Download - Microbiology Revision – Lecture 1
Microbiology Revision – Lecture 1
Dr Anna Goyder and Dr Helen McKenna
19/03/13 - 21/03/13
Outline
2 lectures x 90mins each:
• 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
ActinomycesBacillus (anthracis, cereus)Clostridium (difficile, botulinum, perfringens)Diphtheria (corynebacterium diphtheriae)Listeria
Diplococcus
Neisseria
Moraxella
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
• OBLIGATECANNOT use O2/grow
where there is oxygen
Bacteroides
Clostridium
Actinomyces
• FACULATIVECan grow where there is OR
isn’t oxygen
Staphylococcus, E. Coli, Listeria
Antimicrobials
• Antibiotics
• Antivirals
• Antifungals
Antibiotics (antibacterials)
• A) Cell wall synthesis inhibitors• B) Protein synthesis inhibitors• C) DNA synthesis inhibitors• D) RNA synthesis inhibitors• E) Anti-folate drugs
Antibiotics (antibacterials)
• 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
1. Penicillins
2. Cephalosporins Crossreactivity – caution if hx
anaphylaxis1st generation – gram + > -2nd generation – gram + and -3rd generation – gram - > +
- have T in them – T for ‘third’ cefotaxime, ceftazidime, ceftriaxone
3. Carbapenems B R O A D spectrum
GlycopeptidesRequire therapeutic drug monitoring
(TDM)
1. VancomycinUsually IV – covers MOST GRAM +
incl MRSA - but NOT VRE!Exception - oral vancomycin – for
C. Difficile diarrhoea (where metronidazole has failed)
2. Teicoplanin
Antibiotics (antibacterials)
• 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. Macrolides2. Tetracyclines 3. Aminoglycosides 4. Chloramphenicol5. Oxazolidinones
erythromycin, clarithromycin, azithromycin
doxycycline, lymecycline
gentamicin, amikacin – TDM needed
(for your EYES only)
Linezolid – don’t need to know any more
Antibiotics (antibacterials)
• 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 –
MetronidazoleUseful against anaerobes and protozoa
3. Nitrofurantoin - UTIs
Antibiotics (antibacterials)
• 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)
• 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
TrimethoprimUTIs
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
ClassificationDNA viruses
Double-stranded:Adenovirus Herpes virus Pox viruses
Double-stranded plus reverse transcriptase:Hepadnavirus
Single stranded:Parvovirus
RNA viruses
Double-stranded:Reovirus
(+)Single-stranded:PicornavirusTogavirusFlavivirus
(+) Single-stranded plus reverse transcriptase:Retrovirus
(-)Single-stranded:OrthomyxovirusParamyxovirusRhabdovirus
ClassificationDNA 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
Clinical Site of latent infection
Pregnancy Test Treatment
HSV1+2
Painful vesicular rashOrofacial/GenitalCutaneous disseminationVisceral involvement:Oesophagitis, ColitisHepatitis
Sensory nerve ganglia
Primary maternal infection in 3rd trimester:Neonate:Lesions of Skin, Eyes, Mouth (SEM)Disseminated disease (especially to BRAIN)
PCR
Test for Ab
Aciclovir/Valaciclovir (pro-drug)Ophthalmic: topical idoxuridine
CS (Avoid PROM)
VZV Varicella zoster (chicken pox)Flu-like prodromeCentripetal crops of vesicles
Sensory nerve ganglia (Herpes zoster – shingles)
Early pregnancy:Congenital Varicella syndrome:ScarringEye defectsLimb hypoplasiaMicrocephaly and LD
7 day pre/post-partum:Mother: increased risk pneumonia/encephalitis
Neonatal VaricellaPurpura fulminans
Vesicle fluid:PCR/EM/Ab
If exposed: check for AbIf not immune: VZIgIf confimed/rash: aciclovir
CMV Usually asymptomatic (40% infected by 16)Rarely – maculopapular rashImmunosuppressed:Encephalitis, retinitis, pneumonitis, hepatitis, BM suppression, enterocolitis
B cells Commonest congenital viral infectionAsymptomaticHearing defectsCognitive impairment10% Cytomegalic inclusion disease:IUGR, hepatosplenomegaly, chorioretinitis, encephalitis, thrombocytopenia
Hepatitis: GanciclovirHIV: CidofavirSevere: Foscarnet
