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Microbiology Revision –
Lecture 1
Dr Anna Goyder and Dr Helen McKenna
19/03/13 - 21/03/13
Outline
2 lectures x 90mins each:
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Bacteria and Abx
Viruses and Antivirals
Vaccinations
Infections by system:
- CNS
- Cardio
- Resp
- GI/hepatitis
- GU/gynae
- Musculoskeletal
• Mycobacterial
• Zoonoses
• Malaria
Bacteria
Bacteria simplified
• Gram positive
- Cocci
staphylococcus streptococcus enterococcus
- Rods/bacilli
ABCDL (see next slide)
• Gram negative
- Cocci
the diplococci - neisseria (gonorrhoea, meningitidis
‘meningococcus’), moraxella
- Rods/bacilli
ENTERICS - E Coli, salmonella, shigella, klebsiella, proteus,
campylobacter, helicobacter, vibrio… ie most other things!
- Coccobacilli haemophilus, legionella, brucellosis, bordetella,
chlamydia* rickettsia*
*obligate intracellular
- Spiral spirochetes – treponema (syphilis), leptospira (Weil’s), borrelia (lyme)
Gram + rods:
ABCD L
Actinomyces
Bacillus
(anthracis, cereus)
Clostridium (difficile, botulinum, perfringens)
Diphtheria
(corynebacterium diphtheriae)
Listeria
Diplococcus
Moraxella
Neisseria
Anaerobes
• WHAT ARE THEY?
Anaerobes
• Do NOT require O2 for growth
• Therefore suspect them in unhealthy/dying
tissues/reduced blood supply, necrotic tissue
• From GI tract including mouth E.g. suspect in bites,
• Foul smell! Free gas under skin! Nasty
• Treat with metronidazole, cephamycins (cefoxitin, cefotetan,
cefmetazole, flomoxef)
• Aminoglycosides do NOT cover anaerobes – O2
needed for them to enter the cell.
Anaerobes
• OBLIGATE
• FACULATIVE
CANNOT use O2/grow
where there is oxygen
Can grow where there is OR
isn’t oxygen
Bacteroides
Clostridium
Actinomyces
Staphylococcus, E. Coli,
Listeria
Antimicrobials
• Antibiotics
• Antivirals
• Antifungals
Antibiotics (antibacterials)
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A) Cell wall synthesis inhibitors
B) Protein synthesis inhibitors
C) DNA synthesis inhibitors
D) RNA synthesis inhibitors
E) Anti-folate drugs
Antibiotics (antibacterials)
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A) Cell wall synthesis inhibitors
B) Protein synthesis inhibitors
C) DNA synthesis inhibitors
D) RNA synthesis inhibitors
E) Anti-folate drugs
A. Cell wall synthesis inhibitors
β-lactams
Glycopeptides
1. Penicillins
Require therapeutic drug monitoring
(TDM)
2. Cephalosporins
Crossreactivity – caution if hx
anaphylaxis
1st generation – gram + > 2nd generation – gram + and 3rd generation – gram - > +
- have T in them – T for ‘third’
cefotaxime, ceftazidime, ceftriaxone
1. Vancomycin
Usually IV – covers MOST GRAM +
incl MRSA - but NOT VRE!
