W8 Clinical Management of Sepsis and Meningitis

Question 1

What is the definition of Sepsis?

Answer 1

Syndrome defined as life-threatening organ dysfunction due to dysregulated host response to infection

Or in short, Sepsis is a life threatening condition that arises when the bodied response to an infection injures its own tissues and organs”

Question 2

Is sepsis and septic shock the same thing?
What is sepsis described as?

Answer 2

• No, septic shock is a subset of sepsis
• Septic shock described circulatory, cellular and metabolic abnormalities
• DEC risk of mortality

Question 3

What causes sepsis?

Answer 3

• The exact cause of sepsis is unknown
• Thought to be due to a multifactorial response to a pathogen which is amplified by:

1. Patient factors:
   * Genetics
   * Age
   * Co-morbidities
2. Pathogen factors
   * The type of pathogen
   * Virulence
   * Burden
3. Environmental factors

• Theory suggests…
• Coagulation and immune responses are switched on by infection- causes dysfunction of one or more organs with variable severity

Question 4

What are the signs and symptoms of sepsis? (6)

Answer 4

Sweaty skin
Disorientation
Shivering
High Heart rate
Extreme pain
Shortness of breath

Question 5

9 Symptoms of sepsis? (in detail)

Answer 5

1. Clammy or sweaty skin
2. Shortness of breath
3. Extreme pain or discomfort
4. Rigors- due to fever or hypothermia
5. Sudden changes or deterioration to functional ability
   * Balance
   * Walking
   * Unable to dress self / wash
   * Ability to carry out day to day task
6. Altered behaviour/changes in mental state
7. High heart rate
8. Signs of dehydration
9. Signs of infection
   TYPICAL SYMPTOMS”
   * Dysuria (pain when urinating)
   * Productive cough
   * Infected wound – red /sloughy
   Others: Dry mucosal membranes, Mottled skin, Cyanosis (lips and tongues), Delayed capillary refill, Break in skin integrity- signs of infection
   NON-SPECIFIC Symptoms
   * Malaise
   * Agitation
   * Behaviour changes

Question 6

Acronym for SEPSIS?

Answer 6

S lurred speech or confusion
E xtreme shivering or muscle pain
P assing no urine (in a day)
S evere breathlessness
I feel like im going to die!
S kin mottled or discoloured

Question 7

Who are the risk groups for Sepsis? (6)

Answer 7

People with weakened immune systems
People with chronic conditions ( diabetes, cancer, lung disease or kidney disease)
Children younger than 1 year
Adults 65+
People with recent severe illness or hospitalisation
Previous Sepsis survivors (prone to reoccurring sepsis)

Question 8

What are the risk factors for sepsis?

Answer 8

1. AGE
   * Very young: <1 year old
   * Older patients: >75 years
   * Very frail patients
2. Patients with an impaired immune function
   * Treated for cancer with chemotherapy
   * Impaired immune function e.g. diabetes
   * Patients taking long term steroids
   * Patients on immunosuppressant drugs e.g. “biologics” – used to treat IBD / RA
3. Recent surgery
   * Surgery within the last 6 weeks
   * Invasive procedure (biopsy)
4. Breaches in skin integrity
   * Cuts
   * Burns
   * Blisters
   * Skin infection e.g. cellulitis
5. Misuse of IV drugs
6. Indwelling lines or catheters
   * PICC line (for Chemo admin)
   * Central line
   * Canula
7. • Given birth in last 6 weeks – esp. if invasive
     procedure (C-section, forceps delivery)
     * Miscarried in last 6 weeks
     * Termination in last 6 week

Question 9

Diagnosis:
Why can sepsis be hard to identify?

Answer 9

• Symptoms are very non-specific
• Not all patients will present in the same way
• Misconception – high temperature = infection, patients with sepsis can also present with hypothermia (low body temp)

Question 10

What does diagnosis of sepsis rely on?