If primary infection/reactivation in pregnancy – refer to Fetal medicine(but no treatment)
EBV Infectious mononucleosis (sore throat, lymphadenopathy, maculopapular rash with ampicillin)Post-Tx lymphoproliferative disease, lymphomaHIV: oral hairy leukoplakia
B cells No adverse outcome in pregnancy Monospot
Serology
HHV 8
Kaposi’s sarcomaCastleman’s disease (body cavity-associated lymphoma)
B cellsEpithelial cells
HHV 6 + 7 Immunocompromised:Graft failure, hepatitis
T cellsEpithelial 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-strandedparamyxovirus)
CongestionConjunctivitisKoplik’s spotsRash starts behind ears and forehead
Secondary bacterial infection:Otitis mediaPneumoniaPneumonitisEncephalitisSSPE
Rare
Fetal lossPre-term deliveryNot associated with fetal anomalies
Ig to attenuate
LIVE vaccine
Mumps(RNA- single-strandedparamyxovirus)
ParotitisOrchitisOophoritisPancreatitisMeningitis and deafness
LIVE vaccine
Influenza(RNA-single strandedorthomyxovirus)
A: pAndemicB: outBreakC
BronchitisSecondary bacterial pneumonia
In pregnancy:Still birthPre-term delivery
A: amantadineA+B: neuraminidase inhibitorsZanamavir (inhaled)Oselatamavir (oral)
Rubella(RNA+ single-strandedtogavirus)
50% subclinicalPinpoint macular rashlymphadenopathy
1st trimester (90% if <10 weeks)Fetal lossCongenital Rubella SyndromeCataracts, glaucomaHeart defectsDeafnessMental retardation>20 weeks: no risk
LIVE vaccine
Enterovirus(Polio, coxsackie, echovirus)RNA+ single-stranded
Hand, foot and mouth diseaseEncephalitisMyocarditis
Congenital myocarditisNeonatal hepatitis and IDDM
Parvovirus B19(DNASingle-stranded)
AsymptomaticErythema infectiosumPolyarthropathyTransient aplastic crisis
< 20 weeks:3% hydrops fetalisOther anomalies rare
>20 weeks: no risk
Intrauterine transfusion
Antivirals
HSV: Encephalitis, Disseminated (Genital, Oal)VZV: immunocompromise, pregnancy, pneumonitisAciclovirGuanosine analogue-Blocks viral DNA extensionRequires activation by viral TK
CMV (lacks TK)GanciclovirResistant: 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
UK ScheduleDTaP/IPV/Hib 2, 3, 4 monthsPCV 2, 4 monthsMen C 3, 4 months
Hib + MenC 12 months boosterMMR + PCV 12-13 months
DTaP/IPV/MMR 3-5 yearsBCG high risk babies, 10-14y
HPV (16 and 18 - oncogenic) girls 12-13yDT + IPV 13-18 years
Rubella seronegative women
Which of the following is a LIVE vaccine?
A Diphtheria
B Yellow fever
C Rabies
D Tetanus
E 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 Abscess Myelitis Neurotoxin
FeverHeadacheVomitingPhotophobia
Nuchal rigidityKernig’s signFocal neurologyLong tract signs (6th and 3rd CN)Rash
(VIRAL: no focal neurology or alteration of consciousness)
Fever HeadacheDisturbance of brain function(reduced level of consciousness,disorientation,seizures)
VIRAL
HSVEBVMumpsInfluenzaAdenoArboJapanese BRabies
ACICLOVIR
Mass effect: focal neurology, seizures(Fever in <50%)
StrepStaphGram –TBFungiParasitesActinomycesNocardia
Reduced nerve transmission
VIRAL
PolioEBV
Paralysis
Clostridia
-Flaccid (Clostridium botulinum)
-Rigid (Clostridium tetani)
MeningitisACUTE Subacute/
Chronic
Neonates Children Elderly
E. ColiGram negative bacilliGroup B strep
Neisseria meningitidis (meningococcus)Strep pneumoniae (pneumococcus)VIRAL
Gram negative bacilliPneumococcusLISTERIATBSyphilis (treponema)
LeptospiraTBSyphilisBorreliaCryptococcus
Interpreting CSFClarity
Cells (x10^6) Gram stain
Protein Glucose Organism
Normal Clear WCC 0-5 No organisms
0.15 – 0.4 2.2 – 3.3(60% of blood glucose)
Purulent Meningitis
Turbid WCC 100-2000
neutrophils
Organisms
Increased0.5 – 3.0
Decreased0 – 2.2
Bacterial:MeningococcusPneumococcusListeria
Aseptic Meningitis
Clear/Slightly turbid
WCC 15-500
Lymphocytes
No organisms
Increased0.5 - 1
Normal VIRALPartially treated bacterialEncephalitisAbscessTB/fungal
TB Clear/Slightly turbid