Exception - oral vancomycin – for
C. Difficile diarrhoea (where
metronidazole has failed)
3. Carbapenems
B R O A D spectrum
2. Teicoplanin
Antibiotics (antibacterials)
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A) Cell wall synthesis inhibitors
B) Protein synthesis inhibitors
C) DNA synthesis inhibitors
D) RNA synthesis inhibitors
E) Anti-folate drugs
B. Inhibitors of protein synthesis
5 to remember:
1. Macrolides
2. Tetracyclines
3. Aminoglycosides
4. Chloramphenicol
5. Oxazolidinones
erythromycin, clarithromycin, azithromycin
doxycycline, lymecycline
gentamicin, amikacin – TDM needed
(for your EYES only)
Linezolid – don’t need to know any more
Antibiotics (antibacterials)
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A) Cell wall synthesis inhibitors
B) Protein synthesis inhibitors
C) DNA synthesis inhibitors
D) RNA synthesis inhibitors
E) Anti-folate drugs
C. DNA synthesis
1. Quinolones –
Ciprofloxacin, Moxifloxacin, Levofloxacin (think
Ciprofloxaquin, Moxifloxaquin etc)
Act on DNA Gyrase
Active mostly against Gram negatives –
use for UTIs, bacterial gastroenteritis
2. Nitroimidazoles –
Metronidazole
Useful against anaerobes and protozoa
3. Nitrofurantoin - UTIs
Antibiotics (antibacterials)
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A) Cell wall synthesis inhibitors
B) Protein synthesis inhibitors
C) DNA synthesis inhibitors
D) RNA synthesis inhibitors
E) Anti-folate drugs
D. RNA synthesis
• Rifampicin, Rifabutin
Treatment - as part of combination therapy
because resistance develops quickly –
mycobacteria – TB
Prophylaxis – single agent - Meningococcal
Antibiotics (antibacterials)
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A) Cell wall synthesis inhibitors
B) Protein synthesis inhibitors
C) DNA synthesis inhibitors
D) RNA synthesis inhibitors
E) Anti-folate drugs
E. Anti-folate drugs
Trimethoprim
UTIs
Sulphonamides
Co-trimoxazole ‘Septrin’
= Trimethoprim + Sulphamethoxazole
P. Jiroveci prophylaxis in AIDs
TB treatment
• RIPE – Rifampicin, Isoniazid, Pyrazinamide, Ethambutol
• Normally 2m of 4 drugs, then 4m of 2 drugs
Exceptions – spinal (12 months), MDR TB (minimum 18
months)
• Side Effects –
- Ethambutol - E for Eye – optic neuritis
- R/I/P – hepatotoxicity
- Isoniazid – peripheral neuropathy – co-prescribe pyridoxine
Viruses
Classification
DNA viruses
RNA viruses
Double-stranded:
Adenovirus
Herpes virus
Pox viruses
Double-stranded:
Reovirus
Double-stranded plus reverse transcriptase:
Hepadnavirus
Single stranded:
Parvovirus
(+)Single-stranded:
Picornavirus
Togavirus
Flavivirus
(+) Single-stranded plus reverse
transcriptase:
Retrovirus
(-)Single-stranded:
Orthomyxovirus
Paramyxovirus
Rhabdovirus
Classification
DNA viruses
Double-stranded:
Adenovirus
Herpes virus (LATENT)
Pox viruses
Double-stranded plus reverse transcriptase:
Hepadnavirus Hepatitis B
Single stranded:
Parvovirus B19 – slapped cheek, 5th disease
RNA viruses
Double-stranded:
Reovirus Rotavirus
(+) Single-stranded
Picornavirus Enteroviruses (polio, echo,
coxsackie), rhinovirus, Hepatitis A
Togavirus Rubella
Flavivirus
(+) Single-stranded plus reverse
transcriptase:
Retrovirus HIV 1, 2; HTLV1
(-)Single-stranded:
Orthomyxovirus Influenza A, B, C
Paramyxovirus Measles, Mumps, RSV
Rhabdovirus Rabies
HSV1
+2
VZV
Clinical
Site of latent
infection
Pregnancy
Test
Treatment