Answer 10

1. THOROUGH HISTORY SYMPTOMS:
   *Signs or symptoms of infection causing significant illness or deterioration
   *Concerns from relatives due to changes in appearance /
   behaviour e.g. confusion, altered conscious state
   RISK OF SEPSIS:
   *Identifying risk factors for sepsis - >1 risk factor
   OTHER:
   *Risk of antimicrobial resistance
   *Immunisation status - ?all childhood vaccination
2. DIAGNOSTIC TESTS
   * Chest X-ray
   * CT scan
   * Urine sample
   * Sputum sample
   * Faeces sample
   * Wound swab
   * Blood cultures
   * Bloods
   * U&Es
   * Lactate
   * CRP
   * Full blood count
   * glucose
   * Arterial blood gases (ABG)
3. THOROUGH PATIENT ASSESSMENT
   Examine the patient:
   * Full examination (cardiac, gastro, resp) – identify
   possible source of infection
   * Capillary refill time – slow refill time = ?poor
   peripheral perfusion
   * Cold peripheries
   * Skin: mottled / ashen skin, cyanosis, breach in
   skin integrity
   * Rashes?
   * Signs of dehydration; dry mucosal membranes
   * Cognitive assessment
   * Observations:
   * Temperature:
   -Fever – common symptom of sepsis
   * Heart rate
   * Respiratory rate- Any signs of resp distress?
   -High or Low RR
   * Blood pressure:
   -40% septic patients – hypotension

Question 11

What diagnostic tests can be done to identify sepsis?

Answer 11

• Chest X-ray
• CT scan
• Urine sample
• Sputum sample
• Faeces sample
• Wound swab
• Blood cultures
• Bloods
• U&Es
• Lactate
• CRP
• Full blood count
• glucose
• Arterial blood gases (ABG)

Question 12

What are the complications of sepsis? (5)

Answer 12

1.Death:
* 5 patients die of sepsis every hour in the UK
* Approximately 20% of patients who are diagnosed with sepsis will die as a result -50,000 cases in the UK annually
* Sepsis claims more lives than lung, bowel, prostate and breast cancer combined
2.Organ failure
3.Coagulopathy
* Disseminated intravenous coagulation (DIC)  formation of microemboli and haemorrhage  loss of peripheral digits or limbs
4.Permanent life changing effects
* 40% sepsis survivors suffer with life changing affects
* Psychological- PTSD, anxiety
* Chronic pain or fatigue
* Reduced mobility
* Neurological disorders  memory loss, difficulty concentrating
5.Increased risk of sepsis or infection in the future

Question 13

When to suspect sepsis?

Answer 13

1. Symptoms or signs of possible infection causing significant illness or deterioration
   * Remember these can be non-specific symptoms
2. One or more risk factors
3. Concerns from relatives regarding patients behaviour or appearance
4. Any red flags–indicating high risk of deterioration

Question 14

What are the Red flags for sepsis? (9)

Answer 14

1. Objective evidence of new or altered mental state
   * New onset confusion
   * Unable to do day to day activities
2. Systolic BP <90 mmHg (or drop of >40 mmHg from normal)
3. Heart rate >130 bpm
4. Respiratory rate >25 bpm
5. Needs oxygen therapy to maintain O2 sats >92% (88% COPD)
6. Skin symptoms
   * Non-blanching rash
   * Mottled
   * Ashen
   * Cyanosis
7. Lactate >2 mmol/L
8. Recent chemo
9. Not passing urine for > 18 hour

Question 15

What are the sepsis six?

Answer 15

Within the first hour of a patient arriving to the hospital with suspected sepsis should have the following done:

1. Give high flow oxygen
2. Take blood cultures
3. Give IV antibiotics
4. Give IV fluids
5. Measure lactate
6. Measure urine output

Question 16

Antibiotic choice
- what is the phrase?

Answer 16

• “START SMART THEN FOCUS”
• Broad spectrum anti-biotics used initially to cover all potential causative agents
• Antibiotics should then be switched to a more narrow spectrum agent
• Antimicrobial review within 48-72 hours
• Rarely only one antimicrobial used=often a combination initially

Question 17

Antibiotic review
What is the next step after IV antibiotics?

