Microbio Flashcards
Causative agents of HAP
More gram -ve organisms (vs CAP) • Enterobacteriales 31% • Staph aureus 19% • Pseudomonas spp. 17% • Acinetobacter baumannii 6% • Fungi e.g. Candida sp. 7%
Atypical CAP organisms
Atypical = organisms without cell wall o Mycoplasma – epidemics every 4-6 years o Legionella - water coolers, AC o Chlamydia psittaci - birds o Coxiella (Q fever) – farm/domestic animals
CURB-65 Score
Confusion Urea >7 RR >30 BP - systolic <90 or diastolic <60 >65 years old
2 points = consider admitting
2-5 = admit + treat as severe
Abx guidelines for atypical CAP
NOT cell-wall active Abx e.g. penicillins (since they don’t have a cell wall)
Sensitive to macrolides e.g. clarithromycin
OR Tetracyclines e.g. doxycycline
Key features of Streptococcus Pneumoniae (CAP)
Gram +ve
Acute onset fever, rigors, rust coloured sputum!
May follow recent viral illness?
Tx = almost always penicillin sensitive (amoxicillin, co-amoxiclav)
Key features of Legionella Pneumophila (CAP)
Atypical CAP Inhalation of water droplets - AC, water coolers Extra-pulmonary Sx - hyponatraemia - hepatitis - confusion - abdominal pain - diarrhoea - lymphopenia
Dx = urine/serum antigen + special buffered charcoal yeast extract culture
Tx = macrolides e.g. clarithromycin
Key features of Haemophilus influenzae (CAP)
Gram -ve
Cocco-bacilli
More common if pre-existing lung disease
Dx: chocolate agar culture
TB Ix Results / Diagnosis
CXR –> upper lobe cavitation is typical (but varies)
Auramine rhodamine stain
Ziehl-Neelsen stain
Key features of PCP / Pneumocystis jirovecii
Insidious onset
- dry cough
- SOB + reduced exercise tolerance
- weight loss
- malaise
Ix:
CXR - bat wing
Immunofluorescence of BAL
Silver stain in cytology lab
Tx = septrin (co-trimoxazole)
Aspergillus fumigatus lung disease - key features
Allergic bronchopulmonary aspergillosis (ABPA)
- chronic wheeze
- eosinophils
- bronchiectasis
Aspergilloma
- fungal ball often in pre-existing cavity
- may cause haemoptysis
Invasive aspergillosis
- immunocompromised
- tx = amphotericin B
CAP Abx Guidelines
Mild-moderate:
- Amoxicillin OR
- Erythromycin/Clarithromycin
Moderate-severe (needing hospital)
- Co-amoxiclav AND clarithromycin
- If penicillin allergic: Cefuroxime AND clarithromycin
Reservoir for Campylobacter
Poultry (100% Uk chickens carry in GI tract)
Cattle
Ix for Campylobacter
Stool culture - 48-72 hours
Reservoir for Salmonella
Poultry
Amphibians/reptiles
Forms of Bartonella henselae infection
Cat scratch disease
- macule at inoculation site
- becomes pustular
- regional lymphadenopathy
- systemic sx
Bacillary Angiomatosis
- immunocompromised people
- skin applies
- disseminated multi organ + vascular involvement
Tx for Bartonella infection
Erythromycin, doxycycline
+ rifampicin if immunocomprised (bacillary angiomatosis)
Tx for Toxoplasmosis
Pregnant = spiramycin
Immunosuppressed = pyrimethamine, sulfadiazine
Presentation of Brucellosis
Mimics extra pulmonary TB
- back pain
- orchitis
- fever
- focal abscesses e.g. psoas, liver
Tx for brucellosis
Doxycycline + gentamicin or rifampicin
6 weeks
Q fever causative organism?
Coxiella burnetii
Tx for coxiella Burnetti?
Doxycycline
Hydroxychloroquine
Tx for rabies
Post exposure vaccine
+/- human normal immunoglobulin (no specific formation)
Rat bite fever presentation
Fever
Polyarthralgia
Maculopapular rash —> purpuric
+/- Endocarditis
Tx for rat bite fever
Penicillins
Causative organism of rat bite fever?