Painful vesicular rash
Orofacial/Genital
Cutaneous dissemination
Visceral involvement:
Oesophagitis, Colitis
Hepatitis
Sensory
nerve ganglia
Primary maternal infection in 3rd trimester:
Neonate:
Lesions of Skin, Eyes, Mouth (SEM)
Disseminated disease (especially to BRAIN)
PCR
Aciclovir/
Valaciclovir (pro-drug)
Ophthalmic: topical
idoxuridine
Varicella zoster (chicken pox)
Flu-like prodrome
Centripetal crops of vesicles
Sensory
nerve ganglia
(Herpes
zoster –
shingles)
Test for Ab
CS (Avoid PROM)
Early pregnancy:
Congenital Varicella syndrome:
Scarring
Eye defects
Limb hypoplasia
Microcephaly and LD
Vesicle fluid:
PCR/EM/Ab
If exposed: check for
Ab
If not immune: VZIg
If confimed/rash:
aciclovir
7 day pre/post-partum:
Mother: increased risk pneumonia/encephalitis
Neonatal Varicella
Purpura fulminans
CMV
EBV
HHV
8
Usually asymptomatic (40%
infected by 16)
Rarely – maculopapular rash
Immunosuppressed:
Encephalitis, retinitis, pneumonitis,
hepatitis, BM suppression,
enterocolitis
B cells
Infectious mononucleosis (sore
throat, lymphadenopathy,
maculopapular rash with ampicillin)
Post-Tx lymphoproliferative
disease, lymphoma
HIV: oral hairy leukoplakia
B cells
Kaposi’s sarcoma
Castleman’s disease (body cavityassociated lymphoma)
B cells
Epithelial
cells
Commonest congenital viral infection
Asymptomatic
Hearing defects
Cognitive impairment
10% Cytomegalic inclusion disease:
IUGR, hepatosplenomegaly, chorioretinitis,
encephalitis, thrombocytopenia
No adverse outcome in pregnancy
Hepatitis: Ganciclovir
HIV: Cidofavir
Severe: Foscarnet
If primary
infection/reactivation in
pregnancy – refer to
Fetal medicine
(but no treatment)
Monospot
Serology
HHV 6 + 7
Immunocomp
romised:
Graft failure,
hepatitis
T cells
Epithelial cells
Questions
Which herpes virus?
A HHV 1/HSV 1
B HHV 2/HSV 2
C HHV 3/ VZV
D HHV 4/ EBV
E HHV 5/CMV
F HHV 6/ Roseola
G HHV 7
H HHV 8
1.
A 50 year old man presents to HIV
clinic with a widespread purple
rash
2.
A 6 year old child presents with 1
week of fever and malaise and
develops crops of vesicles on scalp
and mouth
3.
18 year old student presents with
excessive fatigue and repeated
bouts of pharyngitis. He is found to
have cervical lymphadenopathy
and enlarged spleen.
4.
1 week old baby, not feeding,
vesicular lesions on face and
mouth. Mother had painful genital
rash in last week.
Clinical features
Complications
In Pregnancy
Treatment
Measles
(RNA
- single-stranded
paramyxovirus)
Congestion
Conjunctivitis
Koplik’s spots
Rash starts behind ears and
forehead
Secondary bacterial
infection:
Otitis media
Pneumonia
Pneumonitis
Encephalitis
SSPE
Rare
Ig to attenuate
Fetal loss
Pre-term delivery
Not associated with fetal
anomalies
LIVE vaccine
Mumps
(RNA
- single-stranded
paramyxovirus)
Parotitis
Orchitis
Oophoritis
Pancreatitis
Meningitis and deafness
Influenza
(RNA
-single stranded
orthomyxovirus)
A: pAndemic
B: outBreak
C
Rubella
(RNA
+ single-stranded
togavirus)
LIVE vaccine
Bronchitis
Secondary bacterial
pneumonia
In pregnancy:
Still birth
Pre-term delivery
A: amantadine
A+B: neuraminidase
inhibitors
Zanamavir (inhaled)
Oselatamavir (oral)
50% subclinical
Pinpoint macular rash
lymphadenopathy
1st trimester (90% if <10
weeks)
Fetal loss
Congenital Rubella
Syndrome
Cataracts, glaucoma
Heart defects
Deafness
Mental retardation
>20 weeks: no risk
LIVE vaccine
Enterovirus
