Abx: IV Ceftriaxone (2g q12h) + IV Vancomycin (25-30mg/kg LD, 15mg/kg q8-12h until AUC/MIC of 400-600) + IV Ampicillin (2g q4h)
*vanco covers strep pneumo, ampi covers listeria
Duration of therapy:
N. meningitidis: 5-7
Listeria monocytogenes: =/>21d
Culture-directed therapy for bacterial meningitis
- Strep pneumo (10-14d)
pen sensitive - ampicillin, Pen G
pen resistant, ceph susceptible - ceftriaxone
pen & ceph resistant - vanco + rifampicin - N. meningitidis (5-7d)
pen sensitive - pen G, ampicillin
pen resistant OR mild allergy - ceftriaxone - Listeria monocytogenes (>/= 21d)
pen sensitive - Pen G, ampicillin
**pen ALLERGY - co-trimoxazole, meropenem - Group B Strep (14-21d)
pen sensitive - Pen G, ampicillin
pen MILD allergy - ceftriaxone
Doses (all IV):
*Pen G - 4 MU q4h (not inside dosing table)
Ampicillin - 2g q4h
Ceftriaxone - 2g q12h
Vanco - 25-30mg/kg LD, 15mg/kg q8-12h until AUC/MIC of 400-600
*Rifampicin - 300mg q12h (not inside dosing table)
Co-trimoxazole
Meropenem - 2g q8h
**IF CULTURE -VE: STILL TREAT WITH EMPIRIC ABX FOR 14D (start from 1st day of ACTIVE therapy; unless MSSA bacteremia start counting from 1st day of culture -ve)
Adjunctive therapy in bacterial meningitis
Corticosteroids - Dexamethasone
* recommended for pts w bacterial meningitis beyond neonatal age (>6 weeks)
- allows LESS hearing loss & other neurologic sequelae in H. influenzae & S. pneumoniae meningitis
- allows LESS mortality in S. pneumoniae meningitis
**may decrease antibiotic penetration (less inflammation)
ADR: mental status change, hyperglycemia, HTN
- Administer 10-20mins BEFORE or AT SAME TIME as FIRST dose of abx
- (Adult dose) 10mg q6h (UP TO 4D)
*stop if pt NOT having bacterial meningitis/ species not H. influenzae/ Strep pneumo
Monitoring response from bacterial meningitis therapy
- Resolution of S&S: Most pts improve within 48h
- no need to repeat culture if improving clinically
*if did not improve within 48h -> brain imaging to check for cerebrovascular complications eg. stroke, brain abscess - ADR monitoring:
morbidity common in bacterial meningitis - Focal neurological deficits (hearing impairment, cognitive impairment, seizures)
- After bacterial meningitis infection: pt at HIGH RISK of long-term neurological & neuropsychological deficits (impair daily life activities & QoL)
Chemoprophylaxis for close contacts of pt with bacterial meningitis
- for Neisseria Meningitidis
- Risk of meningococcal disease increased 400-800x for close contacts (HIGHEST RISK: household contacts)
- Beneficial for CLOSE CONTACTS (household/ day care) or EXPOSURE TO ORAL SECRETIONS of index case
- Rifampicin (PO)
adults: 600mg q12h, 4 doses
children: 10mg/kg q12h, 4 doses
infants (<1mth): 5mg/kg q12h, 4h - Ciprofloxacin (PO) *ADULTS ONLY
500mg, 1dose - Ceftriaxone (IM)
125-250mg, 1 dose
Features of C.diff & its infection
Gram +ve
SPORE-forming
ANAEROBIC bacillus
TOXIGENIC strain produces TOXIN A & B
*more clinically impt toxin: toxin B
causative organism of abx-associated DIARRHOEA & COLITIS
*most common cause of nosocomial diarrhea
SPORES transmission: by faecal-oral route
Presentation ranges from ASYMPTOMATIC to FULMINANT disease
Pathogenesis of C. diff infection
colonisation of intestinal tract with C. diff via faecal-oral route (facilitated by abx use: disruption of barrier function of normal colonic flora; provide niche for C Diff multiplication & toxic production)
*TOXIN A & B -> inflammation & diarrhea
*asymptomatic carriers carry ANTIBODIES (high serum levels) which are protective against C diff toxins.