Streptobacillus moniliformis
Spirillum minus
Viral haemorrhagic fevers
- Reservoir & disease
? Bats - Ebola
? Bats - Marburg
Rats - Lassa
Ticks - Congo Crimean haemorrhagic fever
HIV encephalopathy signs on imaging
Basal ganglia calcification
White matter changes
Atrophy —> enlarged ventricles
Methods of vertical HIV transmission
In Utero
intra partum
Breast feeding
Factors affecting maternal —> baby HIV transmission
Major = maternal viral load
Placenta - healthy is protective, toxoplasmosis or malaria co-infection causes unhealthy placenta
PPROM
1st born twin - approx double risk
Breast feeding - 4% transmission for every 6 months
Type I Antimicrobial activity pattern
Concentration dependent killing
Examples:
- aminoglycosides
- daptomycin
- fluoroquinolones
- ketolides
Type 2 antimicrobial activity pattern
Time dependent killing
Examples:
- carbapenems
- cephalosporins
- erythromycin
- linezolid
- penicillins
Type 3 antimicrobial activity pattern
Time dependent killing + moderate-prolonged persistent effects
Examples:
- azithromycin
- clindamycin
- oxazolidinones
- tetracyclines
- vancomycin
Beta lactam Abx MOA
Inactivate enzymes needed for terminal stages of cell wall synthesis (the penicillin binding proteins)
Induce cell lysis
What bacteria will beta-lactams NOT work on?
Bacteria that lack peptidoglycan cell wall
Chlamydia, mycoplasma
Pattern of activity across Cephalosporin generations
Activity against gram -ve increases (and gram +ve decreases)
Cephalosporins
1st gen = Cephalexin
2nd gen = Cefuroxime
3rd gen = Cefotaxime, Ceftriaxone, Ceftazidime
Glycopeptide Abx - examples and MOA
Vancomycin, (Teicoplanin)
Binds to D-Ala, D-Ala
Prevents trans glycosidase and transpeptidase binding
Cell wall lysis as bacterium divides
Side effects of Glycopeptide Abx
Nephrotoxic
+/- Ototoxic
Require drug level monitoring
Aminoglycoside Abx - MOA and examples
Bind to 30S ribosomal subunit
Prevent elongation of polypeptide chain + cause misreading of codons along mRNA
E.g., gentamicin, amikacin, tobramycin
Tetracycline Abx - MOA & examples
Reversibly bind 30S ribosomal subunit
Prevent amino acyl atRNA binding to ribosomal acceptor site - inhibits protein synthesis
E.g. doxycycline
Side effects of doxycycline
Deposited in growing bones - do not give in children, pregnant or breastfeeding women
Teratogenic
Light sensitive rash
Macrolide Abx - MOA & Examples
Bind to 50S ribosomal subunit
Interfere with translocation
E.g., azithromycin, clarithromycin, erythromycin
Chloramphenicol MOA
Binds peptidyl transferase of 50S ribosomal subunit
Inhibits peptide bond formation
Side effects/risks of chloramphenicol
Grey baby syndrome - inability to metabolise drug
Aplastic anaemia
Oxazolidinone Abx - MOA & example
Binds 23S component of 50S subunit
Prevents formation of functional 70s initiation complex
E.g., linezolid
Most common valve affected in Infective Endocarditis in IVDU
Ticuspid
Acute Infective endocarditis - causative organisms
high virulence bacteria
o Strep pyogenes (Group A strep)
o Staph aureus – most common in IVDU
o CoNS – most common in prosthetic valve
Subacute Infective Endocarditis - causative organisms
low virulence bacteria
o Staph epidermidis
o Strep viridans
o HACEK – Haemophilus, Acinetobacter, Cardiobacterium, Eikinella, Kingella
How to interpret Duke’s criteria in IE?
2 major OR 1 major + 3 minor OR 5 minor –> Dx of IE
Gonorrhoea tx?
Ceftriaxone IM 1g - uncomplicated gonorrhoea (anogenital, pharyngeal)
Chlamydia Tx?
Azithromycin 1g STAT or Doxycycline 100mg BD for 7 days
Best sample for NAAT (Chlamydia, Gonorrhoea)
Men = clean catch urine Women = vaginal swab
Causative organism of Syphillis?