(Polio, coxsackie, echovirus)
RNA
+ single-stranded
Hand, foot and mouth
disease
Encephalitis
Myocarditis
Congenital myocarditis
Neonatal hepatitis and IDDM
Parvovirus B19
(DNA
Single-stranded)
Asymptomatic
Erythema infectiosum
Polyarthropathy
Transient aplastic crisis
< 20 weeks:
3% hydrops fetalis
Other anomalies rare
>20 weeks: no risk
Intrauterine transfusion
Antivirals
HSV: Encephalitis,
Disseminated (Genital,
Oal)
VZV:
immunocompromise,
pregnancy, pneumonitis
Aciclovir
Guanosine analogueBlocks viral DNA
extension
Requires activation by
viral TK
CMV (lacks TK)
Ganciclovir
Resistant: Foscarnet
Antivirals
HAART
• Triple therapy – usually 2xNRTI + NNRTI/PI
• Start when CD4 count <250
• NRTIs end in –ine (exceptions: tenofovir and abacavir)
• NNRTIs – nevirapine, efavirenz
• PIs end in -vir (exceptions: tenofovir and abacavir = NRTIs)
Vaccinations
TYPE
LIVE ATTENUATED
More rapid and effective
Contraindications:
Chemotherapy
<6/12 post-BMT
Children on high dose steroids or
cytotoxics
MMR
BCG (mycobacterium bovis, intradermal)
OPV
Yellow Fever
Inactivated
Pertussis
Rabies (diploid cell vaccine – can be used post-exposure given long incubation period)
IPV
HAV
Typhoid
Subunit
Influenza
Meningococcal A and C
Pneumococcal
Conjugate
Hib
Men C
PCV (conjugate pneumococcus)
Toxoid
Tetanus
Diptheria
PASSIVE
Immunoglobulin (human-derived)
Antisera (animal-derived)
“MMR BOY”
UK Schedule
DTaP/IPV/Hib
PCV
Men C
2, 3, 4 months
2,
4 months
3, 4 months
Hib + MenC
MMR + PCV
12 months booster
12-13 months
DTaP/IPV/MMR
BCG
3-5 years
high risk babies, 10-14y
HPV (16 and 18 - oncogenic)
DT + IPV
Rubella
girls 12-13y
13-18 years
seronegative women
Which of the following is a LIVE
vaccine?
A
B
C
D
E
Diphtheria
Yellow fever
Rabies
Tetanus
Pertussis
Breaktime
•
•
•
•
•
5 mins
Only go to the toilet if you’re desperate
Don’t talk about medicine
Talk about something else
Might be a good time to start filling in your
feedback form
SYSTEMS
CNS (including prion disease)
Heart
Respiratory Tract
Gastrointestinal Tract
Urinary Tract
Sexually transmitted diseases
Musculoskeletal and skin
CNS and Prion disease
Meningitis
Encephalitis
Fever
Headache
Vomiting
Photophobia
Fever
Headache
Disturbance
of brain
function
Nuchal rigidity (reduced level
Kernig’s sign
of
Focal
consciousnes
neurology
s,disorientatio
Long tract
n,
signs (6th and seizures)
3rd CN)
Rash
VIRAL
(VIRAL: no focal
neurology or alteration
of consciousness)
HSV
EBV
Mumps
Influenza
Adeno
Arbo
Japanese B
Rabies
ACICLOVIR
Abscess
Myelitis
Neurotoxin
Mass effect:
focal
neurology,
seizures
(Fever in
<50%)
Reduced
nerve
transmission
Paralysis
Strep
Staph
Gram –
TB
Fungi
Parasites
Actinomyces
Nocardia
VIRAL
Polio
EBV
Clostridia
-Flaccid
(Clostridium
botulinum)
-Rigid
(Clostridium
tetani)
Meningitis
ACUTE
Subacute/Chroni
c
Neonates
Children
Elderly
E. Coli
Gram negative
bacilli
Group B strep
Neisseria
meningitidis
(meningococcus)
Strep pneumoniae
(pneumococcus)
VIRAL
Gram negative
bacilli
Pneumococcus
LISTERIA
TB
Syphilis
(treponema)
Leptospira
TB
Syphilis
Borrelia
Cryptococcus
1. Treat empirically as soon as possible:
2. Lumbar Puncture
CEFTRIAXONE
+ VANCOMYCIN if possible penicillinresistance pneumococci
+ AMPICILLIN if immunocompromised
(suspect Listeria)
Contraindicated if clinical evidence of raised
ICP
CT
(Neonate: cefotaxime and amoxicillin)
CONTACTS: rifampicin.
