Week 6 and 7 Micro Flashcards
Types of antibiotic use (Guided vs Empirical vs prophylactic)
Guided: Based on identifying cause of infection, choosing antibiotic based on selectivity testing
Empirical: Best (educated) guess, based on clinical/epidiemological acumen
Prophylactic: preventing before it starts
Narrow vs Broad spectrum
Spectrum: range of bacterial species that an antibiotic can effectively treat
Narrow: Effective against a limited range of bacteria. Useful when infection is known. Limited effect on colonising bacteria
Broad: Effective against wide range bacteria. Treat most causes of infection. But, marked effect on colonising bacteria
Antibiotic action
Bactericial: Sterilises site of infection. Lysis bacteria can lead to toxin release and inflammation
Bacteriostatic: Suppresses growth of bacteria but does not sterilise site of infection. Requires additional factors to clear bacteria.
Antibiotics safe and unsafe in pregnancy
Considered safe:
Most B-lactams
Macrolides
Anti-tuberculants
Unsafe:
Trimethoprim: neural tube defects in 1st trimester Nitrofurantoin: haemolytic anaemia in 3rd trimester Aminoglycisides: ototoxicity in 2/3rd trimester Tetracyclines: bone/teeth abnormalities Quinolones: bone/joint abnormalities
Inherent vs. Acquired resistance
Inherent: bacteria naturally lack a pathway or target which the drug can interact with
Acquired: antibiotic that was previously sensitive not anymore, as bacteria become resistance by inheriting genetic information
4 mechanisms bacteria can use to be resistant to antibiotics
- Produce enzymes e.g. B-lactams
- Change drug target e.g methylation of 23S ribosomal subunit (resistant to erthyromycin)
- Decrease cell permeability (downregulate porins)
- Export drug out from inside cell (pseudomonas produces efflux pump)
4 ways bacteria gain resistance
- Chromosomal mutation
- Gain mobile piece of DNA (plasmid, integron which contains resistance)
- Transformation: bacteria gains genetic information from environment
- Transduction: pieces of DNA transferred between bacteria from virus
Gene transfer
Vertical transfer: parent bacteria passes on genetic information to progeny by binary fission
- spontaneous mutation - occurs less often than transfer of mobile pieces of DNA
Horizontal transfer: mobile pieces of DNA transferred other than traditional reproduction
- Conjugation: requires cell-cell contact between bacteria, and plasmids (circular, double stranded DNA) transferred (which contain information for resistance). Most important horizontal transfer.
- Transduction: pieces of DNA transferred by virus (bacteriophages - viruses which infect bacteria)
- Transformation - when bacteria die, can release DNA. Some bacteria can take up DNA and insert it into their chromosome.
Fitness cost
Antibiotics attack the biological function of the bacteria, so bacteria develop mutations but can lead to a slower growth rate - fitness cost. In a non-selective environment, slower-growing bacteria can be outgrown by wild-type bacteria and die. However, in a selective pressure environment e.g. hospital, the importance of these mutations outweighs the drawback of the slower growth rate, so these bacteria will survive, So increase selection pressure can lead to increased resistance
MRSA
Bacteria strains which resistant to all B-lactams. MecA gene encodes for a variant of the normal penicillin binding protein (allows crosslinking of peptidoglycans in cell wall) which have a decreased affinity for methicillin. So, these bacteria still produce a cell wall, even in presence of B-lactams
Gram -ve bacilli (pink)
E.g. E.Coli, pseudomomas
B-lactamase inhibitors
Clavulanate
Tazobactam
Bind to B-lactamses, allowing B-lactam drugs to work
Coliforms
Gut commensals - Gram -ve bacilli which live in gut e.g. E.coli, Klebsiella, Enterobacter
Also cause UTI, HAP, intra-abdominal sepsis
Extended Spectrum Beta Lactamses
Pseudomonas
Has modifying enzymes and porin down regulation
4 efflux pumps, which one is always expresses so more resistant to antiobiotics than other gram -ves
ESBLs (extended spectrum beta lactamases)
Plasmid encoded resistant, so can hydrolyse Beta -lactam ring in penicillins and cephalosporins
Treatment: Ciprofloxacin, Gentamicin, Meropenem,
Carbapenemases
Hydrolydse meropenems via enzyme, AmpC, and causes porin loss
Ways to reduce resistance
Use narrow spectrum antibiotics
Follow emperical guidelines
Short courses e.g. UTI - 3 days
Infection control for patients who are infected
Non-genetic mechanisms of resistance
- Abscess formation
- Bacteria in resting stage e.g. TB
- Foreign body e.g. biofilms - bacteria in close proximity so can transfer genetic material which contain resistance
Which bacteria has developed resistance to Carbapenems?