Treponema pallidum
• Obligate gram negative
• spirochaete
Tx of Syphillis?
Single dose IM Benzathine Penicillin
Doxycycline if allergic
(think this changes once latent / tertiary ? )
Jarisch Herxheimer reaction?
Seen few hours after Abx Tx in syphillis
Presentaion: Flu like Sx - Headache, myalgia tachycardia, mild hypotension hyperventilation can induce early labour or foetal distress
Tx
- aspirin every 4 hours fo 24-48 hrs
- steroids in CVS or neuro syphillis - can be fatal
Resolves within 24h
Ocular sign of late syphillis?
Argyll Robertson pupil = one that accommodates but does not react to light
Broad spectrum Abx
Co-amoxiclav
Tazocin
Meropenem
Ciprofloxacin
Narrow spectrum Abx
Flucloxacillin
Metronidazole
Gentamicin
Mechanisms of Abx resistance?
- Chemical modification or inactivation of antibiotic
- Alteration or replacement of target
- Reduced accumulation of Abx - increased efflux or reduced uptake
- Bypass Abx sensitive step
Examples of altered targets giving Abx resistance
MRSA
- mecA gene encodes novel penicillin-binding protein (2a) with low affinity for beta-lactams
Streptococcus pneumoniae
- stepwise mutations in penicillin-binding protein genes
Examples of inactivation of Abx as resistance mechanism
Beta lactamases
- Staph aureus & gram -ve bacilli
- NOT the mechanism in MRSA & pneumococci
Extended spectrum beta lactamases
- can also break down cephalosporins
- more common in E. coli, Klebsiella
Abx most likely to cause C. diff diarrhoea?
3 Cs
clindamycin
cephalosporins
ciprofloxacin
Tx for C. diff diarrhoea
1st line = Oral vancomycin for ALL C. Diff
Oral metronidazole NO LONGER 1st line
+ stop offending Abx
HAART Regimen principles
3 different ARV from 2 or more classes: NNRTI NRTI Integrase inhibitors Protease inhibitors
E.g. Bictegravir (II) + tenofovir alafenamide (NRTI) plus emtricitabine (NNRTI)
PCP/PJP Tx?
Tx = Co-trimoxazole (septrin) + Prednisolone if hypoxia
Prophylaxis = Co-trimoxazole (septrin) OR inhaled pentamidine
Yeast examples?
Candida spp.
Cryptococcus (neoformans)
Histoplasma - dimorphic
Pneumocystis jiroveci
Mould examples?
Dermatophytes e.g. Trichophyton rubrum
(Agents of) Mucomycoses
Aspergillus
Ix for (deep) Candida infection?
Beta-D-glucan assay
Sabouraud-dextrose Agar culture –> raised cream coloured colonies
Tx for deep/invasive Candida?
Amphotericin B
+ blood cultures every 48 hrs
continue tx for at least 2 weeks from first -ve blood culture
Cryptococcu serotypes & pattern?
A & D - immunodeficient people, incl ‘neoformans’
B & C - immunocompetent, tropical countries, incl ‘gatii’
What medication is associated with Cryptococus infection?
T cell immunosuppressants e.g. Tacrolimus (CN inhibitor)
Gold standard IX for Cryptococcus infection
Microscopy –> halo on India ink staining
Agents used for Cryptococcus Tx
Induction: Amphotericin B + flucytosine
Consolidation & Maintenance (or mild pulmonary disease only): Fluconazole
Key Ix findings in Aspergillosis infection
CT –> halo sign
Galactomannan antigen detection
cultured on Czapek dox agar
Risk factors for Mucormycoses
Diabetic
Immunosuppresed
Manifestations of Mucormycoses
Rhinocerebral
- orbital & facial cellulitis = black eschars (pus)
- retro orbital extension = proptosis, chemosis, blindness
- brain involvement = reduced GCS
Pulmonary
Cutaneous
Causative organism for fungal infection causing Black Eschar (pus)
Rhinocerebral mucormycosis
Rhizopus
Rhizomucor
Mucor
Mangement of Mucormycoses
Ambisome / Posaconazole
Surgical debridement
Dermatophyte infections - common names
Tinea pedis = Asthlete’s foot, Trichophyton rubrum usually
Tinea corporis = body/abdomen
Tinea captitis = scalp
Tinea cruris = groin
Causative organism for Seborrheic dermatitis
Malassezia globosa/furfur
Tinea versicolor - key features?