3. Vaccine: Hib, MenC
Interpreting CSF
Clarit
y
Cells (x10^6)
Gram
stain
Protein
Glucose
Normal
Clear
WCC 0-5
No
organism
s
0.15 – 0.4
2.2 – 3.3
(60% of blood
glucose)
Purulent
Meningitis
Turbid
WCC 1002000
Organism
s
Increased
0.5 – 3.0
Decreased
0 – 2.2
Bacterial:
Meningococcus
Pneumococcus
Listeria
No
organisms
Increased
0.5 - 1
Normal
VIRAL
Partially treated
bacterial
Encephalitis
Abscess
TB/fungal
Scanty
AFB (or
nothing)
INCREASE
1-6
Decreased
0 – 2.2
TB
(Cryptoccoccus,
Abscess)
neutrophils
Aseptic
Meningitis
TB
Clear/
Slightl
y
turbid
WCC 15-500
Clear/
Slightl
y
turbid
WCC 30-500
Lymphocytes
Lymphocytes
AND
Polymorphs
Organism
Questions
50 year old man
Headache and neck stiffness
Norma
CT brain normal
l
LP – opening pressure 15 cmH20
Clarit
y
Cells (x10^6)
Gram
stain
Protein
Glucose
Clear
WCC 0-5
No
organis
ms
0.15 – 0.4
2.2 – 3.3
(60% of
blood
glucose)
Purule
CSF:
nt
Cloudy
Mening
itis
WCC 100 (70% lymphocytes)
Protein 0.7
Aseptic
Glucose 3.3 (serum glucose 4.7) Mening
itis
Turbi
d
WCC 1002000
Organis
ms
Increased
0.5 – 3.0
Decreased
0 – 2.2
Bacterial:
Meningococcus
Pneumococcus
Listeria
Clear
/
Slight
ly
turbid
WCC 15-500
No
organism
s
Increased
0.5 - 1
Normal
VIRAL
Partially treated
bacterial
Encephalitis
Abscess
TB/fungal
Clear
/
Slight
ly
turbid
WCC 30-500
Scanty
AFB (or
nothing)
INCREAS
E
1-6
Decreased
0 – 2.2
TB
(Cryptoccoccus,
Abscess)
Diagnosis?
A Bacterial meningitis
B Viral meningitis
C TB
D Normal CSF
E Cryptococcal
TB
Lymphocyte
s
Lymphocyte
s
AND
Polymorphs
Organism
20 year old man
Headache and sore throat
Fever
Photophobia
CSF:
Clear
Lymphocytes 2;
Polymorphs 0
Protein 0.3
Glucose 4.1
(serum glucose 5.9)
Diagnosis?
A Guillian-Barre Syndrome
B Viral meningitis
C Bacterial meningitis
D Cerebral Malaria
E Normal CSF
Clarit
y
Cells (x10^6)
Gram
stain
Protein
Glucose
Norma
l
Clear
WCC 0-5
No
organis
ms
0.15 – 0.4
2.2 – 3.3
(60% of
blood
glucose)
Purule
nt
Mening
itis
Turbi
d
WCC 1002000
Organis
ms
Increased
0.5 – 3.0
Decreased
0 – 2.2
Bacterial:
Meningococcus
Pneumococcus
Listeria
Aseptic
Mening
itis
Clear
/
Slight
ly
turbid
WCC 15-500
No
organism
s
Increased
0.5 - 1
Normal
VIRAL
Partially treated
bacterial
Encephalitis
Abscess
TB/fungal
TB
Clear
/
Slight
ly
turbid
WCC 30-500
Scanty
AFB (or
nothing)
INCREAS
E
1-6
Decreased
0 – 2.2
TB
(Cryptoccoccus,
Abscess)
Lymphocyte
s
Lymphocyte
s
AND
Polymorphs
Organism
Which of the following types of viral
meningitis may be associated with a
characteristically LOW CSF glucose level?