WCC 30-500
LymphocytesAND Polymorphs
Scanty AFB (or nothing)
INCREASE1 - 6
Decreased0 – 2.2
TB(Cryptoccoccus,Abscess)
Questions50 year old manHeadache and neck stiffnessCT brain normalLP – opening pressure 15 cmH20
CSF:CloudyWCC 100 (70% lymphocytes)Protein 0.7Glucose 3.3 (serum glucose 4.7)
Diagnosis?A Bacterial meningitisB Viral meningitisC TBD Normal CSFE Cryptococcal
Clarity
Cells (x10^6) Gram stain
Protein Glucose Organism
Normal
Clear WCC 0-5 No organisms
0.15 – 0.4 2.2 – 3.3(60% of blood glucose)
Purulent Meningitis
Turbid
WCC 100-2000
Organisms
Increased0.5 – 3.0
Decreased0 – 2.2
Bacterial:MeningococcusPneumococcusListeria
Aseptic Meningitis
Clear/Slightly turbid
WCC 15-500
Lymphocytes
No organisms
Increased0.5 - 1
Normal VIRALPartially treated bacterialEncephalitisAbscessTB/fungal
TB Clear/Slightly turbid
WCC 30-500
LymphocytesAND Polymorphs
Scanty AFB (or nothing)
INCREASE1 - 6
Decreased0 – 2.2
TB(Cryptoccoccus,Abscess)
20 year old manHeadache and sore throatFeverPhotophobia
CSF:ClearLymphocytes 2; Polymorphs 0Protein 0.3Glucose 4.1 (serum glucose 5.9)
Diagnosis?A Guillian-Barre SyndromeB Viral meningitisC Bacterial meningitisD Cerebral MalariaE Normal CSF
Clarity
Cells (x10^6) Gram stain
Protein Glucose Organism
Normal
Clear WCC 0-5 No organisms
0.15 – 0.4 2.2 – 3.3(60% of blood glucose)
Purulent Meningitis
Turbid
WCC 100-2000
Organisms
Increased0.5 – 3.0
Decreased0 – 2.2
Bacterial:MeningococcusPneumococcusListeria
Aseptic Meningitis
Clear/Slightly turbid
WCC 15-500
Lymphocytes
No organisms
Increased0.5 - 1
Normal VIRALPartially treated bacterialEncephalitisAbscessTB/fungal
TB Clear/Slightly turbid
WCC 30-500
LymphocytesAND Polymorphs
Scanty AFB (or nothing)
INCREASE1 - 6
Decreased0 – 2.2
TB(Cryptoccoccus,Abscess)
Which of the following types of viral meningitis may be associated with a characteristically LOW CSF glucose level?
A Mumps
B CMV
C Measles
D HIV
E Echovirus
Prion disease: Infectious proteinCauses rapid
neurodegeneration (Dementia, ataxia)No
inflammatory/immune reaction
Genetic 15% Sporadic 80% Acquired < 5%
Familial CJD;Gerstmann-Straussler-Sheinker SyndromeFamilial Fatal Insomnia
Sporadic CJD KuruVariant CJDIatrogenic
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: 30-70Slowly progressive ataxia - Death in 2-10yFamily history (dementia, ataxia, psychiatric)
Onset: 65Rapid dementia – death in 6m
Onset: 26Psychiatric symptoms before neurological symptomsDeath in 14 months
EEG: non-specific
MRI: may be increased signal in basal ganglia
Neurogenetics: reveals mutationGSS PRNP P102LFFI PRNP D178N
EEG: pseudoperiodic triphasic complexes (2/3)
MRI: increased signal in basal ganglia
CSF: raised markers of neuronal damage ( 14-3-3; S100)
Neurogenetics: No genetic cause
Brain biopsy: PRP immunohistochemistry
EEG: Non-specific SLOW waves
MRI: positive pulvinar sign (increased signal in bilateral posterior thalamus)
CSF: markers not useful
Neurogenetics: all methionine homozygous at codon 129 (MM)
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 elderlyB More rapidly progressive than sporadic CJDC Initial symptoms are always neurologicalD Tonsillar biopsy is often diagnosticE 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
EndocarditisSubacute versus acute
General points –
•Blind therapy – fluclox/benpen/vancomycin + gent
•If penicillin allergic/MRSA - use vancomycin
•Mortality – 30% with staph, 5% with strep
Who Treatment Complications
Streptococcus viridans
Native valves Benpen +/- gent
Staph epidermidis Prosthetic valve if <2 months post surgery
Fluclox +/- gent(+ rifampicin if prosthetic valve)
Staph aureus IVDUs Fluclox +/- gent Abscesses
Strep bovis Colorectal ca Benpen +/- gent
Culture-negative Endocarditis
• Caused byA) 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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