Aka pityriasis versicolor
Skin depigmentation in individuals with dark skin
Tx = ketoconazole shampoo or antifungal cream
How does onychomycosis Tx differ from Athlete’s foot?
Topical rarely effective
1st line = terbinafine
BUT usually wait to confirm Dx as serious side effects e.g., pancytopenia, agranulocytosis, hepatic derangement
HIV drugs MOA: Tenofovir Raltegravir Nevirapine Saquinavir Maraviroc
Tenofovir = NRTI Raltegravir = integrase inhibitor Nevirapine = NNRTI Saquinavir = protease inhibitor Maraviroc = CCR5 antagonist
Beta haemolytic Streptococcus
Group A - strep pyogenes
Group B - strep agalactiae
y haemolytic Streptococcus
Enterococci e.g. E. faecalis
alpha haemolytic streptococcus
Strep pneumoniae.
Strep viridans.
CSF analysis results in Bacterial meningitis
Turbid
High WCC - polymorphs
Low glucose
High protein?
+ve Gram stain/microscopy
CSF analysis results in viral (aseptic) meningitis
Clear
High WCC - mononuclear (lymphocytes)
Normal glucose
High protein?
Negative gram stain/microscopy
CSF analysis results in TB meningitis
Clear or slightly turbid
High WCC - mononuclear or polymorphs
Low glucose
High protein
Negative gram stain/microscopy OR scanty acid fast bacilli
Purulent meningitis management
A-E assessment + resusitate
Abx:
Ceftriaxone (cefotaxime in neonates instead)
+ amoxicillin/ampicillin if neonate, elderly or immunosuppressed
+ steroids in adults
When would a CT head be done before LP?
(In meningitis/encephalitis where):
- Raised ICP
- Focal neuro deficit
- GCS 12 or below
- Seizures
Empirical Tx for encephalitis
IV aciclovir 10mg/kg TDS
likely will give meningitis Abx as difficult to distinguish - IV ceftriaxone +/- amoxicillin/ampicillin
Definition of R0
Number of people that 1 sick person will infect, on average
If <1, transmission is halted
Indications to defer a live attenuated vaccine
Receiving high dose oral steroids (incl asthma exacerbation)
Received Ig in last 3 months
Pattern of Hep B clearance by age?
90% clearance if >5 years old
10% in neonates
Serology of Hep B ACUTE infection
HBeAg - marker of infectivity
HBsAg
HBcAb (acute IgM)
Serology of Hep B CHRONIC infection
HBSAg
HBcAb (IgG)
Serology of Hep B PAST infection
HBsAb
HBcAb
Serology of Hep B Vaccination
HBsAb
Hep C ‘curative’ Tx
-previrs e.g. telaprevir
NS3/4 protease inhibitors
-asvirs e.g. ledipasvir
NS5A inhibitors
-buvirs e.g. sofosbuvir
Direct polymerase inhibitors
Mycobacterium avium complex (MAC) Tx regimen
Clarithromycin/azithromycin
Rifampicin
Ethambutol
+/- Amikacin/Streptomycin
Pattern of protection of BCG vaccine
will not protect against pulmonary TB 70-80% effective against severe childhood TB Some protection against CNS infection Protection wanes Little evidence in adults
TB Treatment regimen
Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
ALL for 2 months then R + I for 4 more
Main TB drug side effects
Rifampicin - orange secretions
Isoniazid - peripheral neuropathy
Pyrazinamide - hepatotoxicity
Ethambutol - optic neuritis
Most powerful RF for SSI after cardiothoracic surgery?
Staph aureus carriage
Exceptions to giving no Tx (except catheter removal) in Candiduria?