Klebsiella pneumoniae
Antibiotic pescribing steps
Is it required?
Which one?
How should it be administered?
How long?
Adjunctive measures?
Review
When not to give antibiotics
Viral
Self-limiting respiratory tract infections
Uncomplicated UTI
Ingrown toe nails
Systemic inflammatory response e.g. cancer
Symptoms of infection
General:
Fever, sweats, rigors
Localising:
Dysuria
Cough+green/brown sputum, creps
Erythema, heat, swollen
Antibiotics for uncomplicated UTI, lower respiratory tract infections (LRTI), mild cellulitis
Uncomplicated UTI: trimethoprim, nitrofurantoin
LRTI: Amoxillin, doxycycline
Mild cellulitis: flucoxacillin, doxycyline
Severe:
IV combination e.g. B-lactam + gentamicin
<1hr admin
Antibiotics which especially cause C.diff
Cephalosporins
Co-amoxiclav
Clindamycin
Carbapenems
Ciprofloxacin
Systemic inflammatory repsonse
Fever/hypothermia (>38/<36)
RR (>20/min)
HR (>90bpm)
low/high WBC ( < 4 or >12)
Sepsis
Life-threatning organ dysfunction (defined using q-sofa score) due to infection
>2 of:
Altered mental status (GCS <15)
RR >22/min
BP systolic < 100mmHg
Can lead to septic shock: Sepsis induced hypotension, requiring ionotropic support, or hypotension not respdoning to fluid resus
Collateral damage with antibiotic use
Unintended consequences
Anitbiotic resistance
Drug interactions
Diarrhoea
Vasuclar site infection (S. auerus bacteraemia)
Guidlines for systemic inflammatory response (if unknown)
Blood cultures and IV antibiotics within 1 hr
Review anatomical systems
CXR
Add cover for S.aureus (if healthcare assoc.)
Add cover for MRSA (if previous infection, recent carrier)
Add cover for Streptococcal (if pharyngitis, erythoderma, hypotension)
Guidlines for sepsis (unknown)
IV amoxcillin + IV gentamicin
If suspected S.aureus
Add IV flucoxacillin
If suspected MRSA
Add IV vacomycin
If suspected Streptococcal
Add IV clindamycin
Which antibiotics for COPD exacerbation with green sputum
IV amoxicillin or doxycyline
Organisms which cause fever in travellers
Bacteria: Enterotoxigenic or Enteroaggregrative E.coi
Shigella
Salmonella
Campylobacter
Viruses: Norovirus, Rotavirus
Parasites: Giardia (takes weeks to present)
Symptoms: Fever, watery diarrhoea, nausea/vomiting
Management:
Fluids
Antibiotics e.g. Quinolones (only if have co-morbidities)
Types of mosquitoes which spead typhoid and malaria
Malaria: Anopheline mosquito. Evening biter
Typhoid: Aedes mosquito. Day biter.