Risk factors for C. diff infection
Advanced age >65y/o
multiple/ severe comorbidities
immunosuppression
history of CDI
GI surgery
tube feeding
prior hospitalisation (last 1y)
duration of hospitalisation
residence in nursing home/ long-term care facilities
*use of gastric acid suppressive therapy
use of abx
Antibiotics that may cause/ protects against C. diff
almost all antibiotics can cause C. diff infection
Greatest risk:
1. Clindamycin (OR 16.8)
2. 3rd & 4rd gen cephalosporins (OR 5.68)
3. Fluoroquinolones (OR 5.5)
*greatest risk while on abx but still elevated until 12wks later
PROTECTIVE: doxycycline/ tigecycline
- Active against C. diff growth + inhibits toxin production
- Minimal effect on gut flora
C. diff infection pt control & prevention
- isolation
- private room w dedicated toilet OR prioritise pts w stool incontinence - hand hygiene
- environmental cleaning *sporicidal agents
- antimicrobial stewardship
Other modalities to reduce c diff:
- avoid acid suppression (stop any unnecessary use of PPIs)
- use probiotics (but not routinely recommended)
Clinical presentation for the various stages of C diff infection
*watery diarrhea (=/>3 unformed stools in 24h)
mild: DIARRHEA, abdominal cramps
moderate: DIARRHEA, FEVER, NAUSEA, MALAISE // abdominal cramps & distention // *LEUKOCYTOSIS (elevated WBC count // HYPOVOLEMIA
*WBC <15 x 10^9/L AND SCr <133umol/L (1.5mg/dL)
severe: FEVER, DIARRHEA, diffused abdominal cramps & distension, WBC >/= 15 x 10^9/L OR SCr >/= 133umol/L (1.5mg/dL)
fulminant: HYPOTENSION/SHOCK, ILEUS (no peristalsis), MEGACOLON (severe inflammation leading to perforation)
Diagnosis of C. diff infection
- presence of diarrhea (>/= 3 unformed stools within 24h)
OR
radiographic evidence of ileus/ toxic megacolon - +ve stool test result for C.diff OR its toxins
OR
colonoscopic/ histopathologic evidence of pseudomembranous colitis
*lab stool test CANNOT distinguish btw colonisation & infection; testing ONLY for symptomatic pts (& limited to pts w DIARRHEA)
^ensure pt has not taken any laxative 2d prior to test, DO NOT REPEAT <7d (>60% pts w favourable clinical response still continue to test +ve)
Treatment principles for C. diff infection
- DO NOT TREAT asymptomatic pts with +ve C. diff test (confirm symptoms consistent w CDI EXIST prior to prescribing therapy)
- if possible, discontinue any antibiotics NOT specifically treating CDI
- if additional antibiotic therapy necessary:
- select narrowest spectrum agent possible
- avoid agents with STRONG association w CDI (clinda/ 3/4 gen ceph/ FQ)
empiric therapy for INITIAL episode for c diff infection
NON-SEVERE: WBC <15 x 10^9/L AND SCr <133umol/L (1.5mg/dL)
1st line: PO Fidaxomicin 200mg BD OR PO Vancomycin 125mg QDS
Alternative: PO metronidazole 400mg TDS
SEVERE: WBC >15 x 10^9/L OR SCr >133 umol/L (1.5mg/dL)
1st line: PO Fidaxomicin 200mg BD OR PO Vancomycin 125mg QDS
FULMINANT: WBC >15 x 10^9/L AND SCr >133 umol/L (1.5mg/dL)
1st line: IV metronidazole 500mg q8h + PO Vancomycin 500mg QDS +/- per-rectal (enema) Vancomycin 500mg QDS
Duration of therapy: 10d for ALL (may extend to 14d if symptoms not completely resolved)
*fidaxomicin preferred (over vanco/ metro) due to lower recurrence rate BUT not avail in SG
Monitoring response in c diff infection
- Resolution of symptoms: should resolve in 10d, otherwise extend another 4d of treatment (no evidence for lowered recurrence for >14d treatment)
*IF POOR RESPONSE: additional diagnostics/ consider escalation of pharmacologic treatment
**DO NOT CONTINUE TREATMENT >14d if pt needs to continue concurrent abx - culture
DO NOT repeat culture <7d (>60% of pts still test +ve despite clinical response to treatment) - ADR
Recurrent CDI definition & prevalence
*pt recovers from CDI (resolution of CDI symptoms) -> subsequent REAPPEARANCE of symptoms AFTER treatment has been discontinued
~30% of patients experience recurrent CDI WITHIN 30D of treatment
risk factors for recurrent CDI
- administration of OTHER abx during/ after initial treatment for CDI
- DEFECTIVE humoral immune response against C. diff toxins
- advanced age
- severe underlying disease
- continued use of PPIs
Treatment for recurrent CDI
1st recurrence
(if fidaxomicin/ vanco used for initial episode)
PO fidaxomicin 200mg BD x10d
OR
PO fidaxomicin 200mg BD x 5d THEN 200mg every other day x 20d
OR
PO vanco tapered/ pulse *125mg
(if metronidazole used for initial episode)
PO Vancomycin 125mg QDS x 10d
2nd/ subsequent recurrence
PO fidaxomicin 200mg BD x 5d THEN 200mg EOD x20d
PO vanco tapered/pulse *125mg
PO vanco 125mg QDS x 10d THEN RIFAXIMIN 400mg TDS x 20d
Faecal microbiota transplant