Renal transplant pt
Patients undergoing elective UT surgery
Pyelonephritis Tx regimen
Admit
IV co-amoxiclav + gentamicin
Types of viral detection
Indirect - identifies immune response to virus e.g. serology
Direct - identifies fragments of virus e.g. PCR for viral genetic material
Serological screening BEFORE immunosuppression
HIV Hep B, C EBV CMV HSV Varicella zoster HTLV
Monitoring during immunosuppression (Via PCR)
CMV
EBV
BK (renal & BM transplant)
Adenovirus (paediatric BM transplant)
Prophylaxis for HSV in immunosuppression?
Bone marrow transplant - for 1 month (until engraftment)
Solid organ transplant - 3-6 months + if undergoing Tx for rejection
Tx of Shingles in the immunocompromised?
Antiviral + analgesia
IV if disseminated
+ steroids if Ramsay Hunt (facial nerve involvement –> palsy, hearing)
+ topical steroids if Herpes Zoster Ophthalmicus
Tx of Chickenpox in immunocompromised?
Antiviral 7-10 days
Given IV until no new lesions then PO until all lesions crusted over
Tx of post-transplant lymphoproliferative disease
Rituximab
Reduce immunosuppression
+ Monitor EBV levels
CMV prophylaxis/monitoring strategy in immunosuppression
HSCT: viral load 2x/week + Tx if reactivation (until suppressed)
Solid organ: 100 days prophylaxis - Valganciclovir
Diagnosis of JC virus/progressive multifocal leukoencephalopathy
MRI
CSF - PCR
What groups get Progressive multifocal leukoencephalopathy?
HIV+ve - was reducing with ART
Other immunosuppression esp Natalizumab (anti T cell) in MS
Influenza Tx in immunosuppressed
Resistance / severe (ICU) / immunosuppressed= Zanamivir inhaled or IV
Otherwise = Oseltamivir oral for 5 days
Main immunosuppressive medications that can cause HepB reactivation?
B cell agents e.g. Rituximab
IL-6 inhibitors (COVID Tx)
Malaria Diagnosis
Thick blood film = identify parasites
Thin blood film = identify species
Features of severe Falciparum malaria
Hypoglycaemia <2.2 Seizures / impaired consciousness Renal & hepatic impairment Acidosis <7.3 Pulmonary oedema / ARDS Bleeding / DIC Shock - <90/60 Haemoglobinuria Anaemia <80 Parasitaemia >2%
Tx for severe Falciparum malaria
IV artesunate
Tx for mild Falciparum malaria
Artemisin combo Tx
- E.g. Riamet
- Artemether + Lumefantrine
Tx of Neurocysticercosis
Anti-convulsants
Anti-parasitics / Cestocidal
- Praziquantel
- Albendazole
Steroids
- esp if heavy infection - cesticidals alone may be fatal!
+/- surgery e.g. shunt if hydrocephalus
Indications for treating VZV?
Chickenpox in adult
Zoster in adults >50
Primary infection or re-activation in immunocompromised person
Neonatal chickenpox
HSV Encephalitis - IV Tx
Treatment regimen for HSV Encephalitis
IV Acyclovir 10mg/kg IMMEDIATELY - do not delay for Ix results
Continue for 14-21 days if confirmed
Repeat LP towards end of course, before stopping Tx
CMV Tx options
Ganciclovir/Valganciclovir
- CMV disease in immunocompromised
- neonatal congenital CMV
- IV Ig if pneumonitis
Foscarnet
- Ganciclovir contraindicated or resistance
- CMV retinitis
Cidofovir = 3rd line
EXCEPTION to Foscarnet being 2nd line for CMV?
Foscarnet 1st line for pre-engraftment period of BM transplant
(Val)ganciclovir causes BM toxicity
Also used for CMV retinitis - intravitreal formulation
Indications to consider Palivizumab Tx in bronchiolitis
Pre-term
Severe underlying heart or lung disease
SCID
Long term ventilation
Mechanisms of drug resistance in HSV
Mutations in viral thymidine kinase (95%) or viral DNA polymerase (5%)
Cross resistance to (val)ganciclovir as well as (val)aciclovir
Mechanisms of drug resistance in CMV
Protein kinase UL97 mutation most common
Others:
- DNA polymerase UL54
- UL56 terminase
Types of antiviral drug resistance assays
Genotypic
- used for HIV, Hep B & C, CMV
Phenotypic
- used for HSV