Answer 17

• Following 48 – 72 hours of IV antibiotics, patients should be reviewed by a senior clinician
• Decision then needs to be made regarding the ongoing antimicrobial management;
• ?Abx to stop= infection rules out
• IV to oral switch if patient is well enough to switch to oral Abx
  -Clinical improvement of the patient
  -Oral route not compromised

Infection markers showing a trend towards normal:
* Temperature
* Blood pressure stable
* CRP – marking for inflammation; usually lag in 24-48 hours after clinical picture improved
* Pulse <90
* Resp rate <20
* WCC between 4-12
* Suitable oral option available
* Sensitivities back = switch to a more narrow spectrum Abx
* Appropriate to continue on current treatment

Question 18

Antibiotic choice:

What should a clinician consider before prescribing abx? (5)

Answer 18

• Choice of antibiotics will vary from health-boards
• Antimicrobial resistance rates
• Circulating causative agents
• Local antibiotic guideline

1. Likely source of infection?
   * Chest
   * Urine
   * Abdominal
2. Patient characteristics:
   * Allergies
   * Renal / hepatic function
   * Interacting medication
3. Risk of antimicrobial resistance= has the patient had lots of antibiotics recently?
4. Immunisation status
5. Local / national antimicrobial guidelines

Question 19

Antibiotic regimen for Sepis- what 2 things should be considered?

Answer 19

1. Kidney function
2. Allergy status

Question 20

What are the 4 different antibiotic regimens for Sepsis/

Answer 20

Unknown source
Chest
Abdominal
Urine

Question 21

Antibiotic regimen for Sepsis- Unknown source

Answer 21

> 20mls/min renal function + No penicillin allergy = Amoxicillin IV and Gentamycin IV and Clarithromycin and Metronidazole

Question 22

Gentamycin
What class of drug is it?
Bacterial cover?
Dose?
Route?
SE?
C/I?
Monitoring?

Answer 22

Aminoglycoside
Gram negative bacilli
Aminoglycoside
Gram negative bacilli
5 mg/kg once daily
Intravenous (IV) – not absorbed through the gut
* Ototoxicity – deafness
* Nephrotoxicity – renal failure

Contra-indications
* Blindness
* Renal impairment (<20ml/min)
* Myasthenia gravis
* Allergy to aminoglycoside

Monitoring
* Narrow therapeutic index drug= small changes in dose or clearance of the drug can lead to large changes in therapeutic effect and drug levels
* Clearer by the kidney
* Dangerous side effect profile

Essential to monitor:
* Renal function
* Therapeutic drug levels

Question 23

Gentamycin – renal function
What equation to calculate CrCl?

Answer 23

A patients kidney function should be determined BEFORE starting
gentamycin using the cock-croft and gault equation

• Guidelines differ depending on HB:
• SBUHB: only use if CrCL >20 ml/min
• HDUHB: only use if CrCL >30ml/min
• Monitor twice weekly whilst on gentamycin if CrCL stable
• If deterioration in CrCL – daily monitoring maybe indicate
• In obese patients, need to use the
  patients ideal body weight (IBW)
• Adjusted body weight (ABW) if patient
  is >120% of IBW

eCrCl= [(140/age) x Weight (kg)]/ Serum creatinine x1.04 (female) or 1.23 (male)

Question 24

Gentamycin – therapeutic drug monitoring

When?
Range?
How often?

Answer 24

When?- Trough level, 18-24 hours post dose
Range?- <1mg/L
How often?- If level stable (1mg/L)- twice weekly whist on gentamycin

What to do when level >1 mg/L
* Check renal function – if worsening an <20-30 ml/min- alternative Abx needs to be prescribed
* Was the level taken at the correct time?

