S4: meningitis & sepsis, antibiotics & antimicrobial stewardship

Question 1

Outline what the cerebrospinal fluid is

Answer 1

The brain floats in the CSF which acts as a protective cushion
It also surrounds the spinal cord and fills open spaces inside the brain
Helps to maintain a constant pressure inside the skull = intercranial pressure

Question 2

Describe the biochemical and cellular composition of CSF and diagnostic comparison in meningitis (bacterial & viral)

Answer 2

CSF is a clear, plasma-like fluid = contains glucose and some protein (few/no cells)
Bacterial: often cloudy, increased WCC, neutrophils, increased protein, low glucose
Viral: clear, increased WCC, lymphocytes, moderate increase in proteins, normal/slightly decreased glucose

Question 3

Describe the clinical features and assessment of meningitis

Answer 3

General signs of infection
Headache, photophobia, vomiting, neck stiffness on flexion of the neck & irritable
Lumbar puncture to get a sample of CSF: this should be sent for gram stain, PCR & culture

Question 4

Describe microbiological features of Neisseria meningitidis

Answer 4

Gram negative diplococcus (20% of the population carry this bacterium in the oropharynx)
May be found within neutrophils & organism Is surrounded by a polysaccharide capsule
Virulence factors: lipopolysaccharide
Causes both meningitis and septicaemia

Question 5

Describe clinical features of meningococcal disease

Answer 5

Patient: highest for young children, adolescents, and young adults
Headaches, photophobia and vomiting
Triggers an intense immune response leading to fever, sepsis and DIC

Question 6

Describe the pathophysiology of meningococcal meningitis and/or sepsis

Answer 6

Fever, sepsis and DIC due to intense host immune response (entry of bacteria into CSF and bacterial growth within this compartment causes this)
DIC = syndrome of widespread intravascular activation of coagulation

Question 7

Outline the management of Neisseria meningitidis infection

Answer 7

Early recognition
Early administration of antibiotics (if NM is suspected = CEFTRIAXONE)
Urgent investigation, supportive care
Notify public health & prevention (vaccinations)

Question 8

Describe the role of vaccination for Neisseria meningitidis

Answer 8

Vaccines can help prevent meningococcal disease
Meningitis can be caused by several different infections, so several vaccinations offer some protection against it
Meningitis B vaccine = offers protection against meningococcal group B bacteria (most common cause of meningitis in young children in UK)

Question 9

Outline a classification of antimicrobials

Answer 9

Antibacterials, antifungals, antivirals & antiprotozoal
Antibacterials can also be classified as follows:
-bactericidal (kill bacteria) vs bacteriostatic (stops bacteria from replicating)
-broad vs narrow
-target site
-chemical structure

Question 10

Describe the main types of antibiotics and their mechanism of action

Answer 10

Beta-lactam antibiotics = interfere with the synthesis of the bacterial cell wall peptidoglycan (inhibit the transpeptidation enzyme by binding to the penicillin-binding protein on bacteria)
Glycopeptide antibiotics = inhibit cell wall synthesis but at a different stage in the pathway to Beta-lactams
Tetracyclines, aminoglycosides, macrolides, oxazolidinones & lincosamides = affect bacterial protein synthesis
Quinolones = inhibit topoisomerase II, the enzymes that produces a negative supercoil in DNA and thus permits transcription or replication
Sulfonamides & trimethoprim = interfere with folate synthesis or action
Metronidazole = antiprotozoal & against anaerobic bacteria (exact mechanism has not been established)

Question 11

Give the three categories of beta-lactams and their clinical significance

Answer 11

Penicillins = bacterial meningitis, bone and joint infections, pneumonia
Cephalosporins = septicaemia, pneumonia, meningitis 
Carbapenems = extremely broad spectrum (generally safe in penicillin allergy)

Question 12

Give two examples of glycopeptide antibiotics and their clinical significance

Answer 12

Vancomycin and teicoplanin
Generally only used on gram positive species
Used orally exclusively for treatment of C. difficile

Question 13

Give two examples of tetracyclines and their clinical significance

Answer 13

Bind to bacterial ribosomes, preventing binding of tRNA to it, thus preventing the initiation of protein synthesis (bacteriostatic)
Doxycycline, tetracycline
Respiratory tract infections, acne, lyme disease (don’t use on children, pregnant & breastfeeding women as it causes staining of teeth)

Question 14

Give an example of an aminoglycoside and its clinical significance

Answer 14

Leads to misreading of mRNA leading to a loss of function (bactericidal)
Gentamicin
Profound activity against gram negative species (generally reserved for treatment of GN septicaemia)

Question 15

Give examples of macrolides and their clinical significance

Answer 15

Inhibit bacterial protein synthesis by an effect on ribosomal translocation
Bactericidal/bacteriostatic
Clarithromycin, erythromycin
Clinical spectrum very similar to penicillin (+ atypical respiratory pathogens)

Question 16

Give an example of an oxazolidinone and its clinical significance

Answer 16

Linezolid = other antibiotics have failed
Very broad action, suited well to gram positive infections
Pneumonia, skin and soft tissue infections

Question 17

Give an example of a lincosamide and its clinical significance

Answer 17

Acts in same way as macrolides
Clindamycin
Active against gram positive cocci, including many penicillin resistance staph & anaerobic bacteria

Question 18

Give examples of quinolones and their clinical significance

Answer 18

Ciprofloxacin, levofloxacin
Complicated UTIs, gonorrhoea
Side-effects: tendinitis (+/- rupture), aortic dissection, CNS effects

Question 19

Describe the main types of antifungals and their mechanism of action

Answer 19

Azoles = inhibit the fungal cytochrome P450 3A enzyme (leads to inhibition of replication)
Polyenes = site of action is the fungal cell membrane

Question 20

Describe the main types of antivirals and their mechanism of action

Answer 20

Aciclovir = DNA polymerase inhibitors 
Oseltamivir = neuraminidase inhibitors

Question 21

Describe the mechanisms of antimicrobial resistance

Answer 21

1) Enzymatic modification or destruction of antibiotics
2) Enzymatic alteration of antibiotic targets
3) Overexpression of efflux pumps

Question 22

Describe the concept of antimicrobial stewardship

Answer 22

Coordinated interventions designed to improve and measure the appropriate use of antimicrobials by promoting the selection of the optimal antimicrobial drug regimen, dose, duration of therapy and route of administration

Question 23

Outline measures to ensure the appropriate use of antimicrobials

Answer 23

Does the patient need antibiotics?
Can we switch this to oral from IV?
Can we change broad-spectrum antibiotics to narrow-spectrum & targeted antibiotics?
Do you need special authorisation from microbiology?

Question 24

What are the three types of antibiotic resistance?

Answer 24

Intrinsic = a bacterial species is naturally resistant to a certain antibiotic or family of antibiotics, without the need for mutation or gain of further genes 
Acquired = occurs when a particular microorganism obtains the ability to resist the activity of a particular antimicrobial agent to which it was previously susceptible 
Adapted = if there are sub-therapeutic levels of antibiotics, this only causes a mild stress response to the bacteria -> it will respond by becoming resistant to the antibiotic