A
B
C
D
E
Mumps
CMV
Measles
HIV
Echovirus
Prion disease:
Infectious protein
Causes rapid
neurodegeneration (Dementia, ataxia)
No
inflammatory/immune reaction
Genetic
15%
Sporadic 80%
Acquired
< 5%
Familial CJD;
Gerstmann-Straussler-Sheinker Syndrome
Familial Fatal Insomnia
Sporadic CJD
Kuru
Variant CJD
Iatrogenic
Germline mutation in human prion protein
gene (PRP)
All autosomal dominant
? Somatic mutation or spontaneous conversion
(1 in a million)
Eating infected human (Kuru)
or animal CNS matter (VARIANT CJD)
Iatrogenic (GH, surgery, blood)
GSS:
Onset: 30-70
Slowly progressive ataxia - Death in 2-10y
Family history (dementia, ataxia, psychiatric)
Onset: 65
Rapid dementia – death in 6m
Onset: 26
Psychiatric symptoms before neurological
symptoms
Death in 14 months
EEG: non-specific
EEG: pseudoperiodic triphasic complexes (2/3)
EEG: Non-specific SLOW waves
MRI: may be increased signal in basal ganglia
MRI: increased signal in basal ganglia
MRI: positive pulvinar sign (increased signal in
bilateral posterior thalamus)
CSF: raised markers of neuronal damage ( 14-3-3;
S100)
Neurogenetics: reveals mutation
GSS PRNP P102L
FFI PRNP D178N
Neurogenetics: No genetic cause
CSF: markers not useful
Neurogenetics: all methionine homozygous at
codon 129 (MM)
Brain biopsy: PRP immunohistochemistry
TONSILLAR BIOPSY :
PRPsc type 4t (100% sensitive and specific –
no need for brain biopsy)
Questions
Which of the following statements about
variant CJD is true?
A Mainly affects the elderly
B More rapidly progressive than sporadic
CJD
C Initial symptoms are always neurological
D Tonsillar biopsy is often diagnostic
E EEG is usually abnormal
Which of the following statements
is true?
A Familial CJD is more rapidly progressive
than sporadic CJD
B Familial CJD is inherited in a recessive
fashion
C Familial prion disease does not cause
ataxia
D All cases of variant CJD are methionine
homozygous at codon 129
E Tonsillar biopsy is used to diagnose
sporadic CJD
Cardio
Endocarditis
Subacute versus acute
Who
Treatment
Streptococcus
viridans
Native valves
Benpen +/- gent
Staph epidermidis
Prosthetic valve if <2 Fluclox +/- gent
months post surgery (+ rifampicin if
prosthetic valve)
Staph aureus
IVDUs
Fluclox +/- gent
Strep bovis
Colorectal ca
Benpen +/- gent
General points –
•Blind therapy – fluclox/benpen/vancomycin + gent
•If penicillin allergic/MRSA - use vancomycin
•Mortality – 30% with staph, 5% with strep
Complications
Abscesses
Culture-negative Endocarditis
• Caused by
A) taking blood cultures AFTER starting antibiotics
B) Organisms difficult to culture:
brucella, coxiella, chlamydia, mycoplasma,
HACEK organisms:
Haemophilus, Actinobacillus, Cardiobacterium, Eikenella
Kingella
-> do serology
That’s all for now
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