• If level is a true level and is high (>1mg/L)
• Hold gentamycin for 12 hours= retake the level (36 hours post dose)
• If still > 1mg/L = hold for further 12 hours and retake level (48 hours post dose)
• Adjust dose interval accordingly

Question 25

Gentamycin - counselling

Answer 25

• Due to seriousness of side effects – patients should be counselled on the risk of treatment prior to initiation
• This should be documented in the medical notes
• Usually done by prescriber
• Counselling points:
• Risk of ototoxicity and nephrotoxicity = very low risk in short courses
• Gentamycin is a very effective antibiotic
• Bloods will be checked to monitoring kidney function and level of the antibiotic in the blood
• Report any hearing problems e.g. ringing / noises in ear, dizziness or balance problems

Question 26

Metronidazole
Drug class?
Bacterial cover?
Route?
Dose?
SE?
C/I?
Monitoring?
Counselling?

Answer 26

Drug class= Nitroimidazole
Bacterial cover= Anaerobic bacteria and protozoa
Route= Oral and Intravenous
Dose= Oral 400mg TDS or IV 500mg TDS

Very rare s/e:
* Peripheral neuropathy – pins and needles,
* Central neuropathy – dizziness, convulsions
* Blood dyscrasias e.g. low PLT, low eosinophils

Contra-indications= Allergic reaction to metronidazole

Monitoring * No specific monitoring
* Cleared by kidney= dose reduction in severe impairment
* Metabolised by liver= dose reduction in severe impairment

Counselling
* Topical administration: Avoid sun light / UV light when using topically= wear sun cream
* Oral / IV use:
* Avoid alcohol consumption whilst on metronidazole and for at least 48 hours after completing the course
* Disulfiram-like reaction= flushing/ throbbing headache /N&V

Question 27

Vancomycin
Drug class?
Bacterial cover?
Dose?

Answer 27

Drug class= Glycopeptide
Bacterial cover= Aerobic gram-positive
and Anaerobic gram-positive – inc. multi-drug resistance staphylococci
Dose:
*Loading dose= determined by patient actual body weight
*Maintenance dose= determined by patients renal function (obese patients =IBW or AdBW

Where initial loading dose is based on the patients actual body weight AND
ongoing maintenance dose is based on the patient’s renal function (CrCL using IBW / AdBW

Question 28

Vancomycin
Route?
SE?
C/I?
Monitoring?
Administration?

Answer 28

Route Intravenous (IV) – not absorbed through the gut

Side effects
* Ototoxicity
* Nephrotoxicity= monitor kidney function closely
* Infusion-related reactions
* Allergic reactions (cross-sensitivity with teicoplanin)

Contra-indications
* Previous Hx of hearing loss

Monitoring
* Narrow therapeutic index drug=small changes in dose or clearance of the drug can lead to large changes in therapeutic effect and drug levels
* Clearer by the kidney
* Dangerous side effect profile

Essential to monitor:
* Renal function
* Therapeutic drug levels

Administration= Must be given slowly over hours= risk of red man syndrome (infusion-related reaction)
* If patients develop this, stopping the infusion will result in prompt cessation of the reaction

Question 29

Vancomycin - monitoring

Therapeutic drug level:
When?
Range?
How often?

Answer 29

When?
* Trough level
* When its taken depends on the
dose

Range?
* 10 – 15mg/ L
(in more severe infections= 15 -20mg/L)

How often?
* Stable CrCL and vanc level= twice weekly
* Poor renal function=more frequently

Each health board will have their own guidelines on how to manage therapeutic levels outside the desired range

Question 30

Antibiotic regimen Sepsis- Chest source

Answer 30

• If <48 hours since admission:
  Treat as severe community-acquired pneumonia (CURB-65 score = 3)
• If >48 hours since admission:
  Treat as a hospital acquired pneumonia

Question 31

Community acquired pneumonia (CAP) - BACTERIAL
Treatment summary:

Question 32

Hospital acquired pneumonia (HAP) -
BACTERIAL
Treatment- summary:

Question 33

Sepsis – abdominal source

Answer 33

Penicillin allergy- Teicoplanin (IV)
Non-penicillin allergy- Tazocin (IV)
Meropenem

Question 34

Teicoplanin- given for sepsis abdo source
Drug class?
Bacterical cover?
Dose?
Route?
SE?
Monitoring?