Malaria
Most common cause of fever in subsaharan Africa
Organisms:
P.falciparum (worldwide. main cause)
P.vivax (Commonly Asia. Chloroquine resistant. Persistent liver infection)
P.ovale (West Africa. Persistet liver infection)
P.malariae (worldwide)
Symptoms:
Fever, malaise, myalgia, jaundice, cerebral malaria
Treatment: artemether, quinine+doxycyline
Prevention: Nets, DEET, clothing, doxycycline (can cause photosensitisation), malarone (expensive)
Diagnosis: Blood film - thick (haemolysed RBCs, sensitive) thin (monlayer red cells, not as sensitive)
Antigen test - detects malarial antigens. Not as sensitive as thick blood film. Differentiates P.falciparum and non P.falciparum
Typhoid
Organisms: S.typhi and S.paratyphi can cause enteric fever
Human to human, contaminated water
Clinical features: Fever, abdo pain, constipation/diarrhoea, neuro symptoms e.g. headache, enteric encelopathy, septic shock
Treatment: Quinolones (best)
Cephalorsporins (emperical)
Diagnosis: blood culture
Dengue fever
Clinical features: “breakbone fever” - fever, myalgia, arthalgia, headache, rash
Laboratory features: leucopenia, thrombocytopenia
Management: symptomatic
Diangosis: PCR
<1% infections lead to Dengue haemorrhagic fever
- Increased vascular permeability, fever, thrombocytopenia, bleeding
Viral haemorrhagic fever
Ebola, yellow fever
Can take up to 21 days to present
Treatment: Supportive, Ribavirin
Chain of infection
Infectious agents
- Staph. coccus
- Streptococci
Resevoir
Enovironment, animals, humans
Portal of Exit
TB: Respiratory tract
Norovirus: vomit
Modes of Transmission
Direct e.g. contact
Indirect e.g. airborne
Portal of Entry
Resp tract, mucous membranes
Susceptible hosts
Elderly, immunocompromised
Strageties for healthcare assoc infections
Isolation, screening, standard and transmission based precautions, antibiotic stewardship
Aseptic technique
Reduce activity in area
Keep exposure to susceptible site to minimum
Check sterile pack for damage
Hand washing prior
Gloves
Waste disposal
Chronic granulomatous disease
X-linked
Defect in NADPH oxidase
Deficiency in production of oygen radicals, and intracellular killing
Increased risk of bacterial and fungal infections leading to lung, skin abscesses
Wide spread granuloma formation
Pulmonary infections e.g. staph. aureus (as catalse detroys hydrogen peroxide), Aspergillus
Cellular immunity supressed by:
Primary: Di George syndrome
Secondary: Lymphoma, chemo, drugs e.g. corticosteroids, rituximab
Increased risk of viral, fungal, protazoa infections
Humoral immunity suppressed by:
Primary: Bruton’s agammaglobulinaemia
Multiple myeloma, chemo, radiotherapy
Increased risk of Strep.pneumoniae, H. Influenzae, Nisseria meningitidis
Splenic function
Splenic macrophages phagocytose encapsulated bacteria
Site of primary immuniglobulin response
Increased risk of strep.pneumoniae, haemophilus influenzae, nisseria meningitidis
Physical barriers
Skin
Conjunctivae
Mucosa - GI, resp
Mucosal barrier injury
Chemo/radiotherapy affects cells with high mitotic index including mucosa
Leads to mucositis - pain, dysphagia - impairs GI function - alteres nutritional status
PPIs, antiobitcs - alters microbiome
Severe nutritional deficiency
<75% total body weight or rapid weight loss + hypoalbuminaemia
Anorexia, nausea, vomiting, mucositis
Leads to impaired host defese
Iron deficiency leads to reduced neutrophil and T cell function
Organ dysfunction
Tumours can lead to obstruction and infection esp. in lung
Infection in solid organ transplant
Causes are diverse:
- community acquired e.g pneumococcus,
- opportunistic infections e.g. pneumocystis jirovecii, aspergillus
- donor derived e.g. TB, E.coli, HSV
Pulmonary infections rapidly progress
Inflammatory repsonses impaired
- symptoms are diminished
Diagnosis difficult
Febrile neutropenia
Febrile neutropenia = infection until proven otherwise
Also caused by
- malignancies e.g. 100% haemotological malignancies, 50% solid tumours
- Chemo
- Antibiotics
Common pathogens in neutropenic cancer patients
Gram postive
- Coagulase negative staphylococci
- Staph aureus
Gram neg
- E.coli
Anaerobes
- Clostridium
Viruses:
- HSV
Fungal
- Candida
Neutropenic sepsis
Neutrophil count <0.5, or <1 if recent chemo
+
Fever/hypothermia (>38/<36) OR SIRS OR sepsis/septic shock
SIRS: sweat, chills, rigors, malaise
<36/>38, RR > 20, HR > 90, WC <4/ > 12
Sepsis: evidence of infection and organ dysfunction (2 or more of qSOFA: GCS < 15, BP <100, RR > 22)
Septic shock: Sepsis induced hypotension, requiring ionotropes or hypotension unrepsonive to fluid resusication.
Clinical management neutropenic sepsis
Medical emergency
Assess within 15 mins of presentation
Assess sepsis severity with NEWS
Sepsis 6 in one hour
- High flow O2
- Blood cultures
- IV antibiotics
- IV fluids
- Lactate/FBC
- Urine output
Antibiotics for neutropenic sepsis
Standard risk (NEWS <6)
- IV tazocin
High risk (NEWS >7, septic shock)
- IV tazocin + IV gentamicin
If penicillin allergy:
- IV vancomycin + IV ciprofloxacin
If soft tissue infection add vancomycin (in case of MRSA)
If susepct atypical pneumoinia add clarithromycin
What is the most important risk factor for infection?
Neutropenia
Can be caused by chemo/radiotherapy - decreased haemopoietic progenitors - depletes marrow reserves
3 factors to consider in positive blood result for endocarditis
Is it a contaminant?
Coagulase negative Staphylococci most common
If not, what if the source?
What antibiotic to use?
How to take blood cultures for bacterial endocarditis
3 sets blood cultures (First and last one hour apart)
10ml each
From peripheral veins (as central has increased risk of contamination)
Sterile technique
Prior to antibiotics
Treatment streptococcal endocarditis
Benzylpenicillin 4 wks, and gentamicin for 2 wks
Need to monitor renal function
Organisms which cause biliary sepsis
Enteric flora -
Gram neg: E.coli, Klebsiella, Enterobacter
Gram positive: Enterococci
Anaerobes e.g. Clostridia
Treatment:
Gent + Amox + Metranidazole
Needs to be referred to surgical team (to identify obstruction)
4 classes of Necrotising fascitiis
Type I: synergistic infection with aerobes (e.g. Streptococci) and anaerobes (e.g. bacteriodes)
More common in elderly diabetics
Type II: Group A Strep - Streptococcus pyogenes via toxin production
Type III: vibrio vulnificus
Type IV: fungal
Antibiotics for Nec fas
IV benzylpenicillin (streptococcus)
IV flucoxacillin (staphylococcus)
IV gentamicin (gram neg)
IV metranidazole (anaerobes)
IV clindamycin (anaerobes/toxin production)
IV vancomycin (MRSA)
Bacterial GI infections can cause illness in two ways
Infectious: bacterial pathogens develop in gut after ingestion e.g. salmonella
Intoxication: bacterial pathogens grow on food produce exotoxins e.g. Staph aureus
TB
Central casseous granuloma
Epitheloid cells surrouding granuloma
Lymphocytes (outer)
Langerhans giant cell
Why does strong cell mediated immunity fail to clear TB?
Granuloma
Dysentery
Inflammatory disease of large bowel
Pain, bloody stool, fever
Transmission of GI infections
Faecal-oral
Food, fluids, fingers
Person-person
Lab diagnosis of GI infection
Enrichment broth - nutrients promotes growth of certain pathogen
Selective media - supresses growth of background flora, while allowing growth of pathogen
Differential media - distinguishes mixed microorganisms on same plate.
- Salmonella and Shigella are non-lactose fermenters
- Salmonella: black
- Shigella: pink
Risk factors for C.diff
Over 65
Recent hospitilisation
Recent course of antibiotics
When to give antibiotics for diarrohea
Signs of sepsis
C. Diff infection
Significant co-morbidity
How does HIV cause illness?
Infect cells which carry CD4 receptors e.g. T helper cells, macrophages, dendritic cells
Cause depletion of CD4 T helper cells by:
- direct viral killing of cells
- apoptosis of uninfected cells
- CD8 cytotoxic T cells killing infected CD4 cells
Impairs B cell activation and antibody production
Impairs cytotoxic T cell immunity
Once CD4 count below 350: symptomatic (require anti-retovirals)
<200: increased risk of opportunistic infections e.g. thrush, oral hairy leokoplakia, TB, pneumocystis jirovecii
<100: serious infections e.g. CMV, mycoplasma
HIV (symptoms, investigations)
Single stranded RNa retrovirus
Needs to transcribe itself into double stranded RNA so make lots of errors - mutations in HIV genome common
Symptoms:
Fever, weight loss, maculopapular rash, lymphadenopathy, oral thrush
Investigations:
HIV antibody via ELISA, confirmed by Western blot
HIV p24 antigen
Drug targets
NRTI/NNRTI (non/nucleotide reverse transcriptase inhibitors) - stops transcription
Fusion inhibitor - stops CD4 binding, stopping internalisation of virus
Protease inhibitor - stops cleavage of protein to make new viral proteins
Integrase inhibitor - stops enzyme (integrase) from inserting HIV genome into host cell DNA
HIV latency
Period between initial infection and advanced HIV (AIDS)
HIV resistance
HIV can still mutate and develop, when whilst on medication which leads to drug resistance HIV strains
So adherence of medication every day, is essential
HIV clinical markers
CD4 cell count: no. of CD4 T helper cells
600-1200 normal
<200 risk of opportunistic infections
HIV-1 plasma RNA (viral load): measures HIV RNA in plasma
Less than 40 copies/ml - undetectable
Differential diagnosis primary HIV
Infectious mononucleosis
Secondary Syphillis
Drug rash
Viral - Cytomegalovirus
HIV Treatments
HAART (highly active antiretroviral treatment) - triple therapy (cART)
- 2 NRTIs+ 1 non-nucleotide reverse transcriptase inhibitor or protease inhibitor)
Started when CD4 count <350, or symptomatic
Disadvantages:
Requires good adherece
Short term toxicity - rash, CNS symptoms
Long term toxicity - renal, hepatic toxicity
Drug interactions - mediated by CYP450. Can interact with statins, PPIs
Long term mortality affected by: CD4 count, viral load at diagnosis, individuals with an AIDs illness, poor adherence to HAART
Prophylaxis: 2NRTI + PI within 72 hrs
AIDS
Group of life-threatning conditions that are caused by damage to immune system by HIV
Viral: CMV
Bacterial: TB
Fungal: Candidiasis
Protazoal: Cryptosporidium
Malignancies: Kapsoi’s sarcoma (human herpes virus 8)
Other: dementia
Non-infectious causes of diarrohea
IBD - Young people. Bloody stool. May have weight loss
Bowel cancer - Older people. Altered bowel habits. Marked weight loss
Diverticular disease - Older people. Alternating diarrohoea and constipation. May have diverticulitis - diverticulae becomes impacted with faeces leading to infection
Chornic pancreatitis - alcohol
Ischaemic bowel disease - Older people. History of vascular disease or AF
HIV - Enterocytes infected with HIV. Oral thrush, shingles, weight loss, thrombocytopenia
Sepsis
Viruses causing gastroenteritis
Norovirus and sappovirus - Calciviridae family
Affects healthy individuals
Rotavirus/Adenovirus/Astrovirus - affects under 2s, elderly, immunocompromised
Norovirus
SS RNA virus
GII-4 most common in UK
Transmission: Person-person (faecal oral), food borne, water
Vomiting, diarrhoea
Treatment: IV/oral fluids, analgesics
Rotavirus
DS RNA virus
G1 accounts for 70% infections
Clinical features: low infectious dose, person-person
Clinical features: watery diarrhoea, loss of electrolytes leads to dehydration
1st infection after 3 months most severe
Vaccination: Rotarix
Adenovirus 40/41
DS DNA virus
Clinical features: Fever, watery diarrhoea
Treatment: Supportive
Astrovirus
SS RNA virus
Causes less severe gastroenteritis than other viruses
Nisseria gonorrhoea
Gram neg cocci
Presents with purulent discharge and urethritis
Diagnosis:
Urethral gram film
NAAT (nucleic acid amplification test):
- male urine +/- rectal/throat swab
- vulvovaginal swab
Confirm positive NAAT with gonococcal culture
Complications: disseminated gonorrhoea - arthritis, pustules on digits
Treatment: Ceftriaxone, azithromycin
Partner notification
Resistance to penicillins, tetracyclines, quinolones as easily acquire plasmids
Chlamydia trachomatis
Clinical features: asymptomatic
Complications: tubal damage, inflammatory pelvic disease
Treatment: Doxycylcine, Azrithromycin
Lymphogranuloma venereum
Lymphotropic chlamydia
Severe proctitis (inflammation of lining of rectum) - constipation, bleeding
inguinal “bubos” (enlarged LN in groin area)
Nissseria gonorrhae
Gram neg diplococci
Triponeum Pallodium
Syphillis
Primary (chancre (painless ulcer)) - Secondary (rash, flu-like illness) - Tertiary - Gumma (granulotamous lesion), Cardio - aortic regurg, Neuro - meningitis
Treatment: penicillin
Viral STIs
Herpes simplex virus
HSV2 - causes gential herpes
Symptoms: asymptomatic, shallow, painful ulcers
Fever, bilateral lymphadenopathy
Treatment: Aciclovir
Molloscum contagiosum
Pox virus
Pearl-like smooth papules
Pubic area
If extensive/on face - can indicate immunosuppression
Treatment: Self limiting
Human papilloma virus
HPV 6, 11 - genital warts
Warts on genitalia in females, and on penile shaft and urethra in males
Treatment: Imiquimod, Cryotherapy
Natural history HIV
Primary infection - CD4 depleted, symptoms: fever, maculopapular rash, weight loss
Body has immune repsonse against HIV, CD4 count increases
Clinical latency:
Symptoms don’t occur for years
CD4 count slowly decreases
Consitutional symptoms: fever, malaise, swollen LNs
Opportunictic infections: oral thrush, pneumocystic jirovecii
Types of vaccinations
Live attenuated
Promotes full immune repsonse after 1 or 2 doses
Virus is weakened/attenuated
MMR, VZV
Not given to immunocompromised
Inactivated - either whole or part of virus/bacterium
Subtypes:
Toxin mediated - Diptheria
Bacteria mediated (polysaccharide based) - pneumococcal
Conjugate vaccines
Plain polysaccharide antigens don’t stimulate immune system as broadly as protein antigens e.g. diptheria
So polysaccharise vaccines enhanced by conjugation of protein antigens e.g. MenC
Septic arthritis
Joint infection. Medical emergency. Can lead to OA and septic shock
Organisms:
- Gram positive: MSSA, MRSA, streptococci pyogenes
- Gram negative: H. influenzae
Clinical features: fever, single hot joint (hip, knee), loss of movement, pain
Investigations
Bloods - FBC, CRP, blood cultures
Joint aspirate - gram stain, microscopy for culture
Imaging
Treatment: IV antibiotics
Prosthetic joint infections
Pathogens: Staph aureus, Coag negative staphylococci
Low virulence - coag neg
High virulence - MSSA, MRSA
Clinical presentation:
Pain, effusion, warm joint, fever
Spread:
Local spread - 80% infections, organisms from skin surface
Haematogenous spread - 20% infections. Presents later. Can be any organism
Pathogenesis:
Prosthetics need fewer bacteria to cause sepsis
Avascular surface protects bacteria from immune system, antibiotics
Cement can inhibit phagocytosis
Treatment
Antibiotic prophylaxis - Cephalosporins
DAIR - (debride, antitiobitcs, implant retained)
- If prosthesis acute (<30 days), debride, wash joint, IV antibiotics can keep it in (IV Gent+IV Vanc)
If infection over 30 days - remove: Girdlestone procedure (no joint), one/two stage revision
Osteomyelitis
Progressive infection of bone characterised by death of bone and formation of sequestra (piece of bone separated by surrounding bone due to necrosis)
Spread: Haematogenous, contiguous (actual contact)
Pathogens: MSSA, MRSA, Anaerobes
Treatment: Surgery to debulk infection, IV antibiotics
Vertebral discitis
Infection of a disc space and adjacent vertebral end plates
Can cause deformity, SC compression, paraplegia
Organisms: MSSA, MRSA, TB
Investigations and treatments for STIs
Examination:
Genital, anal, proctoscopic exam (exams anal cavity)
Mouth - candida, oral hairy leukoplakia
Investigations:
Bloods - HIV, syphillis, Hep B
NAAT - gonorrhoea, chlamydia
Rectal swab - for gram stain
HSV/syphillis PCR
Treatment:
Gonorrhoea - Ceftriaxone (resistant to penicillin, tetra, quinolones)
Chlamydia - Doxycycline or azithromycin
Syphillis - Pencillin
HSV - Aciclovir
HIV - HAART
VZV
Itchy vesicular rash, fever
Starts on face, chest and spreads to rest of body - centripetal distribution
Reactivation - herpes zoster (shingles) - reactivation of VZV from latency in dorsal root ganglia
Complications: bacterial infection, haemorrhagic varicella
Risk factors: adults, neonates, immunucompromised (risk of disseminated infection - haemorrhagic varicella)
Transmission:
Contagious 48 hours before onset of rash, up to when lesions are crusted over
Respiratory transmission, contact with vesicle fluid
Treatment
Aciclovir - Converted to aciclovir triphosphate, nucleic acid analogue, inhibits viral DNA polymerase, inhibits viral replication
Side effects: nephrotoxicity, NandV
Enterovirus
Hand, food and mouth disease
Common cold-like symptoms, fever
Non-itchy vesicular rash on palms and soles
Painful mouth ulcers
Herpangina - oropharyngeal vesicular rash. Commonly due to coxsackievirus A16, B
Most common enterovirus: coxsackie virus A16, 6
Differentials for vesicular rash
HSV
VZV
Enterovirus
Investigations for VZV, HSV, Enterovirus
Chicken pox - clinical diagnosis
VZV, HSV, Enterovirus - PCR via vesicle swab
Immunocompromised patients
Primary immunodeficiency - SCID (severe combined immunodeficiency)
Chemo/radiotherapy
Pts who recieved solid organ transplant and on immunosuppressive treatment
Pts on high-dose steroids
Immunosuppresive drugs e.g. methotrexate
VZV prophylaxis
Varizellar zoster immunoglobulin
Indicated for:
Significant exposure to chicken pox/herpes zoster
Immunocompromised
No antibodies to VZV
Not indicated for immnunosuppressed with antibodies
Strep pneumoniae
Symptoms: chest symptoms - cough, purulent sputum, pleuritic chest pain
Treatment: Amoxcillin
If severe (3 or more CURB65): IV Clarithromycin + IV amoxcillin
Atypicals: Clarithromycin or Doxycycline
Can cause pleural effusions - parapneumonic effusions (usually self limiting).
However, bacteria can enter fluid and cause infection - complicated pleural effusion.
Can lead to empyema (pus in pleural space)
Treatment: chest drain, IV amox
TB (symptoms, pathophy, investigations, treatment)
Mycobacterium tuberculosis
Others: M.bovis, avium
Symptoms:
weight loss, night sweats, fever
Differential: bronchial carcinoma, CAP
Pathophysiology:
Inhaled TB into lungs, taken up into alveolar macrophages, which are not phagocytosed. Kill macrophages and are released, activating immune response
Leads to primary disease, or more commonly latent disease
Latent TB:
Containment of TB depends on T helper cell mediated immunity. T cella and macrophages forms necrotising (casseous) granuloma, with mostly lymphocytes and macrophages at periphery
Active usually occurs by re-activation from latent TB. HIV, immunosuppressants, corticosteroids can increase risk
Investigations:
Sputum culture: Ziehl-Nielsan stain showing acid-fast bacilli
CXR (exclude bronchail neoplasm, or active TB - Ghon complex (calcified granuloma). When assoc with hilar lymph node - Ranke complex
Sceondary (re-activated) TB - lung apices
Pleural fluid
Pleural biopsy - show necrotising granuloma
Alwayas test for HIV
Treatment:
RIPE
Pyrazinamide - little acitivity agianst slow growing bacilli so stopped after 2 months
Ethambutol stopped if sesitivities known
Isoniazid can lead to peripheral neuropathy as anatagonises pyridoxine. Pyridoxine used as prophylaxis
R, I, P = hepatotoxic
Rifampicin induces hepatic CYP450
Ethambutol = visual problems
Complications TB:
Milary TB - disseminated TB in lung
Nodal TB: cervical
Osteomylitis: esp. bones of vertebral column
CNS TB: Cerebral TB or meningtis TB
Pneumocystis jirovecii
Opportunisitc infection
Fungal
Causes progressive SOB, dry cough
Perihilar interstitial shadowing on CXR
Can lead to pneumothorax
Treatment: Co-trimoxazole and steroids
HIV diagnosis
HIV antibody test: ELISA, confirm with Western blot - gel electrophoresis to detect HIV protein
p24 antigen test
HIV treatment
HAART
2 NRTI and 1 other e.g. NNRTI or PI
Started when CD4 count less than 350
Risk factors for immunocompromised patients
Neutropenia: < 0.5
Risk of gram positive: staph. aureus
neg: E.coli
Damaged skin due to IV lines: staph. aureus
Oral mucositis: strep. viridans
Damaged gut mucosa: E.coli
Impaired cellular immunity: viral, protazoal
Impaired humoral immunity: strep. pneumoniae
Hyosplenism: strep. pneumoniae
Malnutrition
Candida
Candida endophthalmitis
Commonly disseminates to eye
Treatment:
Amphotericin
(Fluconazole in an immunocompetent patient)
PCOS
Symptoms: Annovulation (ammenorhoea), hyperandrogenism (hirsutism, acne)
Present at adolescence
Raised testosterone and LH
Patho
Gonadotrophins
Increased LH (increased LH receptors, supports ovarian theca cells - increased androgens), decreased FSH (decreased conversion of androgens to oestrogen)
Increased androgen biosynthesis
- Increased androgen production from theca cells
- Decreased steroid hormone binding globulin (binds testosterone. Only free testosterone is active)
Increased insulin resistance
- increased insulin secretion - reduces SHBG, increased circulating androgens
Investigations
Testosterone
SHBG
LH/FSH
TMD2
Treatment:
Metformin: not effective for infertility, hirsutism but could be useful for diabetes
COCP: ovarian androgen supppression
Corticosteroids: adrenal androgen suppression
Spironolactone: androgen receptor antagonist
Causes of ammenorrhoea
Primary:
Rokitasnky syndrome
Turner’s syndrome
Kallman’s syndrome
Secondary:
Asherman’s syndrome
PCOS
Prolactinoma
Others:
Pregnancy, OCP, Cushing’s
Hirsutism
Excess hair growth in male pattern due to increased androgens
Causes:
PCOS
Androgen secreting tumour
Adrenal cortex
Glomerulosa: Aldosterone
Fasciculata: Cortisol
Reticularis: Androgens
Adrenal medulla: Catecholamines
p. jirovecii
Opportunistic fungal infection
Causes interstitial plasma cell pneumonia, with foamy exudates in alveoli
CXR: interstitial peri-hilar shadowing
Symptoms: progressive SOB, dry cough, fever and failure to respond to usual antibiotics
Complications: resp failure
Treatment: co-trimoxazole, and steroids
Bacterial Meningitis
Reduced GCS and febrile pt indicates CNS infection and BM
Symptoms: nuchal rigidity, headache, confusion, fever
Causes: strep. pneumoniae, nisseria meningitidis
Complications: CN palsies e.g. sensorineural hearing loss, seizures (more common in pneumococcal)
Risk factors for pneumococcal; >60, alcohol dependence, immunosuppressed, middle ear disease, previous head trauma
Resp viruses
Common cold: Rhinovirus, coronavirus
Pharyngitis: Adenovirus
- sore throat, pharyngeal inflammation
Croup: parainfluezna
- distinctive cough
Acute bronchitis: RSV
Bronchiolitis: RSV
- lower resp tract of young children
- wheeezing, tacycardia, persistent cough
Pneumonia: Influenza, RSV
Common complications: otitis media, sinusitis
Uncommon complications: Reye syndrome