Answer 34

Drug class= Glycopeptide
Bacterial cover = Aerobic gram-positive
* Anaerobic gram-positive – inc. multi drug resistance staphlycocci
Dose= Loading dose= determined by patient actual body weight
* Maintenance dose= determined by patients weight & renal function (obese patients= IBW or AdBW)
Route Intravenous (IV) – long half life allowing for once-daily administration

Side effects
* Blood dyscrasias e.g. low immune cells and platelets
* Nephrotoxicity=monitor kidney function closely
* Infusion-related reactions
* Allergic reactions (cross sensitivity with vancomycin)
* Hearing loss/ototoxicity – not as common (prolonged treatment)

Monitoring
* Therapeutic drug levels are only required if the expected duration of treatment > 7 days
* Rational: ensure the patient isn’t being under-dosed

When to take level?
* Trough level (before dose)
* Before 5th dose
* Target: 15 – 60 mg/L

Essential to monitor:
* Renal function
* Full blood count

Question 35

Sepsis – urine source (urosepsis)
treatment summary: (4)

Answer 35

CrCl>20 = Gentamycin IV

CrCl<20:
No pen allergy= Tazocin IV
Non-severe pen allergy= Meropenem
Severe pen allergy= Ciprofloxacin

Question 36

Bacterial meningitis definition:

Answer 36

Bacterial meningitis is an infection of the surface of the brain (meninges) by bacteria leading to inflammation. The infecting bacteria have usually travelled there from another mucosal surface via the patient’s blood stream.

Question 37

Most common infecting bacteria of meningitis (3)
Who does it affect?
Transmission?

Answer 37

• Meningococcus (Nerisseria meningitidis)
• Pneumococcus (Streptococcus pneumoniae)
• Haemophilus influenzae type b (Hib)
• Can affect all ages but mainly affects babies and young children
• Transmission: aerosol droplets or direct contact with secretions from the upper respiratory tract.
  -Usually requires either frequent or prolonged close contact
• Bacterial meningitis is a notifiable disease = public health dept need to be made aware of the case
• There are other forms of meningitis e.g. viral, fungal, drug induced, autoimmune, cancer induced

Question 38

What are the Risk factors for
MENINGITIS?(8)

Answer 38

1. Smoking
2. PMHx
   * Chronic kidney disease
   * Chronic liver disease
   * Sickle cell disease
   * Cancer= leukaemia / lymphoma
3. Contiguous infections
   * Pneumonia
   * Sinusitis
   * Otitis media
4. Living in crowded households
   * University halls
   * Military barracks
5. Patient Age
   * More prevalent in patients < 2 years old
   * Older patients > 65 years
6. Winter months
   * Bacterial meningitis more prevalent during winter months
7. Immunocompromised state
   * Patients receiving chemotherapy
   * HIV infection
   * Absent / non-functioning spleen
8. Incomplete Immunisation status

Question 39

What are the complications of Meningitis? (4)

Answer 39

1. Death
   -Rate of mortality has fallen in recent years
   -Complications associated with the condition however has not
2. Cerebral infarct (stroke)= results in cellular death of brain tissue
   * Seen in 1 in 4 patients with confirmed bacterial meningitis
3. Neurological complications
   * Hearing loss (34%)
   * Seizures (13%)
   * Cognitive impairment (9%)
4. Physical complications
   * Amputations (8% of children, 3% of adults)
   * Skin scarring

Question 40

Symptoms of Meningitis:

Answer 40

Common non-specific symptoms:
Fever
Nausea/vomiting
Lethargy
Irritability / unsettled behaviour
Children= refusing food/drink
Headache
Muscle pain
Respiratory symptoms= difficulty
breathing

Less common non-specific:
Chills / Shivering
Diarrhoea / abdominal pain
Sore throat

Specific symptoms
Non-blanching rash
Stiff neck
Cold hands/feet = capillary refill >
2 seconds
Unusual skin colour
Hypotension/shock
Photophobia
Back rigidity

Question 41

What are some Meningitis symptoms in Adults?

Answer 41

Fever, cold hands and feet
Drowsy, difficult to wake
Severe, muscle pain
Severe headache
Dislike bright lights
Vomiting
Confusion and irritability
Pale, blotchy skin, Spots/rash (glass test)
Stiff neck
Convulsions/seizures

Question 42

What are some Meningitis symptoms in Children?

Answer 42

Fever, cold hands and feet
Fretful, dislike being handled
Rapid breathing or grunting
Unusual cry, moaning
Stiff neck, dislike bright lights
Refusing food and vomiting
Drowsy, floppy, unresponsive
Pale, blotchy skin. Spots/rash (glass test)
Tense, bulging fontanelle (soft spot)
Convulsion/seizures

Question 43

Diagnosis of meningitis:

Answer 43

1. Thorough history:
   * History of the patients symptoms
   * Identification of risk factors
   * Rule out Dx diagnosis
   -Another type of meningitis
   -Cancer
   -Encephalitis
   -HIV infection
   -Subarachnoid haemorrhage
   -Non-infective causes of meningitis e.g. drug-induced, auto-immune
2. Physical examination
   * Assessment of the severity of the patients condition:
   -Temp
   -Heart rate
   -Blood pressure
   -Conscious level

Identify specific symptoms
-Photosensitivity
-Non-blanching rash

3. Diagnostic tests
   Lumbar puncture (LP)
   * ?raised CNS pressure
   * Obtain spinal fluid sample= ? bacteria present

CT scan of head
* Identify other causes
* ?Stroke

Blood tests
* Blood cultures – identify causative
agent
* FBC –?WCC INC
* HIV test

Question 44

Treatment of meningitis is based on what factors? (4)

Answer 44

1. Patients age
2. Allergies
3. Presence of risk factors;
   * Pregnancy
   * Immuno-compromised
   * Active cancer
   * Diabetes
   * Alcohol misuse
4. Risk of penicillin resistant bacteria
   * Recent travel (last 6 month) where penicillin
   resistance pneumococcai prevalent
   * Canada
   * China
   * Mexico
   * Croatia
   * Greece
   * Italy
   * Pakistan
   * Poland
   * Spain
   * USA

Question 45

Pharmacological Treatment of Meningitis:

EMPIRICAL TREATMENT – PATHOGEN UNKNOWN
AGE: <60 YEAR WITH NO RISK FACTORS

Answer 45

NO PENICILLIN ALLERGY
* DRUG: Ceftriaxone (IV)
* DOSE: 2g ONCE DAILY

PENICILLIN ALLERGIC (SEVERE)
* DRUG: Chloramphenicol (IV)
* DOSE: 25mg/kg every 6 hours

IF PENICILLIN RESISTANCE SUSPECTED, ADD:
* DRUG: Vancomycin (IV)
* DOSE: 15-20mg / kg
OR
* DRUG: Rifampicin (PO)
* DOSE: 600mg BD

IF VIRAL ENCEPHALITIS SUSPECTED, ADD:
* DRUG: Aciclovir (IV)
* DOSE: 10mg / Kg TDS – based on ideal/adjusted body weight

Question 46

Pharmacological Treatment of Meningitis:

EMPIRICAL TREATMENT – PATHOGEN UNKNOWN
AGE: >60 YEAR OR PRESENCE OF RISK FACTORS

Answer 46

NO PENICILLIN ALLERGY
DRUG: Ceftriaxone (IV)
DOSE: 2g ONCE DAILY
PLUS
DRUG: Amoxicillin (IV)
DOSE: 2g 4 hourly

PENICILLIN ALLERGIC (SEVERE)
RUG: Chloramphenicol (IV)
DOSE: 25 mg/kg ONCE DAILY
PLUS
DRUG: Co-trimoxazole(IV)
DOSE: 60-120 mg/kg in 4
divided doses

IF PENICILLIN RESISTANCE SUSPECTED, ADD:
* DRUG: Vancomycin (IV)
* DOSE: 15-20 mg/kg
* DRUG:
* Rifampicin (PO)
* DOSE: 600mg BDOR

IF VIRAL ENCEPHALITIS SUSPECTED, ADD:
* DRUG: Aciclovir (IV)
* DOSE: 10mg / Kg TDS – based on ideal/adjusted